Measurement of renal production of TGF-B1 and endothelin-1 in diabetic and non-diabetic patients

B. Alzahabi, S. Kapoor, T. McGowan, B. Kumik, P. Kurnik, F. N. Ziyadeh, L. Weisberg, Kumar Sharma

Research output: Contribution to journalArticle

Abstract

Transforming growth factor-beta-1 (TGF-b1) and Endothelin-1 (ET1) have been implicated in the pathogenesis of diabetic renal disease. To evaluate if renal production of TGF-b1 and ET-1 is enhanced in diabetic patients, we studied diabetic (D) and non-diabetic patients (N) with varying degrees of renal function undergoing elective cardiac cathetehzation. A thermodilution catheter was inserted into the left renal vein for blood sampling and measurement of renal blood flow (RBF). Renal vein (RV) and aortic (AO) plasma levels of TGF-b1 and ET-1 levels were measured by sandwich ELISA and RIA, respectively. 22 patients were enrolled, 11 N and 11 D ( all NIDDM, 3 taking insulin). Renal vein (RV) levels of TGF-bt were almost two-fold greater in D vs N (15.6 ±1.9 vs 8.4 ±0.8 ng/ml, respectively, P=0.003) but not different in the aortic (Ao) samples (14.2 ±1.9 vs 13.4 ±1.1 ng/ml). 7/11 of D had greater renal vein levels than aortic levels, indicating renal production of TGF-b1 whereas all 11 of N had lower renal vein levels as compared to aortic levels, indicating renal clearance of TGF-b1. Urinary levels of TGF-b1 were significantly elevated in D vs N (2.59 ±0.94 vs 0.23 ± 0.09 ng/mg créât, P=0.01 ), demonstrating that impaired renal clearance was not the explanation for elevated renal vein levels. Renal vein TGF-b1 levels were inversely correlated with GFR in both D and N. Both aortic and renal vein levels of ET-1 were significantly greater in D than in N, (Ao: 42 ±4.3 vs 29.3 ±1.5, P=0.01; RV: 44.1 ±4.4 vs 28.8 ±1.5 fM, P<0.01). We conclude that patients with NIDDM manifest net renal production of TGF-b1 and have elevated systemic levels of ET-1 which may contribute to the development of diabetic nephropathy.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996
Externally publishedYes

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Renal Veins
Endothelin-1
Transforming Growth Factor beta
Kidney
Type 2 Diabetes Mellitus
Blood
Catheters
Thermodilution
Renal Circulation
Diabetic Nephropathies
Insulin
Sampling
Enzyme-Linked Immunosorbent Assay
Plasmas

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Measurement of renal production of TGF-B1 and endothelin-1 in diabetic and non-diabetic patients. / Alzahabi, B.; Kapoor, S.; McGowan, T.; Kumik, B.; Kurnik, P.; Ziyadeh, F. N.; Weisberg, L.; Sharma, Kumar.

In: Journal of Investigative Medicine, Vol. 44, No. 3, 01.01.1996.

Research output: Contribution to journalArticle

Alzahabi, B, Kapoor, S, McGowan, T, Kumik, B, Kurnik, P, Ziyadeh, FN, Weisberg, L & Sharma, K 1996, 'Measurement of renal production of TGF-B1 and endothelin-1 in diabetic and non-diabetic patients', Journal of Investigative Medicine, vol. 44, no. 3.
Alzahabi B, Kapoor S, McGowan T, Kumik B, Kurnik P, Ziyadeh FN et al. Measurement of renal production of TGF-B1 and endothelin-1 in diabetic and non-diabetic patients. Journal of Investigative Medicine. 1996 Jan 1;44(3).
Alzahabi, B. ; Kapoor, S. ; McGowan, T. ; Kumik, B. ; Kurnik, P. ; Ziyadeh, F. N. ; Weisberg, L. ; Sharma, Kumar. / Measurement of renal production of TGF-B1 and endothelin-1 in diabetic and non-diabetic patients. In: Journal of Investigative Medicine. 1996 ; Vol. 44, No. 3.
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AU - Alzahabi, B.

AU - Kapoor, S.

