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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: Urine samples from 30 patients with normal renal function and an ACR <30 mg/g at the time of enrollment were analyzed to measure a set of candidate urine markers including the two lead candidates, agrin and haptoglobin. The stable function group included 18 patients that had no increase in serum creatinine over the next 6 years. The progressor group included 12 patients that had at least a 60% increase in serum creatinine. Seven proteins were measured simultaneously by selected reaction monitoring (SRM) in the baseline sample. The proteins were chosen because they increased in the discovery proteomic analysis (haptoglobin, angiotensinogen, agrin and mannan-binding lectin serine protease 2), decreased in the proteomic analysis (LAMP-2) or were shown to increase in diabetic nephropathy in the literature (NGAL [26–28] and uromodulin [29]). Haptoglobin was able to discriminate between groups in this verification study but agrin was not (Figure 2). Angiotensinogen and NGAL appear to be promising candidate markers but were not further evaluated in this study.


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: Urine samples from 30 patients with normal renal function and an ACR <30 mg/g at the time of enrollment were analyzed to measure a set of candidate urine markers including the two lead candidates, agrin and haptoglobin. The stable function group included 18 patients that had no increase in serum creatinine over the next 6 years. The progressor group included 12 patients that had at least a 60% increase in serum creatinine. Seven proteins were measured simultaneously by selected reaction monitoring (SRM) in the baseline sample. The proteins were chosen because they increased in the discovery proteomic analysis (haptoglobin, angiotensinogen, agrin and mannan-binding lectin serine protease 2), decreased in the proteomic analysis (LAMP-2) or were shown to increase in diabetic nephropathy in the literature (NGAL [26–28] and uromodulin [29]). Haptoglobin was able to discriminate between groups in this verification study but agrin was not (Figure 2). Angiotensinogen and NGAL appear to be promising candidate markers but were not further evaluated in this study.

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