The Relationship between Dose of Mycophenolate Mofetil and the Occurrence of Cytomegalovirus Infection and Diarrhea in Renal Transplant Recipients

Toda, Takaki; Motoki, Takashi; Kurosawa, Nahoko; Owada, Eiji; Achiwa, Kazuhito; Yuhki, Yoshimitsu; Tadano, Kohji; Shimoda, Naohiko; Shindo, Junichi; Harada, Hiroshi; Seki, Toshimori; Hirano, Tetsuo

doi:10.1248/yakushi.125.177

Cited by 5 publications

(3 citation statements)

References 25 publications

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“…Though, some studies [6,17] have also shown higher, but not statistically significant percentage of leucopenia with Azathioprine use when compared to MMF (2 g/day) in patients who developed CMV disease in their cohort. Only higher dose of MMF (3 g/day) was associated with an increased incidence of leucopenia in patients who developed CMV disease when compared with Azathioprine [10,12,18].…”

Section: Discussionmentioning

confidence: 94%

Cytomegalovirus Disease in Renal Transplant Recipients: A Single-Center Experience

et al. 2012

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Cytomegalovirus (CMV) is the most common viral infection following kidney transplant, has been recognized as a major factor for graft loss and increased incidence of acute rejection. Different studies have reported a variable incidence of CMV disease with the use of Mycophenolate mofetil (MMF). We retrospectively analyzed our renal transplant recipients to review the results of CMV disease and to compare CMV disease in patient on Azathioprine and MMF for this purpose we retrospectively reviewed 521 live related kidney transplant recipients at our institute. 74 (14.2 %) live related allograft recipients developed CMV disease after a median interval of 7.18 ± 4.35 months from transplantation. The mean age was 36.15 ± 10.7 years. 63 of the patients were male. Malaise, fever and diarrhea were among most common symptoms. 20 (27.02 %) of the 74 recipients developed transaminitis, 13 (17.2 %) developed CMV gastritis, 5 (9.13 %) recipients developed pneumonia, and 3 (4.05 %) patient developed colitis. 59 (80 %) patients had leucopenia and 41 (56.5 %) developed thrombocytopenia. Mean serum creatinine level was 1.5 ± 0.4 (0.9-2.4) mg/dl before the disease, 1.9 ± 0.6 (1.3-3.6) mg/dl at the time of the diagnosis, and 1.7 ± 0.06 (0.8-4.2) mg/dl at the end of the treatment. CMV disease developed in 9 (36 %) of recipients who received basiliximab as induction therapy and 13 (30.24 %) of recipients who received ATG (p [ 0.05). The incidence of CMV disease was similar in cyclosporine based regimen (13.2 %) and Tacrolimus based regimen 27 (16.16 %) (p = 0.137) and was also similar in Azathioprine 41 (9.5 %) and MMF group 33 (14.3 %) (p = 0.163). There was no significant difference in severity of CMV disease in both groups, except a higher incidence of leucopenia in Azathioprine group (86 vs. 74 %, p \ 0.05) as compared to MMF group. 51 (68.91 %) patient developed graft dysfunction during CMV disease. In conclusion we report a low incidence (14.2 %) and milder form of cytomegalovirus disease at our center. Use of universal cytomegalovirus prophylaxis was associated with a low incidence and milder form of the disease. Incidence of CMV disease was similar between Azathioprine and MMF groups.

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Section: Discussionmentioning

confidence: 94%

Cytomegalovirus Disease in Renal Transplant Recipients: A Single-Center Experience

et al. 2012

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“…[33] showed an increased metabolic ratio of MPAG/MPA in patients under CsA, which is caused by an inhibition of the biliary excretion of MPAG under CsA. Therefore, patients taking tacrolimus might have a bigger exposure of their gut toward MPA and this could explain the higher rate of gastrointestinal side effects under therapy with tacrolimus and MPA [34,35].…”

Section: Discussionmentioning

confidence: 99%

Early conversion from cyclosporine to tacrolimus increases renal graft function in chronic allograft nephropathy at BANFF stages I and II

