Kidney Survival Research Articles

Kidney Survival Impact of Delayed Graft Function Depends on Kidney Donor Risk Index: A Single-Center Cohort Study.

Delayed graft function (DGF) is a significant challenge in renal transplantation, particularly with deceased donors, necessitating early postoperative dialysis. The prolonged effects of medium- and long-term DGF remain uncertain, marked by contradictory graft survival outcomes. This incongruity might arise from the inherent graft resilience and regenerative capacity during transplantation. This study investigates DGF's impact on graft survival, focusing on grafts displaying favorable (KDRI < 1) and unfavorable outcomes (KDRI ≥ 1). In this retrospective cohort study (January 2015-December 2019), we assessed kidney transplants at our center, excluding multiorgan simultaneous cases, primary non-functioning grafts, and surgical complications causing graft loss. Patients were categorized into DGF presence or absence groups. Univariate and multivariate analyses, alongside propensity score matching (PSM), were performed. The study encompassed 322 deceased donor kidneys, with 83 encountering DGF. Grafts with higher KDRI indices (KDRI ≥ 1) and DGF exhibited a notably increased graft loss risk (HR: 4.17, 95% CI: 1.93-9.01). However, lower-KDRI donor grafts displayed no significant disparities between the DGF and non-DGF groups. Delayed graft function (DGF) development significantly contributes to graft loss in kidney transplants, particularly in grafts with KDRI ≥ 1.

Long-Term Experience of a Reference Center on Autosomal Dominant Polycystic Kidney Disease: Associated Demographics, Clinical Presentation, and Kidney Survival in Turkish Population

Long-Term Experience of a Reference Center on Autosomal Dominant Polycystic Kidney Disease: Associated Demographics, Clinical Presentation, and Kidney Survival in Turkish Population

The spectrum of glomerular and vascular kidney pathology associated with myeloproliferative neoplasms

A high prevalence of chronic kidney disease (CKD) occurs in patients with myeloproliferative neoplasms (MPN). However, MPN-related glomerulopathy (MPN-RG) may not account for the entirety of CKD risk in this population. The systemic vasculopathy encountered in these patients raises the hypothesis that vascular nephrosclerosis may be a common pattern of injury in patients with MPN and with CKD. In an exhaustive, retrospective, multicenter study of MPN kidney biopsies in four different pathology departments, we now describe glomerular and vascular lesions and establish clinicopathologic correlations. Our study encompassed 47 patients with MPN who underwent a kidney biopsy that included 16 patients with chronic myeloid leukemia (CML) and 31 patients with non-CML MPN. Fourteen cases met a proposed definition of MPN-RG based on mesangial sclerosis and hypercellularity, as well as glomerular thrombotic microangiopathy. MPN-RG was significantly associated with both myelofibrosis and poorer kidney survival. Thirty-three patients had moderate-to-severe arteriosclerosis while 39 patients had moderate-to-severe arteriolar hyalinosis. Multivariable models that included 188 adult native kidney biopsies as controls revealed an association between MPN and chronic kidney vascular damage, which was independent of established risk factors such as age, diabetes mellitus and hypertension. Therefore, MPN-RG is associated with myelofibrosis and has a poor kidney prognosis. Thus, our findings suggest that the kidney vasculature is a target during MPN-associated vasculopathy and establish a new link between MPN and CKD. Hence, these results may raise new hypotheses regarding the pathophysiology of vascular nephrosclerosis in the general population.

A nationwide survey of MYH9-related disease in Japan.

MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, Döhle body-like granulocyte inclusions, and nephropathy, which may progress to end-stage kidney disease (ESKD). However, information on the effects of renin-angiotensin system (RAS) inhibitors on kidney survival is currently lacking and the outcomes of kidney replacement therapy (KRT) in MYH9-RD are largely unknown. We conducted a cross-sectional nationwide survey by sending questionnaires to 145 institutions in Japan and analyzed data for 49 patients. The median patient age was 27years. Genetic analysis was performed in 37 (76%) patients. Twenty-four patients (65%) had MYH9 variants affecting the motor domain of non-muscle myosin heavy chain-IIA, and these patients had poorer kidney survival than those with variants affecting the tail domain (P = 0.02). There was no significant difference in kidney survival between patients treated with and without RAS inhibitors. Hemodialysis and peritoneal dialysis were performed in 16 and 7 patients, respectively. There were no major bleeding complications during the perioperative period or during follow-up, except for one patient. Most of the 11 patients who underwent kidney transplantation required perioperative red cell concentrate transfusions, but there was no graft loss during the median posttransplant observational period of 2.0 (interquartile range, 1.3-6.8) years. Our study demonstrated no beneficial effect of RAS inhibitors on kidney function in patients with MYH9-RD, indicating the need for further studies with more patients. All modalities of KRT are feasible options for MYH9-RD patients who progress to ESKD, with adequate attention to bleeding complications.

A bibliometric and knowledge-map analysis of antibody-mediated rejection in kidney transplantation

Objectives Antibody-mediated rejection (AMR) is a large obstacle to the long-term survival of allograft kidneys. It is urgent to find novel strategies for its prevention and treatment. Bibliometric analysis is helpful in understanding the directions of one field. Hence, this study aims to analyze the state and emerging trends of AMR in kidney transplantation. Methods Literature on AMR in kidney transplantation from 1999 to 2022 was collected from the Web of Science Core Collection. HistCite (version 12.03.17), CiteSpace (version 6.2.R2), Bibliometrix 4.1.0 Package from R language, and Gephi (https://gephi.org) were applied to the bibliometric analysis of the annual publications, leading countries/regions, core journals, references, keywords, and trend topics. Results A total of 2522 articles related to AMR in kidney transplantation were included in the analysis and the annual publications increased year by year. There were 10874 authors from 118 institutions located in 70 countries/regions contributing to AMR studies, and the United States took the leading position in both articles and citation scores. Halloran PF from Canada made the most contribution to AMR in kidney transplantation. The top 3 productive journals, American Journal of Transplantation, Transplantation, and Transplantation Proceedings, were associated with transplantation. Moreover, the recent trend topics mainly focused on transplant outcomes, survival, and clinical research. Conclusions North American and European countries/regions played central roles in AMR of kidney transplantation. Importantly, the prognosis of AMR is the hotspot in the future. Noninvasive strategies like plasma and urine dd-cfDNA may be the most potential direction in the AMR field.

Machine Learning Model to Predict Graft Rejection After Kidney Transplantation

There are few predictive studies about early posttransplant outcomes taking into account baseline and posttransplant variables. The objective of this study was to create a predictive model for 30-day graft rejection using machine learning techniques. Retrospective study with 1255 patients undergoing transplant from living and deceased donors at a tertiary health service in Brazil. Recipient, donor, transplantation, and postoperative period data were collected from physical and electronic records. We split the data into derivation (training) and validation (test) datasets. Five supervised machine learning algorithms were developed with this subset of variables in the training set: Simple Logistic Regression, Lasso, Multilayer Perceptron, XGBoost, and Light GBM. There were 147 (12.48%) cases of graft rejection within 30 days of transplantation. The best model was XGBoost (accuracy, 0.839; receiver operating characteristic area under the curve, 0.715; precision, 0.900). The model showed that deceased donor transplantation, glomerulopathy as an underlying disease, and donor's use of vasoactive drugs had more than 20% importance as rejection risk factors. The variables with the greatest predictive values were thymoglobulin induction and delayed graft function. We fitted a machine learning model to predict 30-day graft rejection after kidney transplantation that reaches a higher accuracy and precision. Machine learning models could contribute to predicting kidney survival using nontraditional approaches.

Prognostic role of glomerular electron microscopy lesions in IgA nephropathy: "the devil is in the details".

