Abstract Background and Aims Dialysis can be a significant challenge for people already coping with the complexities of severe mental illness (SMI). Despite the increased prevalence of end-stage kidney disease (ESKD) in patients with SMI, there is a lack of detailed evaluation regarding its management in those who exhibit aggressive or oppositional behavior. Method This retrospective, national and multicenter cohort study included patients between January 1, 2015, and December 31, 2023, aged ≥18 years, with a diagnosis of SMI (schizophrenia, bipolar disorder or other inorganic or organic psychotic disorder) associated with ESKD and a history of anti-treatment behavior that impeded the delivery of dialysis care. Results Fifty-one patients with ESKD and SMI from 13 centers were included, with a mean follow-up of 5.5 years and an overall mortality rate of 49% (25 patients). Thirty-nine patients (76.5%) underwent hemodialysis, 7 patients (13.7%) received peritoneal dialysis, and 5 patients (9.8%) opted for conservative treatment. Forced hospitalization at the start of dialysis was necessary in 9 patients (17.6%). When comparing dialysis parameters at baseline and at the end of follow-up, the dialysis regimen was generally well maintained over time (number of scheduled or completed dialysis sessions, duration of dialysis sessions, interdialytic weight gain, Kt/V or blood flow rate). Hyperkalemia above 5.5 mmol/L was common (13.9%). Behavioral disorders worsened in dialysis patients: while verbal aggression towards nursing staff significantly decreased (from 33.3% to 3.9%, P < 0.01), the incidence of conflicts with other patients increased from 3.9% to 46.2% (P < 0.001). At the end of follow-up, emergency consultations were more frequent (17 patients vs 11, p=0.015). During the follow-up, 16 patients (31.3%) changed dialysis centers at least once. Conclusion Despite behavioral challenges, healthcare providers make effective dialysis management possible through their strong commitment and expertise. However, they need the right tools, training, and support to care for SMI patients with CKD.

Abstract Background and Aims The complement system's overactivation typically occurs during transplantation and in the post-transplant phase. Indeed, donor and recipient characteristics, various drugs (mTOR inhibitors, CNIs), viral infections and ischemia-reperfusion injury contribute to different levels of complement activation in this particular setting. Overactivation of the complement system can expose some patients to developed thrombotic microangiopathy (TMA), especially in the case of genetic background predisposition. The Post-transplant de novo TMA incidence ranges from 5% to 20%, representing an open challenge for clinicians. Our study aimed to determine whether patients who developed post-transplant TMA exhibit complement gene variants and whether these variants correlate with the phenotype and the graft outcome. Method We evaluated 7 patients who developed de novo post-transplant TMA between 2022 and 2023. Complement genes variations were screened by Next Generation Sequencing , and Multiplex Ligation Probe Amplification (MLPA). Clinical and biochemical data at the time of onset (T0) and during the follow-up (T1) (median time of 1 year) were collected from patients' records. Correlation between genetic variation and clinical presentation were evaluated. Results In the studied population, 71.4% were female and 28.6% were male, with an average age at transplantation of 49 years; 6/7 patients received transplants from deceased donors. Thrombotic microangiopathy (TMA) developed, on average, after a duration of 61.2 months post-transplant. All patients received the same immunosuppressive therapy (MMF + FK + steroids). Genetic analysis revealed that all patients who developed de novo TMA post-transplant exhibited a delCFHR3-1, with 6 of these being heterozygous and 1 homozygous. Additionally, patient 7 was found to carry a heterozygous deletion affecting SCR 14 of CFH (NM_000186.4; c.2422_2427del). None of the patients exhibited anti-CFH antibodies, which are associated with the presence of the deletion variant in the literature. Serological tests for CH50 and AP50 were within normal ranges, confirming their limited utility in the diagnostic phase, as TMA is a condition characterised by complement dysregulation at the endothelial level rather than in serum. Forty-two percent of patients experienced graft loss. Among these, only one patient had received anti-C5 therapy. The remaining four patients achieved complete resolution of TMA. Of these, one received a C5 inhibitor during the acute phase, while another was treated with plasma therapy. Additionally, one patient in this group exhibited a form of thrombotic microangiopathy (TMA) that appeared to be triggered by treatment with fluoroquinolones. In this last case the complete resolution of the haematological condition and organ damage was observed upon discontinuation of the offending agent. Conclusion The delCFHR3-1 is associated with post-transplant TMA in our study cohort. Although the deletion is regarded as a polymorphic variant, our research suggests the utility of further exploring the role of this variant in complex scenarios such as transplantation, where complement activation is elevated. Further studies are warranted to elucidate the underlying mechanisms and therapeutic implications.

