Chronic allograft nephropathy: prospective randomised trial of cyclosporin withdrawal and mycophenolate mofetil or tacrolimus substitution

McGrath, John; Shehata, Magdi

doi:10.1016/s0041-1345(01)01939-x

Cited by 16 publications

(14 citation statements)

References 5 publications

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“…All studies used renal function as the primary outcome except for one study which used graft survival and pathologic evaluation of repeat graft biopsy at 6 mo (15). Measures of renal function were radio-isotope studies in five studies (11,14,18,20,21) or absolute serum creatinine or related value, such as the slope of reciprocal of the serum creatinine versus time, in the remaining seven trials. …”

Section: Discussionmentioning

confidence: 99%

“…Exclusion criteria varied between studies. Two earlier studies did not mention exclusion criteria (17,18). Most studies excluded patients with an alternate cause of deteriorating renal function and pregnant patients.…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Of the 432 patients taking CsA, three studies had triple therapy with steroids and azathioprine (Aza) (18,19,21) and five studies had "CsAbased immunosuppressive therapy," not otherwise detailed (12,13,16,17,20). The remaining 184 patients were taking a CNI, either CsA or Tac, as dual therapy with steroids (22), or as triple therapy with steroids and mycophenolate mofetil (MMF) (15) or steroids and either Aza or MMF (11).…”

Section: Patient Characteristicsmentioning

confidence: 99%

“…Multiple interventions were evaluated in six of the included studies (14,15,17,18,20,22), and half of these studies compared a conversion to an addition strategy (15,20,22).…”

Section: Management Strategiesmentioning

confidence: 99%

“…Eight studies evaluated the conversion from a CNI to another immunosuppressive regimen. Patients were randomized to convert from CNI to MMF in four studies (12,18,20,22), from CsA to Tac in four studies (16,18 to 20) and from a CNI to Sirolimus (Rapa) in two studies (11,15).…”

Section: Management Strategiesmentioning

confidence: 99%

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Management of Chronic Allograft Nephropathy

Birnbaum

Lipman²,

Paraskevas³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Despite improving immunosuppressive protocols in renal transplantation, chronic allograft nephropathy (CAN) remains a major impediment to long-term graft survival. The optimal immunosuppressive regimen for a patient with CAN is unknown. The aim of this study is to evaluate the various immunosuppressive management strategies of biopsy-proven CAN and of chronic allograft dysfunction (CAD) (no biopsy). A systematic review of randomized trials (n ‫؍‬ 12 trials with 635 patients) was conducted. Studies included patients who were >6 mo post-transplant. All patients were on a calcineurin inhibitor (CNI), most often cyclosporine, and were randomized to convert to mycophenolate mofetil (MMF), tacrolimus, or sirolimus (Rapa) or to add azathioprine, MMF or Rapa to their current regimen. Follow-up time was 6 to 36 mo. The outcome measures evaluated were renal function in 11 of 12 studies and repeat renal biopsy results in one study. The methodological quality scores of the trials were generally low, using the Jadad scale (median value 2/5). Results varied between studies but suggested that CNI withdrawal is safe and that conversion to MMF or Rapa may be beneficial. The incidence of adverse effects ranged from 0% to 68% between the studies, and medication withdrawal occurred in 0% to 24% of patients. The review did not result in a consensus regarding the management of CAN and CAD. Further studies are required to determine the best therapeutic option for patients with CAD and CAN.

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Section: Discussionmentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

Section: Patient Characteristicsmentioning

confidence: 99%

“…Multiple interventions were evaluated in six of the included studies (14,15,17,18,20,22), and half of these studies compared a conversion to an addition strategy (15,20,22).…”

Section: Management Strategiesmentioning

confidence: 99%

Section: Management Strategiesmentioning

confidence: 99%

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Management of Chronic Allograft Nephropathy

Birnbaum

Lipman²,

Paraskevas³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

Karpe

Talaulikar

Walters

2017

Cochrane Database of Systematic Reviews

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CNI avoidance increased acute rejection and CNI withdrawal increases acute rejection but reduced graft loss at least over the short-term. Low dose CNI with induction regimens reduced acute rejection and graft loss with no major adverse events, also in the short-term. The use of mTOR-I reduced CMV infections but increased the risk of acute rejection. These conclusions must be tempered by the lack of long-term data in most of the studies, particularly with regards to chronic antibody-mediated rejection, and the suboptimal methodological quality of the included studies.

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Prospective, Pilot, Open-Label, Short-Term Study of Conversion to Leflunomide Reverses Chronic Renal Allograft Dysfunction

Hardinger

Wang

Schnitzler

et al. 2002

American Journal of Transplantation

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Leflunomide (LEF) is a synthetic isoxazole derivative with anti-inflammatory and antiviral properties, which has been reported to prevent acute rejection and delay progression of chronic allograft nephropathy (CAN) in animal models. We performed a pilot, crossover trial in 22 renal transplant recipients who were converted from azathioprine (AZA) or mycophenolate mofetil (MMF) to LEF in an effort to slow progression of renal dysfunction [deteriorating renal function (n Ω 5), cyclosporine (CyA) nephrotoxicity (n Ω 4) or biopsy-proven CAN (n Ω 13)]. Baseline maintenance immunosuppression consisted of CyA, AZA or MMF and prednisone. Six-month postconversion patient and graft survival was 100% and 91%, respectively. Mean serum creatinine 6 months preconversion was 2.2 ∫ 0.6 mg/dL, at initiation was 3.0 ∫ 1.1 mg/dL, and 6 months postconversion was 2.8 ∫ 1.3 mg/dL. The rate of change in serum creatinine was 35 ∫ 39%/6 months preconversion and ª5 ∫ 21%/6 months postconversion to LEF (p Ω 0.003). Two patients discontinued LEF for diarrhea and myalgia. No readmissions, increase in liver function tests, infections or acute rejection episodes occurred. Mean CyA levels did not change, 146 ∫ 72 ng/ mL pre-LEF vs. 132 ∫ 51 ng/mL post-LEF, p Ω NS. Conversion to LEF reversed progression of chronic renal allograft dysfunction with minimal toxicity.

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Chronic allograft nephropathy: prospective randomised trial of cyclosporin withdrawal and mycophenolate mofetil or tacrolimus substitution

Cited by 16 publications

References 5 publications

Management of Chronic Allograft Nephropathy

Management of Chronic Allograft Nephropathy

Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients

Prospective, Pilot, Open-Label, Short-Term Study of Conversion to Leflunomide Reverses Chronic Renal Allograft Dysfunction

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