Transmission electron microscopy enables examination of ultrastructural glomerular changes; while this tool has already been appliedin IgA nephropathy (IgAN), limited information exists on the prognostic valuein this disease. We aimed to systematically investigate ultrastructural lesions and assess their role in predicting the evolution of IgA nephropathy toend-stage kidney disease. A single-center retrospective study was performed on 107 consecutive IgAN patients (median age 42years, 67% male, estimated glomerular filtration rate 46mL/min, proteinuria 1.0g/g) between 2010 and 2015, who were followed-up until end-stage kidney disease, death, or end of study (January 2021). A pathologist evaluated the Mesangial hypercellularity (M), Endocapillary hypercellularity (E), Segmental glomerulosclerosis (S), and Tubular atrophy/interstitial fibrosis-Crescents (C) (MEST-C) score and transmission electron microscopy lesions according to a comprehensive protocol that encompassed all glomerular structures. Patients were followed up for a median of 7.1years; 32 (43%) reached end-stage kidney disease. Patients who reached kidney failure had higher comorbidity score, more frequent arterial hypertension, lower estimated glomerular filtration rate, and higher MEST-C score. In terms of transmission electron microscopy lesions, patients who progressed to end-stage kidney disease had more frequent podocyte activation, effacement, and presence of microvilli; more frequent signs of endothelial cell activation and fenestration; higher mesangial cell proliferation. In theunivariate Cox proportional hazard regression, higher MEST-C score and lesions detected bytransmission electron microscopy in podocytes, endothelial cells, and mesangial cell proliferation were associated with shorter kidney survival time. In themultivariate Cox proportional hazard regression, only higher MEST-C score, presence of podocytes with microvilli, and mesangial cell proliferation were associated with end-stage kidney disease. This study shows that, besides the MEST-C score, the presence of podocytes with microvilli and mesangial cell proliferation are associated with poor kidney survival in IgAN patients, highlighting the prognostic value of lesions detected bytransmission electron microscopy.

Rare Variants in Complement Gene in C3 Glomerulopathy and Immunoglobulin-Mediated Membranoproliferative Glomerulonephritis.

C3 glomerulopathy and idiopathic immunoglobulin-mediated membranoproliferative glomerulonephritis (Ig-MPGN) are rare complement mediated kidney diseases. Inherited forms of C3 glomerulopathy/Ig-MPGN are rarely described. Three hundred ninety-eight patients with C3 glomerulopathy (n=296) or Ig-MPGN (n=102) from a national registry were screened for 3 complement genes, factor H (CFH), factor I (CFI) and C3. Patients with rare variant (minor allele frequency <0.1%) were included. Epidemiological, clinical and immunological data at diagnosis and kidney outcomes of patients were retrospectively collected. Fifty-three different rare variants including 30 (57%), 13 (24%) and 10 (19%) CFH, CFI and C3 variants, were identified in 66/398 (17%) patients. Thirty-eight (72%) variants were classified as pathogenic including 20/30 (66%) and 11/13 (84%) variants in CFH and CFI respectively, impairing synthesis of factor H or Factor I regulators. Fifteen on 53 (27%) variants were of unknown significance. At diagnosis, 69% of patients were adult (median age of 31 years). With the exception of biological stigma of thrombotic microangiopathy, which was more frequent in patients with CFI variants (5/14 (36%) vs 1/37 (3%) and 0% in CFH group and C3 group, p<0.001), the clinical and histological features were similar among the three variants groups. The kidney outcome was poor regardless of the age at onset and treatment received. Sixty-five percent (43/66) of patients with rare variant reach end stage kidney disease after a median delay of 41 [19-104] months, compared to 28% (55/195) after a median delay of 34 [12-143] months in the non-variant group. Among 36 patients who received a kidney transplant, two years-recurrence was frequent, occurring in 39% (12/31), without difference between variants groups and led to graft failure in 3 cases. In our cohort, 17% of C3 glomerulopathy/Ig-MPGN cases were associated with rare variants in the CFH, CFI, or C3 genes. In the majority of cases, a quantitative deficiency in factor H or factor I is identified. The presence of a rare variant was associated with poor kidney survival.

