INTRODUCTION:Chronic kidney disease and end-stage renal disease are burdened by extremely high cardiovascular mortality. The Cardio-Ankle Vascular Index (CAVI) is a blood-pressure-independent marker of arterial stiffness, but a single measurement may not reflect the time-dependent nature of vascular remodelling in haemodialysis. We hypothesized that a time-weighted CAVI (twCAVI), integrating arterial stiffness with dialysis vintage, would better predict all-cause mortality. METHODS:In this observational cohort study, 94 maintenance haemodialysis patients were followed from February 2016 to December 2024. Arterial stiffness was assessed by CAVI, and twCAVI was defined as mean CAVI × dialysis vintage (months). After preprocessing and feature selection, the association between arterial stiffness and overall survival over approximately 8 years was examined using a Cox proportional hazards model. Internal validity was assessed by 1,000 bootstrap iterations and expressed via Harrell's concordance index (C-index) and time-dependent area under the curve (AUC). RESULTS:The final model retained six predictors: sex, vascular access, creatinine, alkaline phosphatase (ALP), ferritin, and twCAVI. In the multivariate model, male sex (HR 2.56, p = 0.0018), ALP (HR 1.01, p = 0.0082), ferritin (HR 1.002, p = 0.0067) and twCAVI (HR 1.0021, p = 0.0464) were independently associated with higher mortality, while higher creatinine was protective (HR 0.87, p = 0.0445). Central venous catheter use showed a borderline trend towards increased risk compared with arteriovenous fistula (HR 1.68, p = 0.0509). Bootstrap validation yielded a median C-index of 0.75 (95% confidence interval [CI] 0.68-0.83), with time-dependent AUCs generally ≥0.80 up to 102 months. Notably, exploratory survival analyses revealed an age-dependent inverse association between phosphorus levels and mortality, supporting the reverse epidemiology hypothesis in the elderly. CONCLUSION:twCAVI, capturing the cumulative vascular burden risk, is a predictor of mortality in haemodialysis patients and improves long-term risk discrimination. A proof-of-concept web-based calculator was developed to facilitate the educational exploration of this metric.
BACKGROUND:Sclerostin is involved in chronic kidney disease-mineral and bone disorder (CKD-MBD), but its relation to renal magnesium handling remains unclear. We investigated whether urinary and serum sclerostin were associated with fractional excretion of magnesium (FeMg) in proteinuric non-diabetic chronic kidney disease (CKD). METHODS:In this cross-sectional study, 70 adults with proteinuric non-diabetic CKD stage 1 to 5 at a tertiary medical center were enrolled. Urinary sclerostin normalized to urine creatinine (Uscl/Ucre) and serum sclerostin were measured. Their associations with ln-transformed FeMg [ln(FeMg)] were examined using multivariable linear regression with sequential adjustment for age, sex, estimated glomerular filtration rate (eGFR), proteinuria, electrolytes, serum sclerostin, and CKD-MBD markers including plasma intact parathyroid hormone, serum fibroblast growth factor 23, and soluble alpha-Klotho. RESULTS:Urinary sclerostin (Uscl/Ucre) increased across CKD stages, and higher Uscl/Ucre tertiles were associated with higher FeMg. Uscl/Ucre was positively associated with ln(FeMg) in crude analysis (β 0.652; p < 0.001) and this association still existed after adjustment for age, sex, eGFR, serum magnesium, and CKD-MBD markers (β 0.366; p < 0.001). Compared with the lowest tertile, the highest urinary sclerostin tertile was significantly associated with higher ln(FeMg) (β 0.662; p = 0.007). In contrast, serum sclerostin was not associated with ln(FeMg) after adjustment. CONCLUSIONS:In proteinuric non-diabetic chronic kidney disease, urinary but not serum sclerostin is independently associated with fractional excretion of magnesium. Urinary sclerostin may reflect intrarenal processes relevant to tubular magnesium handling.
