Albuminuria, a Therapeutic Target for Cardiovascular Protection in Type 2 Diabetic Patients With Nephropathy

Abstract

Background-Albuminuria is an established risk marker for both cardiovascular and renal outcomes. Albuminuria can be reduced with drugs that block the renin-angiotensin system (RAS). We questioned whether the short-term drug-induced change in albuminuria would predict the long-term cardioprotective efficacy of RAS intervention. Methods and Results-We analyzed data from Reduction in Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL), a double-blind, randomized trial in 1513 type 2 diabetic patients with nephropathy, focusing on the relationship between the prespecified cardiovascular end point (composite) or hospitalization for heart failure and baseline or reduction in albuminuria. Patients with high baseline albuminuria (Ն3 g/g creatinine) had a 1.92-fold (95% CI, 1.54 to 2.38) higher risk for the cardiovascular end point and a 2.70-fold (95% CI, 1.94 to 3.75) higher risk for heart failure compared with patients with low albuminuria (Ͻ1.5 g/g). Among all available baseline risk markers, albuminuria was the strongest predictor of cardiovascular outcome. The association between albuminuria and cardiovascular outcome was driven by those patients who also had a renal event.Modeling of the initial 6-month change in risk parameters showed that albuminuria reduction was the only predictor for cardiovascular outcome: 18% reduction in cardiovascular risk for every 50% reduction in albuminuria and a 27% reduction in heart failure risk for every 50% reduction in albuminuria. Conclusions-Albuminuria is an important factor predicting cardiovascular risk in patients with type 2 diabetic nephropathy. Reducing albuminuria in the first 6 months appears to afford cardiovascular protection in these patients.

Strain vessel hypothesis: a viewpoint for linkage of albuminuria and cerebro-cardiovascular risk

“…5,17 Furthermore, recent clinical trials have shown that reduction of albuminuria is significantly related to improved outcomes in albuminuric subjects. 2,18,19 Thus, the clinical significance of albuminuria is clearly established, and various guidelines for the management of hypertension list albuminuria as a risk factor or a sign of renal damage. Interestingly, the 2007 ESH/ESC guidelines state that the term 'microalbuminuria' may be misleading and also falsely suggests a minor damage.…”

Long-term prevention of diabetic nephropathy: an audit

“…The lack of difference between DN and non-DN patients is unclear but may have been due partly to the short duration of DN (median follow-up with DN 6.5 years, range 0.5-10.5) and consequently well-preserved kidney function. Furthermore, it should be noted that approximately half of the patients regressed to micro-or normoalbuminuria, thereby reducing markedly their risk of cardiovascular events and ESRD [28,29]. Moreover, microalbuminuria per se is a well-established risk factor for cardiovascular disease [30], which may further diminish the difference in prognosis regarding cardiovascular disease and mortality between patients with persistent microalbuminuria and patients with DN.…”

World Kidney Day 2011: Protect your kidneys, save your heart

“…This effect was seen primarily in people with albumin excretion rates of >50 mg/day in a pilot study, and the intervention was shown to be cost-effective in that population [31]. CV endpoints were significantly reduced in direct proportion to the reduction of albuminuria with ACEI therapy, and albuminuria proved to be the only predictor of CV outcome [32]. Other studies have also demonstrated that changes in proteinuria (in diabetics) better predict outcomes than changes in BP achieved with ACEI therapy [33].…”