Abstract Background and Aims The choice between renal replacement therapy or conservative management of end-stage renal disease is complex in the elderly, due to the high prevalence of associated comorbidities, frailty, loss of quality of life and high mortality rate. This decision is especially relevant in particularly aged geographic areas. Several scores have been developed to help the decision of dialysis start among elderly patients, although they tend to lack generalizability as they are usually developed in widely different populations. In the present study we aim to compare two different prognostic scores in a sample of CKD stage 4 and 5 elderly patients from our area. Method We retrospectively identified all consecutive CKD stage 4 or 5 patients aged ≥70 years, reviewed at our outpatient clinic during a six-month period. Two different prognostic scores (1, 2) were applied at the first visit in which options for renal replacement therapy were discussed with the patient, including conservative management. Need for renal replacement therapy initiation and patient survival during the following 5 years after the visit were recorded. The scores are summarized in Table 1. Statistical analysis was performed using IBM SPSS Statistics 26. Results Demographic and clinical characteristics of the study sample are summarized in Table 2. When predicting 6-month mortality, both scores showed an area under the ROC curve of 0.705 (Fig. 1A). The area under the ROC curve decreased for both scores when predicting 5-year mortality (AUC: 0.688 and 0.679 for the Santos J and Wick JP scores, respectively) (Fig. 1B). No survival analysis was performed at the 6-month mark due to the low number of events. Moreover, in Kaplan-Meier analysis, both scores, analyzed as tertiles, were associated with 5-year patient survival (Santos J: Log-Rank: 11.511; P = 0.003; Wick JP: Log-Rank: 11.061; P = 0.004) (Fig. 2C and 2D). Conclusion Although a higher result was associated with lower 5-year survival in both scores, they showed poor discrimination of 6-month and 5-year mortality in our study sample to be considered as part of our daily clinical routine. These results highlight the current need to develop predictive models accurate enough to help both patients and physicians in the decision-making progress of when and if to start dialysis.

Abstract Background and Aims Although ABO-incompatible (ABOi) living donor kidney transplantation is currently performed on a routine basis, it remains a procedure with a high immunologic risk requiring both immunosuppression aimed at diminishing antibody production and removal of circulating antibodies from the recipient's blood. Method We describe two cases of kidney transplant recipients (KTR) who experienced hyperacute antibody-mediated rejection after ABOi transplantation and further testing was performed on their sera using a novel bead-based ABO antibody assay to understand the cause of such unfortunate outcomes. Results Both patients were ABO-O recipients who received ABO-A grafts; neither had donor-specific anti-HLA antibodies (DSA). Both received rituximab >4 weeks and standard immunosuppression according to the Swiss ABOi protocol, starting 10–25 days before transplantation; basiliximab was used for induction at time of transplant. Immunoadsorption was performed before transplant with a nonselective Therasorb column; immunoadsorption effectiveness was analyzed by measuring the anti-A-IgG titer and anti-A-IgM titer by gel column agglutination technique. Case 1: Transplantation was performed after 17 immunoadsorption runs (prolonged due to postponed date of surgery for non-immunological reasons); post-adsorption anti-A titres were negative IgG and <1:8 IgM. After an initial diuresis, the patient became anuric within 24 hours. Biopsy histology revealed hyperacute rejection. Graft nephrectomy was performed two days post-transplant. Case 2: transplantation was performed after 11 immunoadsorption runs; post-adsorption anti-A titres were negative IgG and 1:1 IgM. After an initial diuresis urine output decreased within hours. Biopsy histology showed hyperacute rejection. Plasmapheresis was started empirically approximately 15 hours after transplant despite negative anti-A titer and no anti-HLA DSA, and treatment with high dose steroids, IVIG and eculizumab was administered. Graft nephrectomy was performed seven days post-transplant. Analysis of the original sera with a novel single antigen bead assay for anti-A subtype-specific antibodies showed an initial drop in MFIs of IgG and IgM for both patients. However, at time of transplant, despite acceptable anti-A titers with our standard hemagglutination methods, patient 1 and 2 MFI were still 17200 and 9300, respectively for anti-A-IgG isotype antibodies (II, III and IV averaged) and 3300 and 3800 for anti-A-IgM isotype IgM (II, III and IV averaged). Analysis of sera from the days immediately after transplantation showed a rebound for these subtype-specific anti-A antibodies in Case 1, with an MFI up to 26000 (anti-A-IgG) and 5000 (anti-A-IgM). In Case 2 (where samples were drawn after plasmapheresis) the MFIs of the anti-A-II/III/IV further dropped to 2100 (IgG) and 1200 (IgM). Refer to Fig. 1 for antibody data. Conclusion Hyperacute AMR in these two ABO-A-incompatible kidney transplant cases was likely due to insufficient removal of anti-A antibodies. Whether this is due to insufficient removal of anti-A antibodies by the nonselective Therasorb column needs to be further investigated. These results suggest that for such an immunological high-risk procedure, a switch from titer-based diagnostics to single bead Luminex diagnostics should be considered. Of further note, transcriptome diagnostics might support the histology, but it is not yet established in ABOi graft biopsies.

