Glomerular hyperfiltration and renal disease progression in type 2 diabetes

Abstract

Objective: To describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] ≥120 mL/min/1.73 m(2)), GFR decline, and nephropathy onset or progression in type 2 diabetic patients with normo- or microalbuminuria.

Research design and methods: We longitudinally studied 600 hypertensive type 2 diabetic patients with albuminuria <200 μg/min and who were retrieved from two randomized trials testing the renal effect of trandolapril and delapril. Target blood pressure (BP) was <120/80 mmHg, and HbA(1c) was <7%. GFR, albuminuria, and glucose disposal rate (GDR) were centrally measured by iohexol plasma clearance, nephelometry in three consecutive overnight urine collections, and hyperinsulinemic euglycemic clamp, respectively.

Results: Over a median (range) follow-up of 4.0 (1.7-8.1) years, GFR declined by 3.37 (5.71-1.31) mL/min/1.73 m(2) per year. GFR change was bimodal over time: a larger reduction at 6 months significantly predicted slower subsequent decline (coefficient: -0.0054; SE: 0.0009), particularly among hyperfiltering patients. A total of 90 subjects (15%) were hyperfiltering at inclusion, and 11 of 47 (23.4%) patients with persistent hyperfiltration progressed to micro- or macroalbuminuria versus 53 (10.6%) of the 502 who had their hyperfiltration ameliorated at 6 months or were nonhyperfiltering since inclusion (hazard ratio 2.16 [95% CI 1.13-4.14]). Amelioration of hyperfiltration was independent of baseline characteristics or ACE inhibition. It was significantly associated with improved BP and metabolic control, amelioration of GDR, and slower long-term GFR decline on follow-up.

Conclusions: Despite intensified treatment, patients with type 2 diabetes have a fast GFR decline. Hyperfiltration affects a subgroup of patients and may contribute to renal function loss and nephropathy onset or progression. Whether amelioration of hyperfiltration is renoprotective is worth investigating.

Trial registration: ClinicalTrials.gov NCT00157586 NCT00235014.

Figures

Figure 1

Percent changes at month 6 vs. baseline in mean arterial pressure (A), blood glucose levels (B), and GDR (C) and subsequent GFR decline from month 6 to study end (D) in patients with persistent hyperfiltration compared with patients who had their hyperfiltration at inclusion ameliorated at 6 months. Data are mean and SE.

Figure 2

Progression to micro- or macroalbuminuria. Kaplan-Meier survival analysis of patients with persistent hyperfiltration at month 6 (persistently hyperfiltering) compared with all other patients who were already normofiltering at inclusion or were hyperfiltering at inclusion and had their hyperfiltration ameliorated at month 6 (others) (log rank: 6.13, P = 0.013). Unadjusted and adjusted HRs are shown in the accompanying table. *Adjustment for albuminuria at baseline. **Adjustments for age, sex, and albuminuria; HbA1c and systolic BP at baseline; smoking habit; known duration of diabetes; participation in the BENEDICT or DEMAND trial; treatment arm; and treatment with an ACE inhibitor yes or no. Mo, month.