Background and hypothesis:Equations estimating glomerular filtration rate (GFR) based on creatinine and/or cystatin C incorporate demographic variables such as age and sex. However, clinical determinants may lead to substantial bias in GFR estimation. We aimed to identify clinical factors associated with biased GFR estimation with the Modification of Diet in Renal Disease, Chronic Kidney Disease-Epidemiology Collaboration, and European Kidney Function Consortium equations. Methods:In this retrospective cross-sectional study, we included patients referred for GFR measurement from March 2008 to February 2024 in the Physiology unit of Bichat Hospital, Paris, France. GFR was measured as the urinary clearance of a radio-isotopic tracer and the error of estimated GFR (eGFR), was expressed as log(eGFR/measured GFR) and analyzed with linear regression models. Results:Among 3838 patients (mean age 51 ± 15 years, mean measured GFR 59 ± 26 ml/min/1.73 m²), several clinical variables were associated with significant estimation error in the multivariable analysis. For all creatinine-based equations, underestimation occurred with HIV infection, high BMI, loop diuretics, and cotrimoxazole use, while overestimation occurred with younger age, female sex, lower BMI, history of kidney transplantation, and cirrhosis. For all cystatin C-based equations, underestimation was associated with older age, HIV infection, corticosteroid use, and history of kidney transplantation; overestimation was associated with younger age, female sex, and sub-Saharan African origin. Equations using both biomarkers performed better in conditions affecting each biomarker in opposite directions. By cumulating several conditions, bias can vary from -50% to more than +50% leading to a completely erroneous GFR estimation. Conclusion:Common clinical features are independently associated with biased GFR estimation that can be of high clinical relevance, especially when cumulated. Our results guide GFR evaluation by giving a qualitative and most importantly quantitative estimation of the expected bias depending on individual patient profile and comorbidities.
Background and aims:Acute kidney injury (AKI) is increasingly recognized as a long-term risk factor for chronic kidney disease and cardiovascular disease (CVD). However, it remains uncertain which patients with AKI are at greatest CVD risk. We performed a systematic review and meta-analysis to quantify CVD risks post-AKI and to determine whether these risks differ by AKI severity, duration, and clinical setting. Methods:PubMed and Embase were systematically searched for studies comparing individuals with and without AKI and reporting major adverse cardiovascular events (MACE) or individual outcomes such as myocardial infarction (MI), stroke, heart failure (HF), or cardiovascular mortality. Follow-up was at least 1 year. Relative risks (RRs) were pooled in meta-analyses using random-effect models. Subgroup and metaregression analyses were used to explore heterogeneity across patient and AKI characteristics, and clinical settings. Results:We included 54 studies comprising 1261 090 individuals, of whom 290 648 experienced AKI. Meta-analyses showed that AKI was associated with an RR of 1.97 [95% confidence interval (CI) 1.67-2.27] for MACE (13.9% overall incidence), 1.64 [95% CI 1.38-1.89] for MI (3.5% overall incidence), 1.36 [95% CI 1.13-1.59] for stroke (1.7% overall incidence), 1.92 [95% CI 1.67-2.16] for HF (3.5% overall incidence), and 1.86 [95% CI 1.59-2.13] for cardiovascular mortality (9.4% overall incidence), compared to patients without AKI. Elevated risks were observed across all AKI stages and durations and in patients across all studied clinical settings, including noncardiac care. The highest RRs were shown for more severe AKI stages and longer AKI durations. Older age and lower baseline estimated glomerular filtration rate were associated with even higher risk of MACE compared to patients without AKI. Conclusions:AKI is followed by an increase in CVD risk, even after AKI with low severity. These findings highlight AKI as a clinically relevant CVD risk marker and support the need for targeted post-AKI care management to prevent future cardiovascular events.
Background:Fibrillary glomerulonephritis (FGN) is a very rare glomerular disease characterized by non-branching fibril deposition and DNAJB9 positivity. We aimed to analyze our cohort to better elucidate clinicopathologic features and outcomes of patients with FGN. Methods:Adult patients diagnosed with FGN between 2007 and 2025 and showing DNAJB9 positivity were included. Primary composite outcome was defined as doubling of serum creatinine from baseline, undergoing dialysis or transplantation, development of stage 5 chronic kidney disease or death. Results:Fifty native kidney biopsies of 44 patients were examined; 17 belonged to males (34%). Most common patterns of injury were mesangial (24, 48%) and membranoproliferative (16, 32%). Mean fibril diameter was 13.7 ± 2.5 nm. Eight biopsies (16%) showed atypical variants such as congophilia, light-chain restriction on frozen immunoflorescence and immunoglobulin G (IgG) negativity. Out of 44 patients, 25 (56.8%) had adequate follow-up data; the mean age was 48.4 ± 12.7 years. Over a median of 27 (7.5-89.5) months, 13 patients (52%) reached primary composite outcome, 10 (40%) underwent kidney replacement therapies and 3 (12%) died. Multivariate logistic regression models showed hemoglobin predicted the primary outcome whereas histopathological features or immunosuppressive use did not. Baseline serum C3 was associated with primary outcome (area under the curve 0.759, 0.525-0.916) with 134 mg/dL as cut-off value. The kidney survival rate was 30.8% in patients with serum C3 ≤134 mg/dL and 87.5% in serum C3 >134 mg/dL. However, multivariate regression models failed to show a clear association between serum C3 levels and primary outcome. Conclusions:Atypical histopathological features are not uncommon in FGN, complicating the differential diagnosis. Prognosis is still quite dismal despite immunosuppressive use. Lower baseline hemoglobin might indicate poorer outcomes.
