The changing course of diabetic nephropathy: Low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria

Ellis, Demetrius; Lloyd, Cathy; Becker, Dorothy J.; Forrest, Kimberly Y. -Z. and Trevor J., Orchard (1996). The changing course of diabetic nephropathy: Low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria. American Journal of Kidney Diseases, 27(6) pp. 809–818.

DOI: https://doi.org/10.1016/S0272-6386(96)90518-1

Abstract

Diabetic nephropathy (DN) as manifested by persistent and clinically evident proteinuria, has long been considered an irreversible process that predicts a rapid decline in renal function. The observation of reversal of DN in several individuals enrolled in a prospective study of the natural course of diabetes complications challenged this view and led to the current investigation into the correlates of such regression of proteinuria. DN was defined as a median albumin excretion rate (AER) over 200 μg/min in two or three urine collections obtained at baseline, and again at 2 and 4 years of follow-up. Among 658 individuals with childhood-onset insulin-dependent diabetes mellitus (IDDM), 146 had DN at baseline. Nine subsequently died without renal failure, and 13 were lost to follow-up. Of the 124 subjects with at least survey follow-up data, 32 (24%) developed renal failure, and 78 of the remaining 92 provided full quantitative data. AER decreased by ≥10-fold into the microalbuminuric (20 to 200 μg/min) or normal range (<20 μg/min) in 7 of these individuals and are called “regressors of proteinuria.” Compared with the remaining 71 subjects, the strongest correlate of regression of proteinuria was an improvement in fasting plasma low-density lipoprotein cholesterol (LDL-C) in the 7 regressors (P < 0.008). Improved glycemic control was not a significant predictor of improved AER. Five of the 7 individuals with improved AER had a baseline median AER below 500 μg/min. When the 7 regressors of proteinuria were combined with an additional 38 individuals who also experienced smaller decreases in median AER, such improvement was associated with a more favorable systolic (or diastolic) blood pressure (BP) change (P < 0.01), and a decrease in plasma LDL-C level (P = 0.01). These data suggest that proteinuria in DN may substantially regress in approximately 6% and improve in at least 34% of individuals with IDDM over a 4-year period, often in association with a decrease in plasma LDL-C concentration or stabilization or improvement in BP. Furthermore, the data suggest that the nonreversibility threshold for diabetic nephropathy may be higher (500 μg/min) than previously reported (200 μg/min).

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