Long-term impact of pregnancy on mortality and graft outcomes in kidney transplant recipients: a systematic review and meta-analysis

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Despite some evidence suggesting minimal long-term effects on graft survival, conflicting results on graft function and timing-related risks highlight the need for a comprehensive review. This systematic review and meta-analysis aim to evaluate the long-term impact of pregnancy on patient survival, graft failure, serum creatinine levels, estimated glomerular filtration rate (eGFR), and proteinuria in kidney transplant recipients. Materials and methods : We conducted a systematic review and meta-analysis adhering to PRISMA guidelines and registered with PROSPERO (CRD42024569702). We searched PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE. Studies were eligible if they provided data on adult kidney transplant recipients (>18 years) who became pregnant post-transplant and included a control group of non-pregnant or non-conceived individuals. Results : Among the 6,118 results screened, 19 studies met the eligibility criteria and were included in the meta-analysis. The risk of allograft failure or graft loss was similar between pregnant and non-pregnant controls (OR 1.13, 95% CI: 0.83–1.53, p = 0.43), with a slightly higher adverse outcome rate in pregnant patients (25.4% vs. 19.8%). All-cause mortality risk was also comparable (OR 0.63, 95% CI: 0.38–1.07, p = 0.09), with low heterogeneity (I² = 12%). Creatinine levels were significantly lower before pregnancy compared to after delivery (SMD -0.33, 95% CI: -0.52 to -0.14, p = 0.0008). Conclusion : Pregnancy in kidney transplant recipients leads to increased creatinine levels in postpartum but does not significantly affect long-term graft survival. While creatinine levels generally decrease during pregnancy, they show variability by trimester. The risk of allograft failure and mortality is similar between pregnant and non-pregnant recipients, though adverse outcomes are slightly more frequent in pregnant patients, emphasizing the need for careful monitoring and individualized management. pregnancy graft outcomes graft failure mortality Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 INTRODUCTION The physiological hemodynamic and hormonal changes during pregnancy and postpartum, such as altered kidney blood flow, glomerular filtration rate, weight gain, and conditions associated with pregnancy including preeclampsia, gestational hypertension, gestational diabetes prompt questions about their potential long-term effects on maintenance and function of allografts in kidney transplant recipients. In this context, several studies found that undergoing pregnancy or having a live birth does not negatively impact the long-term survival of kidney allografts or patient survival among kidney transplants ( 1 , 2 ). Although pregnancy in kidney transplant recipients accelerates the decline in eGFR, it does not significantly increase the risk of graft failure, death-censored graft failure, or a 50% reduction in eGFR ( 3 ). However, various factors encountered during pregnancy including drug-treated hypertension are associated with poorer postpregnancy graft survival and a trend toward increased serum creatinine levels in patients with higher prepregnancy serum creatinine ( 2 ). Conversely, some studies report conflicting results, indicating that pregnancy in kidney or kidney-pancreas transplant recipients frequently leads to a decline in graft function, with nearly half of the patients experiencing significant deterioration during pregnancy ( 4 ). The specific risk factors contributing to the adverse post-pregnancy deterioration of graft function remain to be fully identified and understood. The timing of pregnancy warrants further attention, as it could potentially influence graft outcomes as shown by previous evidence. Pregnancy within the first year after kidney transplantation is associated with a higher risk of both acute and death-censored graft loss ( 6 ). This elevated risk of death-censored graft loss persists into the second year following the transplant. However, the risk does not significantly increase in the third-year post-transplant ( 6 ). Previous systematic reviews and meta-analyses have predominantly focused on pregnancy and neonatal outcomes rather than allograft outcomes and function ( 7 , 8 ). A previous meta-analysis showed that while pregnancy in kidney transplant recipients has a minimal impact on long-term graft survival, it may lead to a slight increase in serum creatinine levels within 2 years postpartum. Long-term graft function remains stable, with no significant differences in graft loss when comparing pregnant recipients to nulliparous controls ( 9 ). While a significant proportion of kidney transplant recipients are women of childbearing age, with pregnancy rates in this group typically ranging from 10–30% ( 10 ), addressing this issue is essential to ensure equitable representation of pregnant individuals in transplant medicine. To better understand the risks and implications for women with kidney transplants, there is still a need for a comprehensive meta-analysis that integrates and synthesizes the latest data on kidney graft health with the inclusion of appropriate control kidney transplant recipients who did not conceive after kidney transplant. Therefore, in this systematic review and meta-analysis, we aimed to evaluate the long-term impact of pregnancy on patient survival, graft failure and serum creatinine levels in kidney transplant recipients to inform clinical practice and guide preconception counseling. MATERIALS AND METHODS The protocol of this study was registered with PROSPERO (CRD42024569702). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to report this systematic review and meta-analysis ( 11 ). Search strategy and study selection We systematically searched multiple databases including PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE, targeting studies published in peer-reviewed journals up to August 24, 2024. Our search terms encompassed a combination of pregnancy-related keywords, kidney transplantation-related keywords, and keywords related to specific outcomes including mortality, graft outcomes, serum creatinine and eGFR change, and proteinuria. Further information on the search methodology and the keywords employed can be found in Supplementary Table S1 . The articles were imported into the EndNote 21 and duplicates were excluded automatically and subsequently re-checked automatically upon uploading to Covidence and through manually by the authors during the screening process (LO, SMAR, SU, MG). Three different authors (LO, SMAR, SU) independently screened the title and abstract of each identified article for adherence to predetermined inclusion and exclusion criteria. Each article is screened by at least two authors. The selection of articles for the study was based on consensus among the authors, with any discrepancies discussed with a fourth author (MG). Subsequently, each full-text article found eligible in the screening process underwent a triple-blind review by the authors (LO, SMAR, SU). Any discrepancies regarding the eligibility of full-text articles were discussed with the fourth author (MG). During full-text screening, the references in the full-text articles are reviewed to identify additional eligible articles. The study screening and selection process is outlined in Fig. 1 . Selection criteria Studies that provide data on adult kidney transplant recipients (> 18 years) who have become pregnant after undergoing kidney transplantation, with a non-pregnant or non-conceived control group, are of interest. Included studies must meet the following criteria: 1) they involve adult kidney transplant recipients who have become pregnant post-transplant; 2) they include a control group of previously non-pregnant individuals; 3) they report outcomes of interest such as patient mortality, graft survival, serum creatinine levels, estimated glomerular filtration rate changes, and proteinuria. Studies were excluded if they did not report on long-term prognostic outcomes of post-transplant pregnancy, focusing instead only on immediate or early postpartum outcomes (e.g., those reporting data no later than 8 weeks or only during pregnancy); if they included only kidney transplant patients who became pregnant without a non-pregnant or non-conceived control group; if they did not provide the outcomes of interest; or if they were animal studies, reviews, editorials, letters, commentaries. Additionally, studies that are not available in full text or for which no English translation is available were also excluded. Quality Assessment The assessment of study quality was conducted utilizing the Newcastle-Ottawa scale (NOS), which assigns a maximum total score of nine points, with a score of seven or higher indicative of high quality, a score between four to six indicating moderate quality, and a score of three or lower indicates poor quality. Quality assessment of the studies is performed by three separate authors (LO, SMAR, SU) the results are compared and consensus has been made (Supplementary Table S2 and S3). RESULTS We conducted a comprehensive search across the specified databases, initially retrieving a total of 6118 studies. After removing duplicate publications, 5795 studies remained for screening based on titles and abstracts, and 289 of those underwent further full-text assessment for eligibility. Following the evaluation of predefined inclusion and exclusion criteria, 19 studies were ultimately selected for inclusion in the present meta-analysis (Fig. 1 , Table 1 ). Table 1 Summary of included studies Study Study Type Participant characteristics Outcome measures Key findings Quality assessment First et al (1995) ( 5 ) Case-Control 44 women of reproductive age who had kidney transplantation between 1967 and 1990 ● 18 women with posttransplant pregnancies ● 26 paired nonpregnant controls 23 male controls ● Graft survival ● Serum creatinine changes ● Patient mortality Pregnancy provokes transient improvement in serum creatinine levels, which return to baseline after pregnancy No adverse long-term effect on patient survival or graft function/survival High (Score: 8) Fischer et al (2005) ( 13 ) Case-control 162 women of reproductive age who had kidney transplantation ● 81 women with posttransplant pregnancies ● 81 paired nonpregnant controls ● Patient mortality ● Graft survival ● Serum creatinine Pregnancies in renal recipients do not negatively affect long-term patient and graft survival or graft function, independent of the immunosuppressive