Does Conservative Kidney Management Offer a Quantity or Quality of Life Benefit Compared to Dialysis? A Systematic Review

Does Conservative Kidney Management Offer a Quantity or Quality of Life Benefit Compared to Dialysis? 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A Systematic Review Buur Louise Engelbrecht, Madsen Jens Kristian, Eidemak Inge, Krarup Elizabeth, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-196946/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Patients with stage 5 chronic kidney disease (CKD5) collaborate with their clinicians when choosing their future treatment modality. Most elderly patients with CKD5 may only have two treatment options: dialysis or conservative kidney management (CKM). The objective of this systematic review was to investigate whether CKM offers a quantity or quality of life benefit compared to dialysis for some patients with CKD5. Methods The databases MEDLINE, EMBASE, the Cochrane Library, and CINAHL were systematically searched for studies comparing patients with CKD5 treated with CKM or dialysis. The primary outcomes were mortality and quality of life (QoL). Hospitalization, symptom burden, and place of death were secondary outcomes. For studies reporting hazard ratios, pooled values were calculated, and forest plots conducted. Results Twenty-four primary studies, all observational, were identified. All studies except one reported an increased mortality in patients treated with CKM (pooled hazard ratio 0.53, 95% confidence interval 0.41-0.69). For patients aged ≥ 80 years and for elderly individuals with comorbidities, results were ambiguous. In most studies, CKM seemed advantageous for QoL and secondary outcomes. Findings were limited by the heterogeneity of studies and biased outcomes favouring dialysis. Conclusions In general, patients with CKD5 live for a shorter time on CKM than on dialysis. In patients aged ≥ 80 years old, and in elderly individuals with comorbidities, the survival benefits of dialysis seem to be lost. Regarding QoL, symptom burden, hospitalization, and place of death, CKM may have advantages. Higher quality studies are needed to guide patients and clinicians in the decision-making process. Urology & Nephrology Stage 5 chronic kidney disease end-stage kidney disease dialysis conservative kidney management mortality quality of life Figures Figure 1 Figure 2 Figure 3 Introduction Patients with CKD5 have high mortality rates (1). Most patients are older than 65 years old, and less than 20% are eligible for a kidney transplant (2). Many of these older patients with CKD5 are not eligible for a kidney transplant because they are too frail. Therefore, when dialysis is needed, their treatment options are haemodialysis (HD) or peritoneal dialysis (PD), often in the form of assisted automated PD (AAPD). Dialysis can be burdensome for various reasons, including exhausting travel, complications related to the treatment, or the fact that it is so time-consuming. Thus, while dialysis may prolong patients’ lives, it may adversely affect their QoL (3). For some patients, CKM could be a viable alternative to dialysis. CKM is a treatment strategy that gives patients all the same treatments as those on dialysis, omitting only the dialysis itself (4). Patients and clinicians may find it challenging to discuss and decide on a future treatment modality based on both the best evidence and the individual patient’s preferences. Various aspects have to be considered, which may lead to a complex decision-making process. What is important depends on individual patients and may include survival, QoL, symptom burden, hospitalization, or place of death. Studies of this topic are sparse and heterogeneous, which presents challenges for clinical practice. Usually, clinical guidelines inform clinical practice (5). An international guideline from 2012 (6) approaches the structure and process of CKM as an alternative treatment pathway for patients with CKD5 who choose not to pursue kidney replacement therapy. The guideline reports paucity in many of the areas reviewed. However, MEDLINE was the only database searched in establishing this guideline. A European guideline from 2016 (7) addresses the question: What is the benefit of dialysis in frail and older patients? The guideline discusses many important factors related to treatment decision-making such as mortality, QoL, symptom burden, and hospitalization. For some of the issues, however, only a few studies were identified. A more recent UK guideline from 2018 (8) also addresses this question, but includes only mortality as an outcome. Given the lack of clinical guidelines, systematic reviews are beneficial in summarizing the evidence in studies around a specific topic. A number of systematic reviews of varying quality were published at around the same time as the European guideline (9-12). To date, no randomized controlled trials (RCTs) have been published on this topic. Recognizing the quality of the European guideline from 2016, the objective of this systematic review was to investigate whether CKM involves quantity or quality of life compared to dialysis for some patients with CKD5 in terms of the outcomes of mortality, QoL, hospitalization, symptom burden, and place of death. Materials & Methods The systematic review has been conducted as recommended by the Cochrane Collaboration (13). The process and results have been documented in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement for reporting systematic reviews (14, 15). The protocol for this review was prospectively registered with the Danish Health Authority, and no changes have been made. The review has been conducted by a working group involving doctors and nurses in nephrology as part of the preparation of a national clinical guideline. They have been supported with input from an interprofessional reference group consisting of representatives from the Danish Kidney Association and the Danish professional societies for nephrology, specialized palliative care, geriatrics, and general practitioners. Eligibility Criteria Participants Based on the question Does conservative kidney management offer a quantity or quality of life benefit compared to dialysis? this review examined studies including adults aged 18 years old and above who had been diagnosed with CKD5. Studies that included adults with stage 1-4 chronic kidney disease (CKD1-4) or children were excluded. Interventions Studies investigating CKM interventions or any intervention defined as a treatment strategy without dialysis for patients with CKD5 were considered. Comparators The review included studies comparing interventions for patients treated with HD or PD. Outcomes The primary outcomes were mortality and QoL. Secondary outcomes were hospitalization, symptom burden, and place of death, defined as whether the location of death was in accordance with a patient’s preference. Types of Studies Included This review considered all study designs relevant for answering the PICO (Patient, Intervention, Comparison, Outcome) question, including secondary literature such as systematic reviews, clinical guidelines, and grey literature. Information Sources According to the pre-specified protocol, a comprehensive literature search was conducted by the working group in collaboration with a literary search specialist from October 9, 2018 to May 13, 2019. This searched for guidelines in English, Danish, Norwegian, and Swedish published in electronic databases. The databases searched were Guidelines International Network (G-I-N), NICE (UK), Scottish Intercollegiate Guidelines Network (SIGN), HTA database, SBU (Sweden), Socialstyrelsen (Sweden), Helsedirektoratet (Norway), Kunnskapssenteret (Norway), MEDLINE, EMBASE, and CINAHL. The databases searched for secondary literature as well as primary literature were MEDLINE, EMBASE, the Cochrane Library, and CINAHL [Additional file 1]. Search Strategy A three-phase search strategy was used to locate eligible studies. First, a search for clinical guidelines was conducted, followed by a search for secondary literature (Cochrane reviews, systematic reviews, and meta-analyses). Finally, primary literature was searched with no time limit. The full search protocols are given in the supplementary material [see Additional file 1]. The following search terms were used to identify primary studies: exp Kidney Failure, Chronic/ ((end stage or chronic) adj3 (kidney diseas* or kidney failure* or renal disease* or renal failure*)).ab,kf,ti. AND Conservative Treatment/Palliative Care/ ((conservative or supportive) adj3 (treatment* or management or care)).ab,kf,ti. (nondialy* or non-dialy*).ab,kf,ti. ((without or refus*) adj2 dialys*) .ab,kf,ti. AND “Quality of Life”/ exp Mortality/Patient Readmission/ (“quality of life” or qol or mortality).ab,kf,ti. place of death.ab,kf,ti. (symptom* adj2 burden*).ab,kf,ti. Life Expectancy/ life expectancy.ab,kf,ti. Study Selection The process of selecting studies was administered through the systematic review management tool Covidence (16). Titles were checked for duplicates when entering the eligible literature into Covidence. Two authors independently screened the titles and abstracts of the remaining studies for full-text retrieval. Similarly, two authors independently assessed full-text eligibility for inclusion. Discrepancies in judgement were resolved by consensus. Data Extraction All relevant data and outcomes (mortality, QoL, hospitalization, symptom burden, and place of death) for the PICO question were extracted from each study by two authors independently. Consensus was reached regarding any discrepancies. Risk of Bias within Studies To assess the quality of the studies selected, the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used because only observational studies were included. Assessment was carried out at outcome level and summarized. Risk of Bias across Studies The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of the body of evidence for each relevant outcome in the selected studies (17). Data Synthesis The data extracted from the selected studies was entered into the Review Manager (RevMan5) software (18), used for preparing and updating Cochrane Reviews. Where comparable effect estimates and measures of variance (standard deviation, 95% confidence intervals) were available, data were pooled using an inverse variance random effect model (19) to conduct a meta-analysis, presented as a forest plot. The overall heterogeneity of the studies was tested using the I 2 , indicating the variation across studies that is due to heterogeneity, where heterogeneity is indicated by I 2 over 75% (19). The random effect model was chosen due to an expected heterogeneous effect (19). Mostly, relevant findings are presented narratively. Means with standard deviations (SD), mean differences, and means with confidence intervals at a 95% confidence level (95% CI) were gathered for continuous data where possible. Hazard ratios (HR), relative risks (RR), and odds ratios (OR) with 95% CI were collected from dichotomous data. Results After removal of duplicates, screening of titles and abstracts, and subsequent full-text assessment, a total of one guideline, four systematic reviews, and 24 primary studies were identified. The flow diagram in Figure 1 gives details of the primary literature search process. Flow diagrams for the guideline search and review search are included in the supplementary material [Additional file 2]. Guideline and Systematic Reviews The European guideline (7) covers the evidence