INTRODUCTION:Dialysis patients with established atherosclerotic cardiovascular disease (ASCVD) face exceptionally high risks of mortality and recurrent cardiovascular events, yet remain substantially underrepresented in major statin trials. We aimed to synthesize evidence from studies restricted to this population to evaluate the association between statin therapy and clinical outcomes. METHODS:We systematically searched Embase, MEDLINE, Web of Science, Scopus, and CENTRAL databases from inception through February 20, 2025, for randomized controlled trials and observational studies evaluating statin therapy in adults receiving maintenance dialysis with documented ASCVD. Hazard ratios were pooled using random-effects models. Risk of bias was assessed using the ROBINS-I tool. The primary outcome was all-cause mortality. RESULTS:Fourteen cohort studies comprising 242,118 patients were included in the meta-analysis. Statin therapy was associated with a significant reduction in all-cause mortality (HR 0.85, 95% CI 0.74-0.98; P = 0.027; I² = 53.1%). Associations with cardiac mortality (HR 0.88, 95% CI 0.66-1.16; I² = 79.6%) and major adverse cardiovascular events (HR 0.85, 95% CI 0.59-1.21; I² = 61.8%) were not statistically significant. Leave-one-out sensitivity analyses supported the robustness of the primary finding. Among dialysis patients with established ASCVD, the proportion of statin-treated patients was 35% and increased over time. CONCLUSIONS:Among dialysis patients with established ASCVD, statin therapy is associated with lower all-cause mortality; however, its effect on cardiovascular outcomes remains uncertain. Substantial heterogeneity and a predominance of observational evidence limit causal inference. Well-designed prospective trials in this high-risk population are warranted.
Older adults (OA) exhibit the highest incidence of acute kidney injury (AKI), with outcomes influenced by comorbidities, frailty, and malnutrition. Nutritional status, a potentially modifiable factor, has not been extensively evaluated as a mortality predictor in hospitalized OA with AKI. Our purpose was to report on the mortality risk provided by the nutritional status, comorbidities, and biochemical parameters in OA with AKI. Methods: In this prospective cohort study (July 2024–July 2025) conducted at a tertiary geriatric unit, hospitalized OA with AKI, diagnosed according to KDIGO criteria, underwent a comprehensive nutritional assessment within 48 hours of admission. The Geriatric Nutritional Risk Index (GNRI), Mini Nutritional Assessment, anthropometric measurements, and biochemical markers were recorded. The primary outcome was in-hospital all-cause mortality; secondary outcomes included the analysis of all-cause mortality according to nutritional and clinical factors, such as dysphagia, hyporexia, and GNRI quartiles (Q1–Q4). Logistic regression models were used to identify independent predictors of mortality, and all models were adjusted for AKI severity. Results: Of 742 admissions, 187 patients met the inclusion criteria. The median age was 76.8 years, and 50% were male. GNRI quartile analysis demonstrated a progressive deterioration in anthropometric and biochemical markers from Q4 to Q1. Mortality was higher in the high-risk GNRI group (42.2% vs 30.1%); however, this difference did not reach statistical significance (p = 0.098). In adjusted analyses, dysphagia (adjusted odds ratio [aOR] 6.11; 95% CI 1.82–20.51; p = 0.003), hyporexia (aOR 2.24; 95% CI 1.02–4.92; p = 0.044), and lower GNRI (aOR 1.07 per unit decrease; 95% CI 1.02–1.13; p = 0.004) were independently associated with increased mortality. In contrast, a higher mid-upper arm circumference was independently associated with a protective effect (aOR 0.78; 95% CI 0.67–0.91; p = 0.001). Conclusions: In OA hospitalized with AKI, poor nutritional status, particularly dysphagia, hyporexia, and lower GNRI, was independently associated with increased in-hospital mortality, whereas preserved muscle mass was protective. Early, simple, bedside nutritional assessments may help guide targeted interventions to improve outcomes in this high-risk population.
