The use of darbepoetin alfa in patients with diabetes, chronic kidney disease, and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes (either death or a cardiovascular event or death or a renal event) and was associated with an increased risk of stroke. For many persons involved in clinical decision making, this risk will outweigh the potential benefits. (ClinicalTrials.gov number, NCT00093015.)
In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)
A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.
Albuminuria is the predominant renal risk marker in patients with type 2 diabetic nephropathy on conventional treatment; the higher the albuminuria, the greater the renal risk. Reduction in albuminuria is associated with a proportional effect on renal protection, the greater the reduction the greater the renal protection. The residual albuminuria on therapy (month 6) is as strong a marker of renal outcome as is baseline albuminuria. The antiproteinuric effect of losartan explains a major component of its specific renoprotective effect. In conclusion, albuminuria should be considered a risk marker for progressive loss of renal function in type 2 diabetes with nephropathy, as well as a target for therapy. Reduction of residual albuminuria to the lowest achievable level should be viewed as a goal for future renoprotective treatments.
Limited data are available on the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end stage renal disease (ESRD) among individuals with chronic kidney disease (CKD). We conducted a collaborative meta-analysis of 21,688 participants selected for CKD from 13 cohorts.
After adjustment for potential confounders and albuminuria, a 15 mL/min/1.73 m2 lower eGFR below 45 mL/min/1.73 m2 was significantly associated with mortality (pooled hazard ratio [HR] 1.47 [95% CI: 1.22–1.79]), and ESRD (pooled HR 6.24 [95% CI: 4.84–8.05]). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eight-fold higher albumin:creatinine ratio (ACR) or protein:creatinine ratio (PCR) was significantly associated with mortality (pooled HR 1.40 [95% CI: 1.27–1.55]), without evidence of significant heterogeneity. An eight-fold higher ACR or PCR was also strongly associated with ESRD (pooled HR 3.04 [95% CI: 2.27–4.08]), with significant heterogeneity between HR estimates.
Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD. The associations are stronger for ESRD than for mortality. The observed associations are consistent with CKD classification based on eGFR stages, and suggest that albuminuria provides additional prognostic information among individuals with CKD.
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.
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