relevant for our PICO question until the end of the guideline’s literature search in May 2016. All four of the systematic reviews identified (9, 10, 12, 20) synthesized the evidence. Not all the outcomes selected for the PICO question in this review were discussed in the earlier reviews. Two studies conducted meta-analyses, one including hospitalization and both including mortality as outcomes (9, 12). In the supplementary material, we have provided an overview of the primary studies included in our review compared to studies included in the European guideline and the four systematic reviews selected [Additional file 3]. The supplementary material also provides a list of studies present in the guideline or reviews that we did not include, with references and reasons for exclusion [Additional file 4]. Primary Literature Table 1 presents basic characteristics and data extraction for the 24 primary studies selected. All studies were observational: 9 prospective cohort studies (3, 21-28); 11 retrospective cohort studies (29-39); and 4 cross-sectional studies (40-43). In general, patients on CKM were older and, when reported, had more comorbidities and poorer functional status compared to other groups. The heterogeneity between studies in relation to interventions, comparators, statistical analyses, and treatment modalities affected the possibility of conducting meta-analyses for all outcomes except mortality and hospitalization. Even for these two outcomes, not all studies reported data suitable for meta-analyses. The quality assessments using ROBINS-I are presented in the supplementary material [Additional file 5], showing that only three studies had a low risk of bias, 12 studies had a moderate risk of bias, eight studies had a serious risk of bias, and one study had a critical risk of bias. The directness of bias for most studies was unpredictable or in favour of dialysis. Mortality In total, 18 of both prospective and retrospective primary observational studies comparing CKM and dialysis, patients on CKM had higher mortality rates (3, 21-26, 28-34, 36-39). A meta-analysis is presented in Figure 2. One retrospective study, however, reported a 1.4-fold increase in risk of mortality for patients ≥ 70 years old who were treated with dialysis (35). In a study of patients ≥ 75 years old, the higher mortality rate for those on CKM compared to dialysis was significantly reduced in patients with high comorbidities, especially ischemic heart disease (29). For patients ≥ 80 years, the results seem conflicting. One study investigating octogenarians reported higher mortality for patients on CKM (23). In contrast, three other studies found overall that mortality was equal for patients ≥ 80 years old (21, 30, 31). Quality of life One prospective cohort study found that patients with CKD5 on CKM had poorer self-reported QoL at baseline compared to patients on dialysis, but only with a borderline significance (p = 0.05) (21). At a six-month follow-up, self-reported QoL was higher among patients on CKM compared to those on dialysis (p < 0.01). Another prospective cohort study found no difference in the mental health summary scores at baseline but significant difference in the physical health summary scores (p=0.001). There were, however, no difference in QoL over time (3). In a retrospective cohort study, there were no difference between patients managed conservatively and dialysis patients on physical and mental health summary scores (31). The results of two cross-sectional studies were heterogeneous (40, 42). One study found no difference in self-reported QoL (SF-36) between patients on CKM, HD, or PD (40). Results from the other cross-sectional study varied depending on the tool used to measure QoL. Symptom burden In a small prospective study, commencement of dialysis in a younger cohort of elderly patients was associated with decrease in overall symptom burden (27). Two cross-sectional primary comparative studies found that patients on CKM had a lower symptom burden compared to patients on dialysis (41, 42). A third cross-sectional study comparing a group of patients with CKD5 receiving palliative care and patients on dialysis found overlapping symptom prevalence and intensity between the groups (43). Hospitalization We identified three prospective (21, 22, 24) and three retrospective (33, 34, 38) primary cohort studies comparing the hospitalization of patients. Results were heterogeneous. Most studies found that patients on CKM had fewer hospital admissions or a significantly lower risk of hospitalization than patients on dialysis (22, 24, 33, 38). Figure 3 shows a meta-analysis of the number of admission days. One study observed no difference in number of hospital admissions and number of days spent in hospital between groups (21). Finally, one study comparing patients treated with CKM to patients on PD observed fewer days spent in hospital per person year for the patients treated with PD (34). Place of death Results from two primary studies indicate that patients on CKM more often die at home or in a hospice compared to patients on dialysis, who more often die in hospital (24, 25). Discussion Summary of Evidence This review identified 24 studies comparing patients with CKD5 receiving CKM with those on dialysis to investigate the outcomes of mortality, QoL, symptom burden, hospitalization, and place of death. The studies were of variable quality, and there was substantial heterogeneity in presentation of the data, making it difficult to conduct an adequate meta-analysis for most outcomes. Based on the available evidence, according to our review, CKM does not provide the same or extended survival in patients with CKD5 compared to dialysis. This is in line with previous systematic reviews (9, 12). Overall, in contrast to CKM, dialysis is life prolonging. However, some studies indicate that the two treatment strategies may provide equal rates of mortality for patients who are 80 years old and above, or elderly patients with high comorbidities (21, 29, 30, 35). Thus, information on CKM may be considered in clinical practice in relation to this patient group. Some studies indicate that CKM may result in higher QoL compared to dialysis, and patients who receive CKM seem to have less hospitalization than patients on dialysis (21, 40-42). Regarding symptom burden, results were conflicting. A recently published systematic review (44) concludes that in selected older patients, CKM has the potential to achieve similar QoL compared to a dialysis pathway (44). Most of the studies identified compared patients on HD with those treated with PD or did not report details of dialysis modality. There was very little data comparing patients on CKM with patients on PD. Our findings suggest that there may be differences between these two patient groups for the outcomes of symptom burden and hospitalization. Thus, these aspects should be considered in the decision-making process involved in choosing a patient’s preferred treatment strategy. Only one study investigated whether preferred place of death for patients with CKD5 on either CKM or dialysis was congruent with their actual place of death (24). The study indicated that patients on the CKM pathway more often die at home or in a hospice compared to patients on dialysis, who more often die in hospital. Studies of the general public and of patients with cancer have shown that most people would prefer to die at home (45, 46). Based on our review, dying at home or in a hospice seems more likely to be the outcome for patients managed conservatively compared to patients on dialysis (24, 25). Whether this result fulfils patients’ preferences was, however, unclear. Strengths And Limitations This review was conducted rigorously, using robust processes and relevant software tools. However, the study does have some limitations. All previous studies analysed were of observational design with variable sample size and quality and investigated patient groups that were heterogeneously defined. Furthermore, outcomes were assessed over different time periods. The quality of studies was reduced due to lead time bias when estimating mortality, and by confounders mostly favouring dialysis. Data heterogeneity restricted the use of meta-analysis. A very high heterogeneity (I 2 =97%) were found in the meta-analysis of mortality (See Figure 2). Two Studies (35, 36) are outliers having huge differences between the number of participants in the CKM group and the dialysis group; one study a three-fold difference (35) and the other study a 50-fold difference. Excluding these two studies from the meta-analysis we obtained a low to moderate heterogeneity (I 2 =43%) and still confirming the results of the meta-analysis. Implications for Clinical Practice and Further Research Discussion of treatment options with clinicians is crucial for patients with CKD5 regardless of their preferred modality of treatment. In a recent qualitative study from the UK, 20 patients receiving CKM were interviewed (47). The patients’ experience was that clinicians avoided talking about diagnosis and prognosis related to their disease. The patients expressed a desire to receive information related to their disease and possible treatment choices. At the same time, however, they were ambivalent about receiving detailed knowledge on the progression of their disease. Although the evidence in our review relies on observational data, the results suggest a CKM pathway can be an acceptable alternative to dialysis for patients aged 80 years and above or elderly patients with comorbidities. Consequently, discussion of CKM as a future treatment modality with this group of patients is important. A Canadian survey from 2010 showed that 60% of the patients receiving dialysis regretted having started the treatment (48). The findings of one qualitative review indicated that patients with CKD were capable of prioritizing QoL and freedom over survival (49). Based on the findings of this review, aspects of QoL, symptom burden, and hospitalization should be considered in the decision-making process when choosing the preferred treatment strategy. To date, the evidence of outcomes for patients with CKD5 receiving dialysis compared to patients on a CKM pathway has been drawn from observational studies of varying quality, many of which were retrospective. No randomized controlled studies have yet been published in this area. For ethical reasons, conducting such studies may be very problematic or even impossible. Thus, future research may also have to rely mainly on observational studies. Such studies should be carefully planned, with a prospective design and a strict methodology to minimize bias and the influence of confounders. Comparative studies of patients on CKM or PD may provide a more nuanced basis for discussions of future treatment choices for patients with CKD5. Conclusions In this systematic review, we explored studies evaluating CKM as an alternative to dialysis for adult patients with CKD5 in relation to mortality, QoL, hospitalization, symptom burden, and place of death. Overall, patients with CKD5 on CKM have poorer survival compared to patients on dialysis. However, we observed that for patients aged 80 years and above, or elderly patients with severe comorbidities, the improved survival on dialysis over CKM appears to vanish. Despite some inconsistencies, the results suggest CKM has advantages compared to dialysis for the outcomes of QoL, hospitalization, symptom burden, and place of death. These findings should be addressed when