Background:Up to 8% of renal tumors have a monogenic cause, yet hereditary renal cell carcinoma (hRCC) syndromes such as von Hippel-Lindau (VHL), Tuberous Sclerosis Complex (TSC), Birt-Hogg-Dubé (BHD), and Hereditary Leiomyomatosis and Renal Cell Cancer remain underdiagnosed. Early diagnosis is critical for patient management, genetic counseling, and family screening. We developed and prospectively validated a structured risk assessment tool (hRCC score) for identifying patients at risk of hereditary renal tumors. Methods:A prospective single-center study was conducted at the University Hospital Cologne (2020-2022) including 200 patients with histologically confirmed renal tumors. The hRCC score incorporated age at diagnosis, multifocal/bilateral disease, histology, extrarenal manifestations, and family history. Patients with a score ≥1.5 were referred for genetic testing using a multiplex MLPA (Multiplex Ligand-dependent Probe Amplification)-based panel including TSC, MET, VHL, FH, SDH-A-D, and FLCN. Results:Of 195 eligible patients, 34.4% (n = 67) had a high-risk hRCC score (≥1.5). Overall, 71 (36.4%) underwent genetic testing; a pathogenic or likely pathogenic variant was detected in 50.7% of tested patients, corresponding to 18.5% of the total cohort. The most common diagnoses were TSC (58.3%), VHL (16.7%), and BHD (11.1%). Confirmed hereditary cases had significantly higher mean hRCC scores (4.67 vs 0.48, P < .0001). Extrarenal manifestations and bilateral or multifocal disease were the strongest predictors. The cutoff of 1.5 yielded 97.2% sensitivity and 79.8% specificity. Conclusions:The hRCC score is an effective clinical screening tool for detecting patients at risk for hereditary renal tumors, demonstrating high diagnostic yield and supporting targeted referral for genetic evaluation.
Background:Anemia is a common complication in chronic kidney disease (CKD), especially in hemodialysis patients, causing fatigue and reduced quality of life. Standard treatments involve iron and erythropoietin (EPO). Ascorbic acid (vitamin C) supports iron metabolism by converting ferric to ferrous iron and enhancing absorption and mobilization. This systematic review and meta-analysis evaluated the effectiveness of ascorbic acid in improving hematologic and iron parameters in adult anemic patients undergoing maintenance hemodialysis. Methods:Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was performed in PubMed, EMBASE, Cochrane, Scopus, Web of Science, CINAHL and Google Scholar through May 2025. Only randomized controlled trials and crossover studies assessing ascorbic acid in adult anemic hemodialysis patients were included. The protocol was registered in the International Prospective Register of Systematic Review (PROSPERO) (CRD420251056337). Primary outcomes were hemoglobin (Hb), ferritin, serum iron, transferrin saturation (TSAT) and total iron-binding capacity (TIBC). Meta-analyses used DerSimonian-Laird random-effects models. Results:Of 479 screened articles, 14 studies were included. Ascorbic acid supplementation was associated with a modest but significant increase in Hb [mean difference (MD) 0.94 g/dL; 95% confidence interval (CI) 0.57 to 1.31; P < .01; I² = 87.2%] and TSAT (MD 6.86%; 95% CI 1.93 to 11.78; P < .01; I² = 96.7%). Ferritin levels showed a slight but significant reduction (MD -65.00 ng/mL; 95% CI -117.20 to -12.80; P = .01; I² = 57.2%), along with a decrease in TIBC (MD -22.54 µg/dL; 95% CI -42.37 to -2.72; P = .03; I² = 76.1%). EPO requirements expressed as units/kg/week were significantly reduced (MD -21.29; 95% CI -27.73 to -14.84; P < .01; I² = 0.0%). No significant changes were observed in serum iron levels or EPO dosage expressed as IU/week. Conclusion:Ascorbic acid supplementation may confer modest hematologic benefits in hemodialysis patients with improvements in Hb, TSAT and iron utilization, and a small reduction in weight-adjusted erythropoiesis-stimulating agent dose. However, the certainty of evidence is low, and long-term safety and patient-centered outcomes remain unestablished.
