Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil

Herrero, J.I.; Quiroga, Jorge; Sangro, Bruno; Girala, Marcos; Gómez-Manero, Noemí; Pardo, Fernando; Cienfuegos, Javier A.; Prieto, Jesús

doi:10.1002/lt.500050513

Cited by 106 publications

(89 citation statements)

References 25 publications

(27 reference statements)

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“…In addition, we believe that patients with renal insufficiency should be considered for less nephrotoxic immunosuppressive regimens, including sirolimus and mycophenolate mofetil. 26,27 These drugs should be tested in controlled trials to determine safety and efficacy. In conclusion, approximately one third of patients undergoing OLT have evidence of pretransplant renal impairment.…”

Section: Discussionmentioning

confidence: 99%

Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation

2002

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The objective of this study was to determine the impact of pretransplant renal function on graft and patient survival rates after orthotopic liver transplantation (OLT) using the United Network for Organ Sharing (UNOS) database for adults who underwent OLT between 1988 and 1996. Based on calculated creatinine clearance (CCr) at the time of OLT, patients were classified arbitrarily into those with normal renal function (>70 mL/min) and mild (40-69.9 mL/min), moderate (20-39.9 mL/min), and severe (<20 mL/min) renal insufficiency. Of the 20,281 patients who underwent transplantation, complete data were available for 19,261 patients. Of these, 12,778 (67%) had normal CCr (mean, 118 ؎ 50 mL/min) and 4,419 (22%) had mild (56 ؎ 8.5 mL/min), 1,560 (8%) had moderate (30 ؎ 5.7 mL/min), and 504 (3%) had severe (14 ؎ 3.6 mL/min) renal failure. UNOS status 1 was more common in patients with moderate and severe renal failure. Primary graft nonfunction and 30-day mortality rates were higher and 1-, 2-, and 5-year graft and patient survival rates were lower in patients with moderate or severe renal failure. Multiple regression analysis showed that renal failure was an independent predictor of 30-day and 2-year mortality after adjusting for the recipient's age, sex, etiology of liver disease, diabetes status, body mass index, cold ischemic time, and UNOS status. CCr less than 40 mL/min was associated with significantly lower short-term and long-term graft and patient survival rates. In conclusion, our findings suggest that when Mayo End-Stage Liver Disease (MELD) score is used to prioritize organ allocation, lower-than-expected graft and patient survival rates may be seen. L iver transplantation has been the most important development in the management of end-stage liver disease in the past 2 decades. The immediate outcome of orthotopic liver transplantation (OLT) is dependent on many factors, including pretransplant serum creatinine levels. Renal insufficiency is common in patients before and after liver transplantation. The prevalence of renal impairment in patients undergoing OLT varies from 10% to 20%. 1-3 Although many of these patients may have hepatorenal syndrome (HRS), a potentially reversible condition, it is often difficult to make a firm diagnosis of HRS in patients with terminal liver disease. 4 Approximately 25% of liver transplantations are complicated by renal failure in the immediate postoperative period. [5][6][7][8] In addition, use of immunosuppressants such as cyclosporine and tacrolimus may cause further deterioration in renal function in this population. [7][8][9][10] Preoperative serum creatinine levels have been shown to be an important predictor of postoperative sepsis, 11,12 number of days spent in the intensive care unit, 3,13 need for preoperative and postoperative dialysis, 2,13 overall cost of liver transplantation, 13,14 and short-term graft and patient survival rates. 1,7,8,11,12,15 In one study, 2-year patient and graft survival rates were found to be similar in 31 patients with HRS and 263 with...

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Section: Discussionmentioning

confidence: 99%

Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation

2002

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“…38,39 However, withdrawal of cyclosporine therapy rarely improves renal outcome, although one study reported a slight improvement in renal function in patients successfully converted after 1 year to mycophenolate. 40,41 Furthermore, the added risk for rejection after cyclosporine therapy withdrawal is a major consideration before recommending this approach. Renal diagnoses other than cyclosporine toxicity leading to post-OLT ESRD include hemolytic uremic syndrome, immunoglobulin A (IgA) nephropathy, oxalosis, and membranoproliferative glomerulonephritis (MPGN).…”

Section: End-stage Renal Disease In the Liver Transplant Recipientmentioning

confidence: 99%

Identification of patients best suited for combined liver[ndash ]kidney transplantation: Part II

