Glomerular Hyperfiltration and Renal Disease Progression in Type 2 Diabetes
- Piero Ruggenenti, MD1,2⇓,
- Esteban L. Porrini, MD1,
- Flavio Gaspari, CHEMD1,
- Nicola Motterlini, STATSCID1,
- Antonio Cannata, CHEMIST1,
- Fabiola Carrara, CHEMIST1,
- Claudia Cella, PHARM.CHEM.D.1,
- Silvia Ferrari, CHEMIST1,
- Nadia Stucchi, CHEMIST1,
- Aneliya Parvanova, MD1,
- Ilian Iliev, MD1,
- Alessandro Roberto Dodesini, MD3,
- Roberto Trevisan, MD3,
- Antonio Bossi, MD4,
- Jelka Zaletel, MD5,
- Giuseppe Remuzzi, MD1,2 and
- for the GFR Study Investigators (see Study Organization)
- 1Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy
- 2Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy
- 3Unit of Diabetology, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy
- 4Unit of Diabetology, Treviglio Hospital, Treviglio, Italy
- 5Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center, Ljubljana, Slovenia
- Corresponding author: Piero Ruggenenti, or .
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.
- © 2012 by the American Diabetes Association.
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