Results of Conversion From Cyclosporine to Azathioprine in Cadaveric Renal Transplantation

Gonwa, Thomas A.; Nghiem, Dai D.; Schulak, James A.; Corry, Robert J.

doi:10.1097/00007890-198702000-00012

Cited by 20 publications

(5 citation statements)

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“…Since the initiation of this study in 1981, several alter native ciclosporin treatment strategies have been pro posed, but the optimum dosage schedule and duration of therapy remain uncertain [17,26,[59][60][61], We are cur rently studying low-dose regimens combined with other immunosuppressive agents for the treatment of autoim mune uveitis. It is hoped that this approach will prevent rather than simply delay the development of chronic ciclosporin nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Austin¹,

Palestine²,

Sabnis³

et al. 1989

Am J Nephrol

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Among 73 patients treated with ciclosporin (CS) for autoimmune uveitis, a 50% elevation of serum creatinine was observed in 37% within 3 months of starting CS and in 25% after more than 6 months of relatively uncomplicated therapy. Sequential renal function and histologic evaluations were performed in 17 patients to further characterize the nephrotoxic effects of long-term CS therapy. Inulin clearance remained essentially unchanged in 12 patients despite CS dosage reductions in the majority. In 2 such patients, repeat renal biopsy specimens revealed evidence of progressive irreversible kidney injury even though renal function was stable. Inulin clearance decreased substantially in 3 patients; in 1 case a follow-up renal biopsy showed increased severity of chronic histologic change. For 2 patients, the inulin clearance more than doubled after CS dosage reduction; and in 1 of those cases, repeat renal biopsy showed no evidence of progressive renal scarring. Overall, the morphologic attributes of irreversible kidney injury (designated by a chronicity index including glomerular sclerosis, tubular atrophy and interstitial fibrosis) were increased in 3 of 6 follow-up renal biopsy specimens. Histologic alterations of renal arterioles, including hyaline change, were observed in all CS-treated patients. The hyaline change of arterioles was either extensive in the first renal biopsy specimen or became extensive in the second biopsy in the 3 cases manifesting an increased chronicity index on the follow-up renal biopsy. Thus, parenchymal injury can progress in some cases despite CS dosage reduction and stable renal function; renal arteriolar histologic change is a prominent finding in these patients. Patients that exhibit a substantial improvement in renal function after dosage reduction may experience a more favorable course.

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Section: Discussionmentioning

confidence: 99%

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Austin¹,

Palestine²,

Sabnis³

et al. 1989

Am J Nephrol

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“…This hypercholesterolemia was evident after 3 weeks and persisted for at least 2 years. Gonwa et al [ 13], on the other hand, found no difference when comparing lipid levels of CS patients before transplantation and at latest follow-up (14-17 months), nor after conversion to aza thioprine. These studies included a relatively small num- ber of patients.…”

Section: Introductionmentioning

confidence: 94%

Lipoprotein Levels and Post-Heparin Lipase Activities in Kidney Transplant Recipients: Ciclosporin- versus Non-Ciclosporin-Treated Patients

Arnadottir

Thysell²,

Nilsson‐Ehle³

1991

Am J Nephrol

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Lipid and lipoprotein levels were measured in 118 clinically stable patients who had received a kidney transplant more than 1 year earlier. Seventy-one were treated with ciclosporin (CS), 47 were not. The CS group had significantly higher mean cholesterol (6.54 versus 6.00 mmol/l) and triglyceride (1.83 versus 1.34 mmol/l) concentrations than the non-CS group. LDL/HDL cholesterol ratios were similar in the two groups. The CS patients had higher creatinine and prednisolone doses and used β-blockers and loop diuretics more frequently. Multiple regression analysis did not show an independent correlation between lipid levels and treatment with CS. On the other hand, there was an independent correlation between cholesterol levels and treatment with loop diuretics, suggesting that such treatment contributes to the higher cholesterol levels in kidney transplant recipients. The diabetics had a more favorable lipoprotein profile than the nondiabetics, especially in triglycerides and HDL cholesterol levels. The marked difference in triglyceride levels between the treatment groups prompted us to evaluate the lipoprotein lipase and hepatic lipase activities in 20 hyperlipidemic, nondiabetic patients. Both enzyme activities were moderately reduced with no difference between the treatment groups, suggesting that factors other than CS interfere with the lipase activities in kidney transplant recipients.

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“…One such drug is erythromycin. We (Freeman et al, 1987a) and others (Ptachcinski et al, 1985;Hourmant et al, 1986;Martell et al, 1986;Gonwa et al, 1986;Wadhwa et al, 1987) have previously observed that coadministration of oral CsA and erythromycin in man causes CsA concentrations to increase dramatically. Whether this effect is due to decreased hepatic metabolism or increased absorption is not clear (Freeman et al, 1987a;Gupta et al, 1988).…”

Section: Introductionmentioning

confidence: 87%

The cyclosporin‐erythromycin interaction: impaired first pass metabolism in the pig

Freeman

Grant

Carruthers

1991

British J Pharmacology

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The pharmacokinetic interaction between cyclosporin (CsA) and erythromycin has been studied in the weanling pig model. Blood CsA and metabolite‐1 (M1) concentrations were monitored by high performance liquid chromatography in portal, hepatic and jugular venus blood before and after treatment with erythromycin stearate for 7 days. Erythromycin significantly increased maximum concentration (Cmax) and area under the concentration‐time curve from 0 to 24 h (AUC) of CsA in the peripheral circulation. This was accompanied by a significant reduction in the hepatic extraction ratio calculated from portal and hepatic Cmax and AUC data. The extraction ratio appears to be concentration‐dependent in that values derived from Cmax (high concentrations) were greater than those from AUC (average concentrations). Time to Cmax (tmax) and t1/2 of CsA were essentially unchanged and no significant changes were observed in peripheral M1 kinetics apart from a small increase in tmax. The pharmacokinetic changes observed in the pig suggest that the CsA‐erythromycin interaction is caused by inhibition of hepatic metabolism and the impact of inhibition is greatest during first‐pass when CsA concentrations are at their highest.

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Results of Conversion From Cyclosporine to Azathioprine in Cadaveric Renal Transplantation

Cited by 20 publications

References 0 publications

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Lipoprotein Levels and Post-Heparin Lipase Activities in Kidney Transplant Recipients: Ciclosporin- versus Non-Ciclosporin-Treated Patients

The cyclosporin‐erythromycin interaction: impaired first pass metabolism in the pig

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