How does CKD affect HbA1c?

HOW DOES CHRONIC KIDNEY DISEASE AFFECT HBA1C?: A number of factors determine HbA1c other than the level of glucose exposure alone. In an subset analysis of the Atherosclerosis Risk in Communities study of 941 diabetic people with varying degrees of chronic kidney disease (CKD), as well as 724 who did not have CKD, and mean age in the eighth decade, Jung et al. ask whether HbA1c is reliable as an indicator of glycemia in people with kidney disease (CKD) to the same degree as in those not having kidney disease, and, if not, whether measures of glycated serum proteins may be more useful. The only available measure of glycemia for comparison was a single fasting glucose level, and the authors acknowledge that this gives an incomplete measure, particularly in people with relatively mild diabetes, whose mean HbA1c was 6.4%, with most having levels of 7.5% or lower. In patients of this sort, postprandial glucose levels may better explain variations in mean HbA1c. Recognizing that the dataset may be limited, Jung et al. nevertheless give an intriguingly negative answer to the first question, of the reliability of HbA1c with kidney disease. Using Deming regression analysis, Jung et al. showed that the correlation between HbA1c and fasting glucose weakens as renal function worsens, and, moreover, that this appears particularly to be the case in people with anemia (hemoglobin <130 and <120 g/L for men and women, respectively), confirming earlier observations. Among those diabetic people with neither anemia nor CKD, the correlation coefficient between HbA1c and fasting glucose was r = 0.70, compared with r = 0.35 among those with both anemia and very severe CKD (estimated glomerular filtration rate [eGFR] <30 or <45 mL/min per 1.73 m² with at least microalbuminuria, or eGFR <60 mL/min per 1.73 m² with macroalbuminuria). As far as the second question, of whether the alternative measures, namely fructosamine and glycated albumin, may be more useful with CKD, Jung et al. found that these parameters are equally flawed with CKD. Intriguingly, this suggests that anemia affects indirect measures of glycemic exposure not only by its association with more rapid erythrocyte turnover, but, more generally, also as a marker of a catabolic state with altered plasma protein turnover. How, then, should we assess a given diabetic person's degree of glycemic control in the presence of CKD (or of anemia, which, per Jung et al., was, even without CKD, also associated with a reduction in the correlation between HbA1c and fasting glucose)? Jung et al. suggest the use of continuous glucose monitoring to estimate average glucose. Although becoming recognized as an important tool, this technology is not as generally available as the simpler self-monitoring of blood glucose (SMBG). In an earlier analysis of potential complexities of HbA1c as a measure of glycemic exposure, we showed that self-monitored plasma glucose profiles suggest that approximately 10% of individuals with diabetes have HbA1c substantially above and another 10% have HbA1c substantially below those that may be anticipated based on mean glucose levels. In clinical practice, then, we should consider encouraging older people with diabetes and CKD to perform SMBG to more adequately interpret HbA1c results.