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.

• Authors: Piero Ruggenenti, Esteban L Porrini, Flavio Gaspari, Nicola Motterlini, Antonio Cannata, Fabiola Carrara, Claudia Cella, Silvia Ferrari, Nadia Stucchi, Aneliya Parvanova, Ilian Iliev, Alessandro Roberto Dodesini, Roberto Trevisan, Antonio Bossi, Jelka Zaletel, Giuseppe Remuzzi, GFR Study Investigators
• Journal: Diabetes care (Diabetes Care) Vol. 35 Issue 10 Pg. 2061-8 (Oct 2012) ISSN: 1935-5548 [Electronic] United States
• PMID: 22773704 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Blood Glucose

Topics

• Aged
• Albuminuria (complications)
• Blood Glucose
• Cohort Studies
• Diabetes Mellitus, Type 2 (complications, physiopathology)
• Diabetic Nephropathies (etiology)
• Female
• Glomerular Filtration Rate (physiology)
• Humans
• Kidney Glomerulus (physiopathology)
• Male
• Middle Aged