High protein intake can increase glomerular filtration rate (GFR) in response to excretory overload, which may exacerbate the progression of kidney disease. However, the direct association between glomerular hemodynamic response at the single-nephron level and dietary protein intake has not been fully elucidated in humans. In the present study, we evaluated nutritional indices associated with single-nephron GFR (SNGFR) calculated based on corrected creatinine clearance (SNGFR_Cr). We retrospectively identified 43 living kidney donors who underwent enhanced computed tomography and kidney biopsy at the time of donation at Jikei University Hospital in Tokyo from 2007 to 2018. Total nephron number was estimated with imaging-derived cortical volume and morphometry-derived glomerular density. SNGFR_Cr was calculated by dividing the corrected creatinine clearance by the number of non-sclerosed glomeruli (Nglom_NSG). The mean (± standard deviation) Nglom_NSG/kidney and SNGFR_Cr were 685,000 ± 242,000 and 61.0 ± 23.9 nL/min, respectively. SNGFR_Cr was directly associated with estimated protein intake/ideal body weight (p = 0.005) but not with body mass index, mean arterial pressure, albumin, or sodium intake. These findings indicate that greater protein intake may increase SNGFR and lead to glomerular hyperfiltration.

Recent studies have revealed the pivotal role of complement activation in the pathogenesis of antineutrophil cytoplasmic antibody–associated glomerulonephritis (ANCA-GN). This study investigated the clinicopathologic and prognostic significance of glomerular C3 deposition in the renal histopathology of patients with ANCA-GN. We retrospectively identified 142 patients with ANCA-GN from 6 hospitals in Japan (2004–2020). C3 deposition was defined as C3 staining ≥1+ on a scale of 0 to 2+ using direct immunofluorescence (IF). The primary composite end points included a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), and death. We compared clinicopathologic features and long-term outcomes between patients with and without C3 deposition. C3 deposition was observed in 56 of 142 kidney biopsy samples (39.4%). Patients with C3 deposition had a lower serum C3 level (P = 0.002). During a median follow-up of 2.9 (interquartile range: 0.2–5.7) years, 69 events occurred and the cumulative event-free survival rate at 5 years was significantly lower in the C3-positive group than in the C3-negative group (log-rank: P = 0.002). In multivariable analysis, C3 deposition was significantly associated with the composite end points after adjusting for age, sex, baseline eGFR, serum C3 level, treatment, and the percentage of normal glomerulus, cellular crescents, global sclerosis, and interstitial damage (adjusted hazard ratio [HR] = 2.02, 95% confidence interval: 1.20–3.40, P = 0.008). This study revealed that ANCA-GN patients with glomerular C3 deposition on IF had worse renal and overall survival rates.

Glomerular hypertension is a critical factor in kidney disease progression. Traditionally, nephron number (Nglom) was considered a determinant of glomerular hemodynamics, but emerging evidence suggests a more substantial impact of renal structural factors. This cross‐sectional study aimed to evaluate the relationship between renal histopathological parameters and intraglomerular hydrostatic pressure (Pglo) in healthy donors. Retrospective analyses were conducted on 60 healthy living donors who donated a kidney between January 1, 2007, and September 30, 2022. The non‐sclerotic glomerular number (Nglom_NSG), glomerular volume, cortical volume, and other histopathological parameters were evaluated. Pglo was estimated using Gomez's equation. Pglo was positively associated with cortical volume (standardized regression coefficient [β] = 0.34, p = 0.04) but not with Nglom_NSG (β = 0.12, p = 0.44). Cortical volume was inversely associated with afferent arteriolar resistance (β = −0.33, p < 0.01). These findings suggest that an increase in cortical volume, independent of nephron number, may contribute to an increase in Pglo through a reduction in afferent arteriolar resistance. These results refine current models of glomerular hemodynamics, highlighting the importance of structural renal evaluation, including cortical volume, in assessing early chronic kidney disease risk.