Davis

Gonwa

Wilkinson

2002

Liver Transplantation

116

105

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Liver-kidney transplantation (LKT) should be reserved for those recipients with primary disease affecting both organs. However, increasing transplant list waiting times have increased the development and duration of acute renal failure before liver transplantation. Furthermore, the need for posttransplant calcineurin inhibitors can render healing from acute renal failure difficult. Because of the increasing requests for and controversy over the topic of a kidney with a liver transplant (OLT) when complete failure of the kidney is not known, the following article will review the impact of renal failure on liver transplant outcome, treatment of peri-OLT renal failure, rejection rates after LKT, survival after LKT, and information on renal histology and progression of disease into the beginnings of an algorithm for making a decision about combined LKT. (Liver Transpl 2002;8:193-211.)

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“…Previous experiences in LT recipients with renal functional impairment reported controversial results. In our experience, episodes of graft rejection were well controlled with an increase in CI, 10 but others have observed a poor responses. 12 In the present paper, two patients (18%) developed a rejection episode, both of which responded to increases in CI.…”

Section: Discussionmentioning

confidence: 51%

“…The use of MMF has allowed physicians to reduce cyclosporine exposure in LT recipients with renal functional impairment. 10 Some patients have been maintained on MMF monotherapy, but this strategy poses the risk of graft rejection. 11 The aim of the present study was to examine whether conversion to MMF for stable LT recipients with DM allows the reduction/withdrawal of CI and results in improve metabolic control.…”

Section: D Abetes Mellitus (Dm) Is a Frequent Metabolic Complicatiomentioning

confidence: 99%

Conversion from calcineurin inhibitors to mycophenolate mofetil in liver transplant recipients with diabetes mellitus

Herrero¹,

Quiroga²,

Sangro³

et al. 2003

Transplantation Proceedings

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Diabetes mellitus, a frequent metabolic complication in liver transplant recipients, may be produced by the diabetogenic effect of calcineurin inhibitors cyclosporine and tacrolimus. The aim of this study was to investigate the safety and metabolic effects of a gradual switch from cyclosporine or tacrolimus to mycophenolate mofetil among 12 diabetic liver transplant recipients. One patient was withdrawn from the study due to gastrointestinal side effects. Of the 11 remaining patients, cyclosporine or tacrolimus was completely withdrawn in five patients. Two patients developed suspected acute rejection episodes that were controlled by increasing the tacrolimus dosage. Glycosylated hemoglobin A1C and C-peptide levels were significantly lower at 3 and 6 months after the initiation of mycophenolate mofetil (P < .03 in all cases). Furthermore, urea and uric acid levels were significantly reduced after the change of treatment. In conclusion, a switch from cyclosporine/tacrolimus to mycophenolate mofetil may produce beneficial metabolic effects in diabetic liver transplant recipients, but poses a risk of graft rejection. I D ABETES MELLITUS (DM) is a frequent metabolic complication in liver transplant(LT) recipients. Despite the lack of universal agreement, some studies have observed worsened short-and mid-term survival among diabetic LT recipients. 1-7 Furthermore, DM is a wellknown risk factor for cardiovascular disease, which is one of the leading causes of death of LT recipients in the long term. 8 Calcineurin inhibitors (CI) also predispose to DM through islet cell toxicity, diminished insulin synthesis or release, as well as decreased peripheral insulin sensitivity. 9 Mycophenolate mofetil (MMF) has proven to be useful as a CI-sparing agent. The use of MMF has allowed physicians to reduce cyclosporine exposure in LT recipients with renal functional impairment. 10 Some patients have been maintained on MMF monotherapy, but this strategy poses the risk of graft rejection. 11 The aim of the present study was to examine whether conversion to MMF for stable LT recipients with DM allows the reduction/withdrawal of CI and results in improve metabolic control.From the Liver Unit (J.I.H., J.Q., B.S., J.P.) and

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Conversion of liver transplant recipients on cyclosporine with renal impairment to mycophenolate mofetil

Cited by 106 publications

References 25 publications

Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation

Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation

Identification of patients best suited for combined liver[ndash ]kidney transplantation: Part II

Conversion from calcineurin inhibitors to mycophenolate mofetil in liver transplant recipients with diabetes mellitus

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