discussing future treatment options with patients. More rigorously conducted studies are needed to establish a better base for such a decision-making process. List Of Abbreviations CKD5 Stage 5 chronic kidney disease CKM Conservative kidney management QoL Quality of life HD Haemodialysis PD Peritoneal dialysis AAPD Assisted automated peritoneal dialysis RCTs Randomized controlled trials PRISMA Preferred reporting items for systematic reviews and meta-analyses CKD 1-4 Stage 1-4 chronic kidney disease PICO Patient, Intervention, Comparison, Outcome ROBINS-I Risk Of Bias In Non-randomized Studies of Interventions tool GRADE The Grading of Recommendations Assessment, Development and Evaluation methodology RevMan5 Review Manager software SD Standard deviations 95% CI 95% confidence Interval HR Hazard ratios RR Relative risks OR Odds ratios (OR) Declarations Ethics approval and consent to participate Not applicable Consent for publication Not applicable Availability of data and materials Data sharing is not applicable to this article as no dataset were generated or analysed during the current study Competing interests The authors declare that they have no competing interests Funding The review is part of the preparation of a national clinical guideline, funded by the Danish Health Authority Authors’ contributions All authors collected the data and conducted the analyses. Buur LE drafted the manuscript in collaboration with Finderup J. All authors critically reviewed and provided intellectual input to the manuscript. All authors read and approved the final manuscript. Acknowledgements The authors would like to thank the members of the reference group for their constructive comments and suggestions during the planning and development of this research work. Representatives were: Jan Rishave, Danish Kidney Association; Lisbet Brandi, Danish Society of Nephrology; Karina Bruun, Danish Society of Renal Nurses; Birthe Thoerring, Danish Society of Palliative Medicine; Ellen Holm, Danish Gerontological Society; and Jette Kolding Kristensen, Danish College of General Practitioners. The authors also wish to thank member of the working group Line Staermose Jensen for her work on the national clinical guideline, of which this systematic review is a part. References O'Halloran P, Noble H, Norwood K, Maxwell P, Shields J, Fogarty D, et al. 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Health-related quality of life and symptoms of conservative care versus dialysis in patients with end-stage kidney disease: a systematic review. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020. Gomes B, Calanzani N, Gysels M, Hall S, Higginson IJ. Heterogeneity and changes in preferences for dying at home: a systematic review. BMC palliative care. 2013;12:7. Gomes B, Higginson IJ, Calanzani N, Cohen J, Deliens L, Daveson BA, et al. Preferences for place of death if faced with advanced cancer: a population survey in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain. Annals of oncology : official journal of the European Society for Medical Oncology. 2012;23(8):2006-15. Selman LE, Bristowe K, Higginson IJ, Murtagh FEM. The views and experiences of older people with conservatively managed renal failure: a qualitative study of communication, information and decision-making. BMC nephrology. 2019;20(1):38. Davison SN. End-of-life care preferences and needs: perceptions of patients with chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN. 2010;5(2):195-204. Tong A, Cheung KL, Nair SS, Kurella Tamura M, Craig JC, Winkelmayer WC. Thematic synthesis of qualitative studies on patient and caregiver perspectives on end-of-life care in CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2014;63(6):913-27. Tables Table 1: Table with Details of the Primary Studies Selected for Inclusion Author, year of publication Population Age (years) 1 Intervention, n Comparator, n Main outcome measures and results 1 Almutary, 2016 (40) Non-dialysis group (CKD4 & CKM (CKD5)) Dialysis group (HD & PD) Total group 48.29 (±14.86) CKM (CKD5), 51.84±15.11 HD, 47.71±14.46 PD, 43.08±15.09 CKM (CKD5), 38 HD, 287 PD, 42 Symptom burden (CKD-SBI) Dialysis vs. CKM (CKD5): HD: 23.36±16.99; PD: 12.04±6.58, vs. CKM (CKD5): 8.1±8.04; p <0.001 Carson, 2009 (23) CKD5 Age ≥70 at inclusion CKM, mean 81.6; median 83 Dialysis, mean 76.4; median 75 CKM, 29 Dialysis, 173 Hospitalization rate Hospital days/patient days survived: CKM, 4.3±0.26; RRT, 6.9±0.71 Place of death Home/hospice: CKM, 40%; Dialysis 21%, Hospital: CKM, 36%; Dialysis 70% Chandna, 2011 (38) CKD5 CKM 77.5±7.6 Dialysis 58.5±15.0 CKM, 155 Dialysis, 689 Mortality Mortality in patients aged >75: CKM vs. dialysis, HR: 1.18 (95% CI: 0.79-1.76); p = 0.428. In patients with comorbidity score>4: Dialysis, 25.8±4.4(SE); CKM, 20.4±2.4(SE); p=0.83. Da Silva-Gane, 2012 (3) CKD4-5 HD 60.6±14.9 PD 48.0±15.6 CKM 77.5±6.5 CKM, 30 HD,80 PD, 44 Mortality HD vs. CKM, HR 0.47 (95% CI: 0.20-1.10); p = 0.08 PD vs. CKM, HR: 0.39 (95% CI: 0.10-1.48); p = 0.17 Quality of life No difference over time in groups. Hussain, 2013 (37) CKD5 Age >70 at inclusion CKM, 172 Dialysis, 269 Hospitalization Dialysis vs. CKM, RR 1.6 (95% CI: 1.14-2.25), p <0.05. Iyasere, 2019 (39) CKD5 Median age (IQR) CKM, 83 (80-88) aAPD, 81 (79-88) HD, 82 (78-85) CKM, 28 HD, 28 PD, 28 Quality of life SF-12, PCS: CKM, 28.9±10.0; dialysis, 29.2±8.3; p = 0.90 SF-12, MCS: CKM, 46.3±12.1; dialysis, 49.9±12.9; p = 0.28 Joly, 2003 (22) CKD4-5 Age ≥80 at inclusion CKM 84.1±2.9 Dialysis 83.2±2.9 CKM, 43 Dialysis, 101 Mortality CKM, 8.9 months (95% CI: 4-10); dialysis, 28.9 months (95% CI: 24-38); p <0.0001 Kwok, 2016 (36) CKD5 Age ≥65 at inclusion CKM 79.6±6.8 Dialysis 74.2±6.1 CKM, 432 Dialysis, 126 Mortality CKM, 10.0 months (95% CI: 8.3-11.7); dialysis, 44.6 months (95% CI: 37.3-51.9); p 75 at inclusion CKM, 81.36 Dialyse, 78,17 CKM, 77 Dialysis, 52 Mortality CKM vs. dialysis, HR: 2.90 (95% CI: 1.60-5.26); In patients with comorbidity score >2: Dialysis vs CKM: log rank statistic <0.001, df 1, p = 0.98, In patients with ischaemic heart disease: Dialysis vs CKM: log rank statistic 1.46, df 1, p < 0.27. Raman, 2018 (21) CKD5 Dialysis, 78.9±2.8 CKM, 83.7±4.2 CKM, 81 Dialysis, 123 1-year survival Dialysis vs. CKM, OR 0.38 (95% CI: 0.09-1.60); p = 0.19 Hospitalization Number of admission days (median (IQR)): CKM, 0.8 (0.0-8.7); dialysis, 2.2 (0.7-14.7); p = 0.005. Reindl-Schwaighofer, 2017 (35) CKD5 Age >65 at inclusion HD, 74.06±5.78 CKM, 81.22±7.23 CKM, 174 HD, 8622 Mortality HD vs. CKM, HR: 0.23 (95% CI: 0.18-0.29); p 81, n (%): Dialysis 33 (40) CKM 27 (59) CKM, 46 Dialysis, 83 Quality of life Dialysis vs. CKM, adjusted differences in KDQOL-36 scores (95% CI): KDQOL-burden of disease: -28.59 (-41.77 to -15.42); p < .001 KDQOL-symptoms of disease: -5.93 (-14.61 to 2.73); p = 0.18 KDQOL-effects of disease: -16.49 (-25.98 to -6.99); p <0.001 Shih, 2014 (34) CKD5 Age ≥70 at inclusion CKM, 82.0±6.4 Dialysis, 78.6±7.1 CKM, 2049 Dialysis, 6292 Mortality Dialysis vs. CKM, HR: 1.39 (95% CI: 1.30-1.49), p <0.001 Shum, 2014 (33) CKD5 Age 65-90 at inclusion Overall age, 73.8±5.4 CKM, 75.3±5.7 PD, 73.4±5.3 CKM, 42 PD, 157 Mortality PD vs. CKM, HR: 0.46 (95% CI 0.31-0.68), p <0.001. Hospitalization Days per person year, median [IQR] PD, 16.17 [6.29-43.32] vs. CKM, 38.01 [6.75-76.56]; p = 0.03 Smith, 2003 (24) CKD5 CKM (palliative care population), 71±12; Dialysis, 59±15 CKM, 63 Dialysis, 258 Mortality Dialysis, median survival 8.3 months; CKM, median survival 6.3 months; N.S. Place of death Deaths at home or in a hospice: CKM, 22 of 34 deaths (65%) Dialysis, 11 of 41 deaths (27%); p = 0.001 Tam-Tham, 2018 (32) CKD5 Age ≥65 at inclusion Age 65 to <75 (n, %) Dialysis, 228 (45.6) CKM, 45 (13.3) Age 75 to <85 (n, %) Dialysis, 220 (44.0) CKM, 143 (42.3) Age ≥85 (n, %) Dialysis, 52 (10.4) CKM, 150 (44.4) CKM, 338 Dialysis, 500 Mortality Dialysis vs. CKM (0-3 years), HR: 0.56 (95% CI: 0.44-0.71); p 65 at inclusion CKM, 84 Dialysis, 73 CKM, 8 Dialysis, 12 Symptom burden Change (improvement) in mean symptom POS-score over 6 months: CKM, 1.5; dialysis, 7.58; p <0.002. Teo, 2010 (25) CKD5 CKM, 67.4 ± 11.8 HD, 58.7 ± 12.9 CKM, 16 HD, 102 Mortality CKM, HR: 2.29 (95% CI: 1.16-4.45); HD, HR: 0.59 (95% CI: 0.33-1.05); p = 0.042 Teruel, 2015 (31) CKD5 Median age (IQR) Dialysis, 68 (54,76) CKM, 83 (78,86) CKM, 90 Dialysis, 142 Mortality CKM, 8.2/100 patient months; Dialysis, 0.6/100 patient months; p <0.001 van Loon, 2019 (20) CKD5 Age ≥65 at inclusion CKM, 82±6 Dialysis, 75±7 CKM, 89 Dialysis, 192 12-month survival CKM vs. dialysis, HR: 2.12 (95% CI: 1.12-4.03); p = 0.02 In patients < 80 years old, HR: 5.05 (95% CI: 1.90-13.50); p <0.01 In patients ≥ 80 years old, HR: 1.30 (95% CI: 0.58-2.91); p = 0.53 Six-month quality of life EQ-5D Index, mean (SE) change within group: CKM, 0.047 (0.022); p <0.01 Dialysis, 0.026 (0.014); p = 0.10 Between group difference, p <0.01 Hospitalization Median number [IQR] of admissions: CKM, 1 [1-5]; Dialysis, [1-4]; p = 0.27 Hospitalization Median number [IQR] of admission days: Dialysis, 7 [3-15]; CKM, 4 [2-12]; p = 0.22 Verberne, 2018 (30) CKD5 CKM, 82.6±4.5 Dialysis, 76.2±4.4 CKM, 126 Dialysis, 240 Mortality CKM vs. dialysis, HR: 1.67 (95% CI: 1.19-2.35), p = 0.003 Median [IQR] survival in years in patients ≥70 years old: CKM, 1.3 [0.5-2.5]; dialysis, 3.1 [1.7-6.4]; p <0.001 Median [IQR] survival in years in patients ≥80 years old: CKM, 2.3 [1.3-3.7]; dialysis, 2.9 [1.9-6.0]; p = 0.13 Quality of life No difference between groups Verberne, 2016 (29) CKD5 CKM, 83±4.5 Dialysis, 76±4.4 CKM, 107 Dialysis, 204 Mortality Dialysis vs. CKM, HR: 0.62 (95% CI: 0.42-0.92), p = 0.02. Median [IQR] survival in years in patients ≥80 years old: CKM, 1.4 [0.7-3.0]; dialysis, 2.1 [1.5-3.4]; p = 0.08. Yong, 2009 (42) CKD5 CKM, 73.1 ± 7.1 Dialysis, 58.2 ± 11.4 CKM, 45 Dialysis, 134 Symptom burden Number of symptoms CKM, 8.2 ± 3.9; dialysis 9.3 ± 4.7, p = 0.243 Yuen, 2016 (27) CKD5 CKM, 76.8 ± 9.1 Dialysis, 58.6 ± 12.6 CKM, 335 Dialysis, 265 One-year survival (%) CKM, 57.3 ± 2.9; dialysis, 89.7 ± 2.1 3-year survival (%) CKM, 16 ± 2.7; dialysis, 74.6% ± 3.4 CKD4 and CKD5, stage 4 and 5 chronic kidney disease; CKM, conservative kidney management; HD, haemodialysis; PD, peritoneal dialysis; AAPD, assisted automated peritoneal dialysis; IQR, interquartile range; HR, hazard ratio; eGFR, estimated glomerular filtration rate; SE, standard error; RR, relative risk; CKD-SBI, The CKD Symptom Burden Index; SF-12, short form 12; MCS, mental component summary; PCS, physical component summary; KDQOL, Kidney Disease Quality of Life; POS, Palliative Outcome Scale; EQ-5D, European Quality of life-5 Dimensions. 1 Unless otherwise noted, values are expressed as mean ± SD. Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.docx Additionalfile2.docx Additionalfile3.docx Additionalfile4.docx Additionalfile5.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 10 May, 2021 Reviews received at journal 09 May, 2021 Reviewers agreed at journal 04 May, 2021 Reviews received at journal 17 Apr, 2021 Reviewers agreed at journal 31 Mar, 2021 Reviewers invited by journal 12 Feb, 2021 Editor assigned by journal 11 Feb, 2021 Editor invited by journal 11 Feb, 2021 Submission checks completed at journal 11 Feb, 2021 First submitted to journal 01 Feb, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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A Systematic Review\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePatients with CKD5 have high mortality rates (1). Most patients are older than 65 years old, and less than 20% are eligible for a kidney transplant (2).