Effects of Ciclosporin on Plasma Renin Activity, Catecholamines and Prostaglandins in Patients with Idiopathic Uveitis

Abstract

Animals and humans undergoing treatment with ciclosporin (CS) show a reversible increase in renal vascular resistance and a decrease in glomerular filtration rate. The causes of these abnormalities have not yet been established. We evaluated the effects of a 1-week treatment with CS on creatinine clearance, renal arachidonic acid metabolites, plasma renin activity (PRA), plasma aldosterone levels, urinary excretion and plasma levels of catecholamines in 7 patients with idiopathic uveitis. We show that CS treatment induces a significant (p < 0.05) decrease in creatinine clearance (from 132 ± 0.5 to 108 ± 8 ml/min); urinary 6-keto-PGF₁ excretion (from 17.8 ± 4.9 to 10.9 ± 3.3 ng/mmol creatinine), urinary thromboxane B₂ excretion (from 7.0 ± 1.0 to 3.6 ± 0.9 ng/mmol creatinine), upright PRA (from 4.2 ± 0.9 to 2.3 ± 0.8) and supine PRA (from 2.0 ± 0.5 to 1.1 ± 0.3). We found no change in plasma aldosterone levels and plasma levels and urinary excretion of catecholamines. We suggest that the reversible renal vasoconstriction observed in patients treated with CS may be induced by inhibition of renal prostacyclin synthesis. In this setting inhibition of PRA and angiotensin II formation may impair autoregulation of effective filtration pressure and therefore glomerular filtration rate.

Prevention of Experimental Cyclosporine Nephrotoxicity by Dietary Supplementation with LSL 90202, a Lysine Salt of Eicosapentaenoic Acid

“…Patients chronically receiving C sA have showed un changed [30] or depressed [31,32] urinary P G E 2 and 6-keto-P G F kl excretion. Nevertheless, when treating patients si multaneously with CsA and nonsteroidal anti-inflamma tory agents (cyclo-oxygenase inhibitory drugs), the renal function worsened [33].…”

De novo hypertension after liver transplantation.

“…Similar observations have been made in renal transplant and nontransplant applications in humans. 44 ' 86 It may be relevant that the ratio of thromboxane to prostacyclin metabolites remains heavily skewed in favor of thromboxane. A similar preponderance of vasoconstrictor eicosanoids has been implicated in preeclampsia of pregnancy, which shares many features with posttransplant hypertension.…”

Endocrine Alterations in Kidney Transplant Patients

“…In renal trans plant patients treated with CS-A, the urinary prostaglandin (PG) E? excretion was found to be decreased [27], As CS-A significantly inhibits urinary excretion of 6-keto-PGFi, thromboxane A, and PGFi« in patients with out pre-existing renal disease [28], dimin ished urinary excretion of these prostaglan dins in CS-A-treated KTP may be ex pected.…”