Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion.
Renal toxicity, possibly due to vasoconstriction and vascular injury, is the most relevant side-effect of chronic cyclosporine (CsA) therapy given to prevent graft rejection. In kidney transplant recipients each oral dose of CsA is invariably followed by a transient reduction in renal plasma flow (RPF) and glomerular filtration rate (GFR) that results from a form of acute reversible hypoperfusion. We sought to determine whether the Ca2+ channel blocker, lacidipine, prevented CsA-associated renal hypoperfusion in these patients. Parallel studies on CsA pharmacokinetics, renal function parameters (GFR and RPF), as inulin and p-aminohippurate (PAH) clearances, respectively, and urinary excretion of the vasoconstrictor endothelin in 10 consecutive renal transplant patients given CsA as a part of their immunosuppressive therapy were performed. Patients were studied at different time intervals after CsA alone, CsA and lacidipine (4 mg/day), and again seven days after lacidipine withdrawal. In all patients basal RPF and GFR declined on average 51% (139.3 +/- 20.7 ml/min/1.73 m2) and 50% (32.5 +/- 5.8 ml/min/1.73 m2), respectively, two to four hours after maximum blood CsA concentration was reached. As blood levels of CsA returned to trough, both parameters progressively increased to baseline. Lacidipine administration completely prevented the fall in RPF (pre-CsA: 277.1 +/- 23.6; 6 hr post-CsA: 304.5 +/- 31.1 ml/min/1.73 m2) and GFR (pre-CsA: 66.6 +/- 8.1; 6 hr post-CsA: 70.1 +/- 9.8 ml/min/1.73 m2). When lacidipine treatment was discontinued the abnormal RPF and GFR response to CsA administration was again observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Ruggenenti
P
P
Mario Negri Institute for Pharmacological Research, Ospedali Riuniti di Bergamo, Italy.
Perico
N
N
Mosconi
L
L
Gaspari
F
F
Benigni
A
A
Amuchastegui
C S
CS
Bruzzi
I
I
Remuzzi
G
G
D000328:Adult; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D016572:Cyclosporine / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000097:blood; D004095:Dihydropyridines / Q000627:therapeutic use*; D016232:Endothelins / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012079:Renal Circulation / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D016232:Endothelins; C060285:lacidipine; D016572:Cyclosporine