Clinical Barriers to the Initiation of SGLT2 Inhibitors in Patients with Chronic Kidney Disease: A Retrospective Cross-Sectional Study

Clinical Barriers to the Initiation of SGLT2 Inhibitors in Patients with Chronic Kidney Disease: A Retrospective Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Barriers to the Initiation of SGLT2 Inhibitors in Patients with Chronic Kidney Disease: A Retrospective Cross-Sectional Study aydeniz kansu, erkan sengul, huseyin ciftlik This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9215986/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Despite strong guideline recommendations, the use of sodium–glucose cotransporter-2 (SGLT2) inhibitors remains suboptimal in patients with Chronic Kidney Disease, both in diabetic and non-diabetic populations ( 1 – 3 ). This study aimed to evaluate patient-related factors associated with non-initiation of SGLT2 inhibitors. Methods This retrospective, analytical, cross-sectional study included patients with CKD who were followed at the nephrology clinic of a tertiary care center between April 1, 2023, and June 1, 2024. A total of 995 patients who were not receiving SGLT2 inhibitors were included. Demographic characteristics, comorbidities, ongoing treatments, and laboratory parameters were recorded. Results The mean age of the study population was 72.3 ± 14.4 years; 464 (46.6%) were male and 531 (53.4%) were female. The majority of patients (63.6%) had stage 3 CKD. The most common reasons for not initiating SGLT2 inhibitors were a history or concern of genitourinary infections and absence of Diabetes Mellitus. Rare but serious adverse events such as diabetic ketoacidosis, lower extremity amputation, hypotension, and necrotizing fasciitis were not observed as reasons for non-initiation. Conclusion Current guidelines recommend the use of SGLT2 inhibitors in most patients with CKD and an estimated glomerular filtration rate ≥ 20 mL/min/1.73 m², regardless of underlying etiology, due to their proven benefits in reducing morbidity and mortality. However, a substantial proportion of patients remain untreated, likely due to limited awareness and concerns regarding adverse effects. Notably, the frequent non-use in eligible patients—including those with diabetes—highlights a significant gap between guideline recommendations and real-world clinical practice. Increasing awareness and promoting guideline adherence may improve clinical outcomes in CKD patients ( 5 – 6 ). SGLT2 inhibitors Chronic Kidney Disease Genitourinary Infections Diabetes Mellitus Introduction Chronic kidney disease (CKD) affects approximately 10% of the global adult population and is associated with significant morbidity, mortality, and healthcare costs ( 1 ). The leading causes include diabetes mellitus and hypertension, which together account for the majority of CKD cases worldwide ( 1 ). Progressive loss of kidney function frequently leads to end-stage kidney disease, requiring renal replacement therapy, and is also strongly associated with cardiovascular disease and premature death. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as a transformative class of agents for CKD management. The KDIGO 2024 Clinical Practice Guideline for CKD strongly recommends their use in patients with an eGFR ≥ 20 mL/min/1.73 m², regardless of the presence of diabetes mellitus or the underlying etiology of CKD, based on their well-established benefits in slowing CKD progression and reducing cardiovascular morbidity and mortality ( 1 – 3 ). The landmark DAPA-CKD trial demonstrated that dapagliflozin significantly reduced the composite of sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death in patients with CKD with and without type 2 diabetes ( 2 ). Similarly, the EMPA-KIDNEY trial showed that empagliflozin reduced the risk of kidney disease progression or cardiovascular death across a broad spectrum of CKD etiologies and eGFR ranges ( 3 ). Despite these compelling data and strong guideline endorsement, real-world utilization of SGLT2 inhibitors in CKD patients remains substantially below recommended levels. The clinical barriers driving this treatment gap are incompletely understood. The present study was therefore conducted to identify patient-level and clinical factors associated with non-initiation of SGLT2 inhibitors in a nephrology outpatient cohort. Methods This was a single-center, retrospective, analytical, cross-sectional study conducted at the nephrology outpatient clinic of a tertiary care university hospital. The study was approved by the local ethics committee (approval number 2024-96) and conducted in accordance with the Declaration of Helsinki. Written informed consent was waived due to the retrospective nature of the study. Patients with CKD stages 1–4 who were ≥ 18 years of age and had not been prescribed SGLT2 inhibitors at any point during follow-up were eligible for inclusion. Patients were identified from outpatient nephrology records between April 1, 2023, and June 1, 2024. Exclusion criteria were: patients on renal replacement therapy (dialysis or transplantation), eGFR < 20 mL/min/1.73 m², type 1 diabetes mellitus, and age < 18 years. Patients with incomplete records were also excluded. Demographic data (age, sex), comorbidities, current medications, and laboratory parameters were extracted from electronic medical records. eGFR was calculated using the CKD-EPI 2021 equation. CKD staging was assigned according to KDIGO 2012 criteria. The primary outcome was the documented or inferred clinical reason for non-initiation of SGLT2 inhibitors, as recorded in physician notes or inferred from the clinical record. Reasons were categorized as: genitourinary infection history or concern, absence of diabetes mellitus, acute kidney injury, patient refusal, frailty or hypotension, history of bladder cancer, hypersensitivity, or other/unknown. Statistical analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY). Continuous variables are reported as mean ± standard deviation (SD) or median with interquartile range as appropriate; categorical variables as frequencies and percentages. In line with Clinical Kidney Journal’s 2024 policy, sex-stratified analyses of the primary barriers to SGLT2 inhibitor initiation were performed where the sample size permitted. Where subgroup numbers were insufficient to draw conclusions, this limitation is acknowledged. Results A total of 995 patients were included in the study. The mean age was 72.3 ± 14.4 years, with 464 (46.6%) males and 531 (53.4%) females. According to CKD staging, 9.2% of patients had stage 1, 12.3% had stage 2, 63.6% had stage 3, and 14.9% had stage 4 CKD (Table 1 ). Table 1 Baseline Demographic and Clinical Characteristics Variable Value Age (years), mean ± SD 72.3 ± 14.4 Male, n (%) 464 (46.6%) Female, n (%) 531 (53.4%) Stage 1 CKD 92 (9.2%) Stage 2 CKD 122 (12.3%) Stage 3 CKD 633 (63.6%) Stage 4 CKD 148 (14.9%) Hypertension 850 (85.4%) Diabetes mellitus 307 (30.9%) Coronary artery disease 409 (41.1%) Heart failure 128 (12.9%) Atrial fibrillation 104 (10.4%) Glomerulonephritis 20 (2.0%) Regarding comorbidities, hypertension was present in 85.4% of patients, diabetes mellitus in 30.9%, coronary artery disease in 41.1%, congestive heart failure in 12.9%, atrial fibrillation in 10.4%, and glomerulonephritis in 2.0% (Table 1 ). Analysis of CKD etiology revealed that hypertension was the most common cause (44.9%), followed by diabetes mellitus (26.5%). The etiology was unknown in 17.6% of patients (Table 1 ). In terms of medications, 24.6% of patients were receiving oral antidiabetic agents, 10.7% insulin therapy, and 21.2% statins. The mean systolic blood pressure was 132.2 ± 21.0 mmHg and diastolic blood pressure was 80.4 ± 13.0 mmHg. The mean serum creatinine was 1.8 ± 0.8 mg/dL, with a mean eGFR of 51.2 ± 23.2 mL/min/1.73 m². Other laboratory parameters are summarized in Table 2 . Table 2 Laboratory Parameters Parameter Mean ± SD Median Min–Max Systolic BP 132.2 ± 21.0 130 60–205 Diastolic BP 80.4 ± 13.0 80 40–135 Glucose 113.1 ± 72.1 99 67–529 HbA1c 6.2 ± 5.6 6.1 5.0–15.8 Creatinine 1.8 ± 0.8 1.5 0.6–12.0 eGFR 51.2 ± 23.2 47 20–145 None of the patients had a documented history of hypotension, frailty, diabetic ketoacidosis, lower extremity amputation, hypersensitivity, or necrotizing fasciitis. Genitourinary-related findings, particularly pyuria, were among the most common clinical factors associated with non-initiation. Pyuria was present in 28.4% of patients, although only 7.4% were symptomatic. Acute kidney injury was identified in only one patient (0.1%), and bladder cancer was present in 0.7% of patients (Table 3 ). Table 3 Reasons for Non-Initiation Variable n (%) Non-diabetic 308 (31.0%) Patient refusal 8 (0.8%) Pyuria 283 (28.4%) Symptomatic pyuria 74 (7.4%) Positive urine culture 57 (5.7%) Negative urine culture 48 (4.8%) AKI 1 (0.1%) Bladder cancer 7 (0.7%) Discussion SGLT2 inhibitors are strongly recommended in patients with chronic kidney disease (CKD) due to their well-established benefits in slowing disease progression and reducing cardiovascular morbidity and mortality ( 1 – 3 ). Despite these strong recommendations, their use remains suboptimal in real-world clinical practice. One possible explanation is that SGLT2 inhibitors are still primarily perceived as glucose-lowering agents, which may limit their use, particularly in non-diabetic patients. In addition, concerns regarding potential adverse effects further contribute to underutilization. In the present study, a considerable proportion of patients were not initiated on SGLT2 inhibitors despite having diabetes mellitus. Large-scale trials such as DAPA-CKD and EMPA-REG OUTCOME have demonstrated significant renal and cardiovascular benefits of SGLT2 inhibitors, particularly in diabetic populations ( 2 , 4 ). Given that diabetes mellitus is one of the leading causes of CKD worldwide, SGLT2 inhibitors represent a cost-effective therapeutic strategy with the potential to reduce disease progression as well as morbidity and mortality. The majority of patients in our cohort had stage 3 CKD, with a median albuminuria level suggesting moderate renal involvement. Emerging evidence