\u003c/p\u003e\n\u003cp\u003eMany of these older patients with CKD5 are not eligible for a kidney transplant because they are too frail. Therefore, when dialysis is needed, their treatment options are haemodialysis (HD) or peritoneal dialysis (PD), often in the form of assisted automated PD (AAPD). Dialysis can be burdensome for various reasons, including exhausting travel, complications related to the treatment, or the fact that it is so time-consuming. Thus, while dialysis may prolong patients\u0026rsquo; lives, it may adversely affect their QoL (3). For some patients, CKM could be a viable alternative to dialysis. CKM is a treatment strategy that gives patients all the same treatments as those on dialysis, omitting only the dialysis itself (4).\u003c/p\u003e\n\u003cp\u003ePatients and clinicians may find it challenging to discuss and decide on a future treatment modality based on both the best evidence and the individual patient\u0026rsquo;s preferences. Various aspects have to be considered, which may lead to a complex decision-making process. What is important depends on individual patients and may include survival, QoL, symptom burden, hospitalization, or place of death. Studies of this topic are sparse and heterogeneous, which presents challenges for clinical practice.\u003c/p\u003e\n\u003cp\u003eUsually, clinical guidelines inform clinical practice (5). An international guideline from 2012 (6) approaches the structure and process of CKM as an alternative treatment pathway for patients with CKD5 who choose not to pursue kidney replacement therapy. The guideline reports paucity in many of the areas reviewed. However, MEDLINE was the only database searched in establishing this guideline. A European guideline from 2016 (7) addresses the question: \u003cem\u003eWhat is the benefit of dialysis in frail and older patients?\u003c/em\u003e The guideline discusses many important factors related to treatment decision-making such as mortality, QoL, symptom burden, and hospitalization. For some of the issues, however, only a few studies were identified. A more recent UK guideline from 2018 (8) also addresses this question, but includes only mortality as an outcome. Given the lack of clinical guidelines, systematic reviews are beneficial in summarizing the evidence in studies around a specific topic. A number of systematic reviews of varying quality were published at around the same time as the European guideline (9-12). To date, no randomized controlled trials (RCTs) have been published on this topic.\u003c/p\u003e\n\u003cp\u003eRecognizing the quality of the European guideline from 2016, the objective of this systematic review was to investigate whether CKM involves quantity or quality of life compared to dialysis for some patients with CKD5 in terms of the outcomes of mortality, QoL, hospitalization, symptom burden, and place of death.\u003c/p\u003e"},{"header":"Materials \u0026 Methods","content":"\u003cp\u003eThe systematic review has been conducted as recommended by the Cochrane Collaboration (13). The process and results have been documented in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement for reporting systematic reviews (14, 15). The protocol for this review was prospectively registered with the Danish Health Authority, and no changes have been made. The review has been conducted by a working group involving doctors and nurses in nephrology as part of the preparation of a national clinical guideline. They have been supported with input from an interprofessional reference group consisting of representatives from the Danish Kidney Association and the Danish professional societies for nephrology, specialized palliative care, geriatrics, and general practitioners.\u003c/p\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003ch4\u003eParticipants\u003c/h4\u003e\n\u003cp\u003eBased on the question \u003cem\u003eDoes conservative kidney management offer a quantity or quality of life benefit compared to dialysis?\u003c/em\u003e this review examined studies including adults aged 18 years old and above who had been diagnosed with CKD5. Studies that included adults with stage 1-4 chronic kidney disease (CKD1-4) or children were excluded.\u003c/p\u003e\n\u003ch4\u003eInterventions\u003c/h4\u003e\n\u003cp\u003eStudies investigating CKM interventions or any intervention defined as a treatment strategy without dialysis for patients with CKD5 were considered.\u003c/p\u003e\n\u003ch4\u003eComparators\u003c/h4\u003e\n\u003cp\u003eThe review included studies comparing interventions for patients treated with HD or PD.\u003c/p\u003e\n\u003ch4\u003eOutcomes\u003c/h4\u003e\n\u003cp\u003eThe primary outcomes were mortality and QoL. Secondary outcomes were hospitalization, symptom burden, and place of death, defined as whether the location of death was in accordance with a patient\u0026rsquo;s preference.\u003c/p\u003e\n\u003ch3\u003eTypes of Studies Included\u003c/h3\u003e\n\u003cp\u003eThis review considered all study designs relevant for answering the PICO (Patient, Intervention, Comparison, Outcome) question, including secondary literature such as systematic reviews, clinical guidelines, and grey literature.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eInformation Sources\u003c/h3\u003e\n\u003cp\u003eAccording to the pre-specified protocol, a comprehensive literature search was conducted by the working group in collaboration with a literary search specialist from October 9, 2018 to May 13, 2019. This searched for guidelines in English, Danish, Norwegian, and Swedish published in electronic databases. The databases searched were Guidelines International Network (G-I-N), NICE (UK), Scottish Intercollegiate Guidelines Network (SIGN), HTA database, SBU (Sweden), Socialstyrelsen (Sweden), Helsedirektoratet (Norway), Kunnskapssenteret (Norway), MEDLINE, EMBASE, and CINAHL. The databases searched for secondary literature as well as primary literature were MEDLINE, EMBASE, the Cochrane Library, and CINAHL [Additional file 1].\u003c/p\u003e\n\u003ch3\u003eSearch Strategy\u003c/h3\u003e\n\u003cp\u003eA three-phase search strategy was used to locate eligible studies. First, a search for clinical guidelines was conducted, followed by a search for secondary literature (Cochrane reviews, systematic reviews, and meta-analyses). Finally, primary literature was searched with no time limit. The full search protocols are given in the supplementary material [see Additional file 1]. The following search terms were used to identify primary studies: exp Kidney Failure, Chronic/ ((end stage or chronic) adj3 (kidney diseas* or kidney failure* or renal disease* or renal failure*)).ab,kf,ti. AND Conservative Treatment/Palliative Care/ ((conservative or supportive) adj3 (treatment* or management or care)).ab,kf,ti. (nondialy* or non-dialy*).ab,kf,ti. ((without or refus*) adj2 dialys*) .ab,kf,ti. AND \u0026ldquo;Quality of Life\u0026rdquo;/ exp Mortality/Patient Readmission/ (\u0026ldquo;quality of life\u0026rdquo; or qol or mortality).ab,kf,ti. place of death.ab,kf,ti. (symptom* adj2 burden*).ab,kf,ti. Life Expectancy/ life expectancy.ab,kf,ti.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eStudy Selection\u003c/h3\u003e\n\u003cp\u003eThe process of selecting studies was administered through the systematic review management tool Covidence (16). Titles were checked for duplicates when entering the eligible literature into Covidence. Two authors independently screened the titles and abstracts of the remaining studies for full-text retrieval. Similarly, two authors independently assessed full-text eligibility for inclusion. Discrepancies in judgement were resolved by consensus.\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eAll relevant data and outcomes (mortality, QoL, hospitalization, symptom burden, and place of death) for the PICO question were extracted from each study by two authors independently. Consensus was reached regarding any discrepancies.\u003c/p\u003e\n\u003ch3\u003eRisk of Bias within Studies\u003c/h3\u003e\n\u003cp\u003eTo assess the quality of the studies selected, the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used because only observational studies were included. Assessment was carried out at outcome level and summarized.\u003c/p\u003e\n\u003ch3\u003eRisk of Bias across Studies\u003c/h3\u003e\n\u003cp\u003eThe Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of the body of evidence for each relevant outcome in the selected studies (17).\u003c/p\u003e\n\u003ch3\u003eData Synthesis\u003c/h3\u003e\n\u003cp\u003eThe data extracted from the selected studies was entered into the Review Manager (RevMan5) software (18), used for preparing and updating Cochrane Reviews. Where comparable effect estimates and measures of variance (standard deviation, 95% confidence intervals) were available, data were pooled using an inverse variance random effect model (19) to conduct a meta-analysis, presented as a forest plot. The overall heterogeneity of the studies was tested using the I\u003csup\u003e2\u003c/sup\u003e, indicating the variation across studies that is due to heterogeneity, where heterogeneity is indicated by I\u003csup\u003e2\u003c/sup\u003e over 75% (19). The random effect model was chosen due to an expected heterogeneous effect (19). Mostly, relevant findings are presented narratively. Means with standard deviations (SD), mean differences, and means with confidence intervals at a 95% confidence level (95% CI) were gathered for continuous data where possible. Hazard ratios (HR), relative risks (RR), and odds ratios (OR) with 95% CI were collected from dichotomous data.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eAfter removal of duplicates, screening of titles and abstracts, and subsequent full-text assessment, a total of one guideline, four systematic reviews, and 24 primary studies were identified. The flow diagram in Figure 1 gives details of the primary literature search process. Flow diagrams for the guideline search and review search are included in the supplementary material [Additional file 2].\u003c/p\u003e\n\u003ch3\u003eGuideline and Systematic Reviews\u003c/h3\u003e\n\u003cp\u003eThe European guideline (7) covers the evidence relevant for our PICO question until the end of the guideline\u0026rsquo;s literature search in May 2016. All four of the systematic reviews identified (9, 10, 12, 20) synthesized the evidence. Not all the outcomes selected for the PICO question in this review were discussed in the earlier reviews. Two studies conducted meta-analyses, one including hospitalization and both including mortality as outcomes (9, 12). In the supplementary material, we have provided an overview of the primary studies included in our review compared to studies included in the European guideline and the four systematic reviews selected [Additional file 3]. The supplementary material also provides a list of studies present in the guideline or reviews that we did not include, with references and reasons for exclusion [Additional file 4].