[Kidney failure after liver transplantation]. / Insuffisance rénale après transplantation hépatique.

One third of cirrhotic patients present impaired kidney function. It has multifactorial causes and has a harmful effect on patients' morbi-mortality before and after liver transplant. Kidney function does not improve in all patients after liver transplantation and liver-transplant recipients are at high risk of developing chronic kidney disease. Causes for renal dysfunction can be divided in three groups: preoperative, peroperative and postoperative factors. To date, there is no consensus for the modality of evaluation the risk for chronic kidney disease after liver transplantation, and for its prevention. In the present review, we describe the outcome of kidney function after liver transplantation, and the prognostic factors of chronic kidney disease to determine a risk stratification for each patient. Furthermore, we discuss therapeutic options to prevent kidney dysfunction in this setting, and highlight the indications of combined liver-kidney transplantation.

A 3-month course of ciprofloxacin does not prevent BK virus replication in heavily immunosuppressed kidney-transplant patients.

BACKGROUND: In vitro and retrospective studies of kidney-transplant patients have shown that quinolones can efficiently prevent BK virus (BKV) replication. However, in a prospective study, a 3 month-course of levofloxacin did not decrease the rate of BK viruria in kidney-transplant patients treated with standard immunosuppression. OBJECTIVES: The aim of this study was to assess the effect of a 3-month course of ciprofloxacin prophylaxis on BKV replication in kidney-transplant patients that had received heavy immunosuppression (plasma exchange or immunoadsorption and rituximab) to achieve desensitization before undergoing HLA- and/or ABO-incompatible (ABOi) transplantation. STUDY DESIGN: Twenty-nine patients were given ciprofloxacin (500mg/d) for 3 months, starting immediately after transplantation. The results were compared with results from a previous study where patients had received a similar immunosuppression regimen without ciprofloxacin prophylaxis (n=43). Around 60% of patients had undergone a retransplantation. After transplantation, all patients were given induction therapy, tacrolimus, mycophenolic acid and steroids. BK viruria and viremia were monitored at months 1, 3, 6 and 12 post-transplantation. RESULTS: The rates of BK viruria, BK viremia, and BKV-associated nephropathy did not differ between patients who were given or not given ciprofloxacin prophylaxis. These rates were also identical when patients received quinolones at any time within the first year after transplantation compared to those that had not. The rate of bacterial infection was also similar in patients who had or had not received ciprofloxacin. CONCLUSION: The use of quinolones seemed to not have any beneficial effect in preventing BKV replication in kidney-transplant patients receiving heavy immunosuppression.

Belatacept prophylaxis against organ rejection in adult kidney-transplant recipients.

End-stage renal disease is a major health problem worldwide, with kidney transplantation being the treatment of choice. Calcineurin inhibitors are still the cornerstone of immunosuppressive therapy. However, they have well-known nephrotoxic affects and increase the risk of cardiovascular disease and cancer. In contrast, belatacept is a biological immunosuppressive agent that inhibits the T-cell co-stimulation. It is approved by the US Food and Drug Administration and the European Medicine Agency for use in adult kidney-transplant recipients to prevent acute rejection. Developmental studies show that belatacept is as efficient as calcineurin inhibitors at preventing acute rejection. In addition, kidney function is better and cardiovascular risk factors are reduced in patients given belatacept. Herein, the authors review the published evidence concerning the efficacy and safety of belatacept and discuss its potential specific indications.

Hepatitis E Virus-Induced Cryoglobulinemic Glomerulonephritis in a Nonimmunocompromised Person.

Hepatitis E virus (HEV)-related kidney disease and symptomatic cryoglobulinemia have been observed in solid-organ transplant recipients. However, HEV RNA in the cryoprecipitate has not yet been assessed. We report what to our knowledge is the first documented case of autochthonous HEV-induced cryoglobulinemic crescentic and membranoproliferative glomerulonephritis in an immunocompetent man with no notable medical history. He presented with edema, hypertension, increased serum creatinine level, and nephrotic syndrome. Type II cryoglobulinemia with monoclonal immunoglobulin G (IgG) κ light chain was detected. Anti-HEV IgG and IgM, as well as HEV RNA, were detected in serum and cryoprecipitate. Histologic analysis of a kidney biopsy specimen revealed features of crescentic and membranoproliferative glomerulonephritis. After HEV clearance, kidney and liver parameters improved and HEV RNA and cryoglobulinemia were undetectable. Hence, we conclude that HEV can cause severe kidney disease and should be considered in cases of unexplained glomerular disease.