indicates that SGLT2 inhibitors may provide benefits across a wide range of CKD etiologies, including glomerular diseases. Studies have suggested potential benefits in IgA nephropathy and lupus nephritis, further supporting the broad applicability of these agents ( 3 ). Cardiovascular comorbidities were highly prevalent in our cohort, including coronary artery disease and heart failure. Previous studies have consistently shown that SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular mortality ( 4 ). Therefore, many patients in our cohort could have benefited from these agents beyond renal protection. One of the most important findings of our study is that genitourinary-related concerns—particularly pyuria—were among the most common barriers to treatment initiation. However, only a small proportion of these patients were symptomatic, and urine culture positivity was low. Previous studies have demonstrated that the risk of urinary tract infections with SGLT2 inhibitors is comparable to other antidiabetic therapies, while the increased risk is primarily related to genital infections rather than urinary infections ( 5 , 6 ). Furthermore, diabetes mellitus itself predisposes patients to urinary tract infections, making it difficult to attribute this risk solely to SGLT2 inhibitors. These findings suggest that concerns regarding urinary infections may be overestimated in clinical practice. Importantly, no patients in our cohort were excluded from SGLT2 inhibitor therapy due to major adverse events such as hypotension, frailty, diabetic ketoacidosis, lower extremity amputation, or necrotizing fasciitis. This observation is consistent with the literature, which suggests that SGLT2 inhibitors have a favorable safety profile ( 1 – 3 ). Concerns regarding acute kidney injury (AKI) also appear to be overstated. Only one patient in our study had AKI as a reason for non-initiation. In contrast, meta-analyses have demonstrated that SGLT2 inhibitors may reduce the risk of AKI rather than increase it ( 7 ). Patient refusal was rare in our cohort, suggesting that physician-related perceptions and clinical caution may play a more significant role than patient preference. This highlights the importance of increasing clinician awareness and improving adherence to guideline-based recommendations. Overall, our findings suggest that the underutilization of SGLT2 inhibitors is largely driven by perceived risks rather than true contraindications. Addressing these misconceptions may significantly improve the uptake of these agents and ultimately improve outcomes in patients with CKD. Declarations Ethics approval and consent to participate The study was approved by the Kocaeli City Hospital Scientific Research Ethics Committee, Kocaeli, Turkiye (approval number: 2024-96) and conducted in accordance with the Declaration of Helsinki. Informed consent was waived due to the retrospective design of the study. Consent for publication Not applicable. Funding This study did not receive any specific funding. Author Contribution A.K. designed the study, collected the data, performed the statistical analysis, and wrote the first draft of the manuscript. H.C. contributed to data interpretation and critically revised the manuscript. E.S. supervised the study and critically revised the manuscript. All authors read and approved the final manuscript. Data Availability The datasets used and/or analyzed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author on reasonable request. References Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117–314. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. DAPA-CKD Trial Committees and Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46. The EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117–27. Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. Dave CV, Schneeweiss S, Patorno E. Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors. Diabetes Care. 2019;42(1):98–105. Puckrin R, Saltiel MP, Reynier P, et al. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):503–14. Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845–54. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-9215986","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":630490385,"identity":"e65924e9-3c3a-4331-ae44-99c61c356c25","order_by":0,"name":"aydeniz kansu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYHACAxAyADM/ADEbOylaGGeAtDATpQVKMPOASQLq+Wckb3xcUFBnzD+7/Zm0za9t8nzMDIwfPubg1iJxI63YeIYBm5nEnTNm0rl9tw3bmBmYJWduw2PNjRwzaR4DHhsgg006t+c2I1ALGzMvHi3yN3LMf/MYSNjI30h/Jm3Zc9ueoBYDoC3MPAYGZgY3EsykGX7cTiSoxfDMs2KgwxKMDW/kGFv2NtxObmNmbMbrF7njyRs/8/ypM5x3I/3hjR9/btvOb28++OEjPu8LJCBxGNvAZAMe9UDAfwCZ9we/4lEwCkbBKBiZAABNm0tkTFic5QAAAABJRU5ErkJggg==","orcid":"","institution":"kocaeli şehir hastanesi","correspondingAuthor":true,"prefix":"","firstName":"aydeniz","middleName":"","lastName":"kansu","suffix":""},{"id":630490388,"identity":"575a4d17-1b2a-45a2-b352-2527ff7f4577","order_by":1,"name":"erkan sengul","email":"","orcid":"","institution":"kocaeli şehir