title: The changing course of diabetic nephropathy: low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria.
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 microg/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 > or = 10-fold into the microalbuminuric (20 to 200 microg/min) or normal range (<20 microg/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 microg/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 mg/min) than previously reported (200 microg/min).
authors.affiliation: Division of Nephrology and Endocrinology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ellis
authors.forename: C
authors.initials: C
authors.lastname: Lloyd
authors.forename: D J
authors.initials: DJ
authors.lastname: Becker
authors.forename: K Y
authors.initials: KY
authors.lastname: Forrest
authors.forename: T J
authors.initials: TJ
authors.lastname: Orchard
mesh_terms: D000328:Adult; D000419:Albuminuria; D001794:Blood Pressure; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003404:Creatinine / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000209:etiology / Q000503:physiopathology; D012307:Risk Factors; D012709:Serum Albumin / Q000032:analysis; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D012709:Serum Albumin; D014280:Triglycerides; D003404:Creatinine