Factors related to recurrence of proteinuria in childhood IgA nephropathy.

Proteinuria remission is the most significant predictive factor for kidney outcome in childhood IgA nephropathy (c-IgAN). Even if proteinuria remission can be obtained, some patients have recurrence of proteinuria in the long-term. This is a retrospective analysis of 312 cases of proteinuria remission among 538 consecutive children with biopsy-proven IgAN from 1976 to 2013. To elucidate the incidence and factors related to recurrence of proteinuria in c-IgAN, we compare clinical and pathological findings between patients with and without recurrence of proteinuria. Among 312 patients with remission of proteinuria, 91 (29.2%) had recurrence of proteinuria within the observation period (median 8years). Using a multivariate Cox regression analysis, significant factors associated with recurrence of proteinuria were onset age (HR 1.13 [95%CI: 1.05-1.22], P = 0.002) and presence of hematuria after proteinuria remission (HR 2.11 [95%CI: 1.30-3.45], P = 0.003). The Kaplan-Meier analysis showed significant differences in CKD G3a-G5-free survival between the patients with no-recurrence of proteinuria, recurrence of proteinuria and non-proteinuria remission (P < 0.0001, log-rank test). Kidney survival was 100% in no-recurrence of proteinuria, 92.2% in recurrence of proteinuria, and 65.6% in non-proteinuria remission at 15 years. Cox analyses adjusted by proteinuria remission showed that recurrence of proteinuria (HR 03.10e9 [95%CI: NA], P = 0.003) was a significant factor associated with progression to CKD G3a-G5 in all patients with c-IgAN. Approximately 30% of patients with proteinuria remission had recurrence of proteinuria regardless of treatment. Both remission and recurrence of proteinuria are significant prognostic factors for kidney outcome. A higher resolution version of the Graphical abstract is available as Supplementary information.

The feasibility of incremental peritoneal dialysis for older patients on peritoneal dialysis.

This study was performed to investigate the feasibility of incremental peritoneal dialysis (iPD) in older patients. In this retrospective cohort study, we enrolled peritoneal dialysis (PD) patients with age ≥ 60 years old at our center from 2008 to 2017. The patients were divided into two groups based on the daily PD exchanges: iPD group (≤3 × 2 L exchanges), and full dose group (≥4 × 2 L exchanges). Kaplan-Meier curves and multivariate Cox regression models were applied to evaluate the risks of anuria and mortalities between groups. A total of 238 patients (186 in full dose group and 52 in iPD group) were enrolled. The mean age was 67.8 ± 5.7 years, and 45.8% were females. The baseline glomerular filtration rate was 4.15 ± 2.39 mL/min/1.73 m2 . Multivariate Cox regression models showed that patients in the iPD group patients had significantly decreased risk of anuria (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.24-0.81; p = 0.008), and all-cause mortality (HR, 0.59; 95% CI, 0.36-0.98; p = 0.04). Additionally, the incidence of peritonitis was significantly lower in the iPD group than that in the full dose group (0.115 vs. 0.197 episodes per person-year, p = 0.03) during the 36 months of PD commencement. Older patients with iPD were independently associated with better preservation of residual kidney function and survival outcomes. Moreover, iPD regimens are also associated with reduced incidence of peritonitis. The iPD strategy might offer a feasible option for older patients.

