Glycated albumin, not hemoglobin A1c, predicts cardiovascular hospitalization and length of stay in diabetic patients on dialysis.

BACKGROUND: The utility of glycated hemoglobin (HbA1c) and glycated albumin (GA) in diabetic dialysis patients remains unknown. GA was previously associated with all-cause hospitalization and patient survival. Relationships between GA, HbA1c, and casual plasma glucose (PG) with cause-specific cardiovascular (CV) disease, infectious disease (ID), and vascular access- (VA) related hospitalization rates and length of stay (LOS) were assessed. METHODS: 444 prevalent diabetic dialysis patients had monthly PG, quarterly GA, and all HbA1c values recorded for 2.33 years; hospitalizations within 17 and 30 days of testing were evaluated. Best-fit, time-dependent Cox models were constructed in unadjusted, case-mix-adjusted (age, sex, race, BMI, diabetes duration, dialysis vintage), and case-mix- plus lab-adjusted (hemoglobin, albumin, phosphorus) models. RESULTS: Mean ± SD diabetes duration was 18.5 ± 10.8 years and dialysis vintage 2.9 ± 2.6 years. In fully adjusted models, CV hospitalization rates were associated with increasing GA (HR 1.32; 95% CI 1.11-1.57; p = 0.002 at 17 days; HR 1.21; p = 0.02 at 30 days) and PG (HR 1.10; 95% CI 1.02-1.17; p = 0.01 at 17 days; HR 1.07; p = 0.03 at 30 days), not HbA1c (HR 1.24; 95% CI 0.89-1.73; p = 0.21 at 17 days; HR 1.26; p = 0.10 at 30 days). LOS for CV admissions was positively associated with GA (HR 1.18; 95% CI 1.01-1.39; p = 0.03), not PG (HR 1.04; 95% CI 0.99-1.10; p = 0.15) or HbA1c (HR 1.03; 95% CI 0.92-1.15; p = 0.21). Admissions due to ID and VA complications (and LOS) did not correlate with these assays. CONCLUSIONS: Improved glycemic control based on GA and PG predicted CV-related hospitalizations; GA also predicted CV hospitalization LOS. HbA1c did not predict cause-specific hospitalizations in dialysis populations.

Relationship between assays of glycemia in diabetic subjects with advanced chronic kidney disease.

BACKGROUND: Relative to hemoglobin A(1c) (HbA(1c)), glycated albumin (GA) more accurately reflects recent glycemic control in diabetic patients on hemodialysis and peritoneal dialysis. These assays have yet to be compared in patients with advanced chronic kidney disease (CKD). METHODS: HbA(1c) and GA were simultaneously measured in 303 diabetic subjects: 70 with CKD prior to dialysis (CKD-stage 4), 184 with CKD after transplantation (TXP-stage 3) and 49 non-nephropathy controls. RESULTS: Mean estimated GFR was 76, 46 and 26 ml/min in controls, TXP-3 and CKD-4 cases, respectively. Mean (SD) HbA(1c) (%) and GA (%) concentrations were 7.30 (1.40) and 16.8 (4.9) in controls, 7.28 (1.66) and 21.5 (6.4) in CKD-4 cases, and 7.21 (1.62) and 21.2 (5.5) in TXP-3 cases, respectively. The GA:HbA(1c) ratio differed significantly between non-nephropathy controls and both groups of CKD patients (both p < 0.001), but not between CKD-4 and TXP-3 cases (p = 0.92). The glucose:HbA(1c) ratio was inversely associated with GFR in all 254 nephropathy cases (r = -0.13; p = 0.04), while glucose:GA did not vary significantly based upon GFR (r = -0.08; p = 0.24). CONCLUSIONS: The relationship between glycated albumin and HbA(1c) is influenced by the presence of reduced GFR in diabetic patients with CKD. The accuracy of the HbA(1c) assay in diabetic subjects with severe nephropathy requires further investigation, although HbA(1c) performs relatively well with milder CKD.

End-stage renal disease in African Americans with lupus nephritis is associated with APOL1.

