Glomerular Density in Renal Biopsy Specimens Predicts the Long-Term Prognosis of IgA Nephropathy

Abstract

Background and objectives: An early histopathologic predictor of the renal prognosis, before the occurrence of advanced glomerular sclerosis/interstitial fibrosis and/or apparent renal dysfunction, remains to be established in IgA nephropathy (IgAN). This study aimed to determine whether the glomerular density (GD; nonsclerotic glomerular number per renal cortical area) of biopsy specimens obtained at an early stage of IgAN could predict the long-term renal outcome.Design, setting, participants, & measurements: The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed for 98 patients who had IgAN with an estimated GFR of >60 ml/min per 1.73 m 2 at biopsy (87 ml/min per 1.73 m 2 on average). Results: The individual value of GD in biopsy ranged from 1.2 to 8.1/mm 2 (i.e., approximately a seven-fold variation), and the GD showed a close inverse correlation with mean glomerular volume. Among the various clinicopathologic factors involved, both a cellular/fibrocellular crescent and the GD were found to be significant predictors of progression in multivariate analyses. A low GD in the biopsy specimens was frequently associated with a steeper slope of the renal function and a synergistically enhanced risk for progression with the presence of cellular/fibrocellular crescent. The renal function, proteinuria, degrees of glomerulosclerosis, and interstitial fibrosis at biopsy were not independent predictors of the prognosis in these patients.Conclusions: A strong predictive relationship of low GD with progression observed in this study suggests that GD may serve as an early histopathologic marker of long-term renal prognosis in IgAN.

Glomerular Diseases

“…A recently published paper showed that immunostaining for URG11, a protein involved in hypoxia-induced renal tubular epithelial-mesenchymal transition and fibrosis, was inversely correlated with GFR and independently predicted prognosis in IgAN (26). In another study, the measurement of glomerular density (the number of nonsclerotic glomeruli per cortical area) in biopsy specimens from Japanese patients with IgAN and normal kidney function robustly predicted halving of GFR or ESRD at 10 years (27). Similarly, inclusion of a "C" component (for crescentic disease) into a classification scheme has been advocated (26), although Traditional Risk Factors A variety of clinical and demographic risk factors predict renal outcomes, either independently or in multivariable analyses.…”

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

“…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).…”

Low Glomerular Density with Glomerulomegaly in Obesity-Related Glomerulopathy

“…We recently demonstrated that the individual value of glomerular density (GD; nonsclerotic glomerular number per renal cortical area of biopsy specimen) varies approximately seven-fold in patients with IgA nephropathy (IgAN) who maintain renal function (17). Notably, GD is inversely correlated with glomerular volume (GV), and low GD is a plausible independent predictor of progression in those patients.…”