Background and objectives: A low total nephron number, which is associated with low birth weight (LBW), may indicate increased susceptibility to early-onset renal diseases in children. However, few studies have assessed renal biopsy findings in LBW children. We examined the relationship between LBW and glomerular density (GD) and/or glomerular volume (GV) in renal biopsy samples as a surrogate for total nephron number. Design, setting, participants, & measurements: Renal biopsy findings of children of LBW were compared with those of age-matched control subjects of normal birth weight (NBW) who were histopathologically diagnosed with FSGS or minimal change nephrotic syndrome (MCNS) from 1995 to 2011. The GD and GV were estimated on the basis of measurements obtained by computerized image analysis. Results: A total of 31 subjects (mean age 11 years; eight with low birth weight–FSGS [LBW-FSGS], 10 with normal birth weight–FSGS [NBW-FSGS], and 13 with normal birth weight–minimal change nephrotic syndrome [NBW-MCNS]) were analyzed. The mean birth weight of each group was 777 g (629–1000), 3110 g (2888–3358), and 3120 g (2748–3398), respectively (median [25th–75th percentile]). Age, body mass index, BP, and degrees of globally sclerotic glomeruli at biopsy were comparable between the groups. The GD was lower (LBW-FSGS, 1.4±0.6/mm²; NBW-FSGS, 3.3±1.2/mm²; and NBW-MCNS, 3.6±1.1/mm²; P<0.05) and the GV was greater (LBW-FSGS, 4.1 [3.1–5.1]×10⁶ µm³; NBW-FSGS, 1.6 [1.5–2.1]×10⁶ µm³; and NBW-MCNS, 1.3 [1.1–1.8]×10⁶ µm³ [median, (25th–75th percentile)]; P<0.05) in patients with LBW-FSGS than in the other patient groups. The GD showed close positive correlations with birth weight (r=0.48) and gestational age (r=0.54), independent of renal function and degree of global glomerular sclerosis. Conclusions: A low GD together with marked glomerular enlargement characterizes renal biopsy samples of children born with a LBW at an early stage of gestation.

Methods for estimating nephron number in a clinical setting may be useful for predicting renal outcomes. This study aimed to establish such a method using unenhanced computed tomography (CT) and biopsy-based stereology. Patients or living kidney donors simultaneously subjected to enhanced and unenhanced CT examinations were randomly assigned to development and validation groups. The enhanced CT-measured arterial phase and the venous phase images of kidneys were regarded as the true values for cortical volume and parenchymal volume, respectively. Linear multiple regression analysis was used to create models for estimating cortical volume using explanatory variables including unenhanced CT-measured parenchymal volume. Nephron number was determined as the product of cortical volume and the glomerular density in biopsies of donors. Five equations for estimating cortical volume were created and verified. In donors, estimated nephron number by unenhanced CT was consistent with that by enhanced CT, with minimal errors in all models (636–655 ± 210–219 vs. 648 ± 224 × 10³/kidney). Clinical characteristics combined with parenchymal volume did not improve the equation over parenchymal volume alone. These results support the feasibility of estimating nephron number by a combination of unenhanced CT and biopsy-based stereology, with a possible application for renal disease patients who are often not suitable for contrast media.

Obesity-related glomerulopathy (ORG) is a slowly progressive kidney disease occurring in association with obesity. It is characterized histopathologically by glomerulomegaly, likely caused by single-nephron hyperfiltration that has not been demonstrated in humans because of technical difficulty in measuring single-nephron glomerular filtration rate (SNGFR) in the clinical setting. Total glomerular number per kidney, with or without global glomerulosclerosis, was estimated by the combination of cortical volume assessment via unenhanced computed tomography and biopsy-based stereology. Mean glomerular volume was calculated from the measured area of glomerular tufts. Both SNGFR and single-nephron urinary protein excretion (SNUPE) were estimated by dividing values for estimated glomerular filtration rate and urinary protein excretion by the number of nonsclerotic glomeruli. Living kidney donors were used as healthy controls. A total of 48 ORG patients with average nonsclerotic glomerular numbers of 456,000 ± 235,000 per kidney were included. The values for SNGFR in ORG patients with chronic kidney disease (CKD) stages 1 and 2 were higher than for nonobese and obese controls (97 ± 43 vs. 59 ± 21 vs. 64 ± 21 nl/min, respectively, P = 0.001). Nonsclerotic glomerular number decreased with advancing stages of renal functional impairment. The presence of ORG with more advanced CKD stages was associated with lower SNGFR and marked elevation in SNUPE levels, with no difference in the mean glomerular volume between the stages. These results provide functional evidence for single-nephron hyperfiltration in patients with ORG, and identify compensatory failure to maintain effective SNGFR as a feature of advanced-stage ORG.

