RENAL HEMODYNAMIC EFFECTS OF L-ARGININE AND SODIUM-NITROPRUSSIDE IN HEART TRANSPLANT RECIPIENTS

Abstract

406 Background: Long-term treatment with Cyclosporine A (CsA) induces renal vasoconstriction with subsequent end-organ damage. An altered L-arginine (L-arg)/nitric oxide (NO) pathway may play a key role in CsA induced nephrotoxicity. The aim of the present study was to study the effect of L-arg (dosage: 17 mg/kg/min over 30 minutes), the precursor of NO-synthesis and sodium-nitroprusside (SNP; dosage: 1.0 μg/kg/min over 30 minutes), an endothelium-independent vasodilator, on renal plasma flow (RPF) and glomerular filtration rate (GFR) in 12 stable cardiac transplant recipients on long-term CsA treatment (mean age: 60.2±9.4 years, time after cardiac transplant: 55.8±21.2 months, creatinine clearance: 60.5±9.1 ml/min), 10 patients with chronic nephropathy (mean age : 64.2±9.3 years, creatinine clearance: 52.7±3.8 ml/min) and 13 healthy, age matched controls (mean age: 59.5±8.5 years, creatinine clearance: 112.6±15.8 ml/min) in a double-blind, placebo-controlled, randomized, 3-way cross over study. Results: In healthy subjects L-arg induced an increase in RPF (p=0.009) and GFR (p=0.001). By contrast, in heart transplant recipients and patients with chronic nephropathy L-arg did not induce an increase in renal hemodynamics. SNP reduced RPF (p=0.050) and GFR (p=0.005) in patients with chronic nephropathy, but did not affect renal hemodynamics in healthy controls and heart transplant recipients. Conclusion: Our data indicate that the renal hemodynamic response to L-arg is different in heart transplant recipients under chronic CsA treatment and healthy subjects. By contrast no evidence for an altered renal reactivity to exogenous NO was apparent in cardiac transplant patients. This likewise supports the hypothesis, that patients under long-term CsA treatment have an altered L-arg-NO pathway.