HISTOMORPHOMETRIC CORRELATES OF RENAL-FAILURE IN IGA NEPHROPATHY

It is generally accepted that the severity of renal insufficiency in p atients correlates with the severity of tubulointerstitial abnormaliti es, but not with the severity of glomerular abnormalities in kidney bi opsies. We recently challenged this view by demonstrating significant correlations of glomerular structural abnormalities with renal functio n in a histomorphometric study of biopsies from patients with various kidney diseases. We set out to confirm these findings in biopsies from patients with a single disease entity. IgA nephropathy was selected. An additional objective of the study was to determine the prognostic v alue of our histological predictors of renal function. Histomorphometr ic measurements were done in silver- and PAS-stained paraffin sections of biopsies from 83 patients with primary IgA nephropathy. The result s were correlated with creatinine clearance at the time of biopsy. The prognostic value of the histomorphometric parameters and of several c linical characteristics were determined in a Cox proportional hazard m odel. All glomerular histomorphometric indices correlated with the sev erity of renal insufficiency, but quantitative estimates of the glomer ular depositon of periodic acid-Schiff positive extracellular matrix ( PAS-index) seemed to be the most important glomerular structural-funct ional correlate (r = 0.53, p<0.001). However, the correlation of quant itative estimates of the severity of interstitial extracellular matrix accumulation with renal function (quantitative interstitial index) wa s superior (r = 0.76, p<0.001). Creatinine clearance at biopsy and ini tial proteinuria were the strongest clinical predictors of renal survi val. The severity of tubulointerstitial extracellular matrix accumulat ion was the strongest histological predictor of an adverse outcome. In conclusion, quantitative estimates of the severity of glomerular and tubulointerstitial extracellular matrix accumulation both correlate we ll with the severity of renal failure in biopsies from patients with I gA nephropathy. Creatinine clearance at biopsy, initial proteinuria an d the severity of tubulointerstitial extracellular matrix accumulation are the best predictors of renal survival. On a more general note, th e paradigm of the absence of correlation of glomerular pathology with renal function should be abandoned.