Clinical Journal of the American Society of Nephrology

Background. Chronic kidney disease (CKD) affects 10-13% of adults worldwide but remains largely undiagnosed until advanced stages. Hospitalization provides an opportunity for early detection through opportunistic urine albumin-to-creatinine ratio (UACR) measurement. Methods. We conducted a prospective three-arm study of opportunistic CKD screening in general internal medicine wards at Hadassah Mt. Scopus (MS), Hadassah Ein Kerem (EK), and Shaare Zedek Medical Center (SZMC) in Jerusalem (Protocol HMO-23-0300). Adult inpatients without known CKD or recent UACR were enrolled. Pathological UACR was defined as [≥]30 mg/g. Confirmed CKD required two pathological measurements [≥]90 days apart (KDIGO-compatible). eGFR was computed using the 2021 CKD-EPI race-free equation. Pooled proportions were estimated by fixed-effects logit meta-analysis; odds ratios by DerSimonian-Laird random-effects models. Results. A total of 158 patients were enrolled (MS n=50, EK n=57, SZMC n=51). Pathological first UACR was identified in 43/158 patients (27.2%; 95% CI 21.3-34.1%; I2=0% across centers). Of 24 patients with a second UACR available, 14 (58%) confirmed CKD, yielding a pooled confirmed-CKD rate of 8.9% of all screened patients. In-hospital mortality was significantly higher among patients with pathological UACR (9.3% vs ~2%; Fisher's exact p=0.012). In per-center multivariate logistic regression, three predictors reached pooled significance: BUN (OR 1.10 per mg/dL, 95% CI 1.04-1.17, p=0.002, I2=0%), heart failure (OR 3.21, 95% CI 1.34-7.70, p=0.009, I2=0%), and diabetes mellitus (OR 2.54, 95% CI 1.11-5.82, p=0.028, I2=17%). Cardiac/vascular admissions had the highest pathological UACR rate (~42%); GI/hepatic admissions had 0%. Conclusions. Opportunistic inpatient UACR screening identifies previously unrecognized CKD in approximately 9% of general internal medicine patients, with consistent results across three independent centers. BUN elevation, heart failure, and diabetes are the strongest independent predictors. Pathological UACR carries significant short-term mortality risk, supporting integration of routine screening into inpatient care pathways.

Introduction: B cell depletion with rituximab leads to complete or partial remission (CR/PR) in only ~60% of patients with primary membranous nephropathy (PMN). Adding belimumab to rituximab may result in greater depletion of memory B cells, limit the re-emergence of autoreactive B cells, and improve clinical responses. Methods: REBOOT Part A (NCT03949855) is a single arm, open-label, pharmacokinetic study where all participants had proteinuria [≥] 4g/day and detectable serum anti-phospholipase A2 receptor (anti-PLA2R) antibodies. Participants received belimumab 200 mg subcutaneously weekly for 52 weeks and rituximab 1000 mg intravenously at weeks 4 and 6. Assessments included belimumab exposure at week 4 and CR/PR at week 104. Results: Seventeen participants started belimumab. Belimumab exposure was not significantly reduced in those with high (> 9 g/day) proteinuria at week 4. Among all treated participants, 59% (10/17) achieved CR/PR at week 104, while in per protocol analyses, 91% (10/11) achieved CR/PR at week 104. All participants in per protocol analyses had normal serum albumin and undetectable serum anti-PLA2R by week 104. Circulating memory B cells increased before rituximab and were depleted by rituximab. B cell re-constitution occurred after week 52 with primarily naive and transitional B cells. Belimumab with rituximab was well-tolerated, with one participant discontinuing belimumab due to infection. Conclusion: In this study, a high proportion of participants receiving belimumab with rituximab achieved CR/PR. Thus, a multi-targeted approach to B cell depletion may improve immunologic and clinical outcomes in PMN and is being studied in a larger, randomized, placebo-controlled clinical trial.