Background and hypothesis: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are anti-hyperglycaemic agents, with cardioprotective effects, however their renal protective effects remain unclear. We aimed to assess the effects of GLP1-RAs on renal outcomes in patients with or without diabetes. Methods: We performed a systematic review and meta-analysis with Medline, EMBASE and the Cochrane Register searched to December 2024. The primary outcome was the composite of kidney failure (defined as estimated glomerular filtration rate <15 mL/min/1.73 m2) or dialysis requirement, worsening of renal function and changes in proteinuria. Subgroup analysis was performed based on diabetic status, a (CKD) and individual GLP1-RA drugs. Relative risks (RR) with 95% confidence intervals (CI) for individual trials were pooled using random effects models. Results: We identified 19 trials including 90 882 patients. Mean age was 60.8 years and mean follow-up was 25.9 months. GLP1-RAs were associated with a 19% reduction in the risk of primary renal outcome (RR 0.81, 95% CI 0.73–0.89), a 12% reduction in renal functional decline (RR 0.88, 95% CI 0.81–0.95) and a 0.45 mL/min/1.73 m2 reduction in yearly loss [16 trials, mean difference (MD) 0.45, 95% CI 0.10–0.81]. GLP1-RAs also reduced microalbuminuria by 24% (RR 0.76, 95% CI 0.71–0.82), HbA1c (units: %) by 0.61 (MD –0.61, 95% CI –0.76 to –0.49) and body weight by 5 kg (MD –5.24, 95% CI –7.46 to –3.02). Although there were no significant differences in progression to kidney failure (RR 0.86, 95% CI 0.71–1.05), GLP1-RAs reduced the incidence of major adverse cardiovascular events by 15% (RR 0.85, 95% CI 0.81–0.90) and all-cause mortality by 14% (RR 0.86, 95% CI 0.82–0.91). No significant differences were seen in severe adverse events (RR 0.96, 95% CI 0.90–1.01). However, there were more gastroenterological side effects. Conclusions: GLP1-RAs demonstrated cardiovascular and renal benefits. Further high-quality randomized trials assessing their effects in patients without diabetes, with or without proteinuria and/or CKD are needed.

Alterations in glomerular filtration can considerably influence the dynamics and functions of the Bowman capsule. Despite the potentially important role in maintaining normal renal functions, few studies have focused on Bowman capsule volume in normal human kidneys. We analyzed specimens from biopsies performed 1 hour after kidney transplantation from living donors without apparent renal disease. The measurements of all cross-sectional areas of the Bowman capsules and glomerular capillaries were used to estimate the mean Bowman capsule volume (BV) and glomerular capillary volume (GV) in each subject. The G/B ratio was defined as the ratio of GV to BV. The morphometric findings were examined in relation to the clinical findings in donors just before kidney transplantation. We analyzed 37 adults with a mean creatinine clearance of 111 ml/min. The mean BV and GV of these subjects were 6.10 ± 2.46 × 106 μm3 and 3.83 ± 1.52 × 106 μm3, respectively. Both the BV and GV varied up to 6-fold and were significantly higher in elderly, obese, or hypertensive subjects in comparison to nonelderly, nonobese, or normotensive subjects, whereas the renal function of each subgroup was similar. The G/B ratio (0.63 ± 0.05) was unaffected, and BV and GV were strongly correlated regardless of these clinical factors (r = 0.980 [95% confidence interval = 0.961-0.990], P < 0.001). In the normal adult kidney, there may be an optimal BV to GV ratio for maintaining effective filtration in a variety of clinical situations, including advanced age, obesity, and hypertension.