regimen. High (Score: 8) Gorgulu et al (2010) ( 15 ) Case-Control 57 women of reproductive age who had kidney transplantation ● 19 patients with posttransplant pregnancies ● 38 paired nonpregnant controls ● Serum creatinine ● Graft survival ● Patient mortality Graft outcomes such as serum creatinine level and acute rejection episodes or graft survival did not differ significantly between the groups. High (Score: 8) Gutiérrez et al (2009) ( 27 ) Case-Control 54 women of reproductive age who had kidney transplantation ● 27 women with posttransplant pregnancies ● 27 paired nonpregnant controls ● Graft survival ● Serum creatinine ● Patient mortality There were no acute rejection episodes or graft losses during pregnancy and puerperium. Renal function at the end of pregnancy was lower among the pregnant compared to the control group. At 1 and 10 years, renal function was similar among the groups; pregnancy did not have a significant effect on graft function. High (Score: 8) Kaatz et al (2023) ( 28 ) Case-Control 80 women of reproductive age who had single kidney or combined kidney-pancreas transplantation ● 40 women with posttransplant pregnancies ● 40 paired nonpregnant controls ● eGFR/serum creatinine changes ● Proteinuria ● Graft survival ● Patient mortality ● Pregnancies after transplantation showed good maternal and allograft outcomes. ● Pre-pregnancy factors, except for a declining renal allograft function in the year before pregnancy, were not helpful in predicting the outcomes. High (Score: 8) Kashanizad eh et al (2007) ( 19 ) Retrospective Cohort 86 female kidney transplant recipients with at least one posttransplant pregnancy and 125 kidney transplant recipients with no pregnancy matched for age, cause of end-stage renal disease (ESRD), treatment protocol, and first creatinine (Cr) between 1996 and 2002 ● Graft survival ● Patient survival ● Serum creatinine Two (3.3%) patients in group I and 2 (1.6%) patients in group II died during the follow-up. Eight (9.2%) patients in group 1 and 9 (7.2%) in group II lost their allografts. The five-year patient graft survival rates were not significantly different between the study groups. Only 10.6% of the pregnant group had elevated serum creatinine levels while at the same time, 28% of the nonpregnant group had elevated serum creatinine levels. There was no correlation between the number of pregnancies and creatinine levels. High (Score: 8) Kim et al (2008) ( 16 ) Case-Control 48 women who conceived after undergoing renal transplantation and 187 transplanted non-pregnant controls matched according to age at transplantation, immunosuppressive regimen, and time of transplantation between 1991 and 2005 ● Graft survival ● Serum creatinine The graft failure rate from transplantation to the end of follow-up did not differ between the pregnant and nonpregnant groups. The 10- and 15-year graft survival rates were 78.5% and 67.3%, respectively, in the pregnant group, and 75.0% and 58.1%, respectively, in the control group. The 10-year graft survival rates were also similar in the 11 women who became pregnant less than or equal to 12 months after transplantation and 37 who became pregnant more than 12 months after transplantation. Serum creatinine levels did not differ significantly between the groups at the end of the follow-up period. High (Score: 8) Levidiotis et al (2009) ( 1 ) Retrospective Cohort 120 parous women matched with 120 nulliparous women by year of transplantation, duration of transplant, age at transplantation 5 year, and pre delivery creatinine for parous women or serum creatinine for nulliparous women ● Graft survival ● Patient survival Five-year unadjusted graft survival rates for patients and control subjects were 89% and 85.3%, respectively; 10-year rates were 66.4% and 74.8%, respectively; and 15-year rates were 56.5% and 55.7, respectively. Unadjusted patient survival rates censored for graft failure for patients and control subjects at 5 year were 99.2% and 95.2%, respectively; 10-yr patient survival rates were 94.0% and 91.7%, respectively; and 15-yr survival rates were 89.6% and 86.8%, respectively. First live birth was not associated with a poorer 20-year graft or patient survival. High (Score: 8) Pour-Reza-Gholi et al (2005) ( 29 ) Retrospective Cohort Retrospective data on 74 pregnancies in 60 patients were reviewed and completed through phone interviews were compared with information on a control group of female kidney recipients. ● Graft survival ● Serum creatinine One-, 3-, 5-, and 10-year graft survival was 100%, 96.5%, 94.5%, and 77.1% in the pregnant group versus 93.2%, 85.7%, 81%, and 64.7% in the control group, respectively. Chronic graft dysfunction and graft loss were seen in 24 and 18 cases of the pregnant group and in 17 and 17 cases of the control group, respectively. The last creatinine level was not significantly different in the pregnant versus the control group. High (Score: 8) Radaelli et al (2023) ( 20 ) Case-Control 78 pregnant women (cases), with a total of 97 gestations and a matched control group of 78 female KT patients ● Graft survival ● Patient survival ● Serum creatinine ● Proteinuria Graft survival was higher in cases than in controls in 5 years (85.6% vs 71.5%, p = 0.012) and 10 years (71.9% vs 55.0%, p = 0.012) of follow-up. Patient survival was also higher in cases than controls in 5 years (98.6% vs 85.8%, p = 0.004) and 10 years (95.2% vs 80.3%, p = 0.004) of follow-up. Median creatinine before conception and one year after did not differ (1.2 vs. 1.2 mg/dL). Median UPCR before pregnancy and one year after did not differ (0.3 vs. 0.29). High (Score: 8) Rahamimov et al (2006) ( 21 ) Case-Control 39 women became pregnant after renal transplantation and 177 women did not become pregnant after renal transplantation. These controls were matched to the pregnant group based on 12 factors known to affect graft survival. ● Graft survival ● Graft function The survival rates for grafts (61.6%) and patients (84.8%) from transplantation to the end of a 15-year follow-up in women who conceived after transplantation were comparable to those of the 177 women in the matched control group, who had survival rates of 68.7% and 78.8%, respectively. Additionally, there were no significant differences in long-term graft function between the two groups. High (Score: 9) Salmela et al (1993) ( 30 ) Case-Control 66 women of reproductive age who had kidney transplantation ● 22 women with posttransplant pregnancies ● 44 paired nonpregnant controls 39 male transplant patients who became fathers posttransplant ● Graft survival ● Patient mortality ● Serum creatinine changes Pregnancy accelerated the deterioration of graft function, and long-term graft survival is significantly worse in patients with posttransplant pregnancies High (Score: 8) Sibanda et al (2007) ( 2 ) Retrospective Cohort 193 pregnancies were reported in 176 kidney transplant recipients, considering 17 of the women were multiparous. • Graft survival • Patient mortality • Serum creatinine changes Pregnancy after kidney transplantation was associated with a favorable outcome for both the mother and the fetus. In the absence of poor prepregnancy renal function and existence of an hypertensive state, the long term graft survival remained optimal. High (Score: 8) Stoumpos et al (2016) ( 31 ) Case-control Obstetric and kidney transplant outcomes who have been pregnant between 1973 and 2013 have been analyzed. Additionally, a case-cohort study with 138 pregnancies, 89 of them being renal transplant recipients have been analyzed. • Graft survival • Patient mortality • Serum creatinine changes • eGFR Pregnancy did not adversely affect long-term graft survival or overall patient outcomes, albeit high rates of obstetric complication. Serum creatinine changes and eGFR remained stable. High (Score: 9) Sturgiss et al (1995) ( 18 ) Case-control 36 kidney allograft recipients. 18 of these became pregnant and rest of the nulliparous population was assigned as the control. • Graft survival • Patient mortality • Serum creatinine changes Pregnancy in kidney transplant recipients did not negatively impact long-term graft function or patient survival. Serum creatinine levels remained stable even after 15-years post-transplant follow-up. High (Score: 8) Svetitsky et al (2018) ( 32 ) Retrospective Cohort A total of 22 pregnancies that resulted in live births were observed in 18 women who underwent kidney or combined kidney-pancreas transplants • Graft survival • Serum creatinine changes • eGFR, • proteinuria Pregnancy following kidney or simultaneous kidney-pancreas transplantation did not significantly affect long-term graft function (serum creatinine, eGFR) or increase proteinuria compared to controls, but comprehensive follow-up is recommended. High (Score: 8) Creatinine values before pregnancy and after delivery were reported in seven studies ( 12 – 18 ). Kidney transplant patients had significantly lower creatinine values before pregnancy compared to the post-delivery follow-up period, with a standardized mean difference (SMD) of -0.33 (95% CI: -0.52 to -0.14, p = 0.0008). The heterogeneity across the studies was low (I² = 18%). In a sensitivity analysis, excluding the study by Fischer et al. ( 13 ) eliminated the heterogeneity entirely, while still maintaining the statistical significance of the effect (p = 0.03) (Fig. 2 ). We also compared creatinine values throughout the entire pregnancy duration to the initial baseline values. Five studies provided data on creatinine levels before pregnancy and during the first trimester in kidney transplant patients ( 13 – 17 ). In the pooled analysis, creatinine levels tended to decrease during the first trimester; however, this effect did not reach statistical significance (SMD 0.88, 95% CI: -0.40 to 2.17, p = 0.18). The results were limited by high heterogeneity (I² = 97%) (Fig. 3 ). After excluding the study by Fischer et al. ( 13 ) creatinine levels were found to be higher in the pre-conception period compared to the first trimester (SMD 0.25, 95% CI: 0.02 to 0.48, p = 0.04), with low heterogeneity (I² = 0%). These results should be interpreted with caution, as the significant variation in heterogeneity before and after the exclusion of Fischer et al. ( 13 ) suggests that the findings may be sensitive to specific studies and may not be fully generalizable. Conversely, creatinine values before pregnancy were significantly higher compared to those reported in the second trimester (SMD 0.22, 95% CI: 0.01 to 0.43, p = 0.04), with low heterogeneity across studies (Fig. 4 ) ( 12 , 14 – 17 ). These findings align with the expectation that creatinine levels tend to decline as