hastanesi","correspondingAuthor":false,"prefix":"","firstName":"erkan","middleName":"","lastName":"sengul","suffix":""},{"id":630490391,"identity":"24412eab-1b9b-4abb-ae23-95001ded0f4c","order_by":2,"name":"huseyin ciftlik","email":"","orcid":"","institution":"kocaeli şehir hastanesi","correspondingAuthor":false,"prefix":"","firstName":"huseyin","middleName":"","lastName":"ciftlik","suffix":""}],"badges":[],"createdAt":"2026-03-24 20:53:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9215986/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9215986/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":109243716,"identity":"015e1bba-ca31-41b6-8cd7-a9dced633c15","added_by":"auto","created_at":"2026-05-14 07:26:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":143888,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9215986/v1/5dc08c5b-ab70-49e0-b23d-84ab51e0c1ca.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Barriers to the Initiation of SGLT2 Inhibitors in Patients with Chronic Kidney Disease: A Retrospective Cross-Sectional Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChronic kidney disease (CKD) affects approximately 10% of the global adult population and is associated with significant morbidity, mortality, and healthcare costs (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The leading causes include diabetes mellitus and hypertension, which together account for the majority of CKD cases worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Progressive loss of kidney function frequently leads to end-stage kidney disease, requiring renal replacement therapy, and is also strongly associated with cardiovascular disease and premature death.\u003c/p\u003e \u003cp\u003eSodium\u0026ndash;glucose cotransporter-2 (SGLT2) inhibitors have emerged as a transformative class of agents for CKD management. The KDIGO 2024 Clinical Practice Guideline for CKD strongly recommends their use in patients with an eGFR\u0026thinsp;\u0026ge;\u0026thinsp;20 mL/min/1.73 m\u0026sup2;, regardless of the presence of diabetes mellitus or the underlying etiology of CKD, based on their well-established benefits in slowing CKD progression and reducing cardiovascular morbidity and mortality (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe landmark DAPA-CKD trial demonstrated that dapagliflozin significantly reduced the composite of sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death in patients with CKD with and without type 2 diabetes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Similarly, the EMPA-KIDNEY trial showed that empagliflozin reduced the risk of kidney disease progression or cardiovascular death across a broad spectrum of CKD etiologies and eGFR ranges (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Despite these compelling data and strong guideline endorsement, real-world utilization of SGLT2 inhibitors in CKD patients remains substantially below recommended levels. The clinical barriers driving this treatment gap are incompletely understood. The present study was therefore conducted to identify patient-level and clinical factors associated with non-initiation of SGLT2 inhibitors in a nephrology outpatient cohort.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a single-center, retrospective, analytical, cross-sectional study conducted at the nephrology outpatient clinic of a tertiary care university hospital. The study was approved by the local ethics committee (approval number 2024-96) and conducted in accordance with the Declaration of Helsinki. Written informed consent was waived due to the retrospective nature of the study. Patients with CKD stages 1\u0026ndash;4 who were \u0026ge;\u0026thinsp;18 years of age and had not been prescribed SGLT2 inhibitors at any point during follow-up were eligible for inclusion. Patients were identified from outpatient nephrology records between April 1, 2023, and June 1, 2024.\u003c/p\u003e \u003cp\u003eExclusion criteria were: patients on renal replacement therapy (dialysis or transplantation), eGFR\u0026thinsp;\u0026lt;\u0026thinsp;20 mL/min/1.73 m\u0026sup2;, type 1 diabetes mellitus, and age\u0026thinsp;\u0026lt;\u0026thinsp;18 years. Patients with incomplete records were also excluded.\u003c/p\u003e \u003cp\u003eDemographic data (age, sex), comorbidities, current medications, and laboratory parameters were extracted from electronic medical records. eGFR was calculated using the CKD-EPI 2021 equation. CKD staging was assigned according to KDIGO 2012 criteria. The primary outcome was the documented or inferred clinical reason for non-initiation of SGLT2 inhibitors, as recorded in physician notes or inferred from the clinical record. Reasons were categorized as: genitourinary infection history or concern, absence of diabetes mellitus, acute kidney injury, patient refusal, frailty or hypotension, history of bladder cancer, hypersensitivity, or other/unknown. Statistical analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY). Continuous variables are reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median with interquartile range as appropriate; categorical variables as frequencies and percentages.