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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2011  |  Volume : 22  |  Issue : 4  |  Page : 757-760
Combined liver and kidney transplantation in a highly sensitized and positively cross-matched patient

1 Nephrology Division, Department of Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
2 Department of Hepatobiliary Sciences, King Abdulaziz Medical City, Riyadh, Saudi Arabia
3 Department of Pathology, King Abdulaziz Medical City, Riyadh, Saudi Arabia

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Date of Web Publication9-Jul-2011


Combined liver kidney transplantation (CLKT) has been used on many occasions and proved to be a successful event for both liver and kidney in highly sensitized patients. Our aim was to review the immunological and other laboratory results of a CLKT in a highly sensitized patient. CLKT was used to treat a highly sensitized, 42-year-old female. She was suffering from end-stage liver disease due to hepatitis C virus (HCV) infection and renal disease due to diabetic nephropathy. Cross-matching, panel reactive assay (PRA) and routine laboratory tests for liver and renal function were carried out before and after the CLKT. Prior to the CLKT, the patient was highly sensitized with human leukocytes antigens (anti-HLA) class I antibodies (>90%). Patient was offered CLKT from a deceased donor. She had donor-specific antibodies, class I and II. Both T and B CDC cross-matches (XM) were positive pre-transplant and eight hours post-transplant. Both cross-match and PRA results became completely negative six days post CKLT. Almost 30 months post CLKT, her renal function is normal and negative for class I and II PRA. Liver graft appears to be protective for renal graft when they are combined even in highly sensitized patients. CLKT is very useful in overcoming sensitization in addition to treating end-stage liver and renal diseases.

How to cite this article:
Alqurashi S, Alsayyari AA, Abdullah K, Alwan A, Hajeer AH. Combined liver and kidney transplantation in a highly sensitized and positively cross-matched patient. Saudi J Kidney Dis Transpl 2011;22:757-60

How to cite this URL:
Alqurashi S, Alsayyari AA, Abdullah K, Alwan A, Hajeer AH. Combined liver and kidney transplantation in a highly sensitized and positively cross-matched patient. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2021 Apr 13];22:757-60. Available from: https://www.sjkdt.org/text.asp?2011/22/4/757/82682

   Introduction Top

Liver and kidney transplantations are well established procedures for treating end-stage liver and renal disease. In kidney transplantation, a positive cross-match is considered a contraindication for transplantation as it predicts antibody-mediated hyper acute rejection. [1] Currently, this is not the case in combined liver and kidney transplantation (CLKT) [2],[3] . This has been attributed to different reasons: the development of new immunosuppressant medications, our understanding of immunemediated pathology of the allografts, and finally to the rapid development in immuno-assays. We report here a case of CLKT across positive cross-matching.

   Case Report Top

A 42-year-old woman known for her longstanding diabetes mellitus, hypertension, liver cirrhosis secondary to hepatitis C virus (HCV), and advanced chronic kidney disease secondary to diabetic nephropathy, underwent an uneventful surgical operation to receive a CLKT from a deceased donor on 5 th Aug 2007, after 20 days of hemodialysis therapy.

Her panel of reactive assay (PRA) before transplantation revealed a high percentage of sensitization (96% class I, 50% class II by flow cytometry). In addition, the complement-dependent cytotoxicity (CDC) (long incubation) cross-match at the time of liver transplant was positive for both T and B cells. The patient showed donor-specific antibodies for both class I and II human leukocytes antigens (HLA). Specificities of these antibodies were A2 and DR7, in addition to other non-donor antibodies, such as DR10 and DR15 (ELISA, Biotest). Donor HLA type included A2, 24; B51(5); DR4, 7; DQ6(1), and DQ2.

Laboratory results showed improvement after the CLKT [Table 1]; pre-and post-transplantation included creatinine, electrolytes, liver function tests (LFT), HCV polymerase chain reaction (PCR), and 24-hour urinary protein.
Table 1: Renal and liver function after the combined liver and kidney transplantation (CLKD).

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The patient received induction immunosuppressive therapy including anti-thymocyte globulin 3 mg/kg, which was discontinued due to persistent thrombocytopenia and leukopenia, intravenous immunoglobulin (IVIG) 2 g/kg, and i.v. Methylprednisolone 500 mg. Later, she was maintained on mycophenolate sodium, prednisone (tapered slowly over three months to 5 mg every other day), and tacrolimus (trough level from 8 to 12 during the first month after transplantation, and from 5 to 10 thereafter).

There was a dramatic decrease in the percentage of sensitization on the PRA as early as six days post-transplant, and this was maintained even after 24 months [Figure 1]. Class I specific PRA by flow cytometry started at 96% before the operation and decreased to completely negative PRA after 22 months post CKLT, while class II PRA started at 50% and decreased to 14% (DR10) after almost 22 months post-transplantation.
Figure 1: Class I and II flow PRA results at the time of CLKT and up to 560 days post CLKT.

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Pre-transplant creatinine was 269 μmol/L, with a measured glomerular filtration rate (GFR) by diethylenetriaminopentacetic acid (DTPA) of 25 mL/min. Current creatinine is 68 μmol/L. Furthermore, the 24-hour proteinuria pretransplant was 7.5 g/day, and currently is less than 150 mg/day. However, the patient developed active and persistent replication of HCV indicated by HCV PCR results and elevated liver enzymes despite treatment with ribavirin and pegylated interferon for one year.

   Discussion Top

Our patient showed improved renal and liver function post CLKT. However, she suffered from HCV reactivation which was treated by pegylated interferon and ribavirin for one year, but showed persistent viral replication. However, the sensitization status of the patient improved remarkably.

Early review of the UNOS database by Katznelson in 1995, with regards to CLKT, demonstrated no improvement in graft survival in CLKT versus isolated renal transplantation. Both the groups had similar one-year graft survival for greater than two HLA mismatched combinations and comparable rates of delayed graft function for highly sensitized patients. [4] Again during the same period in 1994, Saidman suggested much reduced one-year renal allograft survival of CLKT performed with a positive cross-match. [5]

However, recently, encouraging data showed an improvement in renal allograft outcomes when performed as a part of CLKT. Analysis of UNOS database by Fong et al [6] supported allograft enhancing effect of CLKT with increased rates of rejection-free graft survival and decreased chronic rejection, although with lower overall patient and graft survival rates. [6]

Simpson et al [7] showed that patients who received CLKT had a lower incidence of chronic rejection, a higher rate of rejection-free graft survival, and a longer graft half-life compared with patients who received kidney after liver transplantation. Positive cross-matches have been observed to convert to negative cross-matches after CLKT, and low renal allograft rejection rates are observed despite the presence of cytotoxic antibody. [8] The elimination of donor-specific antibody has been consistently demonstrated by serial cross-matches pre-and post-liver transplantation. [9],[10] This documented immunological tests improvement was associated with good clinical outcomes.

One year follow-up of crossmatch-positive recipients of either liver transplantation or CLKT did not demonstrate different graft survival, acute cellular rejection or defined "steroid resistant rejection" episodes when compared to crossmatch-negative recipients. [11] Creput et al [12] did a retrospective study in a highly sensitized patient who received CLKT; recipients demonstrated only a 4% rate of renal allograft rejection despite a 31% rate of acute rejection of the liver allograft. Similar work by Ruiz showed one-year rejection rates of 10% for renal allograft and 23% for hepatic allograft in 99 CLKT recipients. [13]

One case report has suggested that CLKT may produce non-complement fixing antibodies as a possible mechanism for protection of the renal allograft despite the positive cross-match. [14] Interestingly, Olausson et al described the protective effect of a simultaneous auxillary liver allograft as a strategy to achieve success with renal transplantation in the case of a positive cross-match. [15] The auxiliary liver transplants were able to convert the positive to negative cross-match in five out of seven patients, with good renal function and no reported rejection. Two unsuccessful cases demonstrated evidence of humoral rejection of the renal allograft combined with hepatic arterial thrombosis of the liver allografts in both cases: biliary leak in one case, and histological evidence of rejection of the liver in the other.