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world and a significant proportion of patients develop kidney failure within 30 years. Circulating undergalactosylated IgA, a key driver of IgAN, has been shown to induce endothelial damage. Glomerular endothelial activation is believed to contribute to complement activation and potentially contribute to disease progression. However, the clinical utility of plasma endothelial biomarkers in IgAN is unclear and no study has analyzed the relationship between endothelial biomarkers and loss of kidney function over time in IgAN. We aimed to study the association between plasma endothelial biomarkers at time of kidney biopsy and CKD progression over time, assessed using eGFR slope. We also wanted to compare biomarker levels between patients with IgAN, healthy controls, and disease controls at baseline. Method We conducted a single-center prospective cohort study including 44 patients with IgAN and 19 disease controls, 11 membranous nephropathy (MN) and 8 hypertensive nephropathy (HN), recruited as part of BIONEF-DS, a biomarker study which has consecutively recruited patients undergoing a kidney biopsy at Danderyd Hospital, Stockholm, Sweden, since 2019. We also included 40 age-matched healthy controls (HC). Plasma levels of VCAM-1, ICAM-1, E-selectin, VE-cadherin, and Syndecan 1 were measured at time of biopsy using Meso Scale® (Meso Scale Diagnostics, Maryland, USA), a highly sensitive multi-array assay based on electrochemiluminescence. First, we compared plasma biomarker levels between the four groups and their relation to albuminuria, eGFR and clinical parameters at baseline using Spearman's Rank Order correlation and Kruskal Wallis ANOVA. Secondly, we used linear regression to analyze the association between biomarker levels and eGFR slope amongst patients with IgAN. Results Baseline characteristics of the patients and controls are shown in Table 1. There was no significant difference in age between IgAN patients and HC, whereas patients with IgAN were significantly younger than disease controls (P < 0.0001). Blood pressure was similar in all groups. Kidney function and albuminuria did not differ between IgAN and disease controls, whereas HC had significantly better-preserved kidney function (P < 0.0001) and no albuminuria. Patients with IgAN had significantly higher levels of ICAM-1, VCAM-1, Syndecan-1 and Thrombomodulin compared to HC (P = 0.02 for ICAM-1; P < 0.001 for others) but similar levels to disease controls. Amongst patients with IgAN, there were weak positive correlations between U-ACR and E-selectin, VCAM-1 and Syndecan-1 (P < 0.05 for all). There were significant negative associations between all biomarkers and eGFR at baseline (P < 0.05 for all). ICAM-1 levels were significantly lower amongst IgAN patients treated with RAASi (P < 0.01). We found no significant association to MEST-C score. Only three patients were on cortisone at baseline. For the longitudinal part of the study, median follow-up was 3.3 years (2.1–4.1) and median eGFR slope was −1.4 mL/min/1.73 m2/year (−4.1–0.9). There was a significant positive association between E-selectin and eGFR slope (P < 0.05) (Fig. 1). Conclusion We found a significant elevation of key endothelial and glycocalyx biomarkers amongst patients with IgAN compared to healthy controls, with the highest levels found amongst patients with high-grade albuminuria and decreased kidney function. Importantly, patients with IgAN had similar levels of plasma endothelial biomarkers as patients with HN and MN, despite the disease controls being significantly older and with more cardiovascular comorbidities. IgAN patients with the highest levels of E-selectin at baseline improved their kidney function over time, likely as an effect of treatment. Future studies should assess the association between baseline endothelial biomarkers and CKD progression in a larger and more ethnically diverse patient population. It would also be of interest to conduct serial biomarker measurements to study the effect of different therapies on endothelial biomarkers in IgAN.

