THE NEPHROPATHY OF NON-INSULIN-DEPENDENT DIABETES - PREDICTORS OF OUTCOME RELATIVE TO DIVERSE PATTERNS OF RENAL INJURY

Nephropathy of non-insulin-dependent diabetes mellitus (NIDDM) is the most common cause of end-stage renal failure (ESRF) in Western countri es. This study investigates the clinical and histologic putative predi ctors of disease progression, with the final goal to identify patients at risk who may benefit from early diagnosis and intervention. It exa mines by repeated measurements of BP, blood glucose, serum creatinine, and urinary protein excretion rate 65 consecutive NIDDM patients with clinical, persistent proteinuria and biopsy-documented typical diabet ic glomerulopathy (class I; n = 30), predominant nephroangiosclerosis (class II; n = 23), or nondiabetic type glomerulopathy (class III; n = 12), whose severity of renal tissue involvement was precisely quantif ied by a global histologic score. Baseline parameters and progression to renal end points, i.e., doubling of baseline serum creatinine, dial ysis, or transplantation, were univariately and multivariately correla ted by proportional hazards regression models. The median kidney survi val time in the overall study population was 3.07 yr. Thirty-seven per cent of patients reached an end point during a median (range) follow-u p of 1.8 yr (0.4 to 5.7 yr). By univariate and multivariate analysis, kidney survival significantly correlated with baseline urinary protein excretion rate (P = 0.04 and P = 0.04, respectively) and renal tissue injury score (P = 0.0001 and P = 0.02, respectively), but not with th e histologic classes. Patients with a urinary protein excretion rare l ess than or equal to 2 g/24 h, or >2 g/24 h with a histologic score <7 , never reached an end point. All patients with urinary protein excret ion >2 g/24 h and a histologic score >13 progressed to ESRF over a med ian of 1.6 yr. No differences in other baseline parameters or in BP an d diabetes control during follow-up accounted for these different outc omes. In NIDDM as well as in nondiabetic chronic renal disease, quanti fication of urinary protein excretion rate-independent of the pattern of underlying glomerular involvement-reliably discriminates progressor s from nonprogressors and, combined with precise quantification of ren al tissue injury, reliably predicts risk of ESRF. This information may be used to set guidelines for early diagnosis and appropriate interve ntion to reduce the number of diabetic patients who will need renal re placement therapy in years to come.