Importance: Recently, proteinuria has been accepted as a surrogate end point for clinical trials in focal segmental glomerulosclerosis (FSGS) ang IgA nephropathy. However, proteinuria has not been evaluated in Apolipoprotein L1 (APOL1)-mediated kidney disease (AMKD). Methods: Real world data (RWD) analysis of 128 patients of African ancestry with APOL1 high risk genotypes, without diabetes, enrolled in the Million Veteran Program (MVP; n=109) or the biorepository at Vanderbilt University (BioVU; n=19), who had urine albumin-creatinine ratio (UACR) >= 420 mg/g (PCR~0.9 g/g) with a concurrent GFR value. The main predictor was change in the log-UACR at 12 months. The primary outcome was annual GFR slope over 24 months. Secondary outcomes included a kidney composite of a sustained 30% GFR decline, end stage kidney disease (ESKD) or death and ESKD as a single outcome. Linear regression and Cox proportional hazards models were used to assess the effect of changes in UACR and the outcomes. Results: In the pooled analysis the mean age was 56.8 (SD 15.5) y, 116 were male (90.6%) and three patients had diagnosis of FSGS at baseline. Mean baseline eGFR was 46.8 (SD 16.1) mL/min/1.73m2, mean baseline UACR was 1240.8 (1107.7) mg/g, mean eGFR slope was -4.67[-6.00, -3.33] mL/min/1.73m2/year and the geometric mean percentage changes in the UACR at 12 months were -57.5% [-65.0%, -48.4%]. For every 1 unit of log (UACR) increment at 12 months, the annual eGFR slope decreased by -1.80 [-2.56, -1.03] mL/min/1.73m2 in the pooled analysis. For every 1 unit of log (UACR) increment at 12 months, the Cox regression showed a 61% increase in the risk of a kidney composite (p=0.002) and a 98% increase in the risk of ESKD (p<0.001). It was estimated that a 50% reduction of UACR at 12 months was associated with a 28% reduction in the kidney composite endpoint (adjusted hazard ratio [aHR]=0.72; 95% confidence interval [CI]:0.59-0.88; p=0.002), and a 38% reduction in the risk of ESKD (aHR=0.62; 95% CI:0.49-0.80; p<0.001). Conclusions and relevance: Changes in UACR at 12 months significantly modify the rate of decline of GFR over 24 months and clinically meaningful endpoints, supporting the use of UACR changes as surrogate endpoint in AMKD.

Abstract Objective: To synthesize the available evidence on the association between SARS-CoV-2-related microvascular thrombosis and acute kidney injury (AKI), with emphasis on renal outcomes, mortality, and renal replacement therapy requirements. Methods: This systematic review followed the PRISMA 2020 statement and was prospectively registered in PROSPERO (CRD420251132701). PubMed/MEDLINE, Scopus, and Embase were searched for systematic reviews, including meta-analyses, and umbrella reviews investigating the association between SARS-CoV-2-related microvascular thrombosis and acute kidney injury. Two reviewers independently performed study selection, data extraction, and methodological quality assessment using AMSTAR-2 and ROBIS. Evidence was synthesized through a structured narrative synthesis supported by quantitative data extracted from the included reviews. Results: Six evidence syntheses evaluating kidney involvement, thrombotic events, and microvascular mechanisms in COVID-19 were included. AKI incidence was 9.2% (95%CI 4.6-13.9) among hospitalized patients and 32.6% (95%CI 8.5-56.6) among critically ill patients. In children with multisystem inflammatory syndrome associated with SARS-CoV-2, AKI incidence was 20% (95%CI 14-28). Microvascular or thrombotic events were associated with adverse renal outcomes (OR 2.14; 95%CI 1.32-3.48). AKI was associated with increased mortality (OR 4.68; 95%CI 1.06-20.70) and greater likelihood of renal replacement therapy requirement (OR 2.87; 95%CI 1.45-5.68). The certainty of evidence ranged from moderate to high for the principal outcomes. Conclusion: Current evidence supports an important association between microvascular thrombotic injury and COVID-19-associated AKI. These findings reinforce the relevance of endothelial dysfunction and thromboinflammatory pathways in kidney involvement during COVID-19 and highlight the need for early renal monitoring, risk stratification, and kidney-protective strategies in high-risk patients. Keywords: COVID-19; Acute Kidney Injury; Microvascular Thrombosis; SARS-CoV-2; Renal Replacement Therapy; Systematic Review