pregnancy progresses, contrasting with the anticipated rise following delivery. Although creatinine levels tended to increase in the last trimester, the effect was not statistically significant (SMD − 0.51, 95% CI: -1.36 to 0.34, p = 0.24) (Fig. 5 ) ( 13 – 17 ). Excluding the study Fischer et al. ( 13 ) from the analysis eliminated heterogeneity, but the creatinine levels remained similar during the both time-frames. Creatinine values were comparable between the first and second trimesters (SMD 0.02, 95% CI: -0.21 to 0.26, p = 0.84) (Fig. 6 ) ( 14 – 17 ). However, the comparison between the first and third trimesters was influenced by substantial heterogeneity. In the pooled analysis, the heterogeneity was high, and the effect did not reach statistical significance (p = 0.11) (Fig. 7 ). Notably, after excluding the study by Fischer et al. ( 13 ) creatinine values were significantly lower in the first trimester compared to the third trimester (SMD − 0.30, 95% CI: -0.30 to -0.06, p = 0.01). Data concerning the risk of allograft failure or graft loss was comparable between pregnant patients and non-pregnant controls (OR 1.13, 95% CI: 0.83–1.53, p = 0.43) (Fig. 8 ). However, the incidence of adverse kidney outcomes was slightly higher in pregnant patients (25.4% vs. 19.8%). Similarly, the risk of all-cause mortality was similar in pregnant and non-pregnant KT patients (OR 0.63, 95% CI: 0.38–1.07, p = 0.09), with low heterogeneity across studies (I 2 = 12%) (Fig. 9 ) ( 1 , 5 , 13 , 18 – 21 ). The publication bias was displayed as a funnel plot, in case of studies investigating graft loss (Fig. 10 ). DISCUSSION This systematic review and meta-analysis including 19 studies found that the risk of allograft failure or graft loss was similar between pregnant and non-pregnant controls, although there was a slightly higher rate of adverse outcomes in pregnant patients. The risk of all-cause mortality was similar between the two groups in our study. While acute rejection rates in pregnant kidney transplant recipients are relatively low and similar across various regions (ranging from 3–8%) in the literature, the impact of pregnancy on long-term graft survival in previous studies was less clear ( 8 ). In this regard, a previous meta-analysis showed that the overall graft loss rates at 1, 2, and 5 years after pregnancy are not significantly different from those in non-pregnant recipients ( 8 ). Some studies suggest that pregnancy does not adversely affect graft survival and may even have favorable outcomes in certain cases. However, these findings could be influenced by selection bias, as those who become pregnant after a kidney transplant are often younger, and healthier, which may skew the results. Another meta-analysis on this subject found that while the incidence of graft loss increases over time postpartum—9.4% within 2 years, rising to 38.5% after more than 10 years—pregnancy generally does not have a significant long-term impact on graft function, with stable serum creatinine levels observed beyond 2 years ( 9 ), as in line with our findings. Notably, there was a marginally higher serum creatinine increase of 0.18 mg/dL within 2 years postpartum ( 9 ). Key risk factors for adverse outcomes included preconceptional hypertension, proteinuria, and high pre-pregnancy serum creatinine levels, but the type of delivery and immunosuppressive regime did not significantly affect graft survival ( 9 ). Pregnant kidney transplant patients generally face low risks of maternal death and worsening kidney function if their initial kidney function is normal, though these risks increase with pre-existing kidney impairment ( 22 , 23 ). The research, involving 92 pregnancies in 67 women from 1972 to 2019, found that pre-pregnancy kidney function significantly affects both pregnancy and graft outcomes ( 24 ). Women with a higher pre-pregnancy eGFR (≥ 50 mL/min/1.73m²) had better pregnancy outcomes and longer post-pregnancy graft survival compared to those with lower pre-pregnancy eGFR (< 50 mL/min/1.73m²) ( 24 ). Conversely, pregnancies in women with lower pre-pregnancy eGFR were associated with greater declines in kidney function and higher rates of maternal and fetal complications ( 24 ). Nevertheless, the full clinical picture of the alterations in serum creatinine in the trimesters and post-pregnancy varies between the studies. A study evaluating 34 pregnancies in kidney transplant recipients found that graft dysfunction, defined as an increase in serum creatinine at least 0.3 mg/, occurred in 15 cases, primarily due to preeclampsia, rejection, or infections ( 25 ). Despite these issues, most graft dysfunctions were temporary, with no significant long-term difference in graft function before and after pregnancy, though graft rejection remained a significant risk for graft loss ( 25 ). In another study, pregnancy outcomes in women who had undergone kidney transplantation found that although 78.9% of pregnancies resulted in live births, there was a high rate of preterm birth (56.5%) and hypertensive disorders (76%) ( 26 ). Therefore, prematurity, low birth rates, and intrauterine growth retardation were among the adverse neonatal outcomes in this group ( 23 ). Prepregnancy serum creatinine levels were indicative of risk; higher levels were associated with increased rates of pre-eclampsia and poorer graft function post-pregnancy, with one-third of women experiencing graft deterioration during pregnancy, and 63.2% of those with worsening graft function did not return to baseline within two years postpartum ( 26 ). Overall, the importance of pregnancy-associated conditions cannot be underestimated when evaluating kidney function. In our study, creatinine levels were significantly lower before pregnancy compared to after delivery. During pregnancy, creatinine levels did not change significantly in the first trimester but were higher before pregnancy than in the second trimester. There was an observed increase in creatinine from pre-conception to the first trimester when one study was excluded. Creatinine levels did not significantly change between the first and third trimesters. Conclusion Overall, given the high prevalence of pregnancy among women of childbearing age who are kidney transplant recipients, it is crucial to thoroughly address the potential concerns related to maternal, fetal, and allograft outcomes. Several studies have previously shown an increased rate of pregnancy-related complications in kidney transplant recipients. However, the allograft outcomes and patient mortality seemed to be unaffected in most of the studies, as in our meta-analysis. Despite these findings, it is important to consider limitations such as publication bias and the evolution of transplant management practices over time. Our study encompasses research spanning several decades, which may introduce variability in treatment protocols and patient management, potentially influencing the results. Additionally, applying these findings broadly to specific high-risk populations, such as individuals with already low GFR or other pre-existing risk factors, may be misleading. It is crucial to recognize that these groups might experience different outcomes, and the generalized results may not fully capture their unique risks and needs. Future research should investigate both the specific risk factors or obstetric complications affecting graft and patient outcomes in pregnant kidney transplant recipients, the impact of transplant-related management strategies on these outcomes, and the allograft prognosis of pregnancy with reduced kidney function. Declarations Funding: This study was not funded by any grant. Conflict of Interest and disclosure: Authors declare that they have no conflict of interest. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Acknowledgement: None Contribution of authors: Contributed substantially to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work: Mehmet Kanbay, Crischentian Brinza, Sama Mahmoud Abdel-Rahman, Selen Unlu, Lasin Ozbek, Mustafa Guldan, Alexandru Burlacu Drafted the work or revised it critically for important intellectual content: Mehmet Kanbay, Alexandru Burlacu, Ozgur Aktas, Adrian Covic, Andreea Covic References Levidiotis V, Chang S, McDonald S. Pregnancy and maternal outcomes among kidney transplant recipients. J Am Soc Nephrol. 2009;20(11):2433–40. Sibanda N, Briggs JD, Davison JM, Johnson RJ, Rudge CJ. Pregnancy after organ transplantation: a report from the UK Transplant pregnancy registry. Transplantation. 2007;83(10):1301–7. Kattah AG, Albadri S, Alexander MP, Smith B, Parashuram S, Mai ML, et al. 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The Kidney and Pregnancy Study Group of the Italian Society of Nephrology. J Nephrol. 2018;31(5):665–81. Ghafari A, Sanadgol H. Pregnancy after renal transplantation: ten-year single-center experience. Transplant Proc. 2008;40(1):251-2. Schwarz A, Schmitt R, Einecke G, Keller F, Bode U, Haller H, et al. Graft function and pregnancy outcomes after kidney transplantation. BMC Nephrol. 2022;23(1):27. Aivazoglou L, Sass N, Silva HT, Jr., Sato JL, Medina-Pestana JO, De Oliveira LG. Pregnancy after renal transplantation: an evaluation of the graft function. Eur J Obstet Gynecol Reprod Biol. 2011;155(2):129–31. Mohammadi FA, Borg M, Gulyani A, McDonald SP, Jesudason S. Pregnancy outcomes and impact of pregnancy on graft function in women after kidney transplantation. Clin Transplant. 2017;31(10). Gutierrez MJ, Gonzalez P, Delgado I, Gutierrez E, Gonzalez E, Siqueira RC, et al. Renal allograft function and cardiovascular risk in recipients of kidney transplantation after successful pregnancy. Transplant Proc. 2009;41(6):2399 – 402. Kaatz R, Latartara E, Bachmann F, Lachmann N, Koch N, Zukunft B, et al. Pregnancy after Kidney Transplantation-Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health. J Clin Med. 2023;12(4). Pour-Reza-Gholi F, Nafar M, Farrokhi F, Entezari A, Taha N, Firouzan A, et al. Pregnancy in kidney transplant recipients. Transplant Proc. 2005;37(7):3090-2. Salmela KT, Kyllonen LE, Holmberg C, Gronhagen-Riska C. Impaired renal function after pregnancy in renal transplant recipients. Transplantation. 1993;56(6):1372–5. Stoumpos S, McNeill SH, Gorrie M, Mark PB, Brennand JE, Geddes CC, et al. Obstetric and long-term kidney outcomes in renal transplant recipients: a 40-yr single-center study. Clin Transplant. 2016;30(6):673–81. Svetitsky S, Baruch R, Schwartz IF, Schwartz D, Nakache R, Goykhman Y, et al. Long-Term Effects of Pregnancy on Renal Graft Function in Women After Kidney Transplantation Compared With Matched Controls. Transplant Proc. 2018;50(5):1461-5. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTableS1.docx SupplementaryTableS2andS3.docx Cite Share Download PDF Status: Published Journal Publication published 10 May, 2025 Read the published version in International Urology and Nephrology → Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5280668","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":368702741,"identity":"284fe4fc-20db-413f-a3f7-ff2b2d254588","order_by":0,"name":"Mehmet 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2","display":"","copyAsset":false,"role":"figure","size":31818,"visible":true,"origin":"","legend":"\u003cp\u003eCreatinine levels before pregnancy versus in the post-delivery period.\u003c/p\u003e","description":"","filename":"Figure2.Creatininebeforepregnancyvsafterdelivery.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/9725f960b814cf0a9fe71ea3.png"},{"id":68655281,"identity":"fee64a05-a875-44f6-9d81-d9a3b52d1582","added_by":"auto","created_at":"2024-11-10 14:03:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":27406,"visible":true,"origin":"","legend":"\u003cp\u003eCreatinine values before pregnancy versus in the first trimester.\u003c/p\u003e","description":"","filename":"Figure3.Creatininebeforepregnancyvs1sttrimester.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/e62887d06988e3778bb193e1.png"},{"id":68655276,"identity":"b40f88e9-80a8-45ea-9b0d-e84c4e98e876","added_by":"auto","created_at":"2024-11-10 14:03:33","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":26953,"visible":true,"origin":"","legend":"\u003cp\u003eCreatinine values before pregnancy versus in the second trimester.\u003c/p\u003e","description":"","filename":"Figure4.Creatininebeforepregnancyvs2ndtrimester.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/0e702eef3d854cb9f03c425d.png"},{"id":68655279,"identity":"99d3699b-d392-4366-9565-79feb3ddf12b","added_by":"auto","created_at":"2024-11-10 14:03:33","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":27125,"visible":true,"origin":"","legend":"\u003cp\u003eCreatinine values before pregnancy versus in the third trimester.\u003c/p\u003e","description":"","filename":"Figure5.Creatininebeforepregnancyvs3rdtrimester.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/1c362903a7e003294557f755.png"},{"id":68655277,"identity":"b854d645-bae1-4812-8c60-17776d76fa88","added_by":"auto","created_at":"2024-11-10 14:03:33","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":24270,"visible":true,"origin":"","legend":"\u003cp\u003eCreatinine values in the first trimester versus the second trimester.\u003c/p\u003e","description":"","filename":"Figure6.Creatinine1sttrimestervs2ndtrimester.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/9a4896ec788324d1d05cc50a.png"},{"id":68655273,"identity":"45054db3-ac1f-4e22-8b56-2ca010923050","added_by":"auto","created_at":"2024-11-10 14:03:33","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":27855,"visible":true,"origin":"","legend":"\u003cp\u003eCreatinine values in the first trimester versus the third trimester.\u003c/p\u003e","description":"","filename":"Figure7.Creatinine1sttrimestervs3rdtrimester.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/b3010ae04c36a2c55b83a3b9.png"},{"id":68655272,"identity":"4aa0f50a-eb30-4614-ba4c-ce4156df0780","added_by":"auto","created_at":"2024-11-10 14:03:33","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":49264,"visible":true,"origin":"","legend":"\u003cp\u003eThe risk of allograft failure of graft loss in pregnant and non-pregnant kidney transplant recipients.\u003c/p\u003e","description":"","filename":"Figure8.Allograftfailureorgraftlosspregnantvsnonpregnant.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/e23f739cb69eb4cef8aec30d.png"},{"id":68655913,"identity":"94369ee4-e9a6-4b0d-b081-7730aab13135","added_by":"auto","created_at":"2024-11-10 14:11:33","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":30622,"visible":true,"origin":"","legend":"\u003cp\u003eAll-cause mortality risk in pregnant versus non-pregnant KT patients.\u003c/p\u003e","description":"","filename":"Figure9.Mortalitypregnantvsnonpregnant.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/e6c6cc35b257b3e98fd2f793.png"},{"id":68656000,"identity":"d5b0acf0-de93-487f-ac1b-ed0fc5a09e70","added_by":"auto","created_at":"2024-11-10 14:19:33","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":17517,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot for assessing publication bias.\u003c/p\u003e","description":"","filename":"Figure10.Funnelplot.png","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/7c39df45896d8be6ca4cc83c.png"},{"id":82537437,"identity":"c495cc7c-0442-4815-b0ef-69286ff60f0a","added_by":"auto","created_at":"2025-05-12 16:06:09","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1168350,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/2246db8f-ebd3-43e9-8f0a-ae2067cb41b7.pdf"},{"id":68655280,"identity":"0d03bb38-bb88-4d26-8106-23fee034251b","added_by":"auto","created_at":"2024-11-10 14:03:34","extension":"docx","order_by":12,"title":"","display":"","copyAsset":false,"role":"supplement","size":12573,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/8c9b21b9adc5c45998e0bbd6.docx"},{"id":68655915,"identity":"f60a6336-3de0-4224-9e7e-70a87983dbc5","added_by":"auto","created_at":"2024-11-10 14:11:34","extension":"docx","order_by":13,"title":"","display":"","copyAsset":false,"role":"supplement","size":10340,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS2andS3.docx","url":"https://assets-eu.researchsquare.com/files/rs-5280668/v1/f02cc9c9974d973245a8f640.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Long-term impact of pregnancy on mortality and graft outcomes in kidney transplant recipients: a systematic review and meta-analysis","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe physiological hemodynamic and hormonal changes during pregnancy and postpartum, such as altered kidney blood flow, glomerular filtration rate, weight gain, and conditions associated with pregnancy including preeclampsia, gestational hypertension, gestational diabetes prompt questions about their potential long-term effects on maintenance and function of allografts in kidney transplant recipients. In this context, several studies found that undergoing pregnancy or having a live birth does not negatively impact the long-term survival of kidney allografts or patient survival among kidney transplants (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Although pregnancy in kidney transplant recipients accelerates the decline in eGFR, it does not significantly increase the risk of graft failure, death-censored graft failure, or a 50% reduction in eGFR (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, various factors encountered during pregnancy including drug-treated hypertension are associated with poorer postpregnancy graft survival and a trend toward increased serum creatinine levels in patients with higher prepregnancy serum creatinine (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Conversely, some studies report conflicting results, indicating that pregnancy in kidney or kidney-pancreas transplant recipients frequently leads to a decline in graft function, with nearly half of the patients experiencing significant deterioration during pregnancy (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The specific risk factors contributing to the adverse post-pregnancy deterioration of graft function remain to be fully identified and understood.\u003c/p\u003e \u003cp\u003eThe timing of pregnancy warrants further attention, as it could potentially influence graft outcomes as shown by previous evidence. Pregnancy within the first year after kidney transplantation is associated with a higher risk of both acute and death-censored graft loss (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). This elevated risk of death-censored graft loss persists into the second year following the transplant. However, the risk does not significantly increase in the third-year post-transplant (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePrevious systematic reviews and meta-analyses have predominantly focused on pregnancy and neonatal outcomes rather than allograft outcomes and function (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). A previous meta-analysis showed that while pregnancy in kidney transplant recipients has a minimal impact on long-term graft survival, it may lead to a slight increase in serum creatinine levels within 2 years postpartum. Long-term graft function remains stable, with no significant differences in graft loss when comparing pregnant recipients to nulliparous controls (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). While a significant proportion of kidney transplant recipients are women of childbearing age, with pregnancy rates in this group typically ranging from 10\u0026ndash;30% (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), addressing this issue is essential to ensure equitable representation of pregnant individuals in transplant medicine. To better understand the risks and implications for women with kidney transplants, there is still a need for a comprehensive meta-analysis that integrates and synthesizes the latest data on kidney graft health with the inclusion of appropriate control kidney transplant recipients who did not conceive after kidney transplant. Therefore, in this systematic review and meta-analysis, we aimed to evaluate the long-term impact of pregnancy on patient survival, graft failure and serum creatinine levels in kidney transplant recipients to inform clinical practice and guide preconception counseling.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThe protocol of this study was registered with PROSPERO (CRD42024569702). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to report this systematic review and meta-analysis (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy and study selection\u003c/h2\u003e \u003cp\u003eWe systematically searched multiple databases including PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE, targeting studies published in peer-reviewed journals up to August 24, 2024. Our search terms encompassed a combination of pregnancy-related keywords, kidney transplantation-related keywords, and keywords related to specific outcomes including mortality, graft outcomes, serum creatinine and eGFR change, and proteinuria. Further information on the search methodology and the keywords employed can be found in Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e. The articles were imported into the EndNote 21 and duplicates were excluded automatically and subsequently re-checked automatically upon uploading to Covidence and through manually by the authors during the screening process (LO, SMAR, SU, MG). Three different authors (LO, SMAR, SU) independently screened the title and abstract of each identified article for adherence to predetermined inclusion and exclusion criteria. Each article is screened by at least two authors. The selection of articles for the study was based on consensus among the authors, with any discrepancies discussed with a fourth author (MG). Subsequently, each full-text article found eligible in the screening process underwent a triple-blind review by the authors (LO, SMAR, SU). Any discrepancies regarding the eligibility of full-text articles were discussed with the fourth author (MG). During full-text screening, the references in the full-text articles are reviewed to identify additional eligible articles. The study screening and selection process is outlined in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSelection criteria\u003c/h3\u003e\n\u003cp\u003eStudies that provide data on adult kidney transplant recipients (\u0026gt;\u0026thinsp;18 years) who have become pregnant after undergoing kidney transplantation, with a non-pregnant or non-conceived control group, are of interest. Included studies must meet the following criteria: 1) they involve adult kidney transplant recipients who have become pregnant post-transplant; 2) they include a control group of previously non-pregnant individuals; 3) they report outcomes of interest such as patient mortality, graft survival, serum creatinine levels, estimated glomerular filtration rate changes, and proteinuria. Studies were excluded if they did not report on long-term prognostic outcomes of post-transplant pregnancy, focusing instead only on immediate or early postpartum outcomes (e.g., those reporting data no later than 8 weeks or only during pregnancy); if they included only kidney transplant patients who became pregnant without a non-pregnant or non-conceived control group; if they did not provide the outcomes of interest; or if they were animal studies, reviews, editorials, letters, commentaries. Additionally, studies that are not available in full text or for which no English translation is available were also excluded.\u003c/p\u003e\n\u003ch3\u003eQuality Assessment\u003c/h3\u003e\n\u003cp\u003eThe assessment of study quality was conducted utilizing the Newcastle-Ottawa scale (NOS), which assigns a maximum total score of nine points, with a score of seven or higher indicative of high quality, a score between four to six indicating moderate quality, and a score of three or lower indicates poor quality. Quality assessment of the studies is performed by three separate authors (LO, SMAR, SU) the results are compared and consensus has been made (Supplementary Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e and S3).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eWe conducted a comprehensive search across the specified databases, initially retrieving a total of 6118 studies. After removing duplicate publications, 5795 studies remained for screening based on titles and abstracts, and 289 of those underwent further full-text assessment for eligibility. Following the evaluation of predefined inclusion and exclusion criteria, 19 studies were ultimately selected for inclusion in the present meta-analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of included studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudy Type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eParticipant characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOutcome measures\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eKey findings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eQuality assessment\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst et al (1995) (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 women of reproductive age who had kidney transplantation between 1967 and 1990\u003c/p\u003e \u003cp\u003e● 18 women with posttransplant pregnancies\u003c/p\u003e \u003cp\u003e● 26 paired nonpregnant controls\u003c/p\u003e \u003cp\u003e23 male controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Serum creatinine changes\u003c/p\u003e \u003cp\u003e● Patient mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePregnancy provokes transient improvement in serum creatinine levels, which return to baseline after pregnancy\u003c/p\u003e \u003cp\u003eNo adverse long-term effect on patient survival or graft function/survival\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFischer et al (2005) (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162 women of reproductive age who had kidney transplantation\u003c/p\u003e \u003cp\u003e● 81 women with posttransplant pregnancies\u003c/p\u003e \u003cp\u003e● 81 paired nonpregnant controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Patient mortality\u003c/p\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Serum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePregnancies in\u003c/p\u003e \u003cp\u003erenal recipients do not negatively affect long-term patient\u003c/p\u003e \u003cp\u003eand graft survival or graft function, independent of the immunosuppressive\u003c/p\u003e \u003cp\u003eregimen.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGorgulu et al (2010) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 women of reproductive age who had kidney transplantation\u003c/p\u003e \u003cp\u003e● 19 patients with posttransplant pregnancies\u003c/p\u003e \u003cp\u003e● 38 paired nonpregnant controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Serum creatinine\u003c/p\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Patient mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGraft outcomes such as serum creatinine\u003c/p\u003e \u003cp\u003elevel and acute rejection episodes or graft survival\u003c/p\u003e \u003cp\u003edid not differ significantly between the groups.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGuti\u0026eacute;rrez et al (2009) (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54 women of reproductive age who had kidney transplantation\u003c/p\u003e \u003cp\u003e● 27 women with posttransplant pregnancies\u003c/p\u003e \u003cp\u003e● 27 paired nonpregnant controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Serum creatinine\u003c/p\u003e \u003cp\u003e● Patient mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThere were no acute rejection episodes or graft losses during pregnancy and puerperium.\u003c/p\u003e \u003cp\u003eRenal function at the end of pregnancy was lower among the pregnant compared to the control group. At 1 and 10 years, renal function was\u003c/p\u003e \u003cp\u003esimilar among the groups; pregnancy did not have a significant effect on graft function.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKaatz et al (2023) (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 women of reproductive age who had single kidney or combined kidney-pancreas transplantation\u003c/p\u003e \u003cp\u003e● 40 women with posttransplant pregnancies\u003c/p\u003e \u003cp\u003e● 40 paired nonpregnant controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● eGFR/serum creatinine changes\u003c/p\u003e \u003cp\u003e● Proteinuria\u003c/p\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Patient mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e● Pregnancies after transplantation showed good maternal and allograft outcomes.\u003c/p\u003e \u003cp\u003e● Pre-pregnancy factors, except for a declining renal allograft function in the year before pregnancy, were not helpful in predicting the outcomes.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKashanizad eh et al (2007) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrospective Cohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86 female kidney transplant recipients with at least one posttransplant pregnancy and 125 kidney transplant recipients with no pregnancy matched for age, cause of end-stage renal disease (ESRD), treatment\u003c/p\u003e \u003cp\u003eprotocol, and first creatinine (Cr) between 1996 and 2002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Patient survival\u003c/p\u003e \u003cp\u003e● Serum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTwo (3.3%) patients in group I and 2 (1.6%) patients in group II died during the follow-up. Eight (9.2%) patients in group 1 and 9 (7.2%) in group II lost their allografts. The five-year patient graft survival rates were not significantly different between the study groups. Only 10.6% of the pregnant group had elevated serum creatinine levels while at the same time, 28% of the nonpregnant group had elevated serum creatinine levels.\u003c/p\u003e \u003cp\u003eThere was no correlation between the number of pregnancies and creatinine levels.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKim et al (2008) (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 women who conceived after undergoing renal transplantation and 187 transplanted non-pregnant controls matched according to age at transplantation, immunosuppressive regimen, and time of transplantation between 1991 and 2005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Serum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThe graft failure rate from transplantation to the end of follow-up did not differ\u003c/p\u003e \u003cp\u003ebetween the pregnant and nonpregnant groups. The 10- and 15-year graft survival rates were 78.5%\u003c/p\u003e \u003cp\u003eand 67.3%, respectively, in the pregnant group, and 75.0% and 58.1%, respectively, in the control group. The 10-year graft survival rates were also similar in the 11\u003c/p\u003e \u003cp\u003ewomen who became pregnant less than or equal to 12 months\u003c/p\u003e \u003cp\u003eafter transplantation and 37 who became pregnant more than 12 months after transplantation. Serum creatinine levels did not differ significantly between the groups at the end of the follow-up period.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLevidiotis et al (2009) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrospective Cohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 parous women matched with 120 nulliparous women by year of\u003c/p\u003e \u003cp\u003etransplantation, duration of transplant, age at transplantation 5\u0026nbsp;year, and pre delivery creatinine for\u003c/p\u003e \u003cp\u003eparous women or serum creatinine for nulliparous women\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Patient survival\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFive-year unadjusted graft survival rates for patients and control subjects were 89% and 85.3%, respectively; 10-year rates were 66.4% and 74.8%, respectively; and 15-year rates were 56.5% and 55.7, respectively.