Effect of Furosemide on Obesity-induced Glomerular Hyperfiltration

Summary

Background: Obesity is associated with a high prevalence of chronic kidney disease. The glomerular hyperfiltration associated with obesity may play a role in the pathogenesis of obesity associated chronic kidney disease. Attenuation of hyperfiltration by pharmacological means may slow down the development and progression of chronic renal failure. The investigators have previously shown that acetazolamide, a proximally acting diuretic that activates TGF by increasing solute delivery to the macula densa, abates glomerular hyperfiltration. The present study was designed to test the hypothesis that this decrease in hyperfiltration is specific to acetazolamide and not due to a non specific diuretic effect. The aim of the present study is to evaluate the effects of the administration of furosemide p.o. to subjects with severe obesity on glomerular hemodynamics. Methods: Ten obese subjects will participate in the study. They will undergo measurement of glomerular filtration rate (inulin clearance) (GFR), renal plasma flow (RPF) (p-aminohippuric acid clearance), filtration fraction, fractional excretion of lithium (FE LI) and blood pressure, before and after administration of oral furosemide 20 to 40 mg bid for 3 days. The effects of furosemide on glomerular hemodynamics in obese subjects will be compared to the previously studied effects of acetazolamide.

Timeline

Start

2009-09

Primary completion

2010-05

Completion

2010-07

Publications

• Background 1. Chagnac A et al: Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol. 2000;278(5):F817-22. 2. Chagnac A et al: The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol. 2003 Jun;14(6):1480-6. 3. Navar LG: Renal autoregulation: perspectives from whole kidney and single nephron studies. Am J Physiol. 1978 May;234(5):F357-70. 4. Deng A etal: Hemodynamics of early tubuloglomerular feedback resetting during reduced proximal reabsorption. Kidney Int. 2002 Dec;62(6):2136-43. 5. Dupont AG et al: Renal pharmacodynamic effects of torasemide and furosemide in normal man.Drug Res. 38(1) 1a 1998 172-175.

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