OBJECTIVE: Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that exhibits familial aggregation and may progress to end-stage renal disease (ESRD). LN is more prevalent among African Americans than among European Americans. This study was undertaken to investigate the hypothesis that the apolipoprotein L1 gene (APOL1) nephropathy risk alleles G1/G2, common in African Americans and rare in European Americans, contribute to the ethnic disparity in risk. METHODS: APOL1 G1 and G2 nephropathy alleles were genotyped in 855 African American SLE patients with LN-ESRD (cases) and 534 African American SLE patients without nephropathy (controls) and tested for association under a recessive genetic model, by logistic regression. RESULTS: Ninety percent of the SLE patients were female. The mean ± SD age at SLE diagnosis was significantly lower in LN-ESRD cases than in SLE non-nephropathy controls (27.3 ± 10.9 years versus 39.5 ± 12.2 years). The mean ± SD time from SLE diagnosis to development of LN-ESRD in cases was 7.3 ± 7.2 years. The G1/G2 risk alleles were strongly associated with SLE-ESRD, with 25% of cases and 12% of controls having 2 nephropathy alleles (odds ratio [OR] 2.57, recessive model P = 1.49 × 10(-9)), and after adjustment for age, sex, and ancestry admixture (OR 2.72, P = 6.23 × 10(-6)). The age-, sex-, and admixture-adjusted population attributable risk for ESRD among patients with G1/G2 polymorphisms was 0.26, compared to 0.003 among European American patients. The mean time from SLE diagnosis to ESRD development was ∼2 years earlier among individuals with APOL1 risk genotypes (P = 0.01). CONCLUSION: APOL1 G1/G2 alleles strongly impact the risk of LN-ESRD in African Americans, as well as the time to progression to ESRD. The high frequency of these alleles in African Americans with near absence in European Americans explains an important proportion of the increased risk of LN-ESRD in African Americans.

Glycated albumin and risk of death and hospitalizations in diabetic dialysis patients.

BACKGROUND AND OBJECTIVES: Relative to hemoglobin (Hb) A(1c), glycated albumin (GA) more accurately reflects glycemic control in patients with diabetes mellitus and ESRD. We determined the association between GA, HbA(1c), and glucose levels with survival and hospitalizations in diabetic dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Quarterly GA levels were measured for up to 2.33 years in 444 prevalent patients with diabetes and ESRD. Proportional hazard time-dependent covariate models were computed with adjustment for demographic characteristics, comorbidities, and laboratory variables. Similar analyses were performed for available HbA(1c) and monthly random serum glucose determinations. RESULTS: The participants were 53% male, 54% African American, 43% Caucasian, 90% on hemodialysis, with a mean (SD) age of 62 (12) years and median follow-up duration of 2.25 years. GA and HbA(1c) mean ± SD 21.5% ± 6.0%, median 20.4% and mean ± SD 6.9% ± 6.6%, median 1.6%, respectively. There were 156 deaths during the observation period. In best-fit models, predictors of death included increasing GA, increasing age, presence of peripheral vascular disease, decreasing serum albumin, and decreasing hemoglobin concentrations. HbA(1c) and random serum glucose concentrations were not predictive of survival. Increasing GA levels were associated with hospitalization in the 17 days after measurement, whereas HbA(1c) was not. CONCLUSIONS: In contrast to the HbA(1c) and random serum glucose values, GA accurately predicts the risk of death and hospitalizations in patients with diabetes mellitus and ESRD. The GA assay should be considered by clinicians who care for patients with diabetes on dialysis.

Comparison of glycated albumin and hemoglobin A1c concentrations in diabetic subjects on peritoneal and hemodialysis.

BACKGROUND: Relative to hemoglobin A(1c) (HbA(1c)), percentage of glycated albumin (GA%) more accurately reflects recent glycemic control in diabetic hemodialysis (HD) patients. METHODS: To determine the accuracy of glycemic assays in a larger sample including patients on peritoneal dialysis (PD), HbA(1c) and GA% were measured in 519 diabetic subjects: 55 on PD, 415 on HD, and 49 non-nephropathy controls. RESULTS: Mean +/- SD serum glucose levels were higher in HD and PD patients relative to non-nephropathy controls (HD 169.7 +/- 62 mg/dL, PD 168.6 +/- 66 mg/dL, controls 146.1 +/- 66 mg/dL; p = 0.03 HD vs controls, p = 0.13 PD vs controls). GA% was also higher in HD and PD patients (HD 20.6% +/- 8.0%, PD 19.0% +/- 5.7%, controls 15.7% +/- 7.7%; p < 0.02 HD vs controls and PD vs controls). HbA(1c) was paradoxically lower in dialysis patients (HD 6.78% +/- 1.6%, PD 6.87% +/- 1.4%, controls 7.3% +/- 1.4%; p = 0.03 HD vs controls, p = 0.12 PD vs controls). The serum glucose/HbA(1c) ratio differed significantly between dialysis patients and controls (p < 0.0001 HD vs controls, p = 0.002 PD vs controls), while serum glucose/GA% ratio was similar across groups (p = 0.96 HD vs controls, p = 0.64 PD vs controls). In best-fit multivariate models with HbA(1c) or GA% as outcome variable, dialysis status was a significant predictor of HbA(1c) but not GA%. CONCLUSIONS: The relationship between HbA(1c) and GA% differs in diabetic patients with end-stage renal disease who perform either PD or HD compared to those without nephropathy. HbA(1c) significantly underestimates glycemic control in peritoneal and hemodialysis patients relative to GA%.