“Post-renal acute kidney injury in patients with cancer: Clinical presentation and kidney and patient outcomes”

Background: Post-renal acute kidney injury (PR–AKI) is frequent in patients with cancer requiring emergent intervention. With our study we aimed to describe the clinical features and prognostic factors for kidney and overall survival (OS) in cancer patients with PR–AKI. Methods: This is a single-center retrospective study that included 306 cancer patients with PR–AKI admitted from January 2011 to December 2021. Previous kidney function, AKI episode, and progression to end-stage kidney disease (ESKD) were compared. Kaplan Meier and Cox proportional regression methods were used for survival analyses. Results: The most frequent type of malignancy was the prostate (52, 17%) followed by the uterus (50, 16.3%). The mean baseline eGFR was 62 ml/min/1.73 m2. AKI stage 3 was present in 157 patients (51.3%) and renal replacement therapy (RRT) was performed in 19 patients (6%). At discharge, 197 patients (64.4%) had a quick recovery, and during follow-up 8 (2.6%) patients progressed to ESKD. The risk factors associated with ESKD were previous decreased kidney function (eGFR&lt;30 ml min 1.73m2) (HR 33.275, [95% CI, 3.997–277.002], p = 0.001); glomerular disease, (HR 8.353, [95%CI, 1.022–68.279], p=0.048); concomitant prerenal AKI (HR 5.670, [95% CI, 1.143–28.131], p = 0.034); and need of RRT (HR 19.519, [95% CI, 4.871–78.215], p &lt; 0.001). Median OS was 6 months (IQR 1–24 months). We found differences in the global survival over 60 months, with longtime survivors including patients with Bricker (42.6% vs16.4%) and genito-urinary cancer (27.6% vs 11.7%). Gastric cancer (HR 2.943, [95%CI, 1.837–4.714], p&lt;0.001), metastatic disease (HR 1.913, [95%CI, 1.464–2.499], p &lt; 0.001), and direct tumoral invasion (HR 1.519, [95%CI, 1.115–2.070], p = 0.008) were related with a decreased survival. Conclusions: Gastric cancer, metastatic disease, and direct tumoral invasion were predictors of short survival. The main predictors of evolution to ESKD were previous kidney function, concomitant glomerular disease, and the need for RT.

Determinants of Kidney Failure in Primary Hyperoxaluria Type 1: Findings of the European Hyperoxaluria Consortium

Primary hyperoxaluria type 1 (PH1) has a highly heterogeneous disease course. Apart from the c.508G>A (p.Gly170Arg) AGXT variant, which imparts a relatively favorable outcome, little is known about determinants of kidney failure. Identifying these is crucial for disease management, especially in this era of new therapies. In this retrospective study of 932 patients with PH1 included in the OxalEurope registry, we analyzed genotype-phenotype correlations as well as the impact of nephrocalcinosis, urolithiasis, and urinary oxalate and glycolate excretion on the development of kidney failure, using survival and mixed model analyses. The risk of developing kidney failure was the highest for 175 vitamin-B6 unresponsive ("null") homozygotes and lowest for 155 patients with c.508G>A and c.454T>A (p.Phe152Ile) variants, with a median age of onset of kidney failure of 7.8 and 31.8 years, respectively. Fifty patients with c.731T>C (p.Ile244Thr) homozygote variants had better kidney survival than null homozygotes (P= 0.003). Poor outcomes were found in patients with other potentially vitamin B6-responsive variants. Nephrocalcinosis increased the risk of kidney failure significantly (hazard ratio [HR] 3.17 [2.03-4.94], P< 0.001). Urinary oxalate and glycolate measurements were available in 620 and 579 twenty-four-hour urine collections from 117 and 87 patients, respectively. Urinary oxalate excretion, unlike glycolate, was higher in patients who subsequently developed kidney failure (P= 0.034). However, the 41% intraindividual variation of urinary oxalate resulted in wide confidence intervals. In conclusion, homozygosity for AGXT null variants and nephrocalcinosis were the strongest determinants for kidney failure in PH1.

