P. Hovind et al., Progression of diabetic nephropathy: Role of plasma homocysteine and plasminogen activator inhibitor-1, AM J KIDNEY, 38(6), 2001, pp. 1376-1380
Among patients with diabetic nephropathy, the decline in glomerular filtrat
ion rate (GFR) varies substantially, ranging from 2 to 20 mL/min per year.
Identification of predictors of progression In diabetic nephropathy is impo
rtant. Plasma total homocysteine (tHcy) rises with urinary albumin excretio
n rate in diabetes, and plasminogen activator inhibitor-1 (PAI-1) has been
correlated with increased matrix accumulation in various glomerulopathies.
In this prospective observational cohort study, we evaluated the importance
of baseline tHcy and PAI-1 as predictors of the rate of decline in GFR. Ba
seline tHcy and PAI-1 were measured in 157 type I diabetic patients with di
abetic nephropathy (92 men; mean age, 41 +/- 10 years; mean diabetes durati
on, 27 +/- 8 years; median GFR, 80 mL/min/1.73 m(2) [range, 23 to 143 mL/mi
n/1.73 m(2)]). Hereafter, GFR was measured yearly with a plasma clearance t
echnique for at least 3 years (median, 7 years [range, 3.0 to 8.3 years]).
The mean rate of decline in GFR was 3.7 +/- 0.3 mL/min per year. A linear r
egression analysis revealed a borderline significant relationship between r
ate of decline in GFR and tHcy (P = 0.069) and PAI-1 (P = 0.087). Analysis
of the rate of decline in GFR and tertiles of tHcy and PAI-1 revealed that
increasing levels of tHcy were correlated with a significantly faster decli
ne in GFR (P = 0.025), whereas increasing levels of PAI-1 were not. After a
djustment for other well-established risk factors for progression of nephro
pathy in a multiple linear regression analysis, however, neither tHcy level
s nor PAI-1 levels were independent predictors of rate of decline in GFR. (
C) 2001 by the National Kidney Foundation, Inc.