\u003c/p\u003e \u003cp\u003eIn line with Clinical Kidney Journal\u0026rsquo;s 2024 policy, sex-stratified analyses of the primary barriers to SGLT2 inhibitor initiation were performed where the sample size permitted. Where subgroup numbers were insufficient to draw conclusions, this limitation is acknowledged.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 995 patients were included in the study. The mean age was 72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4 years, with 464 (46.6%) males and 531 (53.4%) females. According to CKD staging, 9.2% of patients had stage 1, 12.3% had stage 2, 63.6% had stage 3, and 14.9% had stage 4 CKD (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\u003eBaseline Demographic and Clinical Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e464 (46.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e531 (53.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 1 CKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92 (9.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 2 CKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 3 CKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e633 (63.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage 4 CKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e850 (85.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e307 (30.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e409 (41.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (10.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlomerulonephritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (2.0%)\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\u003eRegarding comorbidities, hypertension was present in 85.4% of patients, diabetes mellitus in 30.9%, coronary artery disease in 41.1%, congestive heart failure in 12.9%, atrial fibrillation in 10.4%, and glomerulonephritis in 2.0% (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnalysis of CKD etiology revealed that hypertension was the most common cause (44.9%), followed by diabetes mellitus (26.5%). The etiology was unknown in 17.6% of patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn terms of medications, 24.6% of patients were receiving oral antidiabetic agents, 10.7% insulin therapy, and 21.2% statins.\u003c/p\u003e \u003cp\u003eThe mean systolic blood pressure was 132.2\u0026thinsp;\u0026plusmn;\u0026thinsp;21.0 mmHg and diastolic blood pressure was 80.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0 mmHg. The mean serum creatinine was 1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 mg/dL, with a mean eGFR of 51.2\u0026thinsp;\u0026plusmn;\u0026thinsp;23.2 mL/min/1.73 m\u0026sup2;. Other laboratory parameters are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory Parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMin\u0026ndash;Max\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e132.2\u0026thinsp;\u0026plusmn;\u0026thinsp;21.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60\u0026ndash;205\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e80.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40\u0026ndash;135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e113.1\u0026thinsp;\u0026plusmn;\u0026thinsp;72.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67\u0026ndash;529\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.0\u0026ndash;15.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.6\u0026ndash;12.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e51.2\u0026thinsp;\u0026plusmn;\u0026thinsp;23.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u0026ndash;145\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\u003eNone of the patients had a documented history of hypotension, frailty, diabetic ketoacidosis, lower extremity amputation, hypersensitivity, or necrotizing fasciitis.\u003c/p\u003e \u003cp\u003eGenitourinary-related findings, particularly pyuria, were among the most common clinical factors associated with non-initiation. Pyuria was present in 28.4% of patients, although only 7.4% were symptomatic. Acute kidney injury was identified in only one patient (0.1%), and bladder cancer was present in 0.7% of patients (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReasons for Non-Initiation\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-diabetic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e308 (31.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient refusal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePyuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e283 (28.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSymptomatic pyuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e74 (7.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive urine culture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57 (5.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative urine culture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48 (4.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAKI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBladder cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (0.