title: 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.
  
  
  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: Clinical Research Center for Rare Diseases Aldo & Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. pruggenenti@ospedaliriuniti.bergamo.it
authors: Piero
authors: P
authors: Ruggenenti
authors: Esteban L
authors: EL
authors: Porrini
authors: Flavio
authors: F
authors: Gaspari
authors: Nicola
authors: N
authors: Motterlini
authors: Antonio
authors: A
authors: Cannata
authors: Fabiola
authors: F
authors: Carrara
authors: Claudia
authors: C
authors: Cella
authors: Silvia
authors: S
authors: Ferrari
authors: Nadia
authors: N
authors: Stucchi
authors: Aneliya
authors: A
authors: Parvanova
authors: Ilian
authors: I
authors: Iliev
authors: Alessandro Roberto
authors: AR
authors: Dodesini
authors: Roberto
authors: R
authors: Trevisan
authors: Antonio
authors: A
authors: Bossi
authors: Jelka
authors: J
authors: Zaletel
authors: Giuseppe
authors: G
authors: Remuzzi
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000150:complications; D001786:Blood Glucose; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007678:Kidney Glomerulus / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose