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Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes.

Bhensdadia NM, Hunt KJ, Lopes-Virella MF, Michael Tucker J, Mataria MR, Alge JL, Neely BA, Janech MG, Arthur JM, Veterans Affairs Diabetes Trial (VADT) study gro - Kidney Int. (2013)

Bottom Line: Diabetic nephropathy is the leading cause of end-stage renal disease.We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio <300 mg/g).Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

ABSTRACT
Diabetic nephropathy is the leading cause of end-stage renal disease. The urinary albumin to creatinine ratio is used as a predictor for the development of nephropathy but it is neither sensitive nor specific. Here we used liquid chromatography/mass spectrometry on urine of eight normoalbuminuric patients with type 2 diabetes from the VA Diabetes Trial to identify candidate markers for loss of renal function. Initial verification of seven markers (agrin, haptoglobin, mannan-binding lectin serine protease 2, LAMP-2, angiotensinogen, NGAL, and uromodulin) in the urine of an additional 30 patients showed that haptoglobin was the best predictor of early renal functional decline. We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio <300 mg/g). In comparing the highest to lowest tertiles, the odds ratio for having early renal function decline was 2.70 (CI: 1.15, 6.32) using the haptoglobin to creatinine ratio compared with 2.50 (CI 1.14, 5.48) using the albumin to creatinine ratio after adjusting for treatment group and use of ACE inhibitors. Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance. Thus, the haptoglobin to creatinine ratio may be useful to predict patients with type 2 diabetes at risk of nephropathy before the development of macroalbuminuria or reduced glomerular filtration rate.

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Mentions: Logistic regression was used to further examine the ability of haptoglobin, HCR and ACR to predict ERFD and a creatinine increase of 50% or greater (Table 4). Individuals in the highest tertile of haptoglobin had a non-statistically significant 2-fold increased odds of developing ERFD relative to those in the lowest tertile of haptoglobin after controlling for treatment group and use of an ACE inhibitor. Parallel odds ratios for HCR and ACR were statistically significant with values of 2.70 (95% CI: 1.15, 6.32) and 2.50 (95% CI: 1.14, 5.48), respectively (Figure 3). Since creatinine based estimates of glomerular filtration rate are less accurate than iothalamate or inulin clearance estimates, we determined the ability of HCR to predict the outcomes for other measures of renal function loss. The odds ratios for these outcomes were similar (Table 4). The AUC value for the prediction of ERFD by HCR was 0.614 and by ACR was 0.621. The combined AUC was 0.664. When we used ≥50% increase in creatinine from baseline AUC value for HCR, ACR and combine HCR with ACR were 0.654, 0.709 and 0.751 respectively.


Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes.

Bhensdadia NM, Hunt KJ, Lopes-Virella MF, Michael Tucker J, Mataria MR, Alge JL, Neely BA, Janech MG, Arthur JM, Veterans Affairs Diabetes Trial (VADT) study gro - Kidney Int. (2013)

© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672380&req=5

Mentions: Logistic regression was used to further examine the ability of haptoglobin, HCR and ACR to predict ERFD and a creatinine increase of 50% or greater (Table 4). Individuals in the highest tertile of haptoglobin had a non-statistically significant 2-fold increased odds of developing ERFD relative to those in the lowest tertile of haptoglobin after controlling for treatment group and use of an ACE inhibitor. Parallel odds ratios for HCR and ACR were statistically significant with values of 2.70 (95% CI: 1.15, 6.32) and 2.50 (95% CI: 1.14, 5.48), respectively (Figure 3). Since creatinine based estimates of glomerular filtration rate are less accurate than iothalamate or inulin clearance estimates, we determined the ability of HCR to predict the outcomes for other measures of renal function loss. The odds ratios for these outcomes were similar (Table 4). The AUC value for the prediction of ERFD by HCR was 0.614 and by ACR was 0.621. The combined AUC was 0.664. When we used ≥50% increase in creatinine from baseline AUC value for HCR, ACR and combine HCR with ACR were 0.654, 0.709 and 0.751 respectively.

Bottom Line: Diabetic nephropathy is the leading cause of end-stage renal disease.We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio <300 mg/g).Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

ABSTRACT
Diabetic nephropathy is the leading cause of end-stage renal disease. The urinary albumin to creatinine ratio is used as a predictor for the development of nephropathy but it is neither sensitive nor specific. Here we used liquid chromatography/mass spectrometry on urine of eight normoalbuminuric patients with type 2 diabetes from the VA Diabetes Trial to identify candidate markers for loss of renal function. Initial verification of seven markers (agrin, haptoglobin, mannan-binding lectin serine protease 2, LAMP-2, angiotensinogen, NGAL, and uromodulin) in the urine of an additional 30 patients showed that haptoglobin was the best predictor of early renal functional decline. We then measured this in the urine of 204 patients with type 2 diabetes who did not yet have significant kidney disease (estimated glomerular filtration rate stage 2 or better and an albumin to creatinine ratio <300 mg/g). In comparing the highest to lowest tertiles, the odds ratio for having early renal function decline was 2.70 (CI: 1.15, 6.32) using the haptoglobin to creatinine ratio compared with 2.50 (CI 1.14, 5.48) using the albumin to creatinine ratio after adjusting for treatment group and use of ACE inhibitors. Addition of the haptoglobin to creatinine ratio to a model using the albumin to creatinine ratio to predict early renal function decline resulted in improved predictive performance. Thus, the haptoglobin to creatinine ratio may be useful to predict patients with type 2 diabetes at risk of nephropathy before the development of macroalbuminuria or reduced glomerular filtration rate.

Show MeSH
Related in: MedlinePlus