Anti-phospholipase A2 receptor positive membranous nephropathy: investigating the link between electron microscopy stages and clinical outcome

ABSTRACT This retrospective, observational study sought to examine the relationship between Ehrenreich-Churg electron microscopy (EM) stages and long-term outcomes in anti-PLA2R membranous nephropathy (MN). Seventy-one patients with anti-PLA2R MN (median titer 185.7RU/mL) were followed for a median of 46 months, with end-stage kidney disease (ESKD) as the primary endpoint, and response to treatment as a secondary endpoint. Patients were grouped into stages I-II (41 patients) and stages III-IV (30 patients) for analytical purposes. Notably, the III-IV group demonstrated a lower eGFR, lower anti-PLA2R titer, but a higher chronicity score. Kaplan-Meier analysis showed shorter mean kidney survival time in stages III-IV compared to I-II (p 0.03). However, multivariate analysis using Cox regression indicated that Ehrenreich-Churg stages did not significantly influence kidney survival, but lower eGFR at diagnosis and higher histopathological chronicity score did. Remission was achieved by 64% of patients and no relationship between Ehrenreich-Churg stages and treatment response was found. The only identified risk factor for not achieving remission was the severity of hyposerinemia at diagnosis. In conclusion, while EM stages III-IV are associated with more chronic lesions and stages I-II with more active immunologic disease, the histological chronicity score seems to be a stronger predictor of long-term outcomes.

The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P<.0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P<.0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P<.001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P=.001]. DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease.

Activation of the complement system is involved in the pathogenesis of anti-glomerular basement membrane (anti-GBM) disease. Glomerular deposits of complement 3 (C3) are often detected on kidney biopsies. The primary objective of this study was to analyze the prognostic value of the serum C3 level and the presence of C3 glomerular deposits in patients with anti-GBM disease. We conducted a retrospective cohort study of 150 single-positive patients with anti-GBM disease diagnosed between 1997 and 2017. Patients were categorized according to the serum C3 level (forming a low C3 (C3<1.23 g/L) and a high C3 (C3≥1.23 g/L) groups) and positivity for C3 glomerular staining (forming the C3+ and C3- groups). The main outcomes were kidney survival and patient survival. Of the 150 patients included, 89 (65%) were men. The median [interquartile range (IQR)] age was 45 [26-64]. At diagnosis, kidney involvement was characterized by a median [IQR] peak serum creatinine (SCr) level of 578 [298-977] µmol/L, and 106 (71%) patients required dialysis. Patients in the low C3 group (72 patients) had more severe kidney disease at presentation, as characterized by higher prevalences of oligoanuria, peak SCr ≥500 µmol/L (69%, vs. 53% in the high C3 group; p=0.03), nephrotic syndrome (42%, vs. 24%, respectively; p=0.02) and fibrous forms on the kidney biopsy (21%, vs. 8%, respectively; p=0.04). Similarly, we observed a negative association between the presence of C3 glomerular deposits (in 52 (41%) patients) and the prevalence of cellular forms (83%, vs. 58% in the C3- group; p=0.003) and acute tubulo-interstitial lesions (60%, vs. 36% in the C3- group; p=0.007). When considering patients not on dialysis at diagnosis, the kidney survival rate at 12 months was poorer in the C3+ group (50% [25-76], vs. 91% [78-100] in the C3- group; p=0.01), with a hazard ratio [95% confidence interval] of 5.71 [1.13-28.85] (p=0.04, after adjusting for SCr). In patients with anti-GBM disease, a low serum C3 level and the presence of C3 glomerular deposits were associated with more severe disease and histological kidney involvement at diagnosis. In patients not on dialysis at diagnosis, the presence of C3 deposits was associated with worse kidney survival.

Adding 6-month parameters for the prediction of kidney prognosis in ANCA-associated glomerulonephritis.