Introduction: Diabetes insipidus (DI) is a rare disorder characterized by polyuria, polydipsia, and dilute urine. Nephrogenic diabetes insipidus (NDI) secondary to distal renal tubular acidosis (dRTA) in primary Sjögren's syndrome (pSS) is exceedingly rare in children. Case Presentation: A 16-year-old girl presented with hypokalemic paralysis (potassium 1.89 mmol/L), polyuria (>5 L/day),and growth retardation (height 141 cm, <3rd percentile). Laboratory studies revealed dRTA with secondary NDI. Autoimmune workup confirmed pSS. A systematic literature review identified only five similar pediatric cases. Initial management with hydrochlorothiazide exacerbated hypokalemia and precipitated hypochloremic metabolic alkalosis. Switching to amiloride combined with glucocorticoids and potassium supplementation normalized electrolytes, reduced urine output to 1.5 L/day, and resulted in catch-up growth at the 6-month follow-up. Conclusion: This case highlights the pathophysiologic cascade of pSS-related dRTA causing secondary NDI and underscores the importance of early recognition and tailored diuretic selection in adolescents.
Introduction:Although some international guidelines suggest treatment of protein-energy wasting (PEW) in patients receiving dialysis with oral or parenteral nutritional supplementation, there is a current lack of practical guidance on their implementation. This document, developed by an international expert group, aims to bridge this gap by providing evidence- and consensus-based statements for clinicians on the practical implementation of clinical nutrition in patients on dialysis. Methods:A globally diverse group consisting of 8 nephrologists and 3 dietitians developed this guidance document on oral nutritional supplementation (ONS) and intradialytic parenteral nutrition (PN; IDPN) in patients receiving dialysis. The group started with 46 statements, which were drawn up before 2 parallel on-site meetings in Kuala Lumpur and Frankfurt/Main in November 2024. These statements were discussed there, and after another round of anonymous review, were put up for anonymous voting, reaching a final stage of consensus statements using the method outlined by the European Society for Clinical Nutrition and Metabolism for informed best clinical practice. Results:Altogether, the 20 consensus statements and 34 practice points provide concise guidance to implement and execute nutritional support in patients receiving maintenance dialysis across clinical settings and national health care systems. The rationales for each statement outline the current evidence, interpret it in light of expert experience, and incorporate information gained from the authors' clinical practice. Conclusion:Providing clinical nutrition to patients on dialysis requires a structured approach. Screening and regular nutritional assessment of all patients are the basis of this approach. The oral nutritional support strategy needs to consider patient preferences and may require renal-specific formulas. For patients with PEW, IDPN is a reliable nutritional support option that may be used in selected patients to supplement the oral diet or used in combination with ONS to help meet their nutritional requirements.
Background:Peritonitis is a critical complication in patients undergoing peritoneal dialysis (PD). The association between gastric acid suppressants (GAS), specifically proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), and peritonitis risk remains controversial, with conflicting evidence regarding their safety. Methods:We conducted a target trial emulation using Hong Kong electronic health records (2006-2019), applying a 168-month sequential design to minimize immortal time bias. Using inverse probability of treatment weighting and discrete hazards regression, we estimated hazard ratios (HRs) for peritonitis, all-cause mortality, and peritonitis-related mortality among PPI initiators, H2RA initiators, and non-initiators (95% confidence interval [CI] calculated using 500-resample bootstrapping). We also performed a PPI versus H2RA head-to-head comparison and predictive approaches to treatment effect heterogeneity analysis. Results:Among 11,693 individuals (240,431 person-trials), PPI initiation (vs. non-initiation) was associated with higher risks of peritonitis (HR 1.53, 95% CI 1.31-1.80), all-cause mortality (HR 1.55, 95% CI 1.43-1.67), and peritonitis-related mortality (HR 1.39, 95% CI 1.05-1.58). H2RA use was also associated with increased risk of peritonitis (HR 1.21, 95% CI 1.08-1.35) and all-cause mortality risks (HR 1.13, 95% CI 1.06-1.20). Head-to-head analysis showed no significant increase in peritonitis risk with PPIs versus H2RAs, but revealed an association between PPI use and higher all-cause mortality (HR 1.38, 95% CI 1.23-1.54) and peritonitis-related mortality (HR 1.85, 95% CI 1.07-3.19). Predictive approaches to treatment effect heterogeneity analysis indicated that risk elevations were more pronounced in individuals with higher baseline risk. Conclusions:In patients on PD, GAS initiation is associated with increased peritonitis and mortality compared with non-initiation. Furthermore, PPIs were associated with higher mortality risks than H2RAs. These findings highlight the need for cautious use of acid-suppressive therapy.