Background: Fibrosis, characterised by excessive accumulation of collagen type I (COL1), is a common feature of chronic diseases, including liver diseases (LDs), chronic kidney disease (CKD) and heart failure (HF). COL1 degradation products can be detected in urine by proteomics/ peptidomics analyses and may serve as non-invasive biomarkers of fibrosis. We aimed to identify a common molecular signature of fibrosis across these diseases that may ultimately guide interventions to slow disease progression and prevent organ damage. Methods: Using capillary electrophoresis coupled to mass spectrometry (CE-MS), naturally occurring COL1 degradation products (peptides) in the urine of patients with fibrotic disease, LDs (n=127), CKD (n=263) or HF (n=187), were investigated and compared with the same number of matched controls. Disease-associated COL1 peptides were identified separately for each condition, and peptides showing consistent associations across the three diseases were selected to define a common fibrosis signature. A support vector machine model based on the selected peptides was developed and validated in independent cohorts of patients with LDs (n=110), CKD (n=93), HF (n=32) and controls (n=643). Results: We identified a common fibrotic signature consisting of 50 COL1 degradation products, mainly downregulated in fibrosis. A model based on these peptides achieved a strong performance, with an area under the receiver operating characteristic curve (AUC) of 0.935 (95% confidence interval (CI) 0.917-0.953, p<0.0001) in an external validation cohort comprising pooled disease groups (LDs, CKD, and HF) and controls. Performance was maintained in LDs, CKD and HF, with AUCs of 0.917 (95% CI 0.890-0.944, p<0.0001), 0.951 (95% CI 0.931-0.971, p<0.0001) and 0.950 (95% CI 0.903-0.997, p<0.0001), respectively. The model scores were significantly associated with fibrosis stage in LDs (p=0.0097) and with interstitial fibrosis and tubular atrophy in CKD (p=0.045). Conclusion: A model of urinary COL1 peptides captures a shared collagen degradation signature across organs and diseases, enabling the non-invasive assessment of fibrosis irrespective of its origin. As these peptides exclusively reflect collagen degradation, the findings suggest impaired collagen degradation as a driver in fibrosis. Future clinical studies are warranted to evaluate the utility of this model for early fibrosis detection and earlier implementation of anti-fibrotic interventions.

Background: The dietary approaches to stop hypertension (DASH) diet is often recommended to patients with chronic kidney disease, although evidence regarding its efficacy in this population is limited. Our study tested the hypothesis that increased adherence to the dietary approaches to stop hypertension (DASH) diet score would be associated with longer time to kidney function decline among Veterans. Methods: We conducted a retrospective cohort study of 251,921 Veterans enrolled in the Million Veteran Program (MVP). The DASH diet score was calculated from the food frequency questionnaire and categorized into tertiles. The primary outcome was a composite of: Kidney event or death, where a kidney event was defined as a sustained 40% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Cox regression models compared the hazard for both outcomes by DASH score tertiles. We examined modification by ancestry, sex and other clinical characteristics Results: The median age was 67 years and 90% of Veterans were men. There were 59,269 (23.5%) who experienced the primary composite outcome, during the maximum follow-up of 10 years (median 6.1 years). Crude incidence rates for the kidney event and death outcome were 43.3, 40.4, and 36.8 per 1000 person-years of DASH score by tertiles. DASH score was associated with a lower hazard ratio (HR) for the primary composite outcome; third vs first tertile 0.81 (95% Confidence Interval (CI) 0.80 - 0.83) and second vs first tertile HR 0.90 [95% CI 0.88 - 0.92]. In subgroup analysis for individuals of African ancestry, Admixed American, and Females, only the third tertile of the DASH score was associated with a statistically significant reduction in composite outcome. Conclusion: Beneficial associations of the DASH diet were observed across subgroups. Future research is needed to understand gene and environmental factors that influence the observed subgroup differences

Background: ALECT2 is the third most common cause of renal amyloidosis in the United States, with a strong predilection for Hispanic patients in the Southwest. (PMID:24522497) Despite its regional prevalence, the data on the trajectory of kidney function decline and post-transplant outcomes remain poorly characterized. Methods: This is a retrospective study of patients diagnosed with ALECT2 by kidney biopsy at UNM from January 2014 to April 2024. Pre- and post-biopsy eGFR trajectories and post-transplant allograft function were analyzed. Results: 12 patients had pre-biopsy data available, with the mean age at diagnosis 64 SD 12.0 years, 8(67%) were females, and 8 identified as Hispanic. Mean eGFR at diagnosis was 31 (SD 29) indicating advanced kidney disease with 67% diagnosed as CKD stage 4 or 5. Concomitant kidney pathology was identified in 50% with diabetic nephropathy being present in 2/3 of those. A significant change in the eGFR trajectory identified at the time of biopsy through change point analysis [Figures A,C,D] Among four patients who underwent kidney transplantation, allograft eGFR remained stable over more than 60 months of follow-up [Figure D] Conclusion: In this cohort of predominantly Hispanic patients, ALECT2 amyloidosis presented with advanced CKD and accelerated loss of kidney function, which prompted a biopsy that detected the disease. Post- transplant allograft function was well maintained, supporting kidney transplantation as a viable treatment strategy for ALECT2-associated kidney disease.

Background: Whether benchmark performance reflects robust clinical reasoning rather than surface-level pattern recognition remains uncertain. We evaluated the robustness of state-of-the-art large language models (LLMs) on nephrology board renewal questions using "None of the other answers" (NOTA) substitution. Methods: From 210 Japanese Society of Nephrology board renewal questions (2014-2023), two nephrologists independently reviewed all items. Questions in which NOTA became the sole correct answer after replacement were included, yielding 145 validated questions. GPT-5, GPT-4o, Gemini 2.5 Pro, and Gemini 2.0 Flash were evaluated via application programming interfaces under default settings. The primary endpoint was accuracy, and paired differences were assessed using the exact two-sided McNemar test. Results: Accuracy was significantly lower after NOTA substitution for all models: GPT-4o, 66.21% to 19.31% (drop, 46.90 percentage points [pp]); GPT-5, 87.59% to 73.10% (14.48 pp); Gemini 2.0 Flash, 58.62% to 31.03% (27.59 pp); and Gemini 2.5 Pro, 86.90% to 55.86% (31.03 pp); all P < .001. GPT-5 showed the smallest decline and the highest accuracy in both versions. Conclusions: All evaluated LLMs showed a significant robustness gap after NOTA replacement. Newer models may be more robust, but multiple-choice accuracy remains an incomplete measure of clinical reasoning robustness.

Background: Current understanding of acute kidney injury (AKI) risk factors remains largely descriptive, offering limited precision into how specific biomarker values or physiologic thresholds influence susceptibility. We aimed to synthesize knowledge from machine learning models trained across multiple health systems to identify generalizable, value-specific risk drivers and biomarker interactions contributing to AKI risk. Methods: We analyzed electronic health records (EHRs) from 785,497 adult inpatients between 2010 and 2019 across nine U.S. academic medical centers within PCORnet. Interpretable gradient boosting machine models were independently developed at each health system to quantify predictor-outcome associations. Meta-regression was applied to integrate these site-level results, characterize nonlinear value-risk relationships, and identify bivariate interactions between predictors. Results: Meta-analysis revealed consistent, value-specific risk drivers across health systems. An increase in glucose from 100 mg/dL to 140 mg/dL was associated with a 1.46-fold higher risk of AKI. Chloride and anion gap also demonstrated elevated AKI risk with risk increases overlapping portions of their reference ranges, with anion gap showing a 1.14-fold increase across 4-12 mmol/L and chloride a 1.28-fold increase across 96-100 mEq/L. Electrolytes including potassium, calcium, and sodium showed quadratic associations with AKI risk. Bivariate meta-regression identified interactions between key predictors, highlighting pathways that jointly modulate AKI risk. Conclusion: This cross-system meta-analysis synthesizes machine learning-derived evidence into clinically interpretable knowledge, revealing how specific biomarker ranges and interactions modulate AKI risk. By moving beyond surface-level associations to quantitative, generalizable physiologic thresholds, these findings provide actionable insights to enhance risk stratification and personalized prevention in hospital care.

Background: Early renal function decline is often accompanied by bothersome urological symptoms, yet effective early-stage nutritional interventions remain limited. L-Ergothioneine (EGT), a diet-derived antioxidant concentrated in renal tissue via the OCTN1 transporter, has shown renoprotective potential preclinically, but human interventional data are sparse. Methods: In this single-center, open-label, self-controlled trial, 31 adults (aged 45-70 years) with early renal function decline and persistent urological symptoms ([&ge;]3 months) received oral EGT (120 mg/day) for 90 days; 27 completed the study. Participants served as their own controls. The primary outcome was the within-subject change in eGFR (CKD-EPI 2021 creatinine); secondary outcomes included cystatin C-based eGFR, serum creatinine, UACR, a 10-item voiding diary, and a low-back-pain visual analogue scale (VAS). Within-subject changes were assessed by paired t-test or Wilcoxon signed-rank test. Results: Creatinine-based eGFR increased from 86.04 {+/-} 17.89 to 93.25 {+/-} 19.00 mL/min/1.73 m2 (+8.4%; p = 0.0016) and serum creatinine fell by 7.0% (p = 0.015). However, cystatin C-based eGFR and serum cystatin C were unchanged (p = 0.31 and p = 0.99), so the filtration signal was not corroborated by an independent, muscle-mass-independent marker. UACR showed a non-significant downward trend. Patient-reported outcomes improved most robustly: the total voiding diary score decreased by 57.2% (p < 0.0001) and low-back-pain VAS by 67.2% (p = 0.0002), with significant relief of urgency, frequency, and voiding difficulty. No product-related adverse events occurred. Conclusions: In this uncontrolled study, 90-day EGT supplementation was associated with marked improvement in urological symptoms and in creatinine-based eGFR, although the latter was not confirmed by cystatin C. These changes cannot be attributed to EGT alone and may substantially reflect placebo and natural-history effects. The findings are hypothesis-generating and warrant confirmation in a randomized, placebo-controlled trial using validated symptom instruments. Trial Registration: ChiCTR2500108897; Prospectively registered on 2025-09-08.