\u003c/p\u003e\n\u003ch3\u003ePrimary Literature\u003c/h3\u003e\n\u003cp\u003eTable 1 presents basic characteristics and data extraction for the 24 primary studies selected. All studies were observational: 9 prospective cohort studies (3, 21-28); 11 retrospective cohort studies (29-39); and 4 cross-sectional studies (40-43). In general, patients on CKM were older and, when reported, had more comorbidities and poorer functional status compared to other groups. The heterogeneity between studies in relation to interventions, comparators, statistical analyses, and treatment modalities affected the possibility of conducting meta-analyses for all outcomes except mortality and hospitalization. Even for these two outcomes, not all studies reported data suitable for meta-analyses. The quality assessments using ROBINS-I are presented in the supplementary material [Additional file 5], showing that only three studies had a low risk of bias, 12 studies had a moderate risk of bias, eight studies had a serious risk of bias, and one study had a critical risk of bias. The directness of bias for most studies was unpredictable or in favour of dialysis.\u003c/p\u003e\n\u003ch4\u003eMortality\u003c/h4\u003e\n\u003cp\u003eIn total, 18 of both prospective and retrospective primary observational studies comparing CKM and dialysis, patients on CKM had higher mortality rates (3, 21-26, 28-34, 36-39). A meta-analysis is presented in Figure 2. One retrospective study, however, reported a 1.4-fold increase in risk of mortality for patients \u0026ge; 70 years old who were treated with dialysis (35). In a study of patients \u0026ge; 75 years old, the higher mortality rate for those on CKM compared to dialysis was significantly reduced in patients with high comorbidities, especially ischemic heart disease (29). For patients \u0026ge; 80 years, the results seem conflicting. One study investigating octogenarians reported higher mortality for patients on CKM (23). In contrast, three other studies found overall that mortality was equal for patients \u0026ge; 80 years old (21, 30, 31).\u003c/p\u003e\n\u003ch4\u003eQuality of life\u0026nbsp;\u003c/h4\u003e\n\u003cp\u003eOne prospective cohort study found that patients with CKD5 on CKM had poorer self-reported QoL at baseline compared to patients on dialysis, but only with a borderline significance (p = 0.05) (21). At a six-month follow-up, self-reported QoL was higher among patients on CKM compared to those on dialysis (p \u0026lt; 0.01). Another prospective cohort study found no difference in the mental health summary scores at baseline but significant difference in the physical health summary scores (p=0.001). There were, however, no difference in QoL over time (3). In a retrospective cohort study, there were no difference between patients managed conservatively and dialysis patients on physical and mental health summary scores (31). The results of two cross-sectional studies were heterogeneous (40, 42). One study found no difference in self-reported QoL (SF-36) between patients on CKM, HD, or PD (40). Results from the other cross-sectional study varied depending on the tool used to measure QoL.\u003c/p\u003e\n\u003ch4\u003eSymptom burden\u003c/h4\u003e\n\u003cp\u003eIn a small prospective study, commencement of dialysis in a younger cohort of elderly patients was associated with decrease in overall symptom burden (27). Two cross-sectional primary comparative studies found that patients on CKM had a lower symptom burden compared to patients on dialysis (41, 42). A third cross-sectional study comparing a group of patients with CKD5 receiving palliative care and patients on dialysis found overlapping symptom prevalence and intensity between the groups (43).\u003c/p\u003e\n\u003ch4\u003eHospitalization\u003c/h4\u003e\n\u003cp\u003eWe identified three prospective (21, 22, 24) and three retrospective (33, 34, 38) primary cohort studies comparing the hospitalization of patients. Results were heterogeneous. Most studies found that patients on CKM had fewer hospital admissions or a significantly lower risk of hospitalization than patients on dialysis (22, 24, 33, 38). Figure 3 shows a meta-analysis of the number of admission days. One study observed no difference in number of hospital admissions and number of days spent in hospital between groups (21). Finally, one study comparing patients treated with CKM to patients on PD observed fewer days spent in hospital per person year for the patients treated with PD (34).\u003c/p\u003e\n\u003ch4\u003ePlace of death\u003c/h4\u003e\n\u003cp\u003eResults from two primary studies indicate that patients on CKM more often die at home or in a hospice compared to patients on dialysis, who more often die in hospital (24, 25).\u003c/p\u003e"},{"header":"Discussion","content":"\u003ch3\u003eSummary of Evidence\u003c/h3\u003e\n\u003cp\u003eThis review identified 24 studies comparing patients with CKD5 receiving CKM with those on dialysis to investigate the outcomes of mortality, QoL, symptom burden, hospitalization, and place of death. The studies were of variable quality, and there was substantial heterogeneity in presentation of the data, making it difficult to conduct an adequate meta-analysis for most outcomes.\u003c/p\u003e\n\u003cp\u003eBased on the available evidence, according to our review, CKM does not provide the same or extended survival in patients with CKD5 compared to dialysis. This is in line with previous systematic reviews (9, 12). Overall, in contrast to CKM, dialysis is life prolonging. However, some studies indicate that the two treatment strategies may provide equal rates of mortality for patients who are 80 years old and above, or elderly patients with high comorbidities (21, 29, 30, 35). Thus, information on CKM may be considered in clinical practice in relation to this patient group. Some studies indicate that CKM may result in higher QoL compared to dialysis, and patients who receive CKM seem to have less hospitalization than patients on dialysis (21, 40-42). Regarding symptom burden, results were conflicting. A recently published systematic review (44) concludes that in selected older patients, CKM has the potential to achieve similar QoL compared to a dialysis pathway (44).\u003c/p\u003e\n\u003cp\u003eMost of the studies identified compared patients on HD with those treated with PD or did not report details of dialysis modality. There was very little data comparing patients on CKM with patients on PD. Our findings suggest that there may be differences between these two patient groups for the outcomes of symptom burden and hospitalization. Thus, these aspects should be considered in the decision-making process involved in choosing a patient\u0026rsquo;s preferred treatment strategy.\u003c/p\u003e\n\u003cp\u003eOnly one study investigated whether preferred place of death for patients with CKD5 on either CKM or dialysis was congruent with their actual place of death (24). The study indicated that patients on the CKM pathway more often die at home or in a hospice compared to patients on dialysis, who more often die in hospital. Studies of the general public and of patients with cancer have shown that most people would prefer to die at home (45, 46). Based on our review, dying at home or in a hospice seems more likely to be the outcome for patients managed conservatively compared to patients on dialysis (24, 25). Whether this result fulfils patients\u0026rsquo; preferences was, however, unclear.\u003c/p\u003e"},{"header":"Strengths And Limitations","content":"\u003cp\u003eThis review was conducted rigorously, using robust processes and relevant software tools. However, the study does have some limitations. All previous studies analysed were of observational design with variable sample size and quality and investigated patient groups that were heterogeneously defined. Furthermore, outcomes were assessed over different time periods. The quality of studies was reduced due to lead time bias when estimating mortality, and by confounders mostly favouring dialysis. Data heterogeneity restricted the use of meta-analysis. A very high heterogeneity (I\u003csup\u003e2\u003c/sup\u003e=97%) were found in the meta-analysis of mortality (See Figure 2). Two Studies (35, 36) are outliers having huge differences between the number of participants in the CKM group and the dialysis group; one study a three-fold difference (35) and the other study a 50-fold difference. Excluding these two studies from the meta-analysis we obtained a low to moderate heterogeneity (I\u003csup\u003e2\u003c/sup\u003e=43%) and still confirming the results of the meta-analysis.\u003c/p\u003e\n\u003ch3\u003eImplications for Clinical Practice and Further Research\u003c/h3\u003e\n\u003cp\u003eDiscussion of treatment options with clinicians is crucial for patients with CKD5 regardless of their preferred modality of treatment. In a recent qualitative study from the UK, 20 patients receiving CKM were interviewed (47). The patients\u0026rsquo; experience was that clinicians avoided talking about diagnosis and prognosis related to their disease. The patients expressed a desire to receive information related to their disease and possible treatment choices. At the same time, however, they were ambivalent about receiving detailed knowledge on the progression of their disease. Although the evidence in our review relies on observational data, the results suggest a CKM pathway can be an acceptable alternative to dialysis for patients aged 80 years and above or elderly patients with comorbidities. Consequently, discussion of CKM as a future treatment modality with this group of patients is important. A Canadian survey from 2010 showed that 60% of the patients receiving dialysis regretted having started the treatment (48). The findings of one qualitative review indicated that patients with CKD were capable of prioritizing QoL and freedom over survival (49). Based on the findings of this review, aspects of QoL, symptom burden, and hospitalization should be considered in the decision-making process when choosing the preferred treatment strategy.\u003c/p\u003e\n\u003cp\u003eTo date, the evidence of outcomes for patients with CKD5 receiving dialysis compared to patients on a CKM pathway has been drawn from observational studies of varying quality, many of which were retrospective. No randomized controlled studies have yet been published in this area. For ethical reasons, conducting such studies may be very problematic or even impossible. Thus, future research may also have to rely mainly on observational studies. Such studies should be carefully planned, with a prospective design and a strict methodology to minimize bias and the influence of confounders. Comparative studies of patients on CKM or PD may provide a more nuanced basis for discussions of future treatment choices for patients with CKD5.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this systematic review, we explored studies evaluating CKM as an alternative to dialysis for adult patients with CKD5 in relation to mortality, QoL, hospitalization, symptom burden, and place of death. Overall, patients with CKD5 on CKM have poorer survival compared to patients on dialysis. However, we observed that for patients aged 80 years and above, or elderly patients with severe comorbidities, the improved survival on dialysis over CKM appears to vanish. Despite some inconsistencies, the results suggest CKM has advantages compared to dialysis for the outcomes of QoL, hospitalization, symptom burden, and place of death. These findings should be addressed when discussing future treatment options with patients. More rigorously conducted studies are needed to establish a better base for such a decision-making process.