\u003c/p\u003e \u003cp\u003eUnadjusted patient survival rates censored for graft failure for patients and control subjects at 5\u0026nbsp;year were 99.2% and 95.2%, respectively; 10-yr patient survival rates were 94.0% and 91.7%, respectively; and 15-yr survival rates were 89.6% and 86.8%, respectively.\u003c/p\u003e \u003cp\u003eFirst live birth was not associated with a poorer 20-year graft or patient survival.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePour-Reza-Gholi et al (2005) (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrospective Cohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRetrospective data on 74 pregnancies in 60 patients were reviewed and completed through phone interviews were compared with information on a control group of female kidney recipients.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Serum creatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOne-, 3-, 5-, and\u003c/p\u003e \u003cp\u003e10-year graft survival was 100%, 96.5%, 94.5%, and 77.1% in the pregnant group versus 93.2%, 85.7%, 81%, and 64.7% in the control group, respectively.\u003c/p\u003e \u003cp\u003eChronic graft dysfunction and graft loss were seen in 24 and 18 cases of the pregnant group and in 17 and 17 cases of the control group, respectively. The last creatinine level was not significantly different in the pregnant versus the control group.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadaelli et al (2023) (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 pregnant women (cases), with a total of 97 gestations and a matched control\u003c/p\u003e \u003cp\u003egroup of 78 female KT patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Patient survival\u003c/p\u003e \u003cp\u003e● Serum creatinine\u003c/p\u003e \u003cp\u003e● Proteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGraft survival was higher in cases than in controls in 5 years (85.6% vs 71.5%, p\u0026thinsp;=\u0026thinsp;0.012) and 10 years (71.9% vs 55.0%, p\u0026thinsp;=\u0026thinsp;0.012) of follow-up.\u003c/p\u003e \u003cp\u003ePatient survival was also higher in cases than controls in 5 years (98.6% vs\u003c/p\u003e \u003cp\u003e85.8%, p\u0026thinsp;=\u0026thinsp;0.004) and 10 years (95.2% vs 80.3%, p\u0026thinsp;=\u0026thinsp;0.004) of follow-up.\u003c/p\u003e \u003cp\u003eMedian creatinine before conception and one year after did not differ (1.2 vs. 1.2 mg/dL).\u003c/p\u003e \u003cp\u003eMedian UPCR before pregnancy and one year after did not differ (0.3 vs. 0.29).\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRahamimov et al (2006) (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 women became pregnant after renal transplantation and 177 women did not become pregnant after renal transplantation. These controls were matched to the pregnant group based on 12 factors known to affect graft survival.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Graft function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThe survival rates for grafts (61.6%) and patients (84.8%) from transplantation to the end of a 15-year follow-up in women who conceived after transplantation were comparable to those of the 177 women in the matched control group, who had survival rates of 68.7% and 78.8%, respectively. Additionally, there were no significant differences in long-term graft function between the two groups.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSalmela et al (1993) (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-Control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 women of reproductive age who had kidney transplantation\u003c/p\u003e \u003cp\u003e● 22 women with posttransplant pregnancies\u003c/p\u003e \u003cp\u003e● 44 paired nonpregnant controls\u003c/p\u003e \u003cp\u003e39 male transplant patients who became fathers posttransplant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e● Graft survival\u003c/p\u003e \u003cp\u003e● Patient mortality\u003c/p\u003e \u003cp\u003e● Serum creatinine changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePregnancy accelerated the deterioration of graft function, and\u003c/p\u003e \u003cp\u003elong-term graft survival is significantly worse in patients with posttransplant pregnancies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSibanda et al (2007) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrospective Cohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e193 pregnancies were reported in 176 kidney transplant recipients, considering 17 of the women were multiparous.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026bull; Graft survival\u003c/p\u003e \u003cp\u003e\u0026bull; Patient mortality\u003c/p\u003e \u003cp\u003e\u0026bull; Serum creatinine changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePregnancy after kidney transplantation was associated with a favorable outcome for both the mother and the fetus. In the absence of poor prepregnancy renal function and existence of an hypertensive state, the long term graft survival remained optimal.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStoumpos et al (2016) (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eObstetric and kidney transplant outcomes who have been pregnant between 1973 and 2013 have been analyzed. Additionally, a case-cohort study with 138 pregnancies, 89 of them being renal transplant recipients have been analyzed.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026bull; Graft survival\u003c/p\u003e \u003cp\u003e\u0026bull; Patient mortality\u003c/p\u003e \u003cp\u003e\u0026bull; Serum creatinine changes\u003c/p\u003e \u003cp\u003e\u0026bull; eGFR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePregnancy did not adversely affect long-term graft survival or overall patient outcomes, albeit high rates of obstetric complication. Serum creatinine changes and eGFR remained stable.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSturgiss et al (1995) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase-control\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 kidney allograft recipients. 18 of these became pregnant and rest of the nulliparous population was assigned as the control.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026bull; Graft survival\u003c/p\u003e \u003cp\u003e\u0026bull; Patient mortality\u003c/p\u003e \u003cp\u003e\u0026bull; Serum creatinine changes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePregnancy in kidney transplant recipients did not negatively impact long-term graft function or patient survival. Serum creatinine levels remained stable even after 15-years post-transplant follow-up.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSvetitsky et al (2018) (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRetrospective Cohort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA total of 22 pregnancies that resulted in live births were observed in 18 women who underwent kidney or combined kidney-pancreas transplants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026bull; Graft survival\u003c/p\u003e \u003cp\u003e\u0026bull; Serum creatinine changes\u003c/p\u003e \u003cp\u003e\u0026bull; eGFR,\u003c/p\u003e \u003cp\u003e\u0026bull; proteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePregnancy following kidney or simultaneous kidney-pancreas transplantation did not significantly affect long-term graft function (serum creatinine, eGFR) or increase proteinuria compared to controls, but comprehensive follow-up is recommended.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHigh (Score: 8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCreatinine values before pregnancy and after delivery were reported in seven studies (\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16 CR17\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Kidney transplant patients had significantly lower creatinine values before pregnancy compared to the post-delivery follow-up period, with a standardized mean difference (SMD) of -0.33 (95% CI: -0.52 to -0.14, p\u0026thinsp;=\u0026thinsp;0.0008). The heterogeneity across the studies was low (I\u0026sup2; = 18%). In a sensitivity analysis, excluding the study by Fischer et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) eliminated the heterogeneity entirely, while still maintaining the statistical significance of the effect (p\u0026thinsp;=\u0026thinsp;0.03) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWe also compared creatinine values throughout the entire pregnancy duration to the initial baseline values. Five studies provided data on creatinine levels before pregnancy and during the first trimester in kidney transplant patients (\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In the pooled analysis, creatinine levels tended to decrease during the first trimester; however, this effect did not reach statistical significance (SMD 0.88, 95% CI: -0.40 to 2.17, p\u0026thinsp;=\u0026thinsp;0.18). The results were limited by high heterogeneity (I\u0026sup2; = 97%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). After excluding the study by Fischer et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) creatinine levels were found to be higher in the pre-conception period compared to the first trimester (SMD 0.25, 95% CI: 0.02 to 0.48, p\u0026thinsp;=\u0026thinsp;0.04), with low heterogeneity (I\u0026sup2; = 0%). These results should be interpreted with caution, as the significant variation in heterogeneity before and after the exclusion of Fischer et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) suggests that the findings may be sensitive to specific studies and may not be fully generalizable.\u003c/p\u003e \u003cp\u003eConversely, creatinine values before pregnancy were significantly higher compared to those reported in the second trimester (SMD 0.22, 95% CI: 0.01 to 0.43, p\u0026thinsp;=\u0026thinsp;0.04), with low heterogeneity across studies (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). These findings align with the expectation that creatinine levels tend to decline as pregnancy progresses, contrasting with the anticipated rise following delivery.\u003c/p\u003e \u003cp\u003eAlthough creatinine levels tended to increase in the last trimester, the effect was not statistically significant (SMD \u0026minus;\u0026thinsp;0.51, 95% CI: -1.36 to 0.34, p\u0026thinsp;=\u0026thinsp;0.24) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) (\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Excluding the study Fischer et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) from the analysis eliminated heterogeneity, but the creatinine levels remained similar during the both time-frames.