Background: Initiation of emergency dialysis, often requiring temporary catheter owing to unprepared definitive vascular access, is associated with infectious and vascular complications and suggests advanced chronic kidney disease (CKD) care gaps. Previous studies focused on kidney failure or dialysis timing. This study aimed to predict initiation of emergency dialysis using machine learning and baseline data. Methods: This retrospective cohort study used the Japan Medical Data Center claims data (2014-2022). Adults with an estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 were included. The primary outcome was initiation of emergency dialysis (temporary catheter code without evidence of previous access preparation). Participants were randomly divided into derivation (80%) and validation (20%) cohorts. Logistic regression, support vector machine, XGBoost, LightGBM, and random forest models were evaluated using internal cross-validation, post-hoc calibration of the selected model, and bootstrap confidence intervals. Results: The cohort included 3,062 individuals (derivation; n=2,449, validation; n=613). Emergency dialysis was initiated in 237 participants (7.7%); 185 (7.6%) and 52 (8.5%) in the derivation and validation cohorts, respectively. Validation area under the receiver operating characteristic curve ranged from 0.781-0.799, with the highest value observed for random forest (0.799, 95% confidence interval; 0.740-0.850). Risk stratification showed clear event enrichment in higher predicted risk categories. SHAP analyses identified hemoglobin, proteinuria, baseline eGFR, diabetes history, and diuretic use as key predictors. Decision curve analysis showed greater net benefit than eGFR alone at lower threshold probabilities. Conclusions: Baseline machine learning models showed moderate discrimination for initiation of emergency dialysis and identified clinically plausible predictors. These findings support potential use for risk stratification, although external validation and evaluation within pre-specified care pathways are needed before implementation.

Background IgA vasculitis (IgAV) is the most common systemic vasculitis in children, and its prognosis is largely determined by renal involvement (IgAV nephritis). No routine blood test identifies IgAV or stratifies the risk of nephritis, although aberrant O-glycosylation of the IgA1 hinge region is central to its pathogenesis. We developed a mass-spectrometry assay to profile IgA1 hinge O-glycoforms and define signatures of disease activity and renal involvement. Methods IgA was affinity-purified from 5 uL of plasma from 91 children (27 with acute IgAV, 26 in remission, and 38 age-matched healthy controls; 24 with and 29 without nephritis), trypsin-digested, and hinge-region O-glycopeptides were quantified by LC-MS. Sixty-nine glycoforms were normalized to a total-IgA1 tryptic peptide. Duplicate measurements showed good analytical repeatability, with a median coefficient of variation of 6%. Groups were compared using Mann-Whitney and Kruskal-Wallis tests (Benjamini-Hochberg FDR). Discrimination was assessed by ROC analysis and cross-validated logistic regression panels. Results Acute IgAV showed broad remodeling of the hinge glycoform profile (35 glycoforms differed with excellent discrimination (AUC 0.93-0.95) for the best ones), with an increase in low-sialylated, agalactosylated species and a decrease in complex sialylated species. The profile was normalized in remission (no glycoform differed from the controls). Two distinct renal patterns emerged: disease-associated glycoforms already altered without nephritis and renal-specific glycoforms altered only in nephritis (H2N2S1, H3N3S5, H3N4S4, and H4N4S3). A four-marker panel discriminated nephritis among IgAV children with a cross-validated AUC of 0.86 (IC95 % 0.75-0.94). Conclusions A single mass-spectrometry assay, from a small blood volume, captures an IgAV-associated IgA1 hinge O-glycoform signature that normalizes in remission, together with a distinct renal involvement associated signature. These findings identify candidate IgA1 O-glycoform signatures associated with IgAV activity and documented renal involvement. Prospective longitudinal studies are required to determine whether the renal-associated panel can predict subsequent nephritis.

