Combined liver-kidney transplantation in patients with cirrhosis and renal failure: Effect of a positive cross-match and benefits of combined transplantation

Abstract

Patients with renal failure after liver transplantation have a particularly poor prognosis. Therefore, in the setting of end-stage renal disease requiring dialysis or severe renal insufficiency that will not improve after liver replacement, combined liver-kidney transplantation (LKT) is the preferred approach. We have adopted a policy of LKT in patients with end-stage liver disease and renal insufficiency undergoing dialysis or with a creatinine clearance less than 35 mL/min and evidence of chronic renal dysfunction. Since 1991, we have performed 208 orthotopic liver transplantations. Fourteen patients (8%) have undergone combined LKT, including 6 patients undergoing hemodialysis. Cytotoxic cross-matches (modified Amos technique and antihuman globulin method) were performed on 13 of 14 patients and were positive in 3 patients. Two patients died less than 4 months after LKT and 12 patients are alive and well. Graft survival censored for patient death was 100% for liver allografts and 93% for renal allografts, with a mean follow-up of 39 ؎ 24 months. The most recent serum creatinine level in the patients with the 11 functioning grafts was 1.1 ؎ 0.6 mg/dL. Biopsy-proven acute rejection occurred in 50% of simultaneous liver allografts. By contrast, only a single episode (6%) of renal allograft dysfunction was attributable to acute rejection. All rejection episodes occurred in the first 90 days after transplantation and were steroid sensitive. Three of 14 combined procedures were performed in the setting of a positive cytotoxic cross-match. In 2 recent patients, the results were confirmed by positive cross-matches to the donor's T and B cells by flow cytometry. Flow cytometric cross-matches reverted to negative 1 hour after liver transplantation and several hours before the administration of antithymocyte globulin. The cross-matches remained negative on postoperative days 1 and 7. Presently, all 3 patients with a positive cross-match enjoy normal hepatic and renal function at 631, 706, and 2275 days follow-up. Renal scans were performed in 4 LKT recipients not previously undergoing hemodialysis and indicated varying and unpredictable degrees of function in the native and transplanted kidneys. In conclusion, combined LKT can be performed safely and is associated with a low rate of acute rejection, even in the setting of a positive cross-match. Predicting which patients with renal insufficiency will benefit from LKT remains challenging; however, these results suggest that LKT should be encouraged in patients with evidence of irreversible renal insufficiency who require liver transplantation.

Donor-Directed MHC Class I Antibody Is Preferentially Cleared from Sensitized Recipients of Combined Liver/Kidney Transplants

“…In fact, immediately following liver transplantation, kidney transplantation has been safely performed despite the presumed preoperative presence of alloantibody based on preoperative positive cross-match. Previous studies reported that these patients converted to a negative crossmatch after liver transplantation suggesting decreases in alloantibody (6). Based on these clinical observations, it has been proposed that a liver allograft protects the kidney from hyper acute rejection by either absorbing or neutralizing DSA.…”

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

“…Early acute kidney rejection rates in combined transplantation are on average less than 10% (Table 10). 12,42,43,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]65,80 This is compared with rejection rates of 30% to 50% reported in the literature for temporally matched kidney-only transplant recipients. 65 Thus, even with less HLA matching and a positive cross-match, renal rejection rates appear to be lower when a liver allograft is placed concurrently ( 3).…”

“…81,82 The pathophysiological cause of this effect has not been identified; however, it has been observed that positive pretransplantation cross-matches become negative after placing the new liver, providing support for the theory that liver allograft absorption of anti-HLA antibodies protects the kidney. 47,51,53,61,82 Neutralization of anti-HLA antibodies and cytotoxic lymphocytes by liver allograft production of soluble HLA molecules also may contribute. 83 Last, it is possible that passenger leukocytes within the liver result in greater microchi- merism than after kidney-only transplantation, with the subsequent development of tolerance.…”

Acute Humoral Rejection in an ABO Compatible Combined Liver–Kidney Transplant—The Kidney Is Not Always Protected

“…(1,3,(9)(10)(11). The complete removal of HLA antibodies by the liver allograft converting a crossmatch from positive to negative during combined a liver-kidney transplant has been reported (12). However, the long-term beneficial effect of the liver in combined liver-kidney transplants has been debated (13).…”