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eCKD5 Stage 5 chronic kidney disease\u003c/p\u003e\n\u003cp\u003eCKM Conservative kidney management\u003c/p\u003e\n\u003cp\u003eQoL Quality of life\u003c/p\u003e\n\u003cp\u003eHD Haemodialysis\u003c/p\u003e\n\u003cp\u003ePD Peritoneal dialysis\u003c/p\u003e\n\u003cp\u003eAAPD Assisted automated peritoneal dialysis\u003c/p\u003e\n\u003cp\u003eRCTs Randomized controlled trials\u003c/p\u003e\n\u003cp\u003ePRISMA Preferred reporting items for systematic reviews and meta-analyses\u003c/p\u003e\n\u003cp\u003eCKD 1-4 Stage 1-4 chronic kidney disease\u003c/p\u003e\n\u003cp\u003ePICO Patient, Intervention, Comparison, Outcome\u003c/p\u003e\n\u003cp\u003eROBINS-I Risk Of Bias In Non-randomized Studies of Interventions tool\u003c/p\u003e\n\u003cp\u003eGRADE The Grading of Recommendations Assessment, Development and Evaluation methodology\u003c/p\u003e\n\u003cp\u003eRevMan5 Review Manager software\u003c/p\u003e\n\u003cp\u003eSD Standard deviations\u003c/p\u003e\n\u003cp\u003e95% CI 95% confidence Interval\u003c/p\u003e\n\u003cp\u003eHR Hazard ratios\u003c/p\u003e\n\u003cp\u003eRR Relative risks\u003c/p\u003e\n\u003cp\u003eOR Odds ratios (OR)\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch3\u003eEthics approval and consent to participate\u003c/h3\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch3\u003eAvailability of data and materials\u003c/h3\u003e\n\u003cp\u003eData sharing is not applicable to this article as no dataset were generated or analysed during the current study\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThe review is part of the preparation of a national clinical guideline, funded by the Danish Health Authority\u003c/p\u003e\n\u003ch3\u003eAuthors\u0026rsquo; contributions\u003c/h3\u003e\n\u003cp\u003eAll authors collected the data and conducted the analyses. Buur LE drafted the manuscript in collaboration with Finderup J. All authors critically reviewed and provided intellectual input to the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eThe authors would like to thank the members of the reference group for their constructive comments and suggestions during the planning and development of this research work. Representatives were: Jan Rishave, Danish Kidney Association; Lisbet Brandi, Danish Society of Nephrology; Karina Bruun, Danish Society of Renal Nurses; Birthe Thoerring, Danish Society of Palliative Medicine; Ellen Holm, Danish Gerontological Society; and Jette Kolding Kristensen, Danish College of General Practitioners. The authors also wish to thank member of the working group Line Staermose Jensen for her work on the national clinical guideline, of which this systematic review is a part.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eO'Halloran P, Noble H, Norwood K, Maxwell P, Shields J, Fogarty D, et al. Advance Care Planning With Patients Who Have End-Stage Kidney Disease: A Systematic Realist Review. Journal of pain and symptom management. 2018;56(5):795-807.e18.\u003c/li\u003e\n\u003cli\u003eThiesson H, Heaf J, S\u0026oslash;rensen SS, Povlsen J, L\u0026oslash;kkegaard N, Dieperink H, et al. Danish Nephrology Registry (DNR) - Annual Report 2017 [Available from: h\u003ca href=\"ttp://nephrology.dk/wp-content/uploads/2018/10/%C3%85rsrapport-2017.pdf.\"\u003ettp://nephrology.dk/wp-content/uploads/2018/10/%C3%85rsrapport-2017.pdf.\u003c/a\u003e\u003c/li\u003e\n\u003cli\u003eDa Silva-Gane M, Wellsted D, Greenshields H, Norton S, Chandna SM, Farrington K. 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Quality of life after the initiation of dialysis or maximal conservative management in elderly patients: a longitudinal analysis of the Geriatric assessment in OLder patients starting Dialysis (GOLD) study. BMC nephrology. 2019;20(1):108.\u003c/li\u003e\n\u003cli\u003eRaman M, Middleton RJ, Kalra PA, Green D. Outcomes in dialysis versus conservative care for older patients: A prospective cohort analysis of stage 5 Chronic Kidney Disease. PLoS One. 2018;13(10):e0206469.\u003c/li\u003e\n\u003cli\u003eJoly D, Anglicheau D, Alberti C, Nguyen AT, Touam M, Grunfeld JP, et al. Octogenarians reaching end-stage renal disease: cohort study of decision-making and clinical outcomes. J Am Soc Nephrol. 2003;14(4):1012-21.\u003c/li\u003e\n\u003cli\u003eCarson RC, Juszczak M, Davenport A, Burns A. Is maximum conservative management an equivalent treatment option to dialysis for elderly patients with significant comorbid disease? Clinical journal of the American Society of Nephrology : CJASN. 2009;4(10):1611-9.\u003c/li\u003e\n\u003cli\u003eSmith C, Da Silva-Gane M, Chandna S, Warwicker P, Greenwood R, Farrington K. Choosing not to dialyse: evaluation of planned non-dialytic management in a cohort of patients with end-stage renal failure. Nephron Clinical practice. 2003;95(2):c40-6.\u003c/li\u003e\n\u003cli\u003eTeo BW, Ma V, Xu H, Li J, Lee EJ. Profile of hospitalisation and death in the first year after diagnosis of end-stage renal disease in a multi-ethnic Asian population. Annals of the Academy of Medicine, Singapore. 2010;39(2):79-87.\u003c/li\u003e\n\u003cli\u003eTan T, Brennan F, Brown MA. Impact of dialysis on symptom burden and functional state in the elderly. Renal Society of Australasia Journal. March, 2017;13(1):22-30.\u003c/li\u003e\n\u003cli\u003eYuen S, Suen HP, Kwok O, Yong S, Tse M. Advance care planning for 600 Chinese patients with end-stage renal disease. Hong Kong Journal of Nephrology. 2016;19:19-27.\u003c/li\u003e\n\u003cli\u003eMurtagh FE, Marsh JE, Donohoe P, Ekbal NJ, Sheerin NS, Harris FE. Dialysis or not? A comparative survival study of patients over 75 years with chronic kidney disease stage 5. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2007;22(7):1955-62.\u003c/li\u003e\n\u003cli\u003eVerberne WR, Geers AB, Jellema WT, Vincent HH, van Delden JJ, Bos WJ. Comparative Survival among Older Adults with Advanced Kidney Disease Managed Conservatively Versus with Dialysis. Clinical journal of the American Society of Nephrology : CJASN. 2016;11(4):633-40.\u003c/li\u003e\n\u003cli\u003eVerberne WR, Dijkers J, Kelder JC, Geers ABM, Jellema WT, Vincent HH, et al. Value-based evaluation of dialysis versus conservative care in older patients with advanced chronic kidney disease: a cohort study. BMC nephrology. 2018;19(1):205.\u003c/li\u003e\n\u003cli\u003eTeruel JL, Burguera Vion V, Gomis Couto A, Rivera Gorrin M, Fernandez-Lucas M, Rodriguez Mendiola N, et al. Choosing conservative therapy in chronic kidney disease. Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia. 2015;35(3):273-9.\u003c/li\u003e\n\u003cli\u003eTam-Tham H, Quinn RR, Weaver RG, Zhang J, Ravani P, Liu P, et al. Survival among older adults with kidney failure is better in the first three years with chronic dialysis treatment than not. Kidney international. 2018;94(3):582-8.\u003c/li\u003e\n\u003cli\u003eShum CK, Tam KF, Chak WL, Chan TC, Mak YF, Chau KF. Outcomes in older adults with stage 5 chronic kidney disease: comparison of peritoneal dialysis and conservative management. The journals of gerontology Series A, Biological sciences and medical sciences. 2014;69(3):308-14.\u003c/li\u003e\n\u003cli\u003eShih CJ, Chen YT, Ou SM, Yang WC, Kuo SC, Tarng DC. The impact of dialysis therapy on older patients with advanced chronic kidney disease: a nationwide population-based study. BMC medicine. 2014;12:169.\u003c/li\u003e\n\u003cli\u003eReindl-Schwaighofer R, Kainz A, Kammer M, Dumfarth A, Oberbauer R. Survival analysis of conservative vs. dialysis treatment of elderly patients with CKD stage 5. PLoS One. 2017;12(7):e0181345.\u003c/li\u003e\n\u003cli\u003eKwok WH, Yong SP, Kwok OL. Outcomes in elderly patients with end-stage renal disease: Comparison of renal replacement therapy and conservative management. Hong Kong Journal of Nephrology. 2016;19:42-56.\u003c/li\u003e\n\u003cli\u003eHussain JA, Mooney A, Russon L. Comparison of survival analysis and palliative care involvement in patients aged over 70 years choosing conservative management or renal replacement therapy in advanced chronic kidney disease. Palliative medicine. 2013;27(9):829-39.\u003c/li\u003e\n\u003cli\u003eChandna SM, Da Silva-Gane M, Marshall C, Warwicker P, Greenwood RN, Farrington K. Survival of elderly patients with stage 5 CKD: comparison of conservative management and renal replacement therapy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011;26(5):1608-14.\u003c/li\u003e\n\u003cli\u003eIyasere O, Brown EA, Johansson L, Davenport A, Farrington K, Maxwell AP, et al. Quality of life with conservative care compared with assisted peritoneal dialysis and haemodialysis. Clinical kidney journal. 2019;12(2):262-8.\u003c/li\u003e\n\u003cli\u003eAlmutary H, Bonner A, Douglas C. Which patients with chronic kidney disease have the greatest symptom burden? A comparative study of advanced CKD stage and dialysis modality. Journal of renal care. 2016;42(2):73-82.\u003c/li\u003e\n\u003cli\u003eShah KK, Murtagh FEM, McGeechan K, Crail S, Burns A, Tran AD, et al. Health-related quality of life and well-being in people over 75 years of age with end-stage kidney disease managed with dialysis or comprehensive conservative care: a cross-sectional study in the UK and Australia. BMJ open. 2019;9(5):e027776.\u003c/li\u003e\n\u003cli\u003eYong DS, Kwok AO, Wong DM, Suen MH, Chen WT, Tse DM. Symptom burden and quality of life in end-stage renal disease: a study of 179 patients on dialysis and palliative care. Palliative medicine. 2009;23(2):111-9.\u003c/li\u003e\n\u003cli\u003eVerberne WR, van den Wittenboer ID, Voorend CGN, Abrahams AC, van Buren M, Dekker FW, et al. Health-related quality of life and symptoms of conservative care versus dialysis in patients with end-stage kidney disease: a systematic review. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020.\u003c/li\u003e\n\u003cli\u003eGomes B, Calanzani N, Gysels M, Hall S, Higginson IJ. Heterogeneity and changes in preferences for dying at home: a systematic review. BMC palliative care. 2013;12:7.\u003c/li\u003e\n\u003cli\u003eGomes B, Higginson IJ, Calanzani N, Cohen J, Deliens L, Daveson BA, et al. Preferences for place of death if faced with advanced cancer: a population survey in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain. Annals of oncology : official journal of the European Society for Medical Oncology. 2012;23(8):2006-15.\u003c/li\u003e\n\u003cli\u003eSelman LE, Bristowe K, Higginson IJ, Murtagh FEM. The views and experiences of older people with conservatively managed renal failure: a qualitative study of communication, information and decision-making. BMC nephrology. 2019;20(1):38.\u003c/li\u003e\n\u003cli\u003eDavison SN. End-of-life care preferences and needs: perceptions of patients with chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN. 2010;5(2):195-204.\u003c/li\u003e\n\u003cli\u003eTong A, Cheung KL, Nair SS, Kurella Tamura M, Craig JC, Winkelmayer WC. Thematic synthesis of qualitative studies on patient and caregiver perspectives on end-of-life care in CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2014;63(6):913-27.