Glomerular Hyperfiltration and Renal Disease Progression in Type 2 Diabetes

  1. for the GFR Study Investigators (see Study Organization)
  1. 1Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy
  2. 2Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy
  3. 3Unit of Diabetology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy
  4. 4Unit of Diabetology, Treviglio Hospital, Treviglio, Italy
  5. 5Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center, Ljubljana, Slovenia
  1. Corresponding author: Piero Ruggenenti, pruggenenti{at} or manuela.passera{at}
  1. P.R., E.L.P., and F.G. contributed equally to this study.


OBJECTIVE To describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] ≥120 mL/min/1.73 m2), 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 HbA1c 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 m2 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.

  • Received November 11, 2011.
  • Accepted April 17, 2012.

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