The role of statins in chronic kidney disease.

Chronic kidney disease is associated with cardiovascular event rates that are at least as high as in patients with established atherosclerotic cardiovascular disease or in those with diabetes mellitus. Chronic kidney disease is therefore considered a cardiovascular disease risk equivalent. Treatment of dyslipidemia, which is very common in this population and reflects the pattern seen in the metabolic syndrome, reduces cardiovascular events in patients with chronic kidney disease. Thus, patients with chronic kidney disease should be evaluated and treated for dyslipidemia. Dyslipidemia is a risk factor for the development of impaired kidney function. Dyslipidemia is also associated with progressive renal disease in subjects with no overt renal disease, as well as those with diabetic and nondiabetic kidney disease. Although definitive randomized controlled trials are lacking, the collective evidence suggests that treatment of dyslipidemia is associated with less decline in renal function. The use of potent statins in high doses can lead to transient proteinuria via impairment of proximal tubular receptor--mediated endocytosis, in a dose-dependent manner. Over the long term, however, the use of statins results in a reduction in proteinuria and in the rate of decline of renal function. Several large definitive trials that are currently underway to examine the safety and efficacy of statins in cardiovascular and renal protection should provide more definitive answers on the role of these drugs in this very high risk population.

A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy progresses relentlessly to end-stage renal disease (ESRD). Animal experiments have found that peroxisome proliferator activated receptor-gamma (PPAR-gamma)-based therapy can have a glucose independent effect on renal protection. We hypothesized that PPAR-gamma-based antidiabetic therapy would result in greater reduction in proteinuria compared to sulfonylurea-based therapy. METHODS: In 44 patients with overt diabetic nephropathy, an open-label, blinded end point trial was conducted in which subjects were randomized to either pioglitazone or glipizide to achieve similar glucose control. Proteinuria was assessed by two collections of 24-hour urine samples each month for 4 months. RESULTS: The glipizide group had an adjusted mean increase in proteinuria of 6.1% (95% CI -11.7%, 23.8%), whereas the pioglitazone group had a reduction of 7.2% (95% CI -24.9%, 10.6%). The adjusted reduction with pioglitazone of 13.2% (95% CI -38.4%, 11.9%) was not statistically significant (P= 0.294). Baseline proteinuria, diastolic ambulatory blood pressure, and serum albumin concentration were independent predictors of reduction in proteinuria. The frequency and patterns of adverse events were similar in the two groups. CONCLUSION: In patients with advanced diabetic nephropathy, we found no reduction in proteinuria over 4 months. These data are useful to design larger studies with longer duration of follow-up to demonstrate renal protection of PPAR-gamma agonists.