The Early Natural History of Nephropathy in Type 1 Diabetes

Abstract

Predictors of albumin excretion rate (AER) abnormalities could provide earlier indicators of diabetic nephropathy risk. Data from the Natural History Study, a prospective 5-year observation of renal structure and function in young type 1 diabetic patients, were examined for predictors of AER patterns in normoalbuminuric type 1 diabetic patients. Included were 170 patients (96 females) (aged 16.7 ± 5.9 years, duration of diabetes 8.0 ± 4.3 years) with normal blood pressure, normoalbuminuria (AER <20 μg/min), and eight or more follow-up visits over 5 years. AER, blood pressure, and HbA1c (A1C) were determined quarterly and glomerular filtration rate (GFR) annually. Persistent microalbuminuria (PMA) was defined as 20–200 μg/min in two of three consecutive values within 6–12 months. Four different AER patterns were identified. Group 1 (n = 99): all values <20 μg/min. Group 2 (n = 49): intermittent levels >20 μg/min but not meeting microalbuminuria criteria. Group 3 (n = 14): PMA during follow-up but normoalbuminuria at study exit. Group 4 (n = 8): microalbuminuria at study exit. Group 4 (497 ± 95 nm, P < 0.01) and group 3 (464 ± 113 nm, P = 0.03) patients had greater baseline glomerular basement membrane (GBM) width versus group 1 (418 ± 67 nm). Baseline GFR in group 4 (163 ± 37 ml · min−1 · 1.73 m−2) was higher than group 1 (143 ± 28 ml · min−1 · 1.73 m−2, P = 0.04). A1C was higher in group 2 (9.0 ± 1.2%) than group 1 (8.4 ± 1.1%, P = 0.008). Thus, greater increases in GBM width and GFR were predictors of PMA. Since 64% of the patients that developed microalbuminuria reverted to normoalbuminuria, the risk of diabetic nephropathy as defined by current microalbuminuria criteria is unclear.