Introduction: Pediatric renal vein thrombosis is a rare but well-recognized form of venous thromboembolism. While long-term renal outcomes of neonatal cases are well-described, they are relatively unknown in cases affecting older children. Moreover, the ability of anticoagulation treatment to prevent these outcomes remains unknown. The objective of this study was to assess adverse long-term renal outcomes and determine if anticoagulation reduced their likelihood. Methods: Administrative data analysis utilizing the Pediatric Health Information System database. Renal vein thrombosis occurring in patients under 18 years were assessed. Cases involving tumor thrombus were excluded to focus the analysis only on thrombotic disease. Demographics, co-morbid conditions, anticoagulant therapies, and renal outcomes were assessed over a 9-year period. In sub-analyses, neonatal ([&le;]28 days) and non-neonatal renal vein thromboses were assessed to determine how their characteristics may differ. Results: 383 eligible renal vein thrombosis cases with 796 patient-years of follow-up were identified for analysis. 48.8% of the cases occurred in neonates. 25.3% of the cases occurred in children with pre-existing complex chronic conditions and 9.1% were associated with the onset of nephrotic syndrome. Mortality followed 15.1% of the cases, but causality cannot be assigned from administrative data. Most (80.2%) of the cases were treated with anticoagulation. Acute kidney injury occurred in 24% of cases, chronic kidney disease developed in 22.2%, hypertension in 26.9%, and proteinuria in 3.1%. Anticoagulation did not have a discernable effect on the likelihood of these long-term renal outcomes. Conclusion: Acute kidney injury, chronic kidney disease, and hypertension are prevalent in survivors of childhood renal vein thrombosis. Anticoagulation does not appear to reduce the incidence of long-term renal outcomes, but the low percentage of non-anticoagulated patients suggests treatment bias. Long-term kidney health surveillance is warranted in pediatric renal vein thrombosis survivors.

Vitamin D sterols, phosphorus binders and calcimimetics are used to treat chronic kidney disease mineral and bone disorder (CKD-MBD) in hemodialysis. With few randomized trials, providers may titrate agents differently reflecting equipoise and opportunities for clinical trials. We studied patients initiating in-center hemodialysis at Dialysis Clinic, Inc facilities from 2006-2015 and who remained on hemodialysis for [&ge;]90 days (n=23,549). Multinomial logit models assessed titration among users of each medication at the start of the month considering static and dynamic CKD-MBD laboratories. Similarly parameterized logistic models assessed treatment initiation. Differences across facilities were quantified as random effects and corresponding median odds ratios. We observed patterns of titration associated with CKD-MBD laboratories including albumin-corrected serum calcium (Ca), serum phosphorus and parathyroid hormone (PTH) and minimal impact of patient characteristics. Best fit models incorporated 3 months of lagged Ca and phosphorus values and linear splines for current Ca, phosphorus and PTH values. Absolute titration probabilities for vitamin D sterols and calcimimetics were influenced by all three CKD-MBD parameters, such that Ca and phosphorus values altered the threshold PTH at which escalation and de-escalation probabilities crossed. Median odds ratios indicated the greatest facility variation for vitamin D sterol titration. Providers titrate CKD-MBD medications based largely on the full CKD-MBD laboratory phenotype, including the recent serum Ca, phosphorus and PTH history. Facility variation suggests equipoise in titration of vitamin D sterols with opportunities for clinical trials.

ABSTRACT Importance: The prevalence of chronic kidney disease (CKD) is increasing, with aging being a major contributor. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are well established therapies for CKD; however, adults aged 80 years or older have been underrepresented in previous large-scale trials. Consequently, evidence regarding effects of SGLT2i therapy in this cohort remains limited. Objective: To evaluate the association of SGLT2i initiation with mortality, kidney outcomes and cardiovascular outcomes among patients over 80 years of age and CKD. Design, Setting, Participants: This retrospective cohort study used data from TriNetX Research Network, a multicenter electronic health record database. To ensure comparable standard of care and SGLT2i eligibility, the period for the occurrence of the index event was restricted to January 1, 2021, until January 1, 2025. Propensity score matching was performed to balance comorbidities, laboratory parameters, concomitant medications, and frailty-associated factors between groups. Exposures: Initiation of SGLT2i therapy vs. non-use Main Outcomes and Measures: Outcome analysis focused on all-cause mortality, major adverse kidney events (MAKE) and major adverse cardiovascular events (MACE). Cox proportional hazards models were used to estimate hazard ratios with 95% confidence intervals; following propensity score matching, results were considered as adjusted hazard ratios (aHR). Results: After propensity score matching, 5,038 patients were included in each group. During two years of follow-up, SGLT2i initiation was associated with lower all-cause mortality (aHR 0.818; 95% CI 0.746 - 0.896, p<0.0001) and fewer MAKE events (aHR 0.779; 95% CI 0.0.715 - 0.850, p<0.0001). No significant difference in MACE was observed (aHR 1.007; 95%CI 0.938 - 1.082, p=0.84). Results were generally consistent across subgroups. Risk of acute kidney injury was higher in the SGLT2i group, while incident dialysis and end-stage renal disease were significantly reduced. Acute myocardial infarction and acute heart failure were increased in the SGLT2i group. Conclusion and Relevance: Regarding survival and kidney endpoints, even the oldest CKD patients seem to benefit from SGLT2i treatment, which was associated with reduced mortality as well as improved long-term renal outcomes. MACE showed no significant differences, while specific cardiac events were increased, reflecting possible safety concerns requiring further investigation in this specific age group.

