Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction
Connective tissue growth factor (CTGF; CCN2) plays a role in the development of diabetic nephropathy (DN). Urinary CTGF (uCTGF) is elevated in DN patients and has been proposed as a biomarker for disease progression, but it is unknown which pathophysiological factors contribute to elevated uCTGF. We...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2015/539787 |
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| author | Karin G. F. Gerritsen Jan Willem Leeuwis Maarten P. Koeners Stephan J. L. Bakker Willem van Oeveren Jan Aten Lise Tarnow Peter Rossing Jack F. M. Wetzels Jaap A. Joles Robbert Jan Kok Roel Goldschmeding Tri Q. Nguyen |
| author_facet | Karin G. F. Gerritsen Jan Willem Leeuwis Maarten P. Koeners Stephan J. L. Bakker Willem van Oeveren Jan Aten Lise Tarnow Peter Rossing Jack F. M. Wetzels Jaap A. Joles Robbert Jan Kok Roel Goldschmeding Tri Q. Nguyen |
| author_sort | Karin G. F. Gerritsen |
| collection | DOAJ |
| description | Connective tissue growth factor (CTGF; CCN2) plays a role in the development of diabetic nephropathy (DN). Urinary CTGF (uCTGF) is elevated in DN patients and has been proposed as a biomarker for disease progression, but it is unknown which pathophysiological factors contribute to elevated uCTGF. We studied renal handling of CTGF by infusion of recombinant CTGF in diabetic mice. In addition, uCTGF was measured in type 1 DN patients and compared with glomerular and tubular dysfunction and damage markers. In diabetic mice, uCTGF was increased and fractional excretion (FE) of recombinant CTGF was substantially elevated indicating reduced tubular reabsorption. FE of recombinant CTGF correlated with excretion of endogenous CTGF. CTGF mRNA was mainly localized in glomeruli and medullary tubules. Comparison of FE of endogenous and recombinant CTGF indicated that 60% of uCTGF had a direct renal source, while 40% originated from plasma CTGF. In DN patients, uCTGF was independently associated with markers of proximal and distal tubular dysfunction and damage. In conclusion, uCTGF in DN is elevated as a result of both increased local production and reduced reabsorption due to tubular dysfunction. We submit that uCTGF is a biomarker reflecting both glomerular and tubulointerstitial hallmarks of diabetic kidney disease. |
| format | Article |
| id | doaj-art-ae0716b5b46846f58ca30a86b9f355c0 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-ae0716b5b46846f58ca30a86b9f355c02025-02-03T01:29:10ZengWileyJournal of Diabetes Research2314-67452314-67532015-01-01201510.1155/2015/539787539787Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular DysfunctionKarin G. F. Gerritsen0Jan Willem Leeuwis1Maarten P. Koeners2Stephan J. L. Bakker3Willem van Oeveren4Jan Aten5Lise Tarnow6Peter Rossing7Jack F. M. Wetzels8Jaap A. Joles9Robbert Jan Kok10Roel Goldschmeding11Tri Q. Nguyen12Department of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, NetherlandsDepartment of Internal Medicine, University Medical Center Groningen, 9700 RB Groningen, NetherlandsHaemoScan, 9723 JC Groningen, NetherlandsDepartment of Pathology, Academic Medical Center, 1105 AZ Amsterdam, NetherlandsSteno Diabetes Center, 2820 Gentofte, DenmarkSteno Diabetes Center, 2820 Gentofte, DenmarkDepartment of Nephrology, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, NetherlandsDepartment of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, NetherlandsUtrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3584 CX Utrecht, NetherlandsConnective tissue growth factor (CTGF; CCN2) plays a role in the development of diabetic nephropathy (DN). Urinary CTGF (uCTGF) is elevated in DN patients and has been proposed as a biomarker for disease progression, but it is unknown which pathophysiological factors contribute to elevated uCTGF. We studied renal handling of CTGF by infusion of recombinant CTGF in diabetic mice. In addition, uCTGF was measured in type 1 DN patients and compared with glomerular and tubular dysfunction and damage markers. In diabetic mice, uCTGF was increased and fractional excretion (FE) of recombinant CTGF was substantially elevated indicating reduced tubular reabsorption. FE of recombinant CTGF correlated with excretion of endogenous CTGF. CTGF mRNA was mainly localized in glomeruli and medullary tubules. Comparison of FE of endogenous and recombinant CTGF indicated that 60% of uCTGF had a direct renal source, while 40% originated from plasma CTGF. In DN patients, uCTGF was independently associated with markers of proximal and distal tubular dysfunction and damage. In conclusion, uCTGF in DN is elevated as a result of both increased local production and reduced reabsorption due to tubular dysfunction. We submit that uCTGF is a biomarker reflecting both glomerular and tubulointerstitial hallmarks of diabetic kidney disease.http://dx.doi.org/10.1155/2015/539787 |
| spellingShingle | Karin G. F. Gerritsen Jan Willem Leeuwis Maarten P. Koeners Stephan J. L. Bakker Willem van Oeveren Jan Aten Lise Tarnow Peter Rossing Jack F. M. Wetzels Jaap A. Joles Robbert Jan Kok Roel Goldschmeding Tri Q. Nguyen Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction Journal of Diabetes Research |
| title | Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction |
| title_full | Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction |
| title_fullStr | Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction |
| title_full_unstemmed | Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction |
| title_short | Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction |
| title_sort | elevated urinary connective tissue growth factor in diabetic nephropathy is caused by local production and tubular dysfunction |
| url | http://dx.doi.org/10.1155/2015/539787 |
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