SEQUENTIAL RENAL BIOPSIES IN INSULIN-DEPENDENT DIABETIC-PATIENTS - STRUCTURAL FACTORS ASSOCIATED WITH CLINICAL PROGRESSION

Quantitative structural studies in native kidneys of IDDM patients hav e almost all been cross sectional, and little is known regarding the d ynamics of progression of structural lesions in relation to clinical p rogression. It has been suggested that interstitial may be more import ant than glomerular changes in determining functional outcome. This st udy evaluated renal structure in sequential biopsies from IDDM patient s with established renal lesions to determine whether glomerular, arte riolar and interstitial changes progress together and in concordance w ith measures of renal function. Eleven long-term IDDM patients [age 29 +/- 10 years, duration 17 +/- 7 years (mean +/- SD)] had renal functi on studies and kidney biopsies performed at two occasions 5.6 +/- 1.6 years apart. HbA1 as well as creatinine clearance (C-Cr) did not chang e over this time; albumin excretion rate (AER) increased from 12 (6 to 280) to 19 (5 to 2462) [median (range)] mg/24 hr (P < 0.03). AER incr eased in the three patients with abnormal albuminuria at first observa tion, and two normoalbuminuric patients became microalbuminuric. Blood pressure (BP) did not change; however, the number of patients on anti hypertensive therapy increased from 1 to 5. All structural parameters were abnormal at first evaluation. Mesangial fractional volume [Vv(mes /glom)] and mean glomerular volume increased and the surface density o f the peripheral glomerular basement membrane (GBM) decreased, while G EM width did not change over the five years of the study. Also, arteri olar hyalinosis lesions progressed, while the fractional volume of cor tical interstitium [Vv(interstitium/cortex)] and the percent of global ly sclerosed glomeruli did not change. The only structural change that correlated with the increasing AER was the change in Vv(mes/glom). Ch anges in structural parameters, AER or C-Cr did not significantly corr elate with baseline BP or change in BP over the five years. Although b ased on a small number of patients, this study suggests that at the st age of disease where renal lesions are established and where some IDDM patients are in transition to microalbuminuria or early clinical neph ropathy, continuing mesangial expansion is the central variable. Inter stitial changes were not occurring over this time. Progressive interst itial expansion at the later stages of diabetic nephropathy may thus b e consequent to advanced diabetic glomerular injury.