Renal Outcomes in Patients with Type 2 Diabetes

Results of a systematic review and meta-analysis [Arch Intern Med. 2012;172(10):761-769] did not find evidence showing that intensive glycemic control reduces the risk for significant clinical renal outcomes despite finding that it reduces the risk of microalbuminuria and macroalbuminuria.

Although current guidelines from the American Diabetes Association recommend intensive glycemic control for preventing renal disease based on evidence showing an improvement in albuminuria, a surrogate marker for renal disease, no evidence has shown a direct association between intensive glycemic control and reduced renal disease.  Because intensive glycemic control is not without risk, and has been shown to increase mortality risk in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, recommending intensive glycemic control for patients with diabetes is increasingly problematic for physicians.

To summarize the benefits of intensive glycemic control versus conventional control on kidney-related outcomes for adults with type 2 diabetes, investigators pooled data from 7 randomized clinical trials that compared surrogate renal end points (microalbuminuria and macroalbuminuria) and clinical renal end points (doubling of serum creatinine level, end-stage renal disease [ESRD], and death from renal disease) in patients treated with conventional versus intensive glycemic control.

The selected trials were based on a systematic review of 3 databases for trials published between January 1950, and December 2010 that randomly assigned people with type 2 diabetes to conventional or intensive glycemic control, assessed progression or development of kidney disease, and involved patients with stable disease in the outpatient setting only. No studies of patients undergoing treatment in an acute hospital setting were included.

Data, pooled from the 7 trials, from 28,065 adults who were monitored for 2 to 15 years, were available for analysis. Compared to the patients treated with conventional control, the study found that patients treated with intensive glucose control had a reduced risk for microalbuminuria (risk ratio [RR], 0.86; 95% confidence interval [CI], 0.76-0.96) and macroalbuminuria (RR, 0.74; 95% CI, 0.65-0.85).

However, the pooled analysis did not find an association between intensive glycemic control and clinical renal outcomes. Compared with conventional control, intensive glycemic control was not associated with a reduction in the doubling of the serum creatinine level (RR, 1.06; 95% CI, 0.92-1.22), ESRD (RR, 0.69; 95% CI, 0.46-1.05), or death from renal disease (RR, 0.99; 95% CI, 0.55-1.79].

The cumulative incidence of clinical renal outcomes in the study was low, with <4% of doubling of the serum creatinine level, <1.5% of ESRD, and <0.5% of death from renal disease. In contrast, the pooled cumulative incidence of the surrogate markers was 23% for microalbuminuria and 5% for macroalbuminuria.

Given the results of this pooled analysis, as well as the low incidence of clinical renal outcomes, the investigators concluded that “there is little compelling reason to initiate intensive glycemic control in midstage of disease with the aim of preventing renal failure.”