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1: Table with Details of the Primary Studies Selected for Inclusion\u003c/p\u003e\n\u003ctable border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor, \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eyear of publication \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003ePopulation\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge (years)\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention, n\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003e\u003cstrong\u003eComparator, n\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cstrong\u003eMain outcome measures and results\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eAlmutary, 2016 \u003c/strong\u003e\u003cstrong\u003e(40)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eNon-dialysis group (CKD4 \u0026amp; CKM (CKD5))\u003c/p\u003e\n\u003cp\u003eDialysis group (HD \u0026amp; PD)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eTotal group 48.29 (\u0026plusmn;14.86)\u003c/p\u003e\n\u003cp\u003eCKM (CKD5), 51.84\u0026plusmn;15.11\u003c/p\u003e\n\u003cp\u003eHD, 47.71\u0026plusmn;14.46\u003c/p\u003e\n\u003cp\u003ePD, 43.08\u0026plusmn;15.09\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM (CKD5), 38\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eHD, 287\u003c/p\u003e\n\u003cp\u003ePD, 42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eSymptom burden \u003c/em\u003e(CKD-SBI)\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM (CKD5):\u003c/p\u003e\n\u003cp\u003eHD: 23.36\u0026plusmn;16.99; PD: 12.04\u0026plusmn;6.58, vs. CKM (CKD5): 8.1\u0026plusmn;8.04; p \u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eCarson, 2009 \u003c/strong\u003e\u003cstrong\u003e(23)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026ge;70 at inclusion\u003c/p\u003e\n\u003cp\u003eCKM, mean 81.6; median 83\u003c/p\u003e\n\u003cp\u003eDialysis, mean 76.4; median 75\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 173\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eHospitalization\u003c/em\u003e \u003cem\u003erate\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHospital days/patient days survived:\u003c/p\u003e\n\u003cp\u003eCKM, 4.3\u0026plusmn;0.26; RRT, 6.9\u0026plusmn;0.71\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePlace of death \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHome/hospice: CKM, 40%; Dialysis 21%,\u003c/p\u003e\n\u003cp\u003eHospital: CKM, 36%; Dialysis 70%\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eChandna,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2011 \u003c/strong\u003e\u003cstrong\u003e(38)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eCKM 77.5\u0026plusmn;7.6\u003c/p\u003e\n\u003cp\u003eDialysis 58.5\u0026plusmn;15.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 155\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 689\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMortality in patients aged \u0026gt;75:\u003c/p\u003e\n\u003cp\u003eCKM vs. dialysis, HR: 1.18 (95% CI: 0.79-1.76); p = 0.428.\u003c/p\u003e\n\u003cp\u003eIn patients with comorbidity score\u0026gt;4: Dialysis, 25.8\u0026plusmn;4.4(SE); CKM, 20.4\u0026plusmn;2.4(SE); p=0.83.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eDa Silva-Gane, 2012 \u003c/strong\u003e\u003cstrong\u003e(3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD4-5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eHD 60.6\u0026plusmn;14.9\u003c/p\u003e\n\u003cp\u003ePD 48.0\u0026plusmn;15.6\u003c/p\u003e\n\u003cp\u003eCKM 77.5\u0026plusmn;6.5\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eHD,80\u003c/p\u003e\n\u003cp\u003ePD, 44\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHD vs. CKM, HR 0.47 (95% CI: 0.20-1.10); p = 0.08\u003c/p\u003e\n\u003cp\u003ePD vs. CKM, HR: 0.39 (95% CI: 0.10-1.48); p = 0.17\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eQuality of life\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo difference over time in groups.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eHussain,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2013 \u003c/strong\u003e\u003cstrong\u003e(37)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026gt;70 at inclusion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 172\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 269\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eHospitalization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM, RR 1.6 (95% CI: 1.14-2.25), p \u0026lt;0.05.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eIyasere,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2019 \u003c/strong\u003e\u003cstrong\u003e(39)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eMedian age (IQR)\u003c/p\u003e\n\u003cp\u003eCKM, 83 (80-88)\u003c/p\u003e\n\u003cp\u003eaAPD, 81 (79-88)\u003c/p\u003e\n\u003cp\u003eHD, 82 (78-85)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eHD, 28\u003c/p\u003e\n\u003cp\u003ePD, 28\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eQuality of life\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSF-12, PCS: CKM, 28.9\u0026plusmn;10.0; dialysis, 29.2\u0026plusmn;8.3; p = 0.90\u003c/p\u003e\n\u003cp\u003eSF-12, MCS: CKM, 46.3\u0026plusmn;12.1; dialysis, 49.9\u0026plusmn;12.9; p = 0.28\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eJoly,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2003 \u003c/strong\u003e\u003cstrong\u003e(22)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD4-5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026ge;80 at inclusion\u003c/p\u003e\n\u003cp\u003eCKM 84.1\u0026plusmn;2.9\u003c/p\u003e\n\u003cp\u003eDialysis 83.2\u0026plusmn;2.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 43\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 101\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM, 8.9 months (95% CI: 4-10); dialysis, 28.9 months (95% CI: 24-38); p \u0026lt;0.0001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eKwok,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2016 \u003c/strong\u003e\u003cstrong\u003e(36)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026ge;65 at inclusion\u003c/p\u003e\n\u003cp\u003eCKM 79.6\u0026plusmn;6.8\u003c/p\u003e\n\u003cp\u003eDialysis 74.2\u0026plusmn;6.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 432\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 126\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM, 10.0 months (95% CI: 8.3-11.7); dialysis, 44.6 months (95% CI: 37.3-51.9); p \u0026lt;0.001.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eMurtagh,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2007 \u003c/strong\u003e\u003cstrong\u003e(28)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026gt;75 at inclusion\u003c/p\u003e\n\u003cp\u003eCKM, 81.36\u003c/p\u003e\n\u003cp\u003eDialyse, 78,17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 77\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 52\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM vs. dialysis, HR: 2.90 (95% CI: 1.60-5.26);\u003c/p\u003e\n\u003cp\u003eIn patients with comorbidity score \u0026gt;2:\u0026nbsp; Dialysis vs CKM: log rank statistic \u0026lt;0.001, df 1, p = 0.98, In patients with ischaemic heart disease: Dialysis vs CKM:\u0026nbsp; log rank statistic 1.46, df 1, p \u0026lt; 0.27.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eRaman,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2018 \u003c/strong\u003e\u003cstrong\u003e(21)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eDialysis, 78.9\u0026plusmn;2.8\u003c/p\u003e\n\u003cp\u003eCKM, 83.7\u0026plusmn;4.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 81\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 123\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003e1-year\u003c/em\u003e \u003cem\u003esurvival\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM, OR 0.38 (95% CI: 0.09-1.60); p = 0.19\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHospitalization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNumber of admission days (median (IQR)):\u003c/p\u003e\n\u003cp\u003eCKM, 0.8 (0.0-8.7); dialysis, 2.2 (0.7-14.7); p = 0.005.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eReindl-Schwaighofer, 2017 \u003c/strong\u003e\u003cstrong\u003e(35)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026gt;65 at inclusion\u003c/p\u003e\n\u003cp\u003eHD, 74.06\u0026plusmn;5.78\u003c/p\u003e\n\u003cp\u003eCKM, 81.22\u0026plusmn;7.23\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 174\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eHD, 8622\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHD vs. CKM, HR: 0.23 (95% CI: 0.18-0.29); p \u0026lt; 0.001.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eShah,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2019 \u003c/strong\u003e\u003cstrong\u003e(41)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026ge;75 at inclusion\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMedian age (IQR):\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp; \u003c/em\u003eDialysis, 81 (78\u0026ndash;84)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; CKM, 83 (81\u0026ndash;87)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAge \u0026le;81, n (%):\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Dialysis 50 (6)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; CKM 19 (41)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAge \u0026gt;81, n (%):\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Dialysis 33 (40)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; CKM 27 (59)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 46\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 83\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eQuality of life\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM, adjusted differences in KDQOL-36 scores (95% CI):\u003c/p\u003e\n\u003cp\u003eKDQOL-burden of disease: -28.59 (-41.77 to -15.42); p \u0026lt; .001\u003c/p\u003e\n\u003cp\u003eKDQOL-symptoms of disease: -5.93 (-14.61 to 2.73); p = 0.18\u003c/p\u003e\n\u003cp\u003eKDQOL-effects of disease: -16.49 (-25.98 to -6.99); p \u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eShih,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2014 \u003c/strong\u003e\u003cstrong\u003e(34)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026ge;70 at inclusion\u003c/p\u003e\n\u003cp\u003eCKM, 82.0\u0026plusmn;6.4\u003c/p\u003e\n\u003cp\u003eDialysis, 78.6\u0026plusmn;7.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 2049\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 6292\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM, HR: 1.39 (95% CI: 1.30-1.49), p \u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eShum,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2014 \u003c/strong\u003e\u003cstrong\u003e(33)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge 65-90 at inclusion\u003c/p\u003e\n\u003cp\u003eOverall age, 73.8\u0026plusmn;5.4\u003c/p\u003e\n\u003cp\u003eCKM, 75.3\u0026plusmn;5.7\u003c/p\u003e\n\u003cp\u003ePD, 73.4\u0026plusmn;5.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 42\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003ePD, 157\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePD vs. CKM, HR: 0.46 (95% CI 0.31-0.68), p \u0026lt;0.001.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHospitalization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDays per person year, median [IQR]\u003c/p\u003e\n\u003cp\u003ePD, 16.17 [6.29-43.32] vs. CKM, 38.01 [6.75-76.56]; p = 0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eSmith, \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2003 \u003c/strong\u003e\u003cstrong\u003e(24)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eCKM (palliative care population), 71\u0026plusmn;12; Dialysis, 59\u0026plusmn;15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 63\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 258\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis, median survival 8.3 months; CKM, median survival 6.3 months; N.S.