Nephrotoxicity Following Orthotopic Liver Transplantation

Platz, K.-P.; Mueller, Andrea; Blumhardt, G.; Bachmann, Sigrid; Bechstein, Wolf O.; Kahl, Andreas; Neuhaus, P.

doi:10.1097/00007890-199405820-00007

Cited by 91 publications

(90 citation statements)

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“…Tacrolimus nephrotoxicity occurs in-17 to 44% of renal transplant recipients and in 18 to 42% of liver transplant recipients (18,(43)(44)(45). Heart and lung, transplant recipients have not been systematically studied to define precisely the magnitude of nephrotoxicity in that in that patient population (46,47) The wide range in reported incidence depends not only on the dosing regimen but also on prior clinical experience with the drug (11,17).…”

Section: Clinical Features Of Tacrolimus Nephrotoxicitymentioning

confidence: 99%

Tacrolimus (FK506)-Associated Renal Pathology

Randhawa¹,

Starzl

Demetris³

1997

Advances in Anatomic Pathology

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Section: Clinical Features Of Tacrolimus Nephrotoxicitymentioning

confidence: 99%

Tacrolimus (FK506)-Associated Renal Pathology

Randhawa¹,

Starzl

Demetris³

1997

Advances in Anatomic Pathology

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“…[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 without HRS.…”

mentioning

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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“…Tacrolimus does not seem to be a good alternative to cyclosporine because both drugs seem to be equally nephrotoxic. 5 Mycophenolate mofetil (MMF) is a potent inhibitor of inosine monophosphate dehydrogenase, with a relatively selective effect on lymphocyte activation, which inhibits proliferation of T and B lymphocytes. 6 Its main secondary effects are gastrointestinal and hematologic, 7 thus providing a potential therapeutic alternative in patients developing cyclosporine or tacrolimus neurotoxicity or nephrotoxicity.…”

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confidence: 99%

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

et al. 1999

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The management of liver transplant recipients with renal function impairment remains controversial because cyclosporine withdrawal from triple immunosuppression regimens may be followed by graft rejection. A nonnephrotoxic and powerful immunosuppressant such as mycophenolate mofetil (MMF) could allow a reduction of cyclosporine dosage or its withdrawal and an improvement in renal function in these patients. Eleven patients with serum creatinine levels greater than 1.5 mg/dL, normal graft function, and a rejection-free period of at least 1 year started MMF at a dose of 2000 mg/d (reduced in case of adverse events) while cyclosporine dosage was slowly reduced. At last follow-up (63 ؎ 5 weeks), 7 patients remained free of cyclosporine (6 of those patients are also free of steroids), 2 patients reduced their cyclosporine dose, and 2 patients developed mild acute rejection that responded to a switch to tacrolimus therapy. Serum creatinine and urea levels in the 7 patients free of cyclosporine decreased from 2.22 ؎ 0.13 to 1.90 ؎ 0.19 mg/dL (P ‫؍‬ .05) and 0.95 ؎ 0.10 to 0.60 ؎ 0.10 g/L (P F .001), respectively. Creatinine clearance increased from 38.16 ؎ 5.60 to 47.01 ؎ 6.76 mL/min (P ‫؍‬ .005). Control of arterial hypertension also improved. Tolerance to MMF was good, but 6 patients required dose reductions, mainly because of asymptomatic anemia. In conclusion, in liver transplant recipients with stable graft function, MMF may allow cyclosporine dose reduction or discontinuation, thus improving renal function and the control of arterial hypertension. This change of treatment must be carefully monitored because of the frequent need for MMF dose reduction and the risk for rejection.

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Nephrotoxicity Following Orthotopic Liver Transplantation

Cited by 91 publications

References 0 publications

Tacrolimus (FK506)-Associated Renal Pathology

Tacrolimus (FK506)-Associated Renal Pathology

Pretransplant renal function predicts survival in patients undergoing orthotopic liver transplantation

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

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