High Glycated Albumin and Mortality in Persons with Diabetes Mellitus on Hemodialysis

Abstract

BACKGROUND Monitoring glycemic control with hemoglobin A1c (A1c) in hemodialysis patients may be compromised by anemia and erythropoietin therapy. Glycated albumin (GA) is an alternative measure of glycemic control but is not commonly used because of insufficient evidence of association to clinical outcomes. We tested whether GA measurements were associated with mortality in hemodialysis patients with diabetes mellitus. METHODS The German Diabetes and Dialysis Study (4D) investigated effects of atorvastatin on survival in 1,255 patients with diabetes mellitus receiving hemodialysis. We measured GA during months 0, 6, and 12. Cox proportional hazards analysis was used to measure associations between GA and A1c and all-cause mortality. RESULTS Patients with high baseline GA (fourth quartile) had a 42% higher 4-year mortality compared to those in the first quartile (HR 1.42; 95% confidence interval 1.09–1.85, p=0.009). Repeated measurements of GA during year one also demonstrated that participants in the top quartile for GA (analyzed as a time-varying covariate) had a 39% increased 4-year mortality (HR 1.39; 95% confidence interval 1.05–1.85, p=0.022). The associations between high A1c and mortality using similar analyses were less consistent; mortality in participants with baseline A1c values in the 3rd quartile was increased compared to 1st quartile (HR 1.36; 95% confidence interval 1.04–1.77, p=0.023), but risk was not significantly increased in the 2nd or 4th quartiles, and there was a less consistent association between time-varying A1c values and mortality. CONCLUSIONS High GA measurements are consistently associated with increased mortality in patients with diabetes mellitus on hemodialysis.

Performance of non‐traditional hyperglycemia biomarkers by chronic kidney disease status in older adults with diabetes: Results from the Atherosclerosis Risk in Communities Study

“…In randomized clinical trials, reducing HbA1c in people with CKD has been associated with fewer microvascular complications . There is a growing literature demonstrating the prognostic value of glycated albumin and fructosamine with clinical outcomes, but there have been few studies on the performance of these biomarkers in people with CKD . There are presently no clinical trial data demonstrating the effectiveness of glycated albumin or fructosamine as glycemic targets in people with moderate CKD.…”

“…Both markers reflect average glycemia over the past 2–3 weeks . Prior studies have suggested that HbA1c underestimates hyperglycemia in advanced CKD, but most of these studies have been conducted among individuals with advanced stages of kidney disease, including dialysis patients . However, the vast majority of people with CKD will develop advanced CKD requiring renal replacement therapy and it is unclear whether HbA1c underestimates glycemia in people with early CKD.…”

“…7 Prior studies have suggested that HbA1c underestimates hyperglycemia in advanced CKD, but most of these studies have been conducted among individuals with advanced stages of kidney disease, including dialysis patients. 5,[8][9][10] However, the vast majority of people with CKD will develop advanced CKD requiring renal replacement therapy and it is unclear whether HbA1c underestimates glycemia in people with early CKD. To our knowledge, no studies have conducted head-to-head comparisons of HbA1c, glycated albumin, and fructosamine with fasting glucose.…”

Comparison of Glycemic Markers in Chronic Hemodialysis Using Continuous Glucose Monitoring

“…The notion that GA is diagnostically more informative is also supported by studies showing that GA is a stronger indicator of target-organ damage and microvascular complications of diabetes [14, 24-26]. In addition, prospective observational studies evaluating the prognostic significance of GA in hemodialysis showed that GA, but not HbA1c, was able to predict the risk for future cardiovascular events and all-cause mortality independently from other established cardiovascular risk factors [12, 13, 25]. …”

“…Clinical studies showed that GA provides a more accurate reflection of short-term glycemic control status (approximately of the past 2–3 weeks) [10, 11] and is superior to HbA1c in prognosticating the risk of future cardiovascular events and mortality [12-14]. It has to be noted, however, that these studies are possibly limited by the fact that glycated analogs were tested against a random small sample of glucose measurements obtained via intermittent blood glucose monitoring; these sporadic measurements may be not representative of the high blood glucose variability in hemodialysis patients.…”