Antineutrophil-cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with kidney involvement (AAV-GN) frequently evolves to end-stage kidney disease (ESKD) despite aggressive immunosuppressive treatment. Several risk scores have been used to assess renal prognosis. We aimed to determine whether kidney function and markers of AAV-GN activity after 6 months could improve the prediction of ESKD. This retrospective and observational study included adult patients with AAV-GN recruited from six French nephrology centers (including from the Maine-Anjou AAV registry). The primary outcome was kidney survival. Analyses were conducted in the whole population and in a sub-population that did not develop ESKD early in the course of the disease. When considering the 102 patients with all data available at diagnosis, Berden classification and Renal Risk Score (RRS) were not found to be better than kidney function [estimated glomerular filtration rate (eGFR)] alone at predicting ESKD (C-index=0.70, 0.79, 0.82, respectively). Multivariables models did not indicate an improved prognostic value when compared with eGFR alone.When considering the 93 patients with all data available at 6 months, eGFR outperformed Berden classification and RRS (C-index=0.88, 0.62, 0.69, respectively) to predict ESKD. RRS performed better when it was updated with the eGFR at 6 months instead of the baseline eGFR. While 6-month proteinuria was associated with ESKD and improved ESKD prediction, hematuria and serological remission did not. This work suggests the benefit of the reassessment of the kidney prognosis 6 months after AAV-GN diagnosis. Kidney function at this time remains the most reliable for predicting kidney outcome. Of the markers tested, persistent proteinuria at 6 months was the only one to slightly improve the prediction of ESKD.

Systematic Review of Clinical Characteristics and Genotype-Phenotype Correlation in LAMB2-Associated Disease

Laminin subunit beta-2 (LAMB2)-associated disease, termed Pierson syndrome, presents with congenital nephrotic syndrome, ocular symptoms, and neuromuscular symptoms. In recent years, however, the widespread use of next-generation sequencing (NGS) has helped to discover a variety of phenotypes associated with this disease. Therefore, we conducted this systematic review. A literature search of patients with LAMB2 variants was conducted, and 110 patients were investigated, including 12 of our patients. For genotype-phenotype correlation analyses, the extracted data were investigated for pathogenic variant types, the severity of nephropathy, and extrarenal symptoms. Survival analyses were also performed for the onset age of end-stage kidney disease (ESKD). Among all patients, 81 (78%) presented with congenital nephrotic syndrome, and 52 (55%) developed ESKD within 12 months. The median age at ESKD onset was 6.0 months. Kidney survival analysis showed that patients with biallelic truncating variants had a significantly earlier progression to ESKD than those with other variants (median age 1.2 months vs. 60.0 months, P< 0.05). Although the laminin N-terminal domain is functionally important in laminin proteins, and variants in the laminin N-terminal domain are said to result in a severe kidney phenotype such as earlier onset age and worse prognosis, there were no significant differences in onset age of nephropathy and progression to ESKD between patients with nontruncating variants located in the laminin N-terminal domain and those with variants located outside this domain. This study revealed a diversity of LAMB2-associated diseases, characteristics of LAMB2 nephropathy, and genotype-phenotype correlations.

Favorable outcomes in Hispanic recipients receiving simultaneous pancreas kidney transplantation.

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p<.001). The duration of dialysis was longer in Hispanics (640 vs. 473days, p=.02), and fewer patients received preemptive transplants (10% vs. 29%, p<.01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.

Crescents proportions above 10% are associated with unfavorable kidney outcomes in IgA nephropathy patients with partial crescent formation

Purpose Whether different crescentic proportions determine the progression of IgA nephropathy (IgAN) with crescents in less than 50% of glomeruli remains controversial. We aimed to evaluate the relationship between different proportions of crescents and kidney outcomes in IgAN with partial crescent formation. Methods Patients diagnosed as IgAN, having at least two crescents and in less than 50% of glomeruli, were categorized into three groups: Group I (crescents in ≤10% of glomeruli), Group II (10%< crescents ≤25% of glomeruli) and Group III (crescents >25% of glomeruli). Baseline clinicopathological parameters were evaluated. The kidney endpoint was a composite of a ≥ 40% decline in the initial estimated glomerular filtration rate, end-stage kidney disease, and kidney disease-related death. Results Of 183 IgAN patients with crescents in less than 50% of glomeruli, baseline 24-hour urinary protein and immunosuppressive treatment varied among the three groups (p < 0.05). During a median follow-up of 57 months (interquartile range 28–86), 50 (27.3%) patients reached the composite outcome. Kaplan–Meier survival analysis revealed that kidney survival in Group II (p = 0.049) and Group III (p = 0.008) was significantly shorter than in Group I, with no significant difference between Group II and III (p = 0.2). After adjusting for clinical factors and MEST score based on the multivariate Cox regression analysis, a crescent proportion >10% (HR = 3.431, 95% CI 1.067–11.03, p = 0.039) was predictive of time to unfavorable kidney outcome, with model adjustments improving predictability (c-index: 0.817). Conclusion The proportion of crescents reaching 10% of glomeruli in IgAN was identified as an independent risk factor for kidney survival.

