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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 proteins from four patients who had no change in their serum creatinine over the course of the study were compared by liquid chromatography/tandem mass spectrometry to four that had a least 60% increase in serum creatinine during follow up. Baseline serum creatinine (1.2±0.09 vs. 1.2±0.13 mg/dl), albuminuria (5.6±4 vs. 7.4±3 mg/g Cr) and length of follow up (5.7±0.09 vs. 5.6±0.25 years) were not different between groups. We identified 327 proteins in at least one of the patients (table 1 and supplemental table 1). One hundred seven proteins were expressed in at least one patient in the group that increased their serum creatinine that were not expressed in any patients in the stable group (Figure 1A). From the group of proteins that were expressed only in one group, haptoglobin was the most abundant protein and had the highest fold change. The sequence coverage of haptoglobin by mass spectrometry is shown in supplemental figure 1. Agrin was the only protein that was statistically different between the groups in the proteomic analysis (p<0.05) although it would not have reached statistical significance if we had corrected for multiple comparisons. The best performing candidates were visualized with a volcano plot which maps the p value for the differences between groups against the fold change difference between groups (figure 1B). Hierarchical clustering as shown in heat map (supplemental figure 2) revealed a cluster of 8 proteins including haptoglobin (Apolipoprotein D, Hemopexin, Vitamin D-binding protein, Ceruloplasmin, Alpha-2-HS-glycoprotein, Alpha-1B-glycoprotein and Alpha-1-antitrypsin).


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 proteins from four patients who had no change in their serum creatinine over the course of the study were compared by liquid chromatography/tandem mass spectrometry to four that had a least 60% increase in serum creatinine during follow up. Baseline serum creatinine (1.2±0.09 vs. 1.2±0.13 mg/dl), albuminuria (5.6±4 vs. 7.4±3 mg/g Cr) and length of follow up (5.7±0.09 vs. 5.6±0.25 years) were not different between groups. We identified 327 proteins in at least one of the patients (table 1 and supplemental table 1). One hundred seven proteins were expressed in at least one patient in the group that increased their serum creatinine that were not expressed in any patients in the stable group (Figure 1A). From the group of proteins that were expressed only in one group, haptoglobin was the most abundant protein and had the highest fold change. The sequence coverage of haptoglobin by mass spectrometry is shown in supplemental figure 1. Agrin was the only protein that was statistically different between the groups in the proteomic analysis (p<0.05) although it would not have reached statistical significance if we had corrected for multiple comparisons. The best performing candidates were visualized with a volcano plot which maps the p value for the differences between groups against the fold change difference between groups (figure 1B). Hierarchical clustering as shown in heat map (supplemental figure 2) revealed a cluster of 8 proteins including haptoglobin (Apolipoprotein D, Hemopexin, Vitamin D-binding protein, Ceruloplasmin, Alpha-2-HS-glycoprotein, Alpha-1B-glycoprotein and Alpha-1-antitrypsin).

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