\u003c/p\u003e \u003cp\u003eCreatinine values were comparable between the first and second trimesters (SMD 0.02, 95% CI: -0.21 to 0.26, p\u0026thinsp;=\u0026thinsp;0.84) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e) (\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). However, the comparison between the first and third trimesters was influenced by substantial heterogeneity. In the pooled analysis, the heterogeneity was high, and the effect did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.11) (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). Notably, after excluding the study by Fischer et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) creatinine values were significantly lower in the first trimester compared to the third trimester (SMD \u0026minus;\u0026thinsp;0.30, 95% CI: -0.30 to -0.06, p\u0026thinsp;=\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003eData concerning the risk of allograft failure or graft loss was comparable between pregnant patients and non-pregnant controls (OR 1.13, 95% CI: 0.83\u0026ndash;1.53, p\u0026thinsp;=\u0026thinsp;0.43) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e). However, the incidence of adverse kidney outcomes was slightly higher in pregnant patients (25.4% vs. 19.8%).\u003c/p\u003e \u003cp\u003eSimilarly, the risk of all-cause mortality was similar in pregnant and non-pregnant KT patients (OR 0.63, 95% CI: 0.38\u0026ndash;1.07, p\u0026thinsp;=\u0026thinsp;0.09), with low heterogeneity across studies (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;12%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e) (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The publication bias was displayed as a funnel plot, in case of studies investigating graft loss (Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis systematic review and meta-analysis including 19 studies found that the risk of allograft failure or graft loss was similar between pregnant and non-pregnant controls, although there was a slightly higher rate of adverse outcomes in pregnant patients. The risk of all-cause mortality was similar between the two groups in our study. While acute rejection rates in pregnant kidney transplant recipients are relatively low and similar across various regions (ranging from 3\u0026ndash;8%) in the literature, the impact of pregnancy on long-term graft survival in previous studies was less clear (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In this regard, a previous meta-analysis showed that the overall graft loss rates at 1, 2, and 5 years after pregnancy are not significantly different from those in non-pregnant recipients (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Some studies suggest that pregnancy does not adversely affect graft survival and may even have favorable outcomes in certain cases. However, these findings could be influenced by selection bias, as those who become pregnant after a kidney transplant are often younger, and healthier, which may skew the results. Another meta-analysis on this subject found that while the incidence of graft loss increases over time postpartum\u0026mdash;9.4% within 2 years, rising to 38.5% after more than 10 years\u0026mdash;pregnancy generally does not have a significant long-term impact on graft function, with stable serum creatinine levels observed beyond 2 years (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), as in line with our findings. Notably, there was a marginally higher serum creatinine increase of 0.18 mg/dL within 2 years postpartum (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Key risk factors for adverse outcomes included preconceptional hypertension, proteinuria, and high pre-pregnancy serum creatinine levels, but the type of delivery and immunosuppressive regime did not significantly affect graft survival (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePregnant kidney transplant patients generally face low risks of maternal death and worsening kidney function if their initial kidney function is normal, though these risks increase with pre-existing kidney impairment (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The research, involving 92 pregnancies in 67 women from 1972 to 2019, found that pre-pregnancy kidney function significantly affects both pregnancy and graft outcomes (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Women with a higher pre-pregnancy eGFR (\u0026ge;\u0026thinsp;50 mL/min/1.73m\u0026sup2;) had better pregnancy outcomes and longer post-pregnancy graft survival compared to those with lower pre-pregnancy eGFR (\u0026lt;\u0026thinsp;50 mL/min/1.73m\u0026sup2;) (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Conversely, pregnancies in women with lower pre-pregnancy eGFR were associated with greater declines in kidney function and higher rates of maternal and fetal complications (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Nevertheless, the full clinical picture of the alterations in serum creatinine in the trimesters and post-pregnancy varies between the studies. A study evaluating 34 pregnancies in kidney transplant recipients found that graft dysfunction, defined as an increase in serum creatinine at least 0.3 mg/, occurred in 15 cases, primarily due to preeclampsia, rejection, or infections (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Despite these issues, most graft dysfunctions were temporary, with no significant long-term difference in graft function before and after pregnancy, though graft rejection remained a significant risk for graft loss (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). In another study, pregnancy outcomes in women who had undergone kidney transplantation found that although 78.9% of pregnancies resulted in live births, there was a high rate of preterm birth (56.5%) and hypertensive disorders (76%) (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Therefore, prematurity, low birth rates, and intrauterine growth retardation were among the adverse neonatal outcomes in this group (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Prepregnancy serum creatinine levels were indicative of risk; higher levels were associated with increased rates of pre-eclampsia and poorer graft function post-pregnancy, with one-third of women experiencing graft deterioration during pregnancy, and 63.2% of those with worsening graft function did not return to baseline within two years postpartum (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Overall, the importance of pregnancy-associated conditions cannot be underestimated when evaluating kidney function. In our study, creatinine levels were significantly lower before pregnancy compared to after delivery. During pregnancy, creatinine levels did not change significantly in the first trimester but were higher before pregnancy than in the second trimester. There was an observed increase in creatinine from pre-conception to the first trimester when one study was excluded. Creatinine levels did not significantly change between the first and third trimesters.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOverall, given the high prevalence of pregnancy among women of childbearing age who are kidney transplant recipients, it is crucial to thoroughly address the potential concerns related to maternal, fetal, and allograft outcomes. Several studies have previously shown an increased rate of pregnancy-related complications in kidney transplant recipients. However, the allograft outcomes and patient mortality seemed to be unaffected in most of the studies, as in our meta-analysis. Despite these findings, it is important to consider limitations such as publication bias and the evolution of transplant management practices over time. Our study encompasses research spanning several decades, which may introduce variability in treatment protocols and patient management, potentially influencing the results. Additionally, applying these findings broadly to specific high-risk populations, such as individuals with already low GFR or other pre-existing risk factors, may be misleading. It is crucial to recognize that these groups might experience different outcomes, and the generalized results may not fully capture their unique risks and needs. Future research should investigate both the specific risk factors or obstetric complications affecting graft and patient outcomes in pregnant kidney transplant recipients, the impact of transplant-related management strategies on these outcomes, and the allograft prognosis of pregnancy with reduced kidney function.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study was not funded by any grant.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest and disclosure:\u003c/strong\u003e Authors declare that they have no conflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u0026nbsp;\u003c/strong\u003eThis article does not contain any studies with human participants or animals performed by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u003c/strong\u003e None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContribution of authors:\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eContributed substantially to the conception or design of the work; or the acquisition,\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eanalysis, or interpretation of data for the work:\u0026nbsp;Mehmet Kanbay, Crischentian Brinza,\u0026nbsp;Sama Mahmoud Abdel-Rahman, Selen Unlu, Lasin Ozbek, Mustafa Guldan,\u0026nbsp;Alexandru Burlacu\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eDrafted the work or revised it critically for important intellectual content:\u0026nbsp;Mehmet Kanbay, Alexandru Burlacu, Ozgur Aktas, Adrian Covic,\u0026nbsp;Andreea Covic\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLevidiotis V, Chang S, McDonald S. Pregnancy and maternal outcomes among kidney transplant recipients. J Am Soc Nephrol. 2009;20(11):2433\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSibanda N, Briggs JD, Davison JM, Johnson RJ, Rudge CJ. Pregnancy after organ transplantation: a report from the UK Transplant pregnancy registry. Transplantation. 2007;83(10):1301\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKattah AG, Albadri S, Alexander MP, Smith B, Parashuram S, Mai ML, et al. Impact of Pregnancy on GFR Decline and Kidney Histology in Kidney Transplant Recipients. Kidney Int Rep. 2022;7(1):28\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBachmann F, Budde K, Gerland M, Wiechers C, Heyne N, Nadalin S, et al. Pregnancy following kidney transplantation - impact on mother and graft function and focus on childrens' longitudinal development. BMC Pregnancy Childbirth. 