Introduction:Recurrent focal segmental glomerulosclerosis (FSGS, rFSGS) is a severe complication after kidney transplantation, often resistant to standard therapies and requiring prolonged apheresis. Combined depletion of plasma cells (anti-CD38) and B cells (anti-CD20) has emerged as a potential strategy; however, multicenter real-world data integrating clinical, biological, and histological characterization remain limited. Methods:We retrospectively studied 17 kidney transplant recipients with rFSGS treated with daratumumab (anti-CD38) administered after and/or in combination with anti-CD20 therapy across 12 French centers. Patients were clinically and histologically characterized at treatment initiation. Clinical response, safety, and longitudinal antinephrin antibody trajectories were assessed. Results:Median time from recurrence to daratumumab initiation was 5 months. All patients had previously received B-cell-depleting therapy. After the first daratumumab course (1-8 injections), 7 patients (41%) achieved complete remission (CR) and 4 (24%) achieved partial remission (PR), allowing discontinuation of apheresis in all responders. Median response time was 24 days. During a median follow-up of 8 months, 3 responders relapsed but regained remission after retreatment. Median proteinuria decreased from 3.9 g/g to 1.4 g/g at 1 month (P = 0.029). Among 11 patients tested, 3 had positive antinephrin antibodies. Two patients showed marked posttreatment declines paralleling clinical response, whereas 1 did not. Treatment was well-tolerated. Conclusion:In this multicenter real-world cohort, combined plasma cell and B-cell depletion was associated with meaningful remission rates in refractory rFSGS and was accompanied by dynamic changes in antinephrin antibodies in selected cases. Prospective trials are warranted to define optimal patient selection and dosing, and to clarify its place in therapy.
Introduction:Older adults with chronic kidney disease (CKD) likely face higher dementia risk because of vascular injury and chronic inflammation, potentially intensified among racially minoritized groups and those in rural or deprived neighborhoods. We quantified this association and examined variation by race and ethnicity, urbanicity, and neighborhood deprivation. Methods:We identified 211,321 older adults with CKD stages 3 to 5 from the Medicare 5% sample (2010-2022) using International Classification of Diseases (ICD)-9 and/or ICD-10 codes. Zone Improvement Plan (ZIP)-code level urbanicity was defined using Rural-Urban Commuting Area Codes, and neighborhood deprivation was derived from the American Community Survey. We used cause-specific hazard models with time-varying CKD stage (reference = stage 3) to quantify the adjusted hazard ratio (aHR) of dementia and included interaction terms to test the differential effect of these associations by race and/or ethnicity, urbanicity, and neighborhood deprivation. Results:After adjustment, older adults with CKD stages 4 and 5 had a higher risk of dementia (stage 4 aHR: 1.28, 95% CI: 1.25-1.32; stage 5 aHR: 1.82, 95% CI: 1.76-1.88). These associations differed by race/ethnicity (stage 4 and 5: P interactions < 0.001) and neighborhood deprivation (stage 5: P interaction = 0.04). Among older Black (stage 4 aHR: 1.38, 95% CI: 1.28-1.48; stage 5 aHR: 2.01, 95% CI: 1.88-2.15) and Hispanic adults (stage 4 aHR: 1.33, 95% CI: 1.10-1.62; stage 5 aHR: 1.98, 95% CI: 1.67-2.34), stages 4 and 5 were associated with a higher risk of dementia. Among older adults in high-deprivation neighborhoods, stage 5 was associated with a higher risk of dementia (aHR: 1.89, 95% CI: 1.80-1.99). Conclusion:CKD stages 4 and 5 were associated with a higher dementia risk, particularly among older Black adults and those in high-deprivation neighborhoods. These findings may inform targeted interventions for early detection and management of cognitive decline in advanced CKD.
