title: Independent and additive impact of blood pressure control and angiotensin II receptor blockade on renal outcomes in the irbesartan diabetic nephropathy trial: clinical implications and limitations.
abstract: Elevated arterial pressure is a major risk factor for progression to ESRD in diabetic nephropathy. However, the component of arterial pressure and level of BP control for optimal renal outcomes are disputed. Data from 1590 hypertensive patients with type 2 diabetes in the Irbesartan Diabetic Nephropathy Trial (IDNT), a randomized, double-blind, placebo-controlled trial performed in 209 clinics worldwide, were examined, and the effects of baseline and mean follow-up systolic BP (SBP) and diastolic BP and the interaction of assigned study medications (irbesartan, amlodipine, and placebo) on progressive renal failure and all-cause mortality were assessed. Other antihypertensive agents were added to achieve predetermined BP goals. Entry criteria included elevated baseline serum creatinine concentration up to 266 micromol/L (3.0 mg/dl) and urine protein excretion >900 mg/d. Baseline BP averaged 159/87 +/- 20/11 mmHg. Median patient follow-up was 2.6 yr. Follow-up achieved SBP most strongly predicted renal outcomes. SBP >149 mmHg was associated with a 2.2-fold increase in the risk for doubling serum creatinine or ESRD compared with SBP <134 mmHg. Progressive lowering of SBP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function. Below this threshold, all-cause mortality increased. An additional renoprotective effect of irbesartan, independent of achieved SBP, was observed down to 120 mmHg. There was no correlation between diastolic BP and renal outcomes. We recommend a SBP target between 120 and 130 mmHg, in conjunction with blockade of the renin-angiotensin system, in patients with type 2 diabetic nephropathy.
authors.affiliation: Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A51, Cleveland, OH 44195, USA. pohlm@ccf.org
authors.forename: Marc A
authors.initials: MA
authors.lastname: Pohl
authors.forename: Samuel
authors.initials: S
authors.lastname: Blumenthal
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cordonnier
authors.forename: Fernando
authors.initials: F
authors.lastname: De Alvaro
authors.forename: Giacomo
authors.initials: G
authors.lastname: Deferrari
authors.forename: Gilbert
authors.initials: G
authors.lastname: Eisner
authors.forename: Enric
authors.initials: E
authors.lastname: Esmatjes
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hunsicker
authors.forename: Jose B Lopes
authors.initials: JB
authors.lastname: de Faria
authors.forename: Ruggero
authors.initials: R
authors.lastname: Mangili
authors.forename: Jack
authors.initials: J
authors.lastname: Moore
authors.forename: Efrain
authors.initials: E
authors.lastname: Reisin
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Guntram
authors.initials: G
authors.lastname: Schernthaner
authors.forename: Samuel
authors.initials: S
authors.lastname: Spitalewitz
authors.forename: Hilary
authors.initials: H
authors.lastname: Tindall
authors.forename: Roger A
authors.initials: RA
authors.lastname: Rodby
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Lewis
mesh_terms: D017311:Amlodipine / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D000077405:Irbesartan; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017311:Amlodipine; D000077405:Irbesartan