Liver graft appears to be protective for renal graft when they are combined in highly sensitized patients. Several mechanisms have been proposed to explain this phenomenon, including a role of soluble HLA antigens produced by the liver in inhibiting graft-specific antibodies, microchimerism, and ability of the liver to rapidly regenerate in response to injury.

   References Top

1.Patel R, Terasaki PI. Significance of the positive cross-match test in kidney transplantation. N Engl J Med 1969;280:735.  Back to cited text no. 1
2.Iwatsuki S, Iwaki Y, Kano T, et al. Successful liver transplantation from crossmatch-positive donors. Transplant Proc 1981;13(1.1):286-8.  Back to cited text no. 2
3.Rasmussen A, Davies HF, Jamieson NV, Evans DB, Calne RY. Combined transplantation of liver and kidney from the same donor protects the kidney from rejection and improves kidney graft survival. Transplantation 1995;59(6):919-21.  Back to cited text no. 3
4.Katznelson S, Cecka JM. The liver neither protects the kidney from rejection nor improves kidney graft survival after combined liver and kidney transplantation from the same donor. Transplantation 1996;61(9):1403-5.  Back to cited text no. 4
5.Saidman SL, Duquesnoy RJ, Demetris AJ, et al. Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies. Transpl Immunol 1994;2(1):61-7.  Back to cited text no. 5
6.Fong TL, Bunnapradist S, Jordan SC, Selby RR, Cho YW. Analysis of the United Network for Organ Sharing database comparing renal allografts and patient survival in combined liver-kidney transplantation with the contralateral allografts in kidney alone or kidney-pancreas transplantation. Transplantation 2003; 76(2):348-53.  Back to cited text no. 6
7.Simpson N, Cho YW, Cicciarelli JC, Selby RR, Fong TL. Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: analysis of UNOS Database. Transplantation 2006;82(10):1298-303.  Back to cited text no. 7
8.Morrissey PE, Gordon F, Shaffer D, et al. Combined liver-kidney transplantation in patients with cirrhosis and renal failure: Effect of a positive cross-match and benefits of combined transplantation. Liver Transpl Surg 1998;4(5): 363-9.  Back to cited text no. 8
9.Faenza A, Fuga G, Nardo B, et al. Combined liver kidney transplantation: The experience of the University of Bologna and the case of preoperative positive cross-match. Transplant Proc 2006;38(4):1118-21.  Back to cited text no. 9
10.Mosconi G, Scolari MP, Feliciangeli G, et al. Combined liver-kidney transplantation with preformed anti-HLA antibodies: a case report. Transplant Proc 2006;38(4):1125-6.  Back to cited text no. 10
11.Neumann UP, Lang M, Moldenhauer A, et al. Significance of a T-lymphocytotoxic cross-match in liver and combined liver-kidney transplantation. Transplantation 2001;71(8):1163-8.  Back to cited text no. 11
12.Creput C, Durrbach A, Samuel D, et al. Incidence of renal and liver rejection and patient survival rate following combined liver and kidney transplantation. Am J Transplant 2003; 3(3):348-56.  Back to cited text no. 12
13.Ruiz R, Kunitake H, Wilkinson AH, et al. Longterm analysis of combined liver and kidney transplantation at a single center. Arch Surg 2006;141(8):735-41; discussion 741-2.  Back to cited text no. 13
14.McAlister CC, Gao ZH, McAlister VC, et al. Protective anti-donor IgM production after crossmatch positive liver-kidney transplantation. Liver Transpl 2004;10(2):315-9.  Back to cited text no. 14
15.Olausson M, Mjornstedt L, Norden G, et al. Successful combined partial auxiliary liver and kidney transplantation in highly sensitized crossmatch positive recipients. Am J Transplant 2007;7(1):130-6.  Back to cited text no. 15

Correspondence Address:
Salem Alqurashi
Nephrology Division, King Abdulaziz Medical City, P. O. Box 22490, Riyadh 11426
Saudi Arabia
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PMID: 21743223

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