Glomerular Density-Associated Changes in Clinicopathological Features of Minimal Change Nephrotic Syndrome in Adults

Abstract

Background: Differences in nephron number and/or glomerular size between individuals, in relation to intrauterine growth retardation or low birth weight, have been suggested to affect the clinical course of minimal change nephrotic syndrome (MCNS) in children. However, no previous study has investigated the potential influences of these histological variables on the clinical course of adult patients with MCNS. Methods: The glomerular density (GD; the number of non-sclerotic glomeruli per renal cortical area) and the glomerular volume (GV) were evaluated using renal biopsy specimens from adult patients with a histological diagnosis of MCNS (n = 50). Relationships between these variables and clinicopathological features, including the initial response to corticosteroid therapy, were analyzed. Results: Both the GD (1.5–6.5/mm²) and the GV (1.2–4.4 × 10⁶ µm³) showed about 4-fold variations, and a close inverse correlation was observed between these two variables. Notably, the MCNS patients with a low GD showed a trend towards having similar clinicopathological characteristics as patients with a histological diagnosis of focal segmental glomerular sclerosis, as compared to the MCNS patients with a high GD. In addition, during the initial treatment with corticosteroids, the number of patients achieving complete remission was significantly lower in the MCNS patients with a low GD than that in the MCNS patients with a high GD. Conclusion: These results suggest that the GD in renal biopsies may be an important determinant of the glomerular size variability, and can therefore influence the clinical phenotype, such as the response to corticosteroid therapy, in adult patients with MCNS.

Nephron Hypertrophy and Glomerulosclerosis and Their Association with Kidney Function and Risk Factors among Living Kidney Donors

“…A study in patients with minimal change disease found profile tubular density (number of tubules per area of cortex) to be correlated with glomerular density and inversely correlated with glomerular volume (14). We showed the same finding in kidney donors using the inverse measure, mean profile tubular area (area of cortex per tubule).…”

“…In normal kidneys, the cortex consists only of nephrons and supporting vessels; increases in nephron size will disperse the glomeruli further apart, decreasing their density (11). Recent studies by Tsuboi et al found that larger glomerular volume, lower profile tubular density, and lower profile glomerular density were correlated and predictive of kidney failure and other outcomes in a variety of early glomerulopathies (12)(13)(14)(15). Conceptually, larger glomerular volume, lower profile tubular density (or larger mean profile tubular area), and lower glomerular density are all measures of larger nephron size (nephron hypertrophy).…”

Factors associated with a vicious cycle involving a low nephron number, hypertension and chronic kidney disease

“…63 Furthermore, Rule et al 64 indicated that the GD is associated with the kidney function and other metabolic characteristics, such as body mass index, hypertension and/or high-density lipoprotein cholesterol, based on the findings of renal biopsy samples in healthy adult kidney donors. 64 We also previously demonstrated that the individual value of the GD in renal tissue specimens obtained via percutaneous needle biopsy shows an approximately sevenfold variation in cases of IgA nephropathy (IgAN), 65,66 a fourfold variation in cases of membranous nephropathy (MN) 67 and a fourfold variation in cases of minimal change disease (MCD), 68 even in patients with a preserved renal function. In addition, a low GD on biopsy specimens is associated with a poor long-term renal prognosis and/or blunted response to corticosteroid therapy in these patients.…”

肾小球皮质密度对随访5年的IgA肾病不良预后的预测

“…Besides, GD can serve as a response index to corticosteroids therapy in adult patients with kidney disease. 19 In this way, the treatment of corticosteroids in IgAN with eGFR of <50 ml/min per VALIGA study 21 and STOP-IgAN study. 22 Further prospective studies taking GD into account are needed to evaluate the benefit of corticosteroids in patients with a eGFR of <50 ml/min per 1.73 m 2 .…”