Abstract Background and Aims This study aimed to uncover serum and urine proteome as potential markers that can be helpful in diagnosing kidney disease entirely caused by diabetes mellitus without kidney biopsy. Method Patients with type 2 diabetes (T2D) who underwent kidney biopsy from 2010 to 2020 were retrospectively reviewed. The most combined glomerulonephritis was IgA nephropathy (IgAN) and membranous glomerulonephritis (MN). Thus, among enrolled patients with T2D, we selected age- and sex-matched patients with pure diabetic nephropathy (DN, n = 11), pure non-DN (IgAN, n = 11 and MN, n = 11) for proteomic analysis. The control group was donors for living kidney transplantation (n = 11). Comparative quantitative proteomic analysis was performed using high resolution mass spectrometry coupled with nanoflow liquid chromatography. Resulting relative protein quantity of each group was extracted using label free manner and statistical analysis was performed to discover group specific protein biomarker candidate. And random forest was applied to make serum and urine protein panel to distinguish control, pure DN and non-DN group. Results In serum set, a total of 1,220 proteins were identified and fifteen proteins were clustered to be distinguishable in DN group compared to the other two groups. Random forest analysis, one of machine learning strategies, successfully classified DN from overall subjects (out-of bag error 0, accuracy 100%). Gene ontology analysis indicated that serum DN specific proteins were mainly involved in response to wound healing, antibacterial humoral response, cell development, chemotaxis, and vascular development unlike non-DN specific proteins compared to control group. In urine set, a total of 1,579 proteins were identified and fifteen proteins were clustered to be distinguishable in DN group compared to other two groups. Random forest analysis, one of machine learning strategies, successfully classified DN from overall subjects (out of bag error 0.159, accuracy 84.1%). Furthermore, another six specific proteins in urine set were effective to differentiate between DN and non-DN group by linear support vector machine (AUC = 0.985, 95% CI; 0.933–1). Conclusion Serum and urine proteome can be useful to diagnose diabetes-related kidney disease, exclusively without kidney biopsy and guide the indication of kidney biopsy in T2D patients having kidney damage.

Abstract Background and Aims Previous studies indicate that 40% of patients with advanced chronic kidney disease (CKD), a proportion that increases with age, are managed in primary care despite meeting referral criteria. Older patients are more likely to have stable kidney function or may find hospital visits burdensome. We aimed to describe the proportion of older patients with advanced CKD receiving guideline-adherent care in primary and nephrology care, and describe how clinical characteristics and social determinants of health are associated with guideline adherence. Ultimately, we aim to assess whether primary care can be a suitable setting for managing subgroups of older CKD patients and adequately addressing their needs. Method This dynamic, population-based cohort study, used routine health care data of general practitioner (GP) practices and hospitals within the Extramural Leiden University Medical Center Academic Network (ELAN), linked to individual-level registry data from Statistics Netherlands. We included adults aged ≥65 years with incident or prevalent CKD (eGFR ≤30 ml/min/1.73 m2, confirmed by two measurements taken ≥90 days apart) between 2015 and 2023. Follow-up continued until death, kidney replacement therapy initiation, end of study (01-01-2023) or deregistration from a participating GP. Patients were categorized as managed in primary or nephrology care based on diagnosis-treatment combinations. We used descriptive statistics to assess the proportion of patients in each care setting and adherence to CKD guidelines, stratified by clinical characteristics and social determinants of health. Results We enrolled 1647 patients, with a median follow-up of 2.25 years; 1194 were managed exclusively in primary care and 453 (part of) follow-up in nephrology care. The mean age was 82 ± 9 years (83 ± 9 in primary care vs 79 ± 8 in nephrology care), with a median eGFR of 26 [22; 28] ml/min/1.73 m2. Of these, 973 patients had at least 15 months of follow-up in primary or nephrology care, allowing for guideline-adherence assessment. Patients with shorter follow-up were more likely to be female (55% vs 46%), older (83 ± 9 vs 81 ± 8 years), and classified as frail (30% vs 21%). Differences in adherence to quality indicators were observed between the care settings (see Fig. 1), with nephrology care showing higher adherence to kidney function monitoring (≥2 measurements per year: 68% vs 83%), annual testing of albuminuria (45% vs 65%), hemoglobin (74% vs 87%), LDL (49% vs 60%), and HbA1c (50% vs 65%), as well as higher prescription rates of renin-angiotensin-aldosterone system inhibitor (RAASi) (72% vs 77%). Annual blood pressure measurement and avoidance of NSAIDs were similar across care settings (60% vs 57% and 94% vs 94%, respectively). In both care settings, we observed lower guideline adherence for women across all indicators and a decrease in adherence with age, except for eGFR monitoring in nephrology care and blood pressure monitoring in both care settings. In primary care, patients with diabetes mellitus were more likely to receive guideline-adherent care compared to those without diabetes, with a similar trend observed for patients with hypertension, albeit to a lesser extent. No differences were found between ethnic and socioeconomic groups, or in relation to eGFR and frailty. Conclusion The majority of older patients with advanced CKD are managed in primary care, where guideline adherence is generally acceptable, but less strictly followed than in nephrology care. Among patients with diabetes or hypertension, who are treated in structured care pathways, adherence is higher, suggesting that similar proactive and structured approaches could enhance CKD care. Given the life expectancy and treatment goals of older patients, CKD management should prioritize individual needs and quality of life over strict guideline adherence. Future research should explore whether outcomes, including CKD progression, quality of life and healthcare costs, differ between patients managed in primary and nephrology care.