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePlace of death\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDeaths at home or in a hospice: CKM, 22 of 34 deaths (65%)\u003c/p\u003e\n\u003cp\u003eDialysis, 11 of 41 deaths (27%); p = 0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eTam-Tham, \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2018 \u003c/strong\u003e\u003cstrong\u003e(32)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026ge;65 at inclusion\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAge 65 to \u0026lt;75 (n, %)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Dialysis, 228 (45.6)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; CKM, 45 (13.3)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAge 75 to \u0026lt;85 (n, %)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Dialysis, 220 (44.0)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; CKM, 143 (42.3)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAge \u0026ge;85 (n, %)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; Dialysis, 52 (10.4)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; CKM, 150 (44.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 338\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 500\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM (0-3 years), HR: 0.56 (95% CI: 0.44-0.71); p \u0026lt;0.001\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM (after 3 years), HR: 1.98 (95% CI: 1.16-3.37); p = 0.12\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHospitalization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM, HR: 1.40 (95% CI: 1.16-1.69), p = 0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eTan, \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2017 \u003c/strong\u003e\u003cstrong\u003e(26)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026gt;65 at inclusion\u003c/p\u003e\n\u003cp\u003eCKM, 84\u003c/p\u003e\n\u003cp\u003eDialysis, 73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eSymptom burden\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eChange (improvement) in mean symptom POS-score over 6 months: CKM, 1.5; dialysis, 7.58; p \u0026lt;0.002.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eTeo,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2010 \u003c/strong\u003e\u003cstrong\u003e(25)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eCKM, 67.4 \u0026plusmn; 11.8\u003c/p\u003e\n\u003cp\u003eHD, 58.7 \u0026plusmn; 12.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eHD, 102\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM, HR: 2.29 (95% CI: 1.16-4.45); HD, HR: 0.59 (95% CI: 0.33-1.05); p = 0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eTeruel,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2015 \u003c/strong\u003e\u003cstrong\u003e(31)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eMedian age (IQR)\u003c/p\u003e\n\u003cp\u003eDialysis, 68 (54,76)\u003c/p\u003e\n\u003cp\u003eCKM, 83 (78,86)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 90\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 142\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM, 8.2/100 patient months; Dialysis, 0.6/100 patient months;\u003c/p\u003e\n\u003cp\u003ep \u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003evan Loon, \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2019 \u003c/strong\u003e\u003cstrong\u003e(20)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eAge \u0026ge;65 at inclusion\u003c/p\u003e\n\u003cp\u003eCKM, 82\u0026plusmn;6\u003c/p\u003e\n\u003cp\u003eDialysis, 75\u0026plusmn;7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 89\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 192\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003e12-month survival\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM vs. dialysis,\u003c/p\u003e\n\u003cp\u003eHR: 2.12 (95% CI: 1.12-4.03); p = 0.02\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIn patients \u0026lt; 80 years old, \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHR: 5.05 (95% CI: 1.90-13.50); p \u0026lt;0.01\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIn patients \u0026ge; 80 years old,\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eHR: 1.30 (95% CI: 0.58-2.91); p = 0.53\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSix-month quality of life\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eEQ-5D Index, mean (SE) change within group:\u003c/p\u003e\n\u003cp\u003eCKM, 0.047 (0.022); p \u0026lt;0.01\u003c/p\u003e\n\u003cp\u003eDialysis, 0.026 (0.014); p = 0.10\u003c/p\u003e\n\u003cp\u003eBetween group difference, p \u0026lt;0.01\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHospitalization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMedian number [IQR] of admissions:\u003c/p\u003e\n\u003cp\u003eCKM, 1 [1-5]; Dialysis, [1-4]; p = 0.27\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eHospitalization\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eMedian number [IQR] of admission days:\u003c/p\u003e\n\u003cp\u003eDialysis, 7 [3-15]; CKM, 4 [2-12]; p = 0.22\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eVerberne,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2018 \u003c/strong\u003e\u003cstrong\u003e(30)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eCKM, 82.6\u0026plusmn;4.5\u003c/p\u003e\n\u003cp\u003eDialysis, 76.2\u0026plusmn;4.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 126\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 240\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM vs. dialysis, HR: 1.67 (95% CI: 1.19-2.35), p = 0.003\u003c/p\u003e\n\u003cp\u003eMedian [IQR] survival in years in patients \u0026ge;70 years old:\u003c/p\u003e\n\u003cp\u003eCKM, 1.3 [0.5-2.5]; dialysis, 3.1 [1.7-6.4]; p \u0026lt;0.001\u003c/p\u003e\n\u003cp\u003eMedian [IQR] survival in years in patients \u0026ge;80 years old:\u003c/p\u003e\n\u003cp\u003eCKM, 2.3 [1.3-3.7]; dialysis, 2.9 [1.9-6.0]; p = 0.13\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eQuality of life\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNo difference between groups\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eVerberne,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2016 \u003c/strong\u003e\u003cstrong\u003e(29)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eCKM, 83\u0026plusmn;4.5\u003c/p\u003e\n\u003cp\u003eDialysis, 76\u0026plusmn;4.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 107\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 204\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eMortality\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eDialysis vs. CKM, HR: 0.62 (95% CI: 0.42-0.92), p = 0.02.\u003c/p\u003e\n\u003cp\u003eMedian [IQR] survival in years in patients \u0026ge;80 years old:\u003c/p\u003e\n\u003cp\u003eCKM, 1.4 [0.7-3.0]; dialysis, 2.1 [1.5-3.4]; p = 0.08.\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eYong,\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2009 \u003c/strong\u003e\u003cstrong\u003e(42)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eCKM, 73.1 \u0026plusmn; 7.1\u003c/p\u003e\n\u003cp\u003eDialysis, 58.2 \u0026plusmn; 11.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 134\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eSymptom burden\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNumber of symptoms\u003c/p\u003e\n\u003cp\u003eCKM, 8.2 \u0026plusmn; 3.9; dialysis 9.3 \u0026plusmn; 4.7, p = 0.243\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"96\"\u003e\n\u003cp\u003e\u003cstrong\u003eYuen, \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2016 \u003c/strong\u003e\u003cstrong\u003e(27)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003eCKD5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"168\"\u003e\n\u003cp\u003eCKM, 76.8 \u0026plusmn; 9.1\u003c/p\u003e\n\u003cp\u003eDialysis, 58.6 \u0026plusmn; 12.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"113\"\u003e\n\u003cp\u003eCKM, 335\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"104\"\u003e\n\u003cp\u003eDialysis, 265\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"352\"\u003e\n\u003cp\u003e\u003cem\u003eOne-year survival (%)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM, 57.3 \u0026plusmn; 2.9; dialysis, 89.7 \u0026plusmn; 2.1\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3-year survival (%)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCKM, 16 \u0026plusmn; 2.7; dialysis, 74.6% \u0026plusmn; 3.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCKD4 and CKD5, stage 4 and 5 chronic kidney disease; CKM, conservative kidney management; HD, haemodialysis; PD, peritoneal dialysis; AAPD, assisted automated peritoneal dialysis; IQR, interquartile range; HR, hazard ratio; eGFR, estimated glomerular filtration rate; SE, standard error; RR, relative risk; CKD-SBI, The CKD Symptom Burden Index; SF-12, short form 12; MCS, mental component summary; PCS, physical component summary; KDQOL, Kidney Disease Quality of Life; POS, Palliative Outcome Scale; EQ-5D, European Quality of life-5 Dimensions.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eUnless otherwise noted, values are expressed as mean \u0026plusmn; SD.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Stage 5 chronic kidney disease, end-stage kidney disease, dialysis, conservative kidney management, mortality, quality of life ","lastPublishedDoi":"10.21203/rs.3.rs-196946/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-196946/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground \u003c/p\u003e\u003cp\u003ePatients with stage 5 chronic kidney disease (CKD5) collaborate with their clinicians when choosing their future treatment modality. Most elderly patients with CKD5 may only have two treatment options: dialysis or conservative kidney management (CKM). The objective of this systematic review was to investigate whether CKM offers a quantity or quality of life benefit compared to dialysis for some patients with CKD5.\u003c/p\u003e\u003cp\u003eMethods\u003c/p\u003e\u003cp\u003eThe databases MEDLINE, EMBASE, the Cochrane Library, and CINAHL were systematically searched for studies comparing patients with CKD5 treated with CKM or dialysis. The primary outcomes were mortality and quality of life (QoL). Hospitalization, symptom burden, and place of death were secondary outcomes. For studies reporting hazard ratios, pooled values were calculated, and forest plots conducted.\u003c/p\u003e\u003cp\u003eResults\u003c/p\u003e\u003cp\u003eTwenty-four primary studies, all observational, were identified. All studies except one reported an increased mortality in patients treated with CKM (pooled hazard ratio 0.53, 95% confidence interval 0.41-0.69). For patients aged ≥ 80 years and for elderly individuals with comorbidities, results were ambiguous. In most studies, CKM seemed advantageous for QoL and secondary outcomes. Findings were limited by the heterogeneity of studies and biased outcomes favouring dialysis.\u003c/p\u003e\u003cp\u003eConclusions\u003c/p\u003e\u003cp\u003eIn general, patients with CKD5 live for a shorter time on CKM than on dialysis. In patients aged ≥ 80 years old, and in elderly individuals with comorbidities, the survival benefits of dialysis seem to be lost. Regarding QoL, symptom burden, hospitalization, and place of death, CKM may have advantages. Higher quality studies are needed to guide patients and clinicians in the decision-making process.\u003c/p\u003e","manuscriptTitle":"Does Conservative Kidney Management Offer a Quantity or Quality of Life Benefit Compared to Dialysis? 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