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Enzymes and Protein Markers |
1
Division of Nephrology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, and
2
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213.
a Address correspondence to this author at: Division of Pediatric Nephrology, Children's Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto Street, Pittsburgh, PA 15213. Fax 412-692-7443.
Urinary samples were concentrated rapidly and efficiently and were used
to develop several protein assays that may be of value in monitoring
individuals with progressive renal disorders. Transforming growth
factor-ß1 (TGF-ß1) and retinol binding protein (RBP) were measured
with modification of commercially available methods used to assay serum
specimens; type 3 collagen (T3C) was measured with a new
immunonephelometric assay. The precision characteristics of these
assays are comparable with those reported for microalbuminuria. The
clinical utility of measuring a panel of these markers was demonstrated
in urine samples from 16 control subjects and from 46 individuals with
insulin-dependent diabetes mellitus (IDDM) with various albumin
excretion rates (AERs). TGF-ß1 and T3C were used as markers of
cytokine expression and of the renal fibrogenic process, whereas RBP
excretion served as a marker of tubular injury or dysfunction. Compared
with controls, T3C excretion was significantly increased in 18
normoalbuminuric and further increased in 13 microalbuminuric (AER
20 
200 µg/min) IDDM subjects. RBP excretion was increased in
macroalbuminuric IDDM subjects (AER >200 µg/min, overt nephropathy).
Significant correlations were also found between AER and RBP in all but
macroalbuminuric individuals, whereas TGF-ß1 correlated with T3C
excretion in controls and in normoalbuminuric diabetic subjects.
Urinary RBP but not AER was an excellent predictor of diabetic
nephropathy as defined by serum creatinine (P =
0.0001). This underscores the importance of an early tubulopathy in the
subsequent development of glomerulopathy and overt nephropathy. The
data suggest that longitudinal monitoring of a panel of urinary markers
such as that used in the current study may better define their
relevance in progressive glomerulosclerosis and may also provide
greater insight into the mechanisms underlying such process.
The following articles in journals at HighWire Press have cited this article:
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  A. Mima, H. Arai, T. Matsubara, H. Abe, K. Nagai, Y. Tamura, K. Torikoshi, M. Araki, H. Kanamori, T. Takahashi, et al. Urinary Smad1 Is a Novel Marker to Predict Later Onset of Mesangial Matrix Expansion in Diabetic Nephropathy Diabetes, June 1, 2008; 57(6): 1712 - 1722. [Abstract] [Full Text] [PDF]
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 K. Takebayashi, M. Suetsugu, S. Wakabayashi, Y. Aso, and T. Inukai Retinol Binding Protein-4 Levels and Clinical Features of Type 2 Diabetes Patients J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2712 - 2719. [Abstract] [Full Text] [PDF]
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 R. E. Gilbert, S. A. Kim, K. R. Tuttle, G. L. Bakris, R. D. Toto, J. B. McGill, D. J. Haney, D. J. Kelly, and P. W. Anderson Effect of Ruboxistaurin on Urinary Transforming Growth Factor-{beta} in Patients With Diabetic Nephropathy and Type 2 Diabetes Diabetes Care, April 1, 2007; 30(4): 995 - 996. [Full Text] [PDF]
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 T. A. McGowan, S. R. Dunn, B. Falkner, and K. Sharma Stimulation of Urinary TGF-{beta} and Isoprostanes in Response to Hyperglycemia in Humans Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 263 - 268. [Abstract] [Full Text] [PDF]
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J. J. Wang, S. X. Zhang, K. Lu, Y. Chen, R. Mott, S. Sato, and J.-x. Ma Decreased Expression of Pigment Epithelium-Derived Factor Is Involved in the Pathogenesis of Diabetic Nephropathy Diabetes, January 1, 2005; 54(1): 243 - 250. [Abstract] [Full Text] [PDF]
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 B. F. Schrijvers, A. S. De Vriese, and A. Flyvbjerg From Hyperglycemia to Diabetic Kidney Disease: The Role of Metabolic, Hemodynamic, Intracellular Factors and Growth Factors/Cytokines Endocr. Rev., December 1, 2004; 25(6): 971 - 1010. [Abstract] [Full Text] [PDF]
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R. E. Gilbert, A. Akdeniz, S. Weitz, W. R. Usinger, C. Molineaux, S. E. Jones, R. G. Langham, and G. Jerums Urinary Connective Tissue Growth Factor Excretion in Patients With Type 1 Diabetes and Nephropathy Diabetes Care, September 1, 2003; 26(9): 2632 - 2636. [Abstract] [Full Text] [PDF]
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 H. C. Park, Z. G. Xu, S. Choi, Y. S. Goo, S. W. Kang, K. H. Choi, S. K. Ha, H. Y. Lee, and D. S. Han Effect of losartan and amlodipine on proteinuria and transforming growth factor-{beta}1 in patients with IgA nephropathy Nephrol. Dial. Transplant., June 1, 2003; 18(6): 1115 - 1121. [Abstract] [Full Text] [PDF]
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C. A. Houlihan, A. Akdeniz, C. Tsalamandris, M. E. Cooper, G. Jerums, and R. E. Gilbert Urinary Transforming Growth Factor-{beta} Excretion in Patients With Hypertension, Type 2 Diabetes, and Elevated Albumin Excretion Rate: Effects of angiotensin receptor blockade and sodium restriction Diabetes Care, June 1, 2002; 25(6): 1072 - 1077. [Abstract] [Full Text] [PDF]
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R. E. Gilbert, A. Akdeniz, T. J. Allen, and G. Jerums Urinary transforming growth factor-{beta} in patients with diabetic nephropathy: implications for the pathogenesis of tubulointerstitial pathology Nephrol. Dial. Transplant., December 1, 2001; 16(12): 2442 - 2443. [Full Text] [PDF]
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M. P. Cohen, C. W. Shearman, and G. T. Lautenslager Serum Type IV Collagen in Diabetic Patients at Risk for Nephropathy Diabetes Care, August 1, 2001; 24(8): 1324 - 1327. [Abstract] [Full Text] [PDF]
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M. P. Cohen, G. T. Lautenslager, and C. W. Shearman Increased Collagen IV Excretion in Diabetes: A marker of compromised filtration function Diabetes Care, May 1, 2001; 24(5): 914 - 918. [Abstract] [Full Text]
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