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSGLT2 inhibitors are strongly recommended in patients with chronic kidney disease (CKD) due to their well-established benefits in slowing disease progression and reducing cardiovascular morbidity and mortality (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Despite these strong recommendations, their use remains suboptimal in real-world clinical practice. One possible explanation is that SGLT2 inhibitors are still primarily perceived as glucose-lowering agents, which may limit their use, particularly in non-diabetic patients. In addition, concerns regarding potential adverse effects further contribute to underutilization.\u003c/p\u003e \u003cp\u003eIn the present study, a considerable proportion of patients were not initiated on SGLT2 inhibitors despite having diabetes mellitus. Large-scale trials such as DAPA-CKD and EMPA-REG OUTCOME have demonstrated significant renal and cardiovascular benefits of SGLT2 inhibitors, particularly in diabetic populations (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Given that diabetes mellitus is one of the leading causes of CKD worldwide, SGLT2 inhibitors represent a cost-effective therapeutic strategy with the potential to reduce disease progression as well as morbidity and mortality.\u003c/p\u003e \u003cp\u003eThe majority of patients in our cohort had stage 3 CKD, with a median albuminuria level suggesting moderate renal involvement. Emerging evidence indicates that SGLT2 inhibitors may provide benefits across a wide range of CKD etiologies, including glomerular diseases. Studies have suggested potential benefits in IgA nephropathy and lupus nephritis, further supporting the broad applicability of these agents (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCardiovascular comorbidities were highly prevalent in our cohort, including coronary artery disease and heart failure. Previous studies have consistently shown that SGLT2 inhibitors reduce heart failure hospitalizations and cardiovascular mortality (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Therefore, many patients in our cohort could have benefited from these agents beyond renal protection.\u003c/p\u003e \u003cp\u003eOne of the most important findings of our study is that genitourinary-related concerns\u0026mdash;particularly pyuria\u0026mdash;were among the most common barriers to treatment initiation. However, only a small proportion of these patients were symptomatic, and urine culture positivity was low. Previous studies have demonstrated that the risk of urinary tract infections with SGLT2 inhibitors is comparable to other antidiabetic therapies, while the increased risk is primarily related to genital infections rather than urinary infections (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Furthermore, diabetes mellitus itself predisposes patients to urinary tract infections, making it difficult to attribute this risk solely to SGLT2 inhibitors. These findings suggest that concerns regarding urinary infections may be overestimated in clinical practice.\u003c/p\u003e \u003cp\u003eImportantly, no patients in our cohort were excluded from SGLT2 inhibitor therapy due to major adverse events such as hypotension, frailty, diabetic ketoacidosis, lower extremity amputation, or necrotizing fasciitis. This observation is consistent with the literature, which suggests that SGLT2 inhibitors have a favorable safety profile (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eConcerns regarding acute kidney injury (AKI) also appear to be overstated. Only one patient in our study had AKI as a reason for non-initiation. In contrast, meta-analyses have demonstrated that SGLT2 inhibitors may reduce the risk of AKI rather than increase it (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePatient refusal was rare in our cohort, suggesting that physician-related perceptions and clinical caution may play a more significant role than patient preference. This highlights the importance of increasing clinician awareness and improving adherence to guideline-based recommendations.\u003c/p\u003e \u003cp\u003eOverall, our findings suggest that the underutilization of SGLT2 inhibitors is largely driven by perceived risks rather than true contraindications. Addressing these misconceptions may significantly improve the uptake of these agents and ultimately improve outcomes in patients with CKD.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e The study was approved by the Kocaeli City Hospital Scientific Research Ethics Committee, Kocaeli, Turkiye (approval number: 2024-96) and conducted in accordance with the Declaration of Helsinki. Informed consent was waived due to the retrospective design of the study.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study did not receive any specific funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.K. designed the study, collected the data, performed the statistical analysis, and wrote the first draft of the manuscript. H.C. contributed to data interpretation and critically revised the manuscript. E.S. supervised the study and critically revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are not publicly available due to patient privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117\u0026ndash;314.