Changes in the glomerular density and size in serial renal biopsies during the progression of IgA nephropathy

Abstract

Background. Although there have been many reports on clinicopathological studies of IgAN, information is limited regarding the long-term evolution of a renal histology by analysing samples obtained not only during normal renal function but also after the establishment of an impaired renal function in individual patients. Methods. We analysed 18 pairs of serial biopsy specimens from 18 patients with IgA nephropathy (IgAN) in whom the first renal biopsies were performed while normal renal function was still present and the second biopsies were performed after impaired renal function was established. The glomerular density (GD, number of non-sclerotic glomeruli per renal cortical area) and mean glomerular area (MGA) were compared between the specimens. Results. The GD at the first biopsy of each patient showed a striking variation (1.3-5.2/mm 2 ). As a whole, the GD decreased (2.7 ± 1.2 versus 1.4 ± 0.7/mm 2 ) and the MGA increased (19.7 ± 4.2 × 10 3 versus 23.5 ± 4.5 × 10 3 mm 2 ) between the biopsies, respectively. The degrees of change in the GD and the MGA between the biopsies differed remarkably among the individuals. The patients with a high GD in the first biopsy progressed slowly, but showed a large decrease in the GD and a large increase in the MGA between the biopsies, respectively. The patients with a low GD, who already had enlarged glomeruli in the first biopsy, tended to progress rapidly. Conclusions. Our results suggest that both the nephron number and glomerular enlargement play a crucial role as compensatory mechanisms against renal functional deterioration in progressive IgAN. The GD during normal renal function may determine these compensatory changes and thereby make it possible to predict the renal prognosis in IgAN.

Nefropatia por IgA: análise histológica e correlação clínico-morfológica em pacientes do Estado de Minas Gerais

“…9,10 Além disso, estudos prévios já demonstravam que a atrofia tubular/ fibrose intersticial são preditores de pior prognóstico, refletindo em longo prazo em um rim com déficit de funcionamento por lesões crônicas. 22,[31][32][33] Nossa casuística também evidenciou maiores cifras de proteinúria de 24 h em pacientes M1 em relação a M0. Tais achados são ratificados nos estudos de Kang et al 27 e Halling et al 29 , na própria classificação de Oxford, 9,10 entretanto não foram encontrados na casuística Alamartine et al 28 e Shi et al 30 A hipercelularidade mesangial, segundo alguns estudos prévios, poderia se relacionar a pior prognóstico de função renal por evidenciar presença de lesão renal ativa, o que, quando identificado, necessitaria de um tratamento mais potente aos pacientes.…”

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

“…Interestingly, we found a close inverse correlation between these two histological variables. Our previous studies have shown that there is also a close inverse correlation between GD and GV in renal biopsies of patients with IgAN [12,13]. Studies on autopsy kidneys have shown a close inverse correlation between the total nephron number and GV among people who did not have any evidence of renal disease [19].…”

“…We recently reported that the individual value of glomerular density (GD; the number of nonsclerotic glomeruli per renal cortical area) in a biopsy at the time of normal renal function had a sevenfold variation in IgAN [12,13]. In addition, a low GD in the biopsy was associated with both enlarged glomeruli and a poor long-term renal prognosis in these patients.…”

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

“…We recently performed a study using pairs of serial biopsy specimens from 18 patients with progressive IgAN (8). In these patients, renal biopsies were performed both before and after the establishment of impaired renal function.…”