tacrolimus and Hepatorenal-Syndrome

Hepatorenal syndrome (HRS) was originally defined as a renal dysfunction caused by a decreased renal perfusion due to hemodynamic disturbances in the arterial circulation and an excessive activity of endogenous vasoactive systems in the course of cirrhosis. Considering the latest research, this syndrome may have a more complex pathomechanism. Equally often as in cirrhosis, HRS develops after orthotopic liver transplantation (OLTx) and worsens the prognosis significantly increasing mortality rates in this patient population. The prevalence of renal complications after OLTx and their negative prognostic impact on the survival of both the graft and the recipient prompted the authors of this work to analyze in detail 2 cases of HRS after OLTx to indicate the multiplicity of factors contributing to the pathophysiology of this syndrome. Attention was paid to risk factors for HRS found in the anamnesis before OLTx, especially a pre-existing renal dysfunction. In both cases early post-OLTx complications associated with the transplantation procedure were described: destabilization of the circulatory system, transfusions of blood products, prolonged stay at an intensive care unit, and necessity of introducing continuous renal replacement therapy. In the later period after the OLTx, infections (bacterial, fungal, viral) and drug nephrotoxicity, including the activity of immunosuppressants (tacrolimus), contributed primarily to the renal function impairment.

Topics: Hepatorenal Syndrome; Humans; Kidney; Liver Cirrhosis; Liver Transplantation; Tacrolimus

Polyomaviruses are increasingly recognized as important human pathogens. Among those, BK virus has been identified as the main cause of polyomavirus-associated nephropathy (PVAN), a major cause of renal allograft failure. PVAN has also been well described in the setting of non-renal solid organ transplantation. The reports of PVAN after hematopoietic stem cell transplantation (HCT) are surprisingly very few. Here, we describe a patient with treatment-related myelodysplastic syndrome who received an unrelated donor HCT after ablative conditioning and in vivo T cell depletion with alemtuzumab. He developed a biopsy-proven BK nephropathy, which contributed to his renal failure. Leflunomide as well as cidofovir were given at different times, both in combination with intravenous immunoglobulin. Both treatments were effective in reducing the BK viral load, the cystitis symptoms and both stabilized but did not really improved the renal function. The patient was still dialysis-dependent when he died from Pseudomonas sepsis 13 months after HCT. A critical review of the literature and the treatment modalities for post-HCT PVAN are provided.

Topics: Antiviral Agents; BK Virus; Cystitis; Cytomegalovirus Infections; Fatal Outcome; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Hepatorenal Syndrome; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Kidney Failure, Chronic; Lymphoma, Follicular; Male; Middle Aged; Myelodysplastic Syndromes; Nephritis, Interstitial; Polyomavirus Infections; Postoperative Complications; Reoperation; Tacrolimus; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous

It has been known for some time that a variety of liver diseases affect kidney function, but renal dysfunction associated with orthotopic liver transplantation has received scant attention. Although the mechanisms mediating these abnormalities are incompletely defined, advances in the understanding of renal pathophysiology after liver transplantation have made it possible to develop new treatment strategies. Aggressive and early intervention to diagnose and treat renal complications associated with liver transplantation should be the goal for transplant centres.

Topics: Chronic Disease; Cyclosporine; Hepatitis C; Hepatorenal Syndrome; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Failure; Liver Transplantation; Prostaglandins; Renal Dialysis; Renal Insufficiency; Tacrolimus

Renal dysfunction often complicates the course of liver transplant recipients. Preoperative renal dysfunction, including hepatorenal syndrome (HRS) may be present. Assessment of renal function in the pretransplant patient with end-stage liver disease is fraught with pitfalls. Direct measurement of GFR by a method other than creatinine clearance is recommended wherever possible. Preoperative renal biopsy should also be considered in those patients with renal dysfunction in whom the diagnosis of HRS is not definite. With the routine use of veno venous bypass, renal perfusion is maintained and intraoperative events generally do not play a significant role in the development of postoperative dysfunction. Postoperatively immunosuppressive medications such as CsA or FK506 account for most of the renal dysfunction that is observed. Other factors such as graft dysfunction, sepsis, and nephrotoxic drugs may also participate in renal impairment. The exact mechanism of cyclosporine or FK506 nephrotoxicity remains unknown. In liver transplant recipients, no convincing therapeutic strategies exist to combat nephrotoxicity other than dose reduction of immunosuppressive therapy. Patients with HRS can be successfully treated by liver transplantation with recovery of renal function and with patient survival rates comparable to recipients without HRS, despite increased morbidity.

Topics: Cyclosporine; Glomerular Filtration Rate; Hepatorenal Syndrome; Humans; Intraoperative Period; Kidney; Kidney Diseases; Liver Failure; Liver Transplantation; Postoperative Complications; Preoperative Care; Tacrolimus

The purpose of this study was to ascertain the prognosis of patients with hepatorenal syndrome (HS) prior to orthotopic liver transplantation (OLT) by comparisons with a group of selected patients with normal renal function (NRF) pretransplantation who developed acute renal failure (ARF) in the early postoperative period.. Fifty-two OLT cases developed ARF in the early postoperative period between March 1999 and October 2004; 17 cases experienced HS prior to OLT. ARF was defined as serum creatinine level (Cr) >1.5 mg/dL or a creatinine clearance (CrCl) <50 mL/min. The immunosuppressive therapy was the same in both groups: low doses of tacrolimus were prescribed to reach trough levels of 5 ng/mL in the first week after OLT, where patients were administered monoclonal antibodies and corticosteroids.. No differences were observed between the groups for gender, age or APACHE II Score in the first 24 hours after OLT. Patients with HS pretransplantation showed higher Cr and urea (U) levels than the other group (Cr: 2.1 +/- 0.8 HS vs 0.9 +/- 0.2, P = .000; U: 93.6 +/- 51.9 HS vs 42.1 +/- 19.3, P = .001). The ICU days of stay were similar (12.8 +/- 0.5 HS vs 19.7 +/- 15.2, P = .053). At the end of 1 year follow-up after OLT there were no differences in mortality (35% HS vs 26%), need for renal replacement therapy (23% HS vs 34%), infection (59% HS vs 51%), or rejection (6% HS vs 29%, P = .06).. Patients with HS prior to OLT showed a similar prognosis to a group of selected patients with NRF pretransplantation, but developed ARF in the early postoperative period which was treated with monoclonal antibodies and low doses of tacrolimus.

Topics: Acute Kidney Injury; APACHE; Creatinine; Female; Hepatorenal Syndrome; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Postoperative Complications; Postoperative Period; Retrospective Studies; Tacrolimus; Urea

The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients.. Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD.. At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants.. Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.

Topics: Adult; Calcineurin Inhibitors; Creatinine; Cyclosporine; Female; Hepatorenal Syndrome; Humans; Immunosuppressive Agents; Incidence; Kidney Failure, Chronic; Liver Diseases; Liver Transplantation; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Analysis; Tacrolimus; Time Factors