Marcard

Ivens

Grabensee

et al. 2008

Transplant International

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Switching from cyclosporine to tacrolimus without steroid pulse was suggested as a therapeutic option in chronic allograft nephropathy (CAN). Thirty-one renal transplant recipients with CAN were prospectively converted from cyclosporine to tacrolimus (group A), in parallel 31 matched cyclosporin A (CsA) patients (group B) without CAN were followed up for 30 months. In six matching patients of groups A and B inulin and para-aminohippurate (PAH)-clearances and mycophenolate were measured over a span of 3 months. Transplant biopsies of group A were scored according to BANFF. While group A presented with transplant dysfunction compared with group B before switching (2.7 +/- 0.16 mg/dl vs. 1.7 +/- 0.09 mg/dl; P< 0.001), transplant function was equal 30 months later: it ameliorated in group A (2.0 +/- 0.18 mg/dl vs. 2.7 +/- 0.16 mg/dl; P < 0.001) and decreased in group B (1.9 +/- 0.13 mg/dl vs. 1.7 +/- 0.09 mg/dl, P < 0.05). Especially, patients with biopsy scores I and II according to BANFF benefited from tacrolimus. Within 3 months, mycophenolate acid (MPA) levels increased under tacrolimus (P < 0.05) whereas inulin and PAH-clearances remained unchanged. At switching, antihypertensive treatment was more intense in group B, but this difference evened out. Adverse side effects were more frequent under tacrolimus. Patients with mild to moderate CAN significantly benefited from switching to tacrolimus. Increased MPA-levels under tacrolimus might have contributed to this effect.

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“…Diarrhea occurs more frequently as an adverse effect of MMF in patients treated with TAC. [27][28][29] We suggest that estimating biliary excretion of MPAG is needed to avoid the risk of intestinal injury in combination therapy with TAC during the maintenance period.…”

Section: Discussionmentioning

confidence: 99%

Effects of Calcineurin Inhibitors on Pharmacokinetics of Mycophenolic Acid and Its Glucuronide Metabolite during the Maintenance Period Following Renal Transplantation

Naito

Shinno

Maeda

et al. 2006

Biological & Pharmaceutical Bulletin

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Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF) has been introduced into renal transplant immunosuppressant protocols in combination with calcineurin inhibitors (CNIs) and steroids. This study compared the pharmacokinetic profiles of MPA and its major metabolite MPA glucuronide (MPAG) in combination with tacrolimus (TAC) or cyclosporine (CyA) during the maintenance period (Ͼ6 months) following renal transplantation. There was no difference between TAC and CyA-treated groups in MPA plasma concentration before drug administration (C 0 ). MPA C 0 in TAC and CyA-treated patients did not differ from that in patients who were not treated with a CNI. In patients treated with a CNI, MPAG C 0 was significantly greater in those treated with CyA compared with TAC. The MPAG/MPA ratio in CyA-treated patients was significantly greater than that in the TAC-treated group. We observed that C 0 of MPA was negatively correlated with that of TAC and CyA. Positive correlation between MPA C 0 , MPAG C 0 and serum creatinine was stronger in patients treated with CyA compared with TAC. Our study suggests that CyA, but not TAC, inhibits enterohepatic circulation of MPAG as a secondary excretion pathway, and that renal function makes a major contribution to elimination of MPA and MPAG. We indicate that it may be necessary to estimate biliary excretion of MPAG to avoid the risk of intestinal injury in patients receiving combination therapy with TAC during the maintenance period.

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The Relationship between Dose of Mycophenolate Mofetil and the Occurrence of Cytomegalovirus Infection and Diarrhea in Renal Transplant Recipients

Cited by 5 publications

References 25 publications

Cytomegalovirus Disease in Renal Transplant Recipients: A Single-Center Experience

Cytomegalovirus Disease in Renal Transplant Recipients: A Single-Center Experience

Early conversion from cyclosporine to tacrolimus increases renal graft function in chronic allograft nephropathy at BANFF stages I and II

Effects of Calcineurin Inhibitors on Pharmacokinetics of Mycophenolic Acid and Its Glucuronide Metabolite during the Maintenance Period Following Renal Transplantation

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