Coadministration of Ketoconazole to Cyclosporin-Treated Kidney Transplant Recipients: A Prospective Randomized Study

Sobh, Mohamed; El‐Agroudy, Amgad E.; Moustafa, Fatma; Harras, Foad; El-Bedewy, Mohamed; Ghoneim, Mohamed A.

doi:10.1159/000168892

Cited by 29 publications

(32 citation statements)

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“…Ketoconazole has been used in recent heart and kidney transplant studies. A cost-sparing effect was obtained by reducing the cyclosporin dosage required and because of its ef®cacy in preventing fungal infections and achieving a lower rejection rate [60,61]. However, care should be exercised not only because of drug interactions with azoles, but also because primary or secondary resistance to the antifungal drugs used may occasionally develop [62,63].…”

Section: Prophylaxis Of Fungal Infectionsmentioning

confidence: 99%

Fungal infections in transplant recipients

Nicod

Howarth

2001

Eur Respir J

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Fungi are ubiquitous and the respiratory tract is exposed to aerosolized spores of both fungi that are “pathogenic” even in the normal host, such asCryptococus neoformans, and those that are “opportunistic”, such asCandidaandAspergillusspecies, among others. Although these latter species may occasionally form fungal balls or induce allergic phenomena in the normal host, they produce more invasive diseases in immunosuppressed patients. Among these diseases, pseudomembranous aspergillosis has recently been described.The diagnostic approach to these entities, and, in particular, the thin dividing line between colonization and infection are addressed, along with the diagnostic value of the various procedures.New prophylactic regimens are reviewed such as the possibility of using amphotericin aerosols in combination with systemic azole administration.The authors would emphasize the importance of restoring lung defences by not only decreasing immunosuppressive regimens but also considering the use of newly available recombinant cytokines such as growth factors, to reduce neutropenia, for instance, in addition to antifungal drugs when infection is diagnosed. However, immunomodulation procedures are far from being well established.

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Section: Prophylaxis Of Fungal Infectionsmentioning

confidence: 99%

Fungal infections in transplant recipients

Nicod

Howarth

2001

Eur Respir J

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“…We previously reported that co-administration of keto results in more stable graft function in kidney transplant recipients [6, 8]. Keogh et al [5] noticed that there was a reduction in the rejection rate (despite similar doses of azathioprine, prednisolone, and antithymocyteglobulin) in ketoconazole-treated cardiac transplant recipients.…”

Section: Discussionmentioning

confidence: 99%

“…Inrenal and cardiactransplantssome drugs, particularly ketoconazole and diltiazem, have been given purposefully with CsA in an attempt to markedly reduce the dose and therefore the cost of CsA [4,5,6]. Concurrent administration of ketoconazole and CsA permits a reduction in the CsA dosage of approximately 80%.…”

Section: Introductionmentioning

confidence: 99%

“…In a prospective randomized study including 100 kidney transplant recipients, we previously reported on the safety and financial benefit of ketoconazole and cyclosporine co-administration in kidney transplant recipients [6]. In a more recent study, we documented that long-term use of low-dose keto in CsA-treated kidney transplant recipients is safe and cost-saving and may induce better graft function [8].…”

Section: Introductionmentioning

confidence: 99%

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Co-Administration of Cyclosporine and Ketoconazole in Children with Minimal Change Nephrotic Syndrome

et al. 2005

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Background/Aims: The use of cyclosporine A (CsA) in the treatment of idiopathic nephrotic syndrome was firstly reported in 1986. On the other hand, many studies have documented the benefit of ketoconazole (keto) administration in renal and cardiac transplant adults treated with CsA, but this co-administration has not been reported in children with minimal change disease (MCD). Thus, deliberate use of keto to reduce the need for cyclosporine is not new, but it is particularly relevant because of the high cost of cyclosporine. Methods: This study included 46 children with MCD who were steroid resistant or dependent and received CsA. Among them, 31 received daily keto therapy (keto group) in a dose of 50 mg with concomitant decrease of the CsA dose by one third while 15 patients received CsA alone (non-keto group). Results: The mean (±SD) duration of CsA treatment was 25.7 ± 13.7 months. The characteristics of both groups were comparable. Co-administration of keto significantly improved the response to CsA therapy (from 60 to 94%) and decreased the frequency of renal impairment (from 27 to 3%). Hepatic function remained within the normal range in both groups. Co-administration of keto significantly reduced mean doses of CsA with overall net cost savings of about 34%. Conclusion: From this study, we may conclude that co-administration of low dose ketoconazole to cyclosporine in children with idiopathic MCD is safe. This combination significantly reduces CsA cost and, moreover, keto may improve the response to cyclosporine and may have a favorable effect on the kidney function.

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“…After 1 year of follow-up, it was concluded that addition of ketoconazole to cyclosporine not only saved costs but also had a favorable effect on graft function, chronic cyclosporine nephrotoxicity, chronic rejection, and fungal skin infection. 10 After 54 months, dose reduction of cyclosporine was 72.9%. Moreover, metabolic consequences (lipid profile, bone mineral content, vitamin D blood levels) were not affected by long-term ketoconazole coadministration to cyc losporine.…”

Section: Prospective Randomized Trial Of Azathioprine Versus Cyclospomentioning

confidence: 99%

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Bakr

Nagib²,

Gheith³

et al. 2017

Exp Clin Transplant

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Objectives: We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. Materials and Methods: Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short-and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab.Results: Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection. Conclusions: A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.

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Coadministration of Ketoconazole to Cyclosporin-Treated Kidney Transplant Recipients: A Prospective Randomized Study

Cited by 29 publications

References 13 publications

Fungal infections in transplant recipients

Fungal infections in transplant recipients

Co-Administration of Cyclosporine and Ketoconazole in Children with Minimal Change Nephrotic Syndrome

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