Abstract Background and Aims Chronic active antibody-mediated rejection (cABMR) is a leading cause of allograft failure in kidney transplantation (KT) recipients. However, no effective treatment has been established to date. This study investigated the effectiveness and safety of tocilizumab (TCZ), an anti-IL-6 receptor antibody, in delaying cABMR progression in KT recipients. Method We included 18 KT recipients with cABMR who were treated with TCZ. TCZ was administered monthly at a dose of 8 mg/kg (up to maximum of 800 mg) for 6 months (Fig. 1). The primary outcome was allograft survival, and patients were divided into responders (no allograft failure within a year) and nonresponders (allograft failure within a year). Secondary outcomes included changes in the estimated glomerular filtration rate (eGFR), proteinuria, mean fluorescence intensity (MFI) of anti-HLA antibodies, and adverse events (AEs). Baseline characteristics and outcomes were compared between responders and nonresponders. Results Allograft failure occurred in 44.4% (8/18) patients (Fig. 2A). All nonresponders experienced early allograft failure (mean 5.2 months), while 23.1% (3/13) of responders experienced allograft failure at a mean of 16.1 months post-treatment (Fig. 2B). Initial eGFR was significantly lower in nonresponders compared responders (15.9 mL/min/1.73 m2 vs. 34.4 mL/min/1.73 m2, p = 0.011) and was the only significant predictor of allograft failure (hazard ratio: 0.854, 95% confidence interval: 0.791–0.959). In the receiver operating characteristic (ROC) curve analysis using eGFR at treatment initiation (Fig. 2C), the area under the curve (AUC) was 0.900 (95% confidence interval [CI], 0.740–1.000; p < 0.05). The optimal cutoff value for predicting allograft failure was determined to be an eGFR of 25.5 ml/min/m2, with a sensitivity of 87.5% and a specificity of 90.0%. MFI levels of anti-HLA antibodies decreased in both responders and nonresponders (Fig. 3A). However, TCZ slowed eGFR decline and reduced proteinuria only in responders, while demonstrating no effectiveness in nonresponders (Fig. 3B, 3C, and 3D). No immediate side effects were observed. AEs included infections (n = 5), hypogammaglobulinemia (n = 6), and leukopenia (n = 2), with TCZ discontinued in one case of severe leukopenia. Conclusion TCZ should be selectively used in patients with preserved allograft function, considering the limited evidence, potential risks, and substantial costs.

