Correspondence *Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, 30-1, Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan

Email mabe@med.nihon-u.ac.jp

Commentary

In patients with diabetes, strict glycemic control lowers the risk of cardiovascular events—which are the main cause of death in this setting¹—and improves prognosis among those with chronic kidney disease (CKD) who undergo regular hemodialysis;² therefore, the accurate assessment of glycemic control is important to optimize outcomes.

Glycated hemoglobin (HbA_1c) level, which indicates the percentage of circulating hemoglobin that has chemically reacted with glucose, reflects the blood glucose level over the 120 days preceding the test; glucose levels during the 30 days before the test have the biggest impact on HbA_1c level. The lack of specific guidelines for assessing glycemic control in patients who are receiving hemodialysis has resulted in the HbA_1c assay—which is widely used in the general population—being the test of choice in this setting. However, in patients with diabetes who are on hemodialysis, factors such as anemia (due to reduced erythrocyte life span or iron deficiency), recent transfusions, metabolic acidosis, and administration of erythropoietin affect the accuracy of the HbA_1c assay.³ By increasing the proportion of young erythrocytes in the blood, both anemia and erythropoietin can falsely lower HbA_1c levels, which could in turn lead to a failure to diagnose hyperglycemia.⁴ Approximately 90% of patients on hemodialysis worldwide undergo erythropoietin treatment;⁵ therefore, HbA_1c might be an unsuitable marker for glycemic control in the hemodialysis setting.

On the basis of a study involving Japanese patients on hemodialysis,³ glycated albumin has been proposed to be a better marker of glycemic control than HbA_1c, as levels of glycated albumin in the blood are unaffected by changes in the survival time of erythrocytes. Peacock et al. have now sought to validate the measurement of glycated albumin as an alternative to HbA_1c quantification for the assessment of glycemic control in 307 American patients with diabetes, of whom 258 were undergoing hemodialysis and 49 did not have overt kidney disease.⁶ To quantify the level of glycated albumin, Peacock et al. utilized a new enzymatic assay that relies on an albumin-specific proteinase and, unlike the conventional assay, is not subject to interference by endogenous glycated amino acids or changes in albumin concentration.

Multiple regression analysis confirmed that both HbA_1c and glycated albumin levels were independently associated with serum glucose concentration (P <0.0001 for both). However, Peacock et al. found that the glycated-albumin:HbA_1c ratio was higher in the patients on hemodialysis than in the patients without kidney disease (2.72 vs 2.07; P <0.0001). Thus, in patients on hemodialysis, HbA_1c measurements significantly underestimate blood glucose levels compared with glycated albumin values. In addition, HbA_1c values were independently associated with hemodialysis (P <0.0001) and, in hemodialysis patients, with hemoglobin concentration (P = 0.0027) and erythropoietin dose (P = 0.03). By contrast, glycated albumin level was not significantly associated with hemodialysis, or with hemoglobin level or erythropoietin dose in patients on hemodialysis; therefore, the authors concluded that glycated albumin is a better indicator of glycemic control than HbA_1c.

The average glycated-albumin:HbA_1c ratio in the patients on hemodialysis in Peacock et al.'s study was slightly lower than that reported by Inaba et al. for the Japanese patients who were receiving hemodialysis (2.72 vs 3.81).³ This inconsistency might be due to differences between the two studies in the serum albumin assays used, the erythropoietin doses administered, the mean HbA_1c levels, or the patients' ethnicity. The mean erythropoietin dose given to the American patients on hemodialysis far exceeded that administered to their Japanese counterparts (22,876 U/week vs 5,385 U/week), and the mean HbA_1c level in the American patients on hemodialysis was higher than that in the Japanese participants (6.8% vs 5.85%). The contention by Peacock et al. that discrepancies between the two studies might be due to the large proportion of African Americans (63.6% of the hemodialysis population) in the US study is difficult to understand. African Americans have an increased risk of carrying the hemoglobin S and thalassemia genes, which are both associated with decreased erythrocyte survival and would, thus, be expected to increase, rather than decrease, the glycated-albumin:HbA_1c ratio.

Some issues remain to be clarified. In Peacock et al.'s study, glycated albumin values were measured only once. Measurement of glycated albumin level reflects glycemic control for only the 1–2 weeks preceding the assay, so repeated measurements of glycated albumin (i.e. every 2 weeks or monthly) will be required in future studies. Furthermore, it will be important to determine the clinical stage at which these measurements should be initiated (i.e. at CKD stage 3, 4, or 5, at diagnosis of renal anemia, or upon initiation of erythropoietin therapy). The use of glycated albumin levels to assess glycemic control might be limited to patients with anuria or normoalbuminuria who are receiving hemodialysis. In patients on peritoneal dialysis and those with CKD who have massive proteinuria, glycated albumin levels can be falsely reduced because of the shorter exposure time of albumin to glucose in plasma. Further investigations are also required to establish the target glycated albumin level that predicts the best prognosis for patients with diabetes who are on hemodialysis. Moreover, no long-term, large-scale clinical trials have investigated the use of glycated albumin as an indicator of glycemic control. Thus, whether this parameter is an accurate predictor of morbidity and mortality in patients with diabetes who are on hemodialysis remains to be ascertained.

References

1. Gaede P et al. (2003) Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348: 383–393 | Article | PubMed | ISI |
2. Morioka T et al. (2001) Glycemic control is a predictor of survival for diabetic patients on hemodialysis. Diabetes Care 24: 909–913 | Article | PubMed | ISI | ChemPort |
3. Inaba M et al. (2007) Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol 18: 896–903 | Article | PubMed | ChemPort |
4. Joy MS et al. (2002) Long-term glycemic control measurements in diabetic patients receiving hemodialysis. Am J Kidney Dis 39: 297–307 | Article | PubMed | ISI |
5. Pisoni RL et al. (2004) Anemia management and outcomes from 12 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 44: 94–111 | Article | PubMed |
6. Peacock TP et al. (2008) Comparison of glycated albumin and hemoglobin A_1c levels in diabetic subjects on hemodialysis. Kidney Int 73: 1062–1068 | Article | PubMed | ChemPort |

Contact the journal about this article

Subject areas under which this article appears: Dialysis (hemodialysis, peritoneal dialysis, continuous renal replacement)