The role of thromboxane and prostacyclin in ciclosporin-induced nephrotoxicity.
The aim of the study was to determine the influence of ciclosporin (Cs) on prostacyclin and thromboxane generation. Four groups of patients were studied. Group 1: Controls, n = 10. Group 2: Patients without kidney disease treated with Cs, n = 10. Group 3: Patients after transplantation treated with azathioprine, n = 10. Group 4: Renal transplant recipients receiving Cs, n = 10. Parameters investigated: CIn, CPAH, TxB2 in plasma, serum and urine; 6-oxo-PGF1 alpha in plasma and urine, urinary 2,3-dinor-TxB2 excretion. CPAH and CIn were significantly decreased during Cs treatment. Plasma TxB2 levels were enhanced in patients without kidney disease receiving Cs (group 2) amounting to 189 +/- 106 pg/ml as compared to 12 +/- 4 pg/ml in controls (group 1). In patients without kidney disease (group 2), plasma 6-oxo-PGF1 alpha was increased (20 +/- 9 pg/ml) as compared to controls in group 1. Plasma TxB2 and plasma 6-oxo-PGF1 alpha were increased in renal graft recipients without any difference due to different immunosuppressive drugs. Treatment with Cs was associated with impaired renal function and resulted, in patients without kidney disease, in elevated plasma TxB2 and plasma 6-oxo-PGF1 alpha. This effect could not be proven in renal graft recipients. We suggest that the deleterious effect of Cs on kidney function is presumably not paralleled by corresponding changes in prostaglandin and thromboxane formation.
Heering
P
P
Department of Nephrology, Heinrich Heine University, Düsseldorf, FRG.
Strobach
H
H
Schrör
K
K
Grabensee
B
B
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D016039:Corneal Transplantation; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D015777:Eicosanoids / Q000652:urine; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology; D016031:Liver Transplantation; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D013929:Thromboxane B2 / Q000378:metabolism*
D015777:Eicosanoids; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D016572:Cyclosporine; D001379:Azathioprine; D008775:Methylprednisolone