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

University of Campinas, Conceição de Campinas, São Paulo, Brazil
Journal of the American Society of Nephrology (Impact Factor: 9.34). 11/2005; 16(10):3027-37. DOI: 10.1681/ASN.2004110919
Source: PubMed


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.

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Available from: Roger Rodby, Feb 25, 2014
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    • "Among diabetic patients with high cardiovascular risk randomized to a goal systolic BP o120 mmHg versus standard therapy with a goal o140 mmHg, there was no difference in the risks of composite major cardiovascular events; but increased rates of hyperkalemia and renal dysfunction were observed when targeting a systolic BP of o120 mmHg [65]. In a secondary analysis of the Irbesartan Diabetic Nephropathy Trial (IDNT), progressive lowering of systolic BP to 120 mmHg was associated with improved renal and patient survival, an effect independent of baseline renal function [66]. Thus, given the lack of strong evidence of benefit from reducing systolic BP to below 130 mmHg, some may target o140/90 mmHg as a BP goal for diabetic patients. "
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    • "The use of blockers of the renin-angiotensin system (RAS blockers) as antihypertensive and antiproteinuric medication has been particularly effective in slowing the progression of renal disease in type 2 diabetics [60], and all existing guidelines advise to introduce an angiotensin converting enzymes inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) in diabetic patients with CKD, as soon as microalbuminuria is detected or in case of hypertension [61]. "
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    • "All three groups had a median daily urinary protein excretion of 1.9 grams, and the attained blood pressure in the irbesartan, amlodipine, and placebo groups was 140/77, 141/77, and 144/80 mm Hg, respectively. Secondary analyses of IDNT showed that progressive lowering of blood pressure up to systolic blood pressure of 120 mmHg protects against cardiovascular events and deterioration of renal function, but further reduction in blood pressure is deleterious; a similar trend up to diastolic blood pressure of 85 mmHg was observed for cardiovascular but not renal endpoints [49, 61]. "
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