2019;19(1):376.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFirst MR, Combs CA, Weiskittel P, Miodovnik M. Lack of effect of pregnancy on renal allograft survival or function. Transplantation. 1995;59(4):472\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRose C, Gill J, Zalunardo N, Johnston O, Mehrotra A, Gill JS. Timing of Pregnancy After Kidney Transplantation and Risk of Allograft Failure. Am J Transplant. 2016;16(8):2360-\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShah S, Venkatesan RL, Gupta A, Sanghavi MK, Welge J, Johansen R, et al. Pregnancy outcomes in women with kidney transplant: Metaanalysis and systematic review. BMC Nephrol. 2019;20(1):24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeshpande NA, James NT, Kucirka LM, Boyarsky BJ, Garonzik-Wang JM, Montgomery RA, et al. Pregnancy outcomes in kidney transplant recipients: a systematic review and meta-analysis. Am J Transplant. 2011;11(11):2388\u0026ndash;404.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Buren MC, Schellekens A, Groenhof TKJ, van Reekum F, van de Wetering J, Paauw ND, et al. Long-term Graft Survival and Graft Function Following Pregnancy in Kidney Transplant Recipients: A Systematic Review and Meta-analysis. Transplantation. 2020;104(8):1675\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGill JS, Zalunardo N, Rose C, Tonelli M. The pregnancy rate and live birth rate in kidney transplant recipients. Am J Transplant. 2009;9(7):1541\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePage MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J Clin Epidemiol. 2021;134:178\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarros T, Braga J, Correia A, Correia S, Martins S, Braga A. Pregnancy in kidney transplantation women: perinatal outcomes and impact on kidney function. J Matern Fetal Neonatal Med. 2022;35(26):10355\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFischer T, Neumayer HH, Fischer R, Barenbrock M, Schobel HP, Lattrell BC, et al. Effect of pregnancy on long-term kidney function in renal transplant recipients treated with cyclosporine and with azathioprine. Am J Transplant. 2005;5(11):2732\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026ouml;kce S, Herkiloglu D, Uyar M. Pregnancy outcomes after kidney transplantation. Transplantation Reports. 2021;6(100084).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGorgulu N, Yelken B, Caliskan Y, Turkmen A, Sever MS. Does pregnancy increase graft loss in female renal allograft recipients? Clin Exp Nephrol. 2010;14(3):244\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim HW, Seok HJ, Kim TH, Han DJ, Yang WS, Park SK. The experience of pregnancy after renal transplantation: pregnancies even within postoperative 1 year may be tolerable. Transplantation. 2008;85(10):1412\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLichtenberg S, Freilich Rom D, Aspitz HZ, Keshet R, Rahamimov R, Rozen-Zvi B. Second pregnancy following kidney transplantation is not associated with an increased risk of graft loss in a single center retrospective cohort study. Clin Transplant. 2022;36(8):e14741.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSturgiss SN, Davison JM. Effect of pregnancy on the long-term function of renal allografts: an update. Am J Kidney Dis. 1995;26(1):54\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKashanizadeh N, Nemati E, Sharifi-Bonab M, Moghani-Lankarani M, Ghazizadeh S, Einollahi B, et al. Impact of pregnancy on the outcome of kidney transplantation. Transplant Proc. 2007;39(4):1136-8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRadaelli E, Meinerz G, Jacobina LP, Bruno RM, de Andrade JAM, Garcia VD, et al. Pregnancy after kidney transplantation: 40 years single-center experience. J Bras Nefrol. 2024;46(2):e20230061.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRahamimov R, Ben-Haroush A, Wittenberg C, Mor E, Lustig S, Gafter U, et al. Pregnancy in renal transplant recipients: long-term effect on patient and graft survival. A single-center experience. Transplantation. 2006;81(5):660\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCabiddu G, Spotti D, Gernone G, Santoro D, Moroni G, Gregorini G, et al. A best-practice position statement on pregnancy after kidney transplantation: focusing on the unsolved questions. The Kidney and Pregnancy Study Group of the Italian Society of Nephrology. J Nephrol. 2018;31(5):665\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhafari A, Sanadgol H. Pregnancy after renal transplantation: ten-year single-center experience. Transplant Proc. 2008;40(1):251-2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwarz A, Schmitt R, Einecke G, Keller F, Bode U, Haller H, et al. Graft function and pregnancy outcomes after kidney transplantation. BMC Nephrol. 2022;23(1):27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAivazoglou L, Sass N, Silva HT, Jr., Sato JL, Medina-Pestana JO, De Oliveira LG. Pregnancy after renal transplantation: an evaluation of the graft function. Eur J Obstet Gynecol Reprod Biol. 2011;155(2):129\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohammadi FA, Borg M, Gulyani A, McDonald SP, Jesudason S. Pregnancy outcomes and impact of pregnancy on graft function in women after kidney transplantation. Clin Transplant. 2017;31(10).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGutierrez MJ, Gonzalez P, Delgado I, Gutierrez E, Gonzalez E, Siqueira RC, et al. Renal allograft function and cardiovascular risk in recipients of kidney transplantation after successful pregnancy. Transplant Proc. 2009;41(6):2399\u0026thinsp;\u0026ndash;\u0026thinsp;402.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaatz R, Latartara E, Bachmann F, Lachmann N, Koch N, Zukunft B, et al. Pregnancy after Kidney Transplantation-Impact of Functional Renal Reserve, Slope of eGFR before Pregnancy, and Intensity of Immunosuppression on Kidney Function and Maternal Health. J Clin Med. 2023;12(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePour-Reza-Gholi F, Nafar M, Farrokhi F, Entezari A, Taha N, Firouzan A, et al. Pregnancy in kidney transplant recipients. Transplant Proc. 2005;37(7):3090-2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalmela KT, Kyllonen LE, Holmberg C, Gronhagen-Riska C. Impaired renal function after pregnancy in renal transplant recipients. Transplantation. 1993;56(6):1372\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStoumpos S, McNeill SH, Gorrie M, Mark PB, Brennand JE, Geddes CC, et al. Obstetric and long-term kidney outcomes in renal transplant recipients: a 40-yr single-center study. Clin Transplant. 2016;30(6):673\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSvetitsky S, Baruch R, Schwartz IF, Schwartz D, Nakache R, Goykhman Y, et al. Long-Term Effects of Pregnancy on Renal Graft Function in Women After Kidney Transplantation Compared With Matched Controls. Transplant Proc. 2018;50(5):1461-5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pregnancy, graft outcomes, graft failure, mortality","lastPublishedDoi":"10.21203/rs.3.rs-5280668/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5280668/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground and aim: \u003c/strong\u003ePregnancy in kidney transplant recipients involves complex physiological changes that could potentially impact long-term graft function and survival. Despite some evidence suggesting minimal long-term effects on graft survival, conflicting results on graft function and timing-related risks highlight the need for a comprehensive review. This systematic review and meta-analysis aim to evaluate the long-term impact of pregnancy on patient survival, graft failure, serum creatinine levels, estimated glomerular filtration rate (eGFR), and proteinuria in kidney transplant recipients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and methods\u003c/strong\u003e: We conducted a systematic review and meta-analysis adhering to PRISMA guidelines and registered with PROSPERO (CRD42024569702). We searched PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE. Studies were eligible if they provided data on adult kidney transplant recipients (\u0026gt;18 years) who became pregnant post-transplant and included a control group of non-pregnant or non-conceived individuals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Among the 6,118 results screened, 19 studies met the eligibility criteria and were included in the meta-analysis. The risk of allograft failure or graft loss was similar between pregnant and non-pregnant controls (OR 1.13, 95% CI: 0.83–1.53, p = 0.43), with a slightly higher adverse outcome rate in pregnant patients (25.4% vs. 19.8%). All-cause mortality risk was also comparable (OR 0.63, 95% CI: 0.38–1.07, p = 0.09), with low heterogeneity (I² = 12%). Creatinine levels were significantly lower before pregnancy compared to after delivery (SMD -0.33, 95% CI: -0.52 to -0.14, p = 0.0008).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Pregnancy in kidney transplant recipients leads to increased creatinine levels in postpartum but does not significantly affect long-term graft survival. While creatinine levels generally decrease during pregnancy, they show variability by trimester. The risk of allograft failure and mortality is similar between pregnant and non-pregnant recipients, though adverse outcomes are slightly more frequent in pregnant patients, emphasizing the need for careful monitoring and individualized management.\u003c/p\u003e","manuscriptTitle":"Long-term impact of pregnancy on mortality and graft outcomes in kidney transplant recipients: a systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-10 14:03:28","doi":"10.21203/rs.3.rs-5280668/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"268cbf99-aaaf-489c-bfbe-13e0959e1789","owner":[],"postedDate":"November 10th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-12T15:59:05+00:00","versionOfRecord":{"articleIdentity":"rs-5280668","link":"https://doi.org/10.1007/s11255-025-04572-5","journal":{"identity":"international-urology-and-nephrology","isVorOnly":false,"title":"International Urology and Nephrology"},"publishedOn":"2025-05-10 15:57:02","publishedOnDateReadable":"May 10th, 2025"},"versionCreatedAt":"2024-11-10 14:03:28","video":"","vorDoi":"10.1007/s11255-025-04572-5","vorDoiUrl":"https://doi.org/10.1007/s11255-025-04572-5","workflowStages":[]},"version":"v1","identity":"rs-5280668","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5280668","identity":"rs-5280668","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}