Introduction:Primary nonfunction (PNF) is a serious complication of renal allografts, occurring in a subset of patients with delayed graft function (DGF) who never obtain freedom from dialysis. Prior studies have examined donor and recipient variables implicated in DGF and PNF; however, data on the underlying kidney pathology are largely lacking. Methods:Data from the Scientific Registry of Transplant Recipients (SRTR) was merged with biopsy records, and patients with a history of DGF or PNF were identified. We compared all patients with PNF (n = 61) and DGF with a biopsy within 30 days posttransplantation (n = 714) to identify donor, recipient, and histologic variables associated with PNF. Student t tests and Fisher exact tests were used for evaluation of continuous and categorical variables, respectively. Binary logistic regression was performed for more stringent assessment of PNF predictors. Results:PNF was significantly associated with increased donor age (P = 0.002) and terminal creatinine > 1.5 mg/dl (P = 0.005). There was no impact of recipient age, sex, race, or disease comorbidities (hypertension, diabetes, or obesity). Kidney pathology of allograft biopsies showed an increase in diagnoses of cortical necrosis (P < 0.0001), arterionephrosclerosis (P = 0.0002), oxalate nephropathy (P = 0.03), pyelonephritis (P = 0.009), and antibody-mediated rejection (ABMR) (P = 0.0008) compared with patients with DGF who did not progress to PNF. Conclusion:In patients with DGF progressing to PNF compared with DGF with recovery, cortical necrosis, arterionephrosclerosis, oxalate nephropathy, and ABMR were more common. Identification of these entities on biopsy may identify patients at highest risk of graft failure.
Introduction:Microvascular inflammation (MVI) is a hallmark feature of antibody-mediated rejection (ABMR), but its prognostic significance when it occurs with T-cell-mediated rejection (TCMR) in the absence of other ABMR features remains unclear. Methods:We examined the association between pure TCMR phenotypes, defined by the presence or absence of MVI, and graft survival using restricted mean survival time (RMST), and assessed interactions with rejection involving a "v" lesion. Results:Among 1614 recipients with first biopsy-proven pure TCMR (2010-2023), 85% had no MVI, 8% subthreshold MVI (Banff glomerulitis [g] + peritubular capillaritis [ptc] = 1), and 7% with MVI (g + ptc ≥ 2). Compared with TCMR without MVI, recipients with TCMR + MVI (hazard ratio [HR]; 95% confidence intervals [CI] 1.57 [1.06-2.34]) had a higher risk of all-cause graft loss, whereas subthreshold MVI was not associated with increased risk. The 5-year RMST was lowest in the MVI group (3.93 [3.53-4.26]), compared with the subthreshold group (4.39 [4.11- 4.60]) and the no MVI group (4.32 [4.24-4.40]). Rejection with a "v" lesion modified this association. Recipients with TCMR + MVI and positive "v" lesion had a 2.77-fold higher risk of graft loss (2.77 [1.64-4.67]), whereas no excess risk was observed in those without vascular lesions. Conclusion:Pure TCMR with MVI, particularly in the setting of a "v" lesion, represents a high-risk phenotype associated with poorer graft survival, warranting mechanistic investigations and targeted therapeutic strategies.