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeerspink HJL, Stef\u0026aacute;nsson BV, Correa-Rotter R, et al. DAPA-CKD Trial Committees and Investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThe EMPA-KIDNEY Collaborative Group, Herrington WG, Staplin N, Wanner C, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDave CV, Schneeweiss S, Patorno E. Comparative risk of genital infections associated with sodium-glucose co-transporter-2 inhibitors. Diabetes Care. 2019;42(1):98\u0026ndash;105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePuckrin R, Saltiel MP, Reynier P, et al. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol. 2018;55(5):503\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845\u0026ndash;54.\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":false,"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":"SGLT2 inhibitors, Chronic Kidney Disease, Genitourinary Infections, Diabetes Mellitus","lastPublishedDoi":"10.21203/rs.3.rs-9215986/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9215986/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eDespite strong guideline recommendations, the use of sodium\u0026ndash;glucose cotransporter-2 (SGLT2) inhibitors remains suboptimal in patients with Chronic Kidney Disease, both in diabetic and non-diabetic populations (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). This study aimed to evaluate patient-related factors associated with non-initiation of SGLT2 inhibitors.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective, analytical, cross-sectional study included patients with CKD who were followed at the nephrology clinic of a tertiary care center between April 1, 2023, and June 1, 2024. A total of 995 patients who were not receiving SGLT2 inhibitors were included. Demographic characteristics, comorbidities, ongoing treatments, and laboratory parameters were recorded.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean age of the study population was 72.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4 years; 464 (46.6%) were male and 531 (53.4%) were female. The majority of patients (63.6%) had stage 3 CKD. The most common reasons for not initiating SGLT2 inhibitors were a history or concern of genitourinary infections and absence of Diabetes Mellitus. Rare but serious adverse events such as diabetic ketoacidosis, lower extremity amputation, hypotension, and necrotizing fasciitis were not observed as reasons for non-initiation.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e Current guidelines recommend the use of SGLT2 inhibitors in most patients with CKD and an estimated glomerular filtration rate\u0026thinsp;\u0026ge;\u0026thinsp;20 mL/min/1.73 m\u0026sup2;, regardless of underlying etiology, due to their proven benefits in reducing morbidity and mortality. However, a substantial proportion of patients remain untreated, likely due to limited awareness and concerns regarding adverse effects. Notably, the frequent non-use in eligible patients\u0026mdash;including those with diabetes\u0026mdash;highlights a significant gap between guideline recommendations and real-world clinical practice. Increasing awareness and promoting guideline adherence may improve clinical outcomes in CKD patients (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e","manuscriptTitle":"Clinical Barriers to the Initiation of SGLT2 Inhibitors in Patients with Chronic Kidney Disease: A Retrospective Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-29 20:18:13","doi":"10.21203/rs.3.rs-9215986/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":"754cedf7-5452-4ef2-9e85-e7a7089684cb","owner":[],"postedDate":"April 29th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-14T07:14:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-10T11:09:18+00:00","index":75,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-09T17:21:16+00:00","index":74,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-07T10:22:50+00:00","index":73,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-04T07:06:17+00:00","index":71,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-03T02:52:47+00:00","index":67,"fulltext":""},{"type":"reviewerAgreed","content":"88654295804699386944038993464749963304","date":"2026-05-01T07:41:37+00:00","index":66,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-01T00:15:35+00:00","index":65,"fulltext":""},{"type":"reviewerAgreed","content":"331846542750202600720431424049721508536","date":"2026-04-30T05:19:25+00:00","index":64,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T07:25:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-29 20:18:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9215986","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9215986","identity":"rs-9215986","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}