Chronic Kidney Disease Increases Risk for Hypoglycemia With or Without Diabetes

May 14, 2009 — Patients with chronic kidney disease (CKD) have an increased incidence of hypoglycemia, which is associated with excessive mortality rate, according to the results of a retrospective cohort analysis reported in the May 7 Online First issue of the Clinical Journal of the American Society of Nephrology.

"Adverse consequences of hypoglycemia may at least partially explain the greater risk for cardiovascular disease (CVD) outcomes observed in at least three recent studies of intensive glucose lowering in patients with diabetes," write Maureen F. Moen, from the University of Maryland in Baltimore, and colleagues. "This study set out to determine the incidence of hypoglycemia in patients with...CKD, with and without diabetes, and the association of hypoglycemia with mortality."

The study cohort consisted of 243,222 patients followed up at the Veterans Health Administration who had 2,040,206 glucose measurements, with mortality determined 1 day after glucose measurement.

Compared with patients who did not have CKD (estimated glomerular filtration rate < 60 mL/minute/1.73 m2), those who did had a higher incidence of hypoglycemia, defined as a glucose level of less than 70 mg/dL. For CKD vs no CKD, respectively, the rate of hypoglycemia in patients with diabetes was 10.72 vs 5.33 per 100 patient-months, and it was 3.46 vs 2.23 per 100 patient-months in patients without diabetes. At all levels of hypoglycemia, the odds of 1-day mortality were increased; however, these odds were lower in patients with CKD vs those without CKD.

Adjusted odds ratios for 1-day mortality associated with glucose values of less than 50 mg/dL, 50 to 59 mg/dL, and 60 to 69 mg/dL, respectively, vs a glucose level of 70 mg/dL or more, were 6.09, 4.10, and 1.85 for inpatient records from patients who had CKD; 9.95, 3.79, and 2.54 for inpatient records from patients who did not have CKD; 6.84, 3.28, and 3.98 for outpatient records from patients who had CKD; and 13.28, 7.36, and 4.34 for outpatient records from patients who did not have CKD.

"CKD is a risk for hypoglycemia, with or without diabetes," the study authors write. "The excessive mortality associated with hypoglycemia makes this complication a significant threat to patient safety in CKD....Although the extent to which the increased risk for hypoglycemia is iatrogenic or due to medical therapy is unknown, this metabolic disturbance should be considered an important patient safety outcome in CKD or diabetes populations."

Limitations of this study include retrospective design, data set based on administrative data subject to data recording errors and the potential for nonrandom differences in frequency of laboratory measures between exposure groups, limited generalizability to other populations, and lack of medication records.

"The association of hypoglycemia with one-day mortality underscores the significance of this metabolic disturbance in patients with diabetes and chronic kidney disease," senior author Dr. Jeffrey C. Fink said in a news release.

A National Institute of Diabetes and Digestive and Kidney Diseases grant and an American Society of Nephrology Student Scholarship grant supported this study. The study authors have disclosed no relevant financial relationships.

Clin J Am Soc Nephrol. Published online May 7, 2009.
Clinical Context

Diabetes is the most frequent cause of renal disease worldwide, and it often occurs concurrently with nondiabetic nephropathy. Although strict glycemic control may help prevent end-stage renal disease in diabetic patients with CKD, this can be difficult in these patients because insulin is renally cleared; suboptimal nutrition may reduce glycogen stores; decreased renal mass may lead to reduced renal gluconeogenesis; and commonly used antidiabetic drugs are renally excreted and have a prolonged half-life in patients with CKD.

These factors may all increase the risk for hypoglycemia in patients with CKD. Hypoglycemia has severe health-related consequences, which may at least partially explain the greater risk for adverse cardiovascular disease outcomes.
Study Highlights

* The primary objective of this retrospective cohort analysis was to determine the incidence of hypoglycemia in patients with vs without CKD, both with and without diabetes, in a large national cohort.
* A secondary objective was to evaluate the association of hypoglycemia with subsequent near-term mortality in this population.
* The study sample was 243,222 patients who were followed up at the Veterans Health Administration and who had at least 1 hospitalization.
* These patients had a total of 2,040,206 glucose measurements.
* Mortality was determined 1 day after glucose measurement.
* CKD was defined as estimated glomerular filtration rate of less than 60 mL/minute/1.73 m2.
* Hypoglycemia was defined as a glucose level of less than 70 mg/dL.
* Compared with patients without CKD, those with CKD had a higher incidence of hypoglycemia.
* The risk for hypoglycemia was highest in individuals with both CKD and diabetes.
* For CKD vs no CKD, respectively, the rate of hypoglycemia in patients with diabetes was 10.72 vs 5.33 per 100 patient-months, and it was 3.46 vs 2.23 per 100 patient-months in patients without diabetes.
* At all levels of hypoglycemia, the odds of 1-day mortality were increased, but these odds were somewhat attenuated in patients with CKD vs those without CKD. The investigators suggest that this might relate to an increased quality of care in these patients with CKD vs diabetic patients without CKD.
* Adjusted odds ratios for 1-day mortality associated with glucose values of less than 50 mg/dL, 50 to 59 mg/dL, and 60 to 69 mg/dL, respectively, vs a glucose level of 70 mg/dL or more, were 6.09, 4.10, and 1.85 for inpatient records from patients with CKD; 9.95, 3.79, and 2.54 for inpatient records from patients without CKD; 6.84, 3.28, and 3.98 for outpatient records from patients with CKD; and 13.28, 7.36, and 4.34 for outpatient records from patients without CKD.
* The investigators concluded that CKD is a risk for hypoglycemia, with or without diabetes, and that the excessive mortality associated with hypoglycemia makes this complication a significant threat to patient safety in CKD.
* Limitations of the study include retrospective design, use of administrative data subject to recording errors and potential nonrandom differences between exposure groups, limited generalizability, and lack of medication records.

Clinical Implications

* In a retrospective analysis of a cohort of predominantly male veterans, patients with CKD had a higher incidence of hypoglycemia vs those without CKD. The risk for hypoglycemia was highest in individuals with both CKD and diabetes.
* At all levels of hypoglycemia, the odds of 1-day mortality were increased, but these odds were somewhat attenuated in patients with CKD vs those without CKD, which the investigators suggest that this might relate to an increased quality of care in these patients with CKD vs diabetic patients without CKD.

Source : http://cme.medscape.com/viewarticle/702774?sssdmh=dm1.472244&src=nldne