Management of hyperglycemia, dyslipidemia, and albuminuria in patients with diabetes and CKD: a systematic review for a KDOQI clinical practice guideline.

BACKGROUND In 2007, the National Kidney Foundation (NKF) published clinical practice guidelines and recommendations for treating patients with diabetes and kidney diseases. Given recent studies that may enhance our understanding of the benefits and harms of glycemic, lipid, and albuminuria management in patients with diabetes and chronic kidney disease (CKD), the NKF commissioned a systematic review to evaluate data on the management of these patients. STUDY DESIGN Systematic review and evidence synthesis. SETTING & POPULATION Patients with type 1 or 2 diabetes with or without CKD. SELECTION CRITERIA FOR STUDIES English-language publications indexed in the MEDLINE database from January 2003 to October 2010, as well as cited references in these publications and publications identified after consultation with the NKF Diabetes Work Group were screened. Randomized controlled trials providing evidence for the management of hyperglycemia, dyslipidemia, and albuminuria in individuals with diabetes were included. INTERVENTIONS (1) Intensive glycemic control; (2) lipid management; (3) interventions aimed at prevention of incident albuminuria and/or progression of albuminuria in normotensive patients. OUTCOMES For all interventions, all-cause mortality was the primary outcome and secondary clinical outcomes included death from cardiovascular causes, incident kidney failure, and nonfatal cardiovascular events. Intermediate outcomes included changes in albuminuria and measures of kidney function. For intensive glycemic control only, severe and mild hypoglycemia were secondary and intermediate outcomes, respectively. RESULTS 5 studies (n=27,159) assessed the impact of intensive versus conventional glycemic control strategies on clinical outcomes in type 2 diabetes. Intensive glycemic control reduced the development of micro- and macroalbuminuria, but did not reduce the incidence of primary or secondary clinical outcomes and was associated with a 2.5-fold increase in severe hypoglycemia. 11 studies (n=7,539) assessed lipid management. Statins did not reduce all-cause mortality or stroke compared to placebo in adults with diabetes and CKD. Fenofibrate increased regression of microalbuminuria to normoalbuminuria compared to placebo. 3 studies reported inconsistent effects of different angiotensin II receptor blockers on the incidence of microalbuminuria, and one study reported that telmisartan reduced macroalbuminuria in normotensive participants. No study demonstrated a benefit on primary or secondary clinical outcomes. LIMITATIONS Patients with CKD constituted a subgroup in most studies. Substantial heterogeneity with respect to population, interventions, outcome measures, and duration of follow-up. CONCLUSIONS Intensive glycemic control and lipid interventions did not improve clinical outcomes in patients with type 2 diabetes. Although interventions typically improved albuminuria, evidence was insufficient to determine whether treatment of albuminuria in normotensive patients provides beneficial effects on clinical outcomes. More intensive clinical management of patients with diabetes and CKD has inherent risks, including severe hypoglycemia, which should be considered when formulating treatment strategies.