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Strict Glycemic Control May Not Help Kidney Patients

Dec 15, 2011

Both tight glycemic control and poor glycemic control are associated with worse outcomes in diabetes patients with chronic kidney disease.

According to Dr. Sabin Shurraw of the University of Alberta in Edmonton and colleagues, hemoglobin (Hb)A1c levels above 8.0% were associated with an increased risk of death — but so were levels below 6.5%,  Not surprisingly, poor glycemic control also was associated with kidney disease progression, new end-stage renal disease (ESRD), cardiovascular events, and all-cause hospitalization.

The researchers say studies of glycemic control outcomes have largely excluded patients with renal dysfunction, so while diabetic nephropathy is the leading cause of ESRD in North America, there’s not much information to guide glycemic control once kidneys start to fail.

The National Kidney Foundation recommends that all diabetics, with and without kidney disease, aim for HbA1c levels of 7%, “but very little evidence supports this recommendation,” the investigators wrote in their paper.

Using data on patients who had serum creatinine testing in a single Canadian province in 2005 and 2006, they identified 23,296 patients with diabetes mellitus and estimated glomerular filtration rates between 15 and 60 mL/min/1.73 m2, indicating stage 3 or stage 4 chronic kidney disease. HbA1c levels ranged from 2.8% to 20.0%, with a median of 6.9%. In 11%, HbA1c was higher than 9%.

Over a median follow-up of nearly four years, 3,665 subjects died and 401 developed ESRD. On multivariate analysis, patients with HbA1c greater than 9% were 35% more likely to die than patients with levels below 7%. The relationship of HbA1c to mortality was U-shaped, with the risk starting to climb again when values fell below 6.5%.

“As with participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, it is plausible that (diabetics with chronic kidney disease) who are treated to an level lower than 6.5% might experience iatrogenic harm owing to serious hypoglycemic events or too precipitous a fall in average glucose,” Dr. Shurraw and colleagues suggest.

Patients with HbA1c levels above 9% were also at greater risk for myocardial infarction, stroke, heart failure, cardiovascular events in aggregate, kidney disease progression (defined as a doubling of creatinine levels), and hospitalization due to any cause. The increases in risk were similar for both stage 3 and stage 4 patients. Lower HbA1c levels were not linked to an increased risk of any of these outcomes.

For patients with stage 3 kidney disease, the risk of ESRD was 22% higher with HbA1c at 7% to 9%, and 152% higher with levels above that. In stage 4 disease, glycemic control seemed to play less of a role, with a 3% higher risk of ESRD at 7% to 9% and a 13% increase with higher HbA1c levels.

In a commentary published online November 28th with the study, Dr. David C. Goff of Wake Forest University School of Medicine in Winston-Salem, North Carolina, warns against over-interpreting the differences in ESRD risk in stage 3 vs. stage 4, given statistical concerns and other issues.

“In the absence of strong evidence specific to patients with advanced chronic kidney disease and diabetes mellitus, prudent practice may be to pursue at least moderately intensive risk factor management while minimizing the potential for serious adverse effects of the treatment regimens,” Dr. Goff concludes.

Arch Intern Med 2011;171:1920-1927.