Introduction The hemoglobin, albumin, lymphocytes and platelets (HALP) score, a novel nutritional and inflammatory biomarker, has been used in various chronic disease studies. However, the relationship between the HALP score and chronic kidney disease (CKD) remains poorly elucidated. This study aimed to explore the possible association between the HALP score and CKD. Methods Our analysis encompassed 25,160 adult participants drawn from NHANES cycles spanning 2009 through 2018. Weighted multivariable logistic regression and generalized additive models (GAMs) were employed to evaluate the independent associations between the HALP score and CKD, albuminuria, and low-estimated glomerular filtration rate (eGFR). Threshold effects were examined using two-piecewise linear regression. Subgroup and sensitivity analyses were performed to assess robustness. Receiver operating characteristic (ROC) curve analyses were applied to compare the discriminative capacity of the HALP score with the prognostic nutritional index (PNI), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR). The clinical findings were further validated in a 5/6 nephrectomy rat model. Results After adjustment for multiple confounders, higher HALP scores were inversely associated with the risk of CKD (OR = 0.97, 95% CI: 0.94-0.99) and albuminuria (OR = 0.97, 95% CI: 0.93-0.99). However, after full adjustment for demographic characteristics, physical examination indices and laboratory parameters (Model 3), the correlation between the HALP score and low-eGFR was no longer statistically significant. Non-linear analyses revealed a threshold effect, with CKD risk declining as the HALP score increased up to an inflection point of 52.43 (OR = 0.97, 95% CI: 0.95-0.99), beyond which no further protective effect was observed. A similar threshold effect was identified for albuminuria. Subgroup and interaction analyses indicated no meaningful effect modification by age, sex, BMI, hypertension, or diabetes. Sensitivity analyses confirmed the robustness of the results. ROC analysis demonstrated that the HALP score showed superior discriminative ability for CKD and albuminuria compared with PNI, SII, LMR, and PLR. In the animal experiment, CKD model rats exhibited significantly lower HALP scores than controls. Inverse correlations were observed between the HALP score and serum creatinine (Scr), blood urea nitrogen (BUN), and urinary albumin-to-creatinine ratio (UACR), with UACR showing the strongest correlation, which was consistent with the clinical findings. Conclusion Lower HALP scores are independently associated with increased prevalence of CKD and albuminuria. As an affordable and readily measurable biomarker, the HALP score may facilitate CKD risk assessment.

Rationale & Objective: People who live in rural areas with advanced chronic kidney disease (CKD) face well-documented structural barriers to receiving care, yet little is known about how they experience their illness or perceive interactions with their healthcare teams. We aimed to characterize the lived experiences and care perceptions of adults living in rural areas with advanced, pre-dialysis CKD. Study Design: We conducted semi-structured qualitative interviews with patients and care partners. Setting & Participants: We recruited patients with advanced CKD (stages 4-5, not on dialysis) and their care partners from a single hospital-based nephrology clinic in northern New England serving a predominantly rural population. Analytical Approach: We analyzed interview transcripts using participatory Practical Thematic Analysis (PTA), an inductive, stakeholder-engaged approach to qualitative analysis. Results: We interviewed 12 patients and 4 care partners. Four themes were identified: (1) logistical challenges of rural CKD care were pervasive but frequently normalized as an expected feature of rural life; (2) disease progression and future treatments were sources of uncertainty and concern, with expectations about dialysis often shaped by peer accounts rather than clinical discussion; (3) clinical conversations centered on laboratory results and medications, leaving emotional concerns and psychologic challenges unaddressed; and (4) physical symptoms and lifestyle changes were common but frequently attributed to comorbid conditions rather than to CKD. Limitations: Recruitment from a single clinic with a small, racially homogeneous sample limits transferability. While in-person recruitment may have excluded patients with greater transportation barriers, those who attended represent a population navigating substantial access challenges to receive care. Conclusions: Adults living in rural areas with advanced CKD experience logistical, emotional, and informational challenges broadly consistent with those reported in non-rural CKD populations. Patients normalized geographic barriers and did not consistently identify rurality as a source of disadvantage, even as structural barriers persisted. These findings support the development of structured communication approaches in nephrology care that invite discussion of disease trajectory, daily life impacts, and emotional concerns.