Abstract Background and Aims Fabry disease is a rare X-linked disorder caused by mutations in the GLA gene, leading to a deficiency in α-galactosidase A (α-Gal A) and lysosomal dysfunction. This results in the accumulation of lipid substances, such as globotriaosylceramide (GL-3) and globotriaosylsphingosine (Lyso-GL-3), in organs like the kidneys, heart, and nervous system, causing organ dysfunction. Renal involvement, including proteinuria and renal dysfunction, is a major contributor to disability and mortality. Early detection and treatment, such as enzyme replacement therapy (ERT), are critical; however, ERT is less effective in patients with severe proteinuria. Identifying novel biomarkers for early kidney damage is essential. Myeloid bodies, multilamellar myelin figures observed under electron microscopy, are a hallmark of Fabry disease and are crucial for diagnosis. First identified in urine sediment in 1977, their role in disease progression was confirmed in 2018. However, the prevalence of urinary myeloid bodies and their link to disease progression are not fully understood. This study aims to analyze urinary myeloid bodies in Fabry patients, assess their prevalence, and explore their potential as a non-invasive biomarker for monitoring ERT effectiveness and disease progression. Method This single-center, retrospective study included 25 patients with Fabry disease and 27 controls (2 healthy individuals and 25 patients with other renal diseases). We analyzed 24-hour urine samples for the presence of urinary myeloid bodies and evaluated clinical data, including serum creatinine, estimated glomerular filtration rate (eGFR), 24-hour urinary protein levels, α-Gal A, and Lyso-GL-3. Seven Fabry patients underwent analysis of urine samples before and after one year of ERT. Results Urinary myeloid bodies were detected in 21 Fabry patients (84%), while no myeloid bodies were observed in the control group (Table 1). The median age of the Fabry patient cohort was 43 years, with a male-to-female ratio of 44% to 56%. None of the Fabry patients had a history of cationic amphiphilic drug use. Urinary myeloid bodies were detected in 21 patients (84%) (Fig. 1A–F). Comparison between Fabry patients with and without urinary myeloid bodies revealed no statistically significant differences in age, gender, serum creatinine, eGFR, 24-hour urinary protein, α-Gal A, or Lyso-GL-3 (Table 1). Based on the presence of urinary myeloid bodies and proteinuria, patients were divided into four groups (Fig. 1G). Two patients exhibited neither condition, while fourteen patients presented with both. Seven additional patients showed urinary myeloid body excretion despite the absence of proteinuria. Among the Fabry patients with myeloid bodies, 48% had no proteinuria, and 52% were in CKD stage 1, G1 (Fig. 1H–K). Furthermore, urinary myeloid bodies were detected in four patients under the age of 20, despite the absence of or only minimal proteinuria, and these patients all exhibited a substantial number of myeloid bodies. After one year of ERT, significant reductions in both the count (P = 0.043) and area ratio (P = 0.028) of myeloid bodies were observed (Fig. 1L and M). Conclusion Urinary myeloid bodies are specific to Fabry disease and are associated with early renal injury, even in the absence of proteinuria. These findings suggest that urinary myeloid bodies may serve as a non-invasive biomarker for the early diagnosis of Fabry disease and for monitoring the efficacy of ERT.

Abstract Background and Aims The chronic kidney disease associated with type II diabetes mellitus is often linked to a high risk of deterioration in kidney function. In this context, the glucagon-like peptide-1 receptor agonist (GLP-1RAs) semaglutide has been shown to have a nephroprotective effect which specifically results in reduced proteinuria. Most trials performed to date have failed to show significant effects when applying very robust criteria to evaluate this nephroprotective effect (such as creatinine doubling time or need for dialysis), although very long follow-up times would be required to demonstrate this effect. Of note, the estimated glomerular filtration rate (eGFR) slope may help determine the nephroprotective effect without requiring such long follow-ups. However, the effect of on the eGFR slope in patients with chronic kidney disease (CKD), especially those in stages 3 and 4, has not yet been adequately evaluated. Method Our objective was to determine the effect of adding subcutaneous semaglutide to the treatment of 156 type II diabetic patients with CKD, a high risk of progression, and a negative eGFR slope prior to starting the intervention. Of these patients, 72% had stage 3 or 4 CKD and they were followed for an average of 3 years. Results The mean eGFR slope was −4.24 mL/min/m2 1.73 m2/year prior to semaglutide but after the start of treatment, and with a mean follow-up of 3 years, an improvement in the slope to −0.34 mL/min/m2 1.73 m2/year (p = 0.005) was observed. The additional use of semaglutide in patients already treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) was especially positive with on eGFR slope (−4.52 vs +0.22 mL/min/1.73 m2/year, p=0.0001). This benefit was also observed in patients with an eGFR of less than 60 mL/min/1.73 m2, semaglutide had an even more favourable effect on the slope +1.06 mL/min/1.73 m2/year (p = 0.001). The patients who benefited the most were those with albuminuria of less than 1,000 mg/g creatinine. Conclusion In our real-life study in a population at risk for rapid deterioration of renal function, the administration of subcutaneous semaglutide conferred an improvement in the eGFR slope in the medium and long term, with this difference being especially relevant when its treatment was added to patients treated with SGLT2is.