AU - McGowan, T.

AU - Kumik, B.

AU - Kurnik, P.

AU - Ziyadeh, F. N.

AU - Weisberg, L.

AU - Sharma, Kumar

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N2 - Transforming growth factor-beta-1 (TGF-b1) and Endothelin-1 (ET1) have been implicated in the pathogenesis of diabetic renal disease. To evaluate if renal production of TGF-b1 and ET-1 is enhanced in diabetic patients, we studied diabetic (D) and non-diabetic patients (N) with varying degrees of renal function undergoing elective cardiac cathetehzation. A thermodilution catheter was inserted into the left renal vein for blood sampling and measurement of renal blood flow (RBF). Renal vein (RV) and aortic (AO) plasma levels of TGF-b1 and ET-1 levels were measured by sandwich ELISA and RIA, respectively. 22 patients were enrolled, 11 N and 11 D ( all NIDDM, 3 taking insulin). Renal vein (RV) levels of TGF-bt were almost two-fold greater in D vs N (15.6 ±1.9 vs 8.4 ±0.8 ng/ml, respectively, P=0.003) but not different in the aortic (Ao) samples (14.2 ±1.9 vs 13.4 ±1.1 ng/ml). 7/11 of D had greater renal vein levels than aortic levels, indicating renal production of TGF-b1 whereas all 11 of N had lower renal vein levels as compared to aortic levels, indicating renal clearance of TGF-b1. Urinary levels of TGF-b1 were significantly elevated in D vs N (2.59 ±0.94 vs 0.23 ± 0.09 ng/mg créât, P=0.01 ), demonstrating that impaired renal clearance was not the explanation for elevated renal vein levels. Renal vein TGF-b1 levels were inversely correlated with GFR in both D and N. Both aortic and renal vein levels of ET-1 were significantly greater in D than in N, (Ao: 42 ±4.3 vs 29.3 ±1.5, P=0.01; RV: 44.1 ±4.4 vs 28.8 ±1.5 fM, P<0.01). We conclude that patients with NIDDM manifest net renal production of TGF-b1 and have elevated systemic levels of ET-1 which may contribute to the development of diabetic nephropathy.

AB - Transforming growth factor-beta-1 (TGF-b1) and Endothelin-1 (ET1) have been implicated in the pathogenesis of diabetic renal disease. To evaluate if renal production of TGF-b1 and ET-1 is enhanced in diabetic patients, we studied diabetic (D) and non-diabetic patients (N) with varying degrees of renal function undergoing elective cardiac cathetehzation. A thermodilution catheter was inserted into the left renal vein for blood sampling and measurement of renal blood flow (RBF). Renal vein (RV) and aortic (AO) plasma levels of TGF-b1 and ET-1 levels were measured by sandwich ELISA and RIA, respectively. 22 patients were enrolled, 11 N and 11 D ( all NIDDM, 3 taking insulin). Renal vein (RV) levels of TGF-bt were almost two-fold greater in D vs N (15.6 ±1.9 vs 8.4 ±0.8 ng/ml, respectively, P=0.003) but not different in the aortic (Ao) samples (14.2 ±1.9 vs 13.4 ±1.1 ng/ml). 7/11 of D had greater renal vein levels than aortic levels, indicating renal production of TGF-b1 whereas all 11 of N had lower renal vein levels as compared to aortic levels, indicating renal clearance of TGF-b1. Urinary levels of TGF-b1 were significantly elevated in D vs N (2.59 ±0.94 vs 0.23 ± 0.09 ng/mg créât, P=0.01 ), demonstrating that impaired renal clearance was not the explanation for elevated renal vein levels. Renal vein TGF-b1 levels were inversely correlated with GFR in both D and N. Both aortic and renal vein levels of ET-1 were significantly greater in D than in N, (Ao: 42 ±4.3 vs 29.3 ±1.5, P=0.01; RV: 44.1 ±4.4 vs 28.8 ±1.5 fM, P<0.01). We conclude that patients with NIDDM manifest net renal production of TGF-b1 and have elevated systemic levels of ET-1 which may contribute to the development of diabetic nephropathy.

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