Objective: To determine the absolute risk of starting dialysis versus mortality among adults with chronic kidney disease (CKD) treated at EsSalud from 2013 to 2022, utilizing data from the Renal Health Surveillance system (VISARE). Methods: This retrospective cohort study analyzed clinical records from the VISARE system (EsSalud). We estimated rates of dialysis initiation and death using Fine & Gray competitive risk models. Additionally, we calculated Restricted Mean Survival Time (RMST), adjusting for age, sex, clinical stage, and geographic region. Results: Among 142,770 adults with confirmed CKD and available glomerular filtration rate data, only 15.2% had albumin-to-creatinine ratio measurements, allowing KDIGO staging of 40,404 patients (28.3%). Mortality without having previously started dialysis exceeded the probability of starting renal replacement therapy (RRT) from G1, becoming more marked in G3 of chronic kidney disease (CKD); the possibility of dialysis is only greater, as expected, in G5. This outcome was most prevalent in regions with limited healthcare coverage. The combination of diabetes, hypertension, and age over 55 (the triad) was associated with reduced restricted mean survival time at both 5- and 10-year horizons across all enrollment cohorts. While Lima saw the highest rates of renal replacement therapy initiation, the Andean and Amazonian regions reported the lowest indicators. Conclusions Death without prior dialysis was the dominant outcome from G1 to G3 in this Peruvian cohort with national insurance, with direct implications for prognostic counseling, recalibration of renal failure risk equations, and equitable expansion of nephrology services in underserved regions. Keywords: Renal Insufficiency, Chronic; Competitive Risk; Diabetes Mellitus; Hypertension; Mortality; Mass Screening.

Introduction: Autosomal-dominant tubulointerstitial kidney disease (ADTKD) is characterized by chronic kidney disease (CKD) with an average age of end-stage renal disease (ESRD) of approximately 45 years, bland urinary sediment, the absence of proteinuria and autosomal dominant inheritance. While several causative genes have been found, there remain families in whom no molecular diagnosis has been identified (ADTKD-NMD). Methods: We identified BICC1 truncating variants in several families with ADTKD-NMD in the Wake Forest Rare Inherited Kidney Disease Registry and then screened families in our database and other referred families for BICC1 truncating variants. We performed segregation analysis and characterized affected individuals for clinical and histopathologic phenotypes. We analyzed oligomer formation of BICC1 mutants with wild-type BICC1-, ANKS3- and ANKS6 proteins through co-immunoprecipitation and Western blotting, and we tested for posttranscriptional regulation of the BICC1 target mRNA, Dand5, in a Luciferase reporter assay. Results: We found 6 heterozygous truncating mutations in BICC1 segregating with the ADTKD phenotype in 8 independent pedigrees worldwide. Affected individuals developed kidney failure in the 6th to 7th decade of life that was characterized pathologically by tubular atrophy and interstitial fibrosis. The truncated gene products localized to cytoplasmic bodies and demonstrated various degrees of self-association or binding to the known interaction partners, ANKS3 and ANKS6. While the wild-type BICC1 gene product acts as a posttranscriptional repressor of target mRNAs, all truncation variants exhibited increased expression of substrate mRNA. Conclusions: Truncating variants in BICC1 are a novel cause of ADTKD, segregating with the disease phenotype and upregulating BICC1 target gene expression through a dominant-negative- or a gain-of-function mode of action.

Background: Deceased-donor kidney transplantation is a component of the Brazilian transplant system and takes place within a deceased-donation environment that in-cludes donor identification, notification, family approach and authorization, organ allocation, and logistics. This study described temporal, macroregional, and federative unit-level variation in deceased-donor kidney transplantation in Brazil from 2014 to 2024, together with hospitalization-based indicators and contextual indicators of the deceased-donation environment. Methods: This nationwide descriptive time-series study used publicly available secondary data from the Hospital Information System of the Unified Health System (SIH/SUS), the Brazilian Transplant Registry (RBT/ABTO), and the Brazilian National Transplant System (SNT). Indicators includ-ed the number of transplants, transplant rates per million population, kidney transplant waiting list stock, mean length of hospital stay, in-hospital mortality, potential donor notifications, and family interview and refusal proportions. The three databases were analyzed separately and in parallel, without linkage. Results: The annual number of deceased-donor kidney transplants increased over the study period. The kidney trans-plant waiting list stock also increased. Mean length of hospital stay decreased, and in-hospital mortality decreased over time. Marked macroregional and federative unit-level heterogeneity was observed in transplant activity, hospitalization-based indica-tors, and contextual indicators of the deceased-donation environment. Conclusions: Deceased-donor kidney transplantation increased in Brazil between 2014 and 2024, although regional disparities persisted. These findings support monitoring strategies that incorporate contextual indicators alongside measures of transplant activity. Be-cause this was a descriptive study based on secondary data from distinct sources, the findings should not be interpreted as evidence of causal relationships.