#6423 LONG-TERM PROGNOSIS OF HYPOPROTEIC DIET SUPPLEMENTED WITH KETOANALOGUES IN PATIENTS WITH ADVANCED DIABETIC KIDNEY DISEASE AND SEVERE PROTEINURIA

Abstract Background and Aims Studies support the role of low-protein regimens in managing chronic kidney disease (CKD). In addition, some data emphasize the role of low-protein diets (LPDs) in postponing kidney replacement therapy (KRT) in patients with CKD, even in diabetic patients with heavy proteinuria. Although most results seem to be in favor of a LPD in CKD, even in patients with advanced diabetic kidney disease (DKD), there is insufficient data on long-term kidney and patient outcomes. This is a follow-up study aimed to determine the outcomes in kidney survival and patient survival in patients with DKD and severe proteinuria. Method The follow-up study included all patients with advanced DKD and severe proteinuria who previously participated in a twelve-month uni-centric prospective study looking to assess variations in kidney function and proteinuria. At baseline, 97 patients with DKD, with stable stage 4+ CKD and proteinuria of nephrotic-range, who proved adherent to protein restriction were enrolled and received LPD (0.6 g mixed protein/kg-day) supplemented with ketoanalogues of essential amino acids (Ketosteril®, Bad Homburg, Germany, 1 tb/10 kg dry ideal body weight per day) for 12 months. Ninety-two patients completed the study (5 patients received kidney transplant). The efficacy outcomes were assessed by the decline of kidney function and proteinuria. Safety parameters were evaluated by anthropometric measurements (Body Mass Index), Subjective Global Assessment score and serum albumin. Compliance to the LPD was assessed by urinary urea from a 24-hour urine collection to estimate protein intake (ePI) and a 3-day food diary to estimate the energy intake. After the end of the study, the patients continued to remain compliant to the nutritional intervention. The primary composite endpoint was the need for KRT or patient death. The census moment was either the occurrence of the primary endpoint or the 31st of January, 2023. Results At baseline, patients had a median age of 61 years (95% CI 58 to 67), 66% were men, with poorly controlled diabetes assessed by the level of the glycated hemoglobin [8.1% (95% CI 8.0 to 8.3)]. All patients had a good nutritional status (SGA A). The median estimated glomerular filtration rate (eGF) was 12.6 mL/min (95% CI 11.7 to 13.1) and the median proteinuria was 5.2 g/g creatininuria (95% CI 5.0 to 5.2). After 12 months, a significant reduction in proteinuria was observed (67%), as well as a reduction in the kidney function decline by almost 80% compared to the period before the inclusion and a preserved good nutritional status (SGA A). The median follow-up was 105 months (95% CI 103 to 106). After almost 9 years of follow-up, 83.7% of patients remained alive, despite significant comorbidities. The median survival was 62 months (95% CI 47 to 85). Seventy-six percent of patients required KRT, with a predilection for hemodialysis. The median period of time until KRT was 26 months (95% CI 24 to 29). In a Kaplan-Meier survival analysis, the compliance to the sLPD was associated with better kidney survival (p = 0.03). Conclusion Low-protein diets supplemented with ketoanalogues of essential amino acids seem to be associated with a better kidney outcome on long-term in patients with advanced diabetic kidney disease and heavy proteinuria.