De novo donor-specific anti-HLA antibodies mediated rejection in liver-transplant patients.

The incidence and consequences of de novo donor-specific anti-HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver-transplant patients, without preformed anti-HLA DSAs, were tested for anti-HLA antibodies, with single-antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver-enzyme levels until the last follow-up, that is, 34 (1.5-77) months. Twenty-one patients (14%) developed de novo DSAs. Of these, five patients had C1q-binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody-mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B-cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient- and graft-survival rates did not differ between patients with and without DSAs. In conclusion, liver-transplant patients with liver abnormalities should be screened for DSAs and AMR.

Interference of therapeutic antibodies used in desensitization protocols on lymphocytotoxicity crossmatch results.

BACKGROUND: Therapeutic antibodies used to desensitize patients awaiting a human leukocyte antigen (HLA) or ABO-mismatched graft are suspected to interfere with the lymphocytotoxicity crossmatch (LCT-XM) test when they are present in the tested sera because of their potential ability to activate or inhibit the complement. METHODS: The most frequent therapeutic antibodies (Abs) used in desensitization protocols (intravenous immunoglobulins, rituximab, basiliximab, eculizumab, antithymocyte globulin) were added to a negative- or a positive-control serum at various concentrations, and tested in vitro in a LCT-XM test. RESULTS: Rituximab turned the LCT-XM positive on B cells at 0.2 µg/mL and antithymocyte globulin turned the LCT-XM positive with T and B cells at 20 µg/mL and 200 µg/mL, respectively. Treatment with dithiothreitol sera, supplemented with rituximab (0.2 and 2 µg/mL) and antithymocyte globulins (20 and 200 µg/mL), partially or totally reduced this positive interference. Intravenous immunoglobulin, eculizumab, and basiliximab did not trigger any interference with the negative control serum. In a positive LCT-XM, eculizumab did not annihilate activation of the rabbit complement. Intravenous immunoglobulins (25 g/L) could partially or totally reduced lysis score of positive crossmatch with weak lysis scores. CONCLUSION: If eculizumab within the serum did not annihilate rabbit complement activation and basiliximab did not interfere with the crossmatch reaction, treatments based on rituximab, antithymocyte globulin and intravenous immunoglobulins need to be taken into account when interpreting a positive or negative crossmatch test.

Pretransplant urinary proteome analysis does not predict development of chronic kidney disease after liver transplantation.

BACKGROUND & AIMS: Chronic kidney disease (CKD) is a common complication after liver transplantation. Kidney biopsies cannot be easily performed before liver transplantation to predict patients at high risk for CKD. The aim of our study was to determine whether pre-, peri- and post-transplant factors, as well as peptides present in preliver transplant urine samples were associated with loss in kidney function at 6 months post-transplantation using proteome analysis. METHODS: Eighty patients who underwent a liver transplantation and that had pretransplant glomerular filtration rate (GFR) value of ≥60 mL/min/1.73 m² (MDRD) were included in the study. RESULTS: GFR decreased significantly after transplantation. At month 6 post-transplantation, 40 patients displayed a CKD, i.e. eGFR of <60 mL/min/1.73 m², while the other 40 patients did not. Although thousands of peptides were identified, none was significantly associated with the development of CKD at 6 months after liver transplantation. Moreover, using a urinary peptidome classifier to detect preexisting CKD, no difference was found in CKD scores between the 2 groups. After analysis of a large number of pre-, peri- and post-transplant parameters, viral hepatitis as a cause for liver transplantation was the sole independent predictive factor for CKD. No difference in peptides with differential urinary abundance between patients who received a graft for virus related liver disease vs. all other causes of liver disease was observed. CONCLUSION: Urinary peptidome analysis before liver transplantation failed to identify a peptide pattern associated with the development of CKD at 6 months after liver transplantation.