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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    ABSTRACT: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with diabetes. This complication reflects a complex pathophysiology, whereby various genetic and environmental factors determine susceptibility and progression to end-stage renal disease. DN should be considered in patients with type 1 diabetes for at least 10 years who have microalbuminuria and diabetic retinopathy, as well as in patients with type 1 or type 2 diabetes with macroalbuminuria in whom other causes for proteinuria are absent. DN may also present as a falling estimated glomerular filtration rate with albuminuria as a minor presenting feature, especially in patients taking renin–angiotensin–aldosterone system inhibitors (RAASi). The pathological characteristic features of disease are three major lesions: diffuse mesangial expansion, diffuse thickened glomerular basement membrane, and hyalinosis of arterioles. Functionally, however, the pathophysiology is reflected in dysfunction of the mesangium, the glomerular capillary wall, the tubulointerstitium, and the vasculature. For all diabetic patients, a comprehensive approach to management including glycemic and hypertensive control with RAASi combined with lipid control, dietary salt restriction, lowering of protein intake, increased physical activity, weight reduction, and smoking cessation can reduce the rate of progression of nephropathy and minimize the risk for cardiovascular events. This review focuses on the latest published data dealing with the mechanisms, diagnosis, and current treatment of DN.
    09/2014; 33(3). DOI:10.1016/j.krcp.2014.08.001
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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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    International Journal of Hypertension 02/2013; 2013:696598. DOI:10.1155/2013/696598
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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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    ABSTRACT: Hypertension is both an important cause and consequence of chronic kidney disease. Evidence from numerous clinical trials has demonstrated the benefit of blood pressure control. However, it remains unclear whether available results could be extrapolated to patients with chronic kidney diseases because most studies on hypertension have excluded patients with kidney failure. In addition, chronic kidney disease encompasses a large group of clinical disorders with heterogeneous natural history and pathogenesis. In this paper, we review current evidence supporting treatment of hypertension in various forms of chronic kidney disease and highlight some of the gaps in the extant literature.
    05/2011; 2011:132405. DOI:10.4061/2011/132405
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