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A Population-Based Cohort Study

Sabin Shurraw, MD; Brenda Hemmelgarn, MD, PhD; Meng Lin, MSc; Sumit R. Majumdar, MD, MSc; Scott Klarenbach, MD, MSc; Braden Manns, MD, MS; Aminu Bello, MD, PhD; Matthew James, MD, PhD; Tanvir Chowdhury Turin, MD, PhD; Marcello Tonelli, MD, SM; for the Alberta Kidney Disease Network

Arch Intern Med. 2011;171(21):1920-1927. doi:10.1001/archinternmed.2011.537

Background  Better glycemic control as reflected by lower hemoglobin A_1c (HbA_1c) level may prevent or slow progression of nephropathy in people with diabetes mellitus (DM). Whether a lower HbA_1c level improves outcomes in people with DM and chronic kidney disease (CKD) is unknown.

Methods  From all people with serum creatinine measured as part of routine care in a single Canadian province from 2005 through 2006, we identified those with CKD based on laboratory data (estimated glomerular filtration rate [eGFR], <60.0 mL/min/1.73 m²]) and DM using a validated algorithm applied to hospitalization and claims data. Patients were classified based on their first HbA_1c measurement; Cox regression models were used to assess independent associations between HbA_1c level and 5 study outcomes (death, progression of kidney disease based on a doubling of serum creatinine level, or new end-stage renal disease [ESRD], cardiovascular events, all-cause hospitalization).

Results  We identified 23 296 people with DM and an eGFR lower than 60.0 mL/min/1.73 m². The median HbA_1c level was 6.9% (range, 2.8%-20.0%), and 11% had an HbA_1c value higher than 9%. Over the median follow-up period of 46 months, 3665 people died, and 401 developed ESRD. Regardless of baseline eGFR, a higher HbA_1c level was strongly and independently associated with excess risk of all 5 outcomes studied (P < .001 for all comparisons). However, the association with mortality was U-shaped, with increases in the risk of mortality apparent at HbA_1c levels lower than 6.5% and higher than 8.0%. The increased risk of ESRD associated with a higher HbA_1c level was attenuated at a lower baseline eGFR (P value for interaction, <.001). Specifically, among those with an eGFR of 30.0 to 59.9 mL/min/1.73 m², the risk of ESRD was increased by 22% and 152% in patients with HbA_1c levels of 7% to 9% and higher than 9%, respectively, compared with patients with an HbA_1c level lower than 7% (P < .001), whereas corresponding increases were 3% and 13%, respectively, in those with an eGFR of 15.0 to 29.9 mL/min/1.73 m².

Conclusions  A hemoglobin A_1c level higher than 9% is common in people with non–hemodialysis-dependent CKD and is associated with markedly worse clinical outcomes; lower levels of HbA_1c (<6.5%) also seemed to be associated with excess mortality. The excess risk of kidney failure associated with a higher HbA_1c level was most pronounced among people with better kidney function. These findings suggest that appropriate and timely control of HbA_1c level in people with DM and CKD may be more important than previously realized, but suggest also that intensive glycemic control (HbA_1c level <6.5%) may be associated with increased mortality.

Author Affiliations: Divisions of Nephrology, University of Alberta, Edmonton (Drs Shurraw, Majumdar, Klarenbach, Bello, and Tonelli and Mr Lin), and University of Calgary, Foothills Medical Centre, Calgary (Drs Hemmelgarn, Manns, James, and Turin), Alberta, Canada.
Group Information: A list of members of the Alberta Kidney Disease Network can be found at http://www.akdn.info/.

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