Decreased chronic cellular and antibody-mediated injury in the kidney following simultaneous liver-kidney transplantation

Abstract

In simultaneous liver-kidney transplantation (SLK), the liver can protect the kidney from hyperacute rejection and may also decrease acute cellular rejection rates. Whether the liver protects against chronic injury is unknown. To answer this we studied renal allograft surveillance biopsies in 68 consecutive SLK recipients (14 with donor-specific alloantibodies at transplantation [DSA+], 54 with low or no DSA, [DSA-]). These were compared with biopsies of a matched cohort of kidney transplant alone (KTA) recipients (28 DSA+, 108 DSA-). Overall 5-year patient and graft survival was not different: 93.8% and 91.2% in SLK, and 91.9% and 77.1% in KTA. In DSA+ recipients, KTA had a significantly higher incidence of acute antibody-mediated rejection (46.4% vs. 7.1%) and chronic transplant glomerulopathy (53.6% vs. 0%). In DSA- recipients at 5 years, KTA had a significantly higher cumulative incidence of T cell-mediated rejection (clinical plus subclinical, 30.6% vs. 7.4%). By 5 years, DSA+ KTA had a 44% decline in mean GFR while DSA+SLK had stable GFR. In DSA- KTA, the incidence of a combined endpoint of renal allograft loss or over a 50% decline in GFR was significantly higher (20.4% vs. 7.4%). Simultaneously transplanted liver allograft was the most predictive factor for a significantly lower incidence of cellular (odds ratio 0.13, 95% confidence interval 0.06-0.27) and antibody-mediated injury (odds ratio 0.11, confidence interval 0.03-0.32), as well as graft functional decline (odds ratio 0.22, confidence interval 0.06-0.59). Thus, SLK is associated with reduced chronic cellular and antibody-mediated alloimmune injury in the kidney allograft.

Liver Allograft Provides Immunoprotection for the Cardiac Allograft in Combined Heart–Liver Transplantation

“…Our preliminary (unpublished) data show that T cell alloreactivity is decreased in simultaneous liver-kidney transplant recipients, compared with solitary kidney transplant recipients with similar pharmacologic immunosuppression. This protective effect appears to be related directly to the status of the liver allograft, as it is lost in patients with recurrent fibrosis/cirrhosis (9). Because all the SHLT patients in the current cohort had functional liver allografts, it is not surprising that the cumulative incidence of TCMR in this group was significantly lower.…”

“…3 Hyperlipidemia defined as low-density lipoprotein ≥130 mg/dL, triglycerides ≥150 ng/mL, or high-density lipoprotein <40 mg/dL in men and <50 mg/dL in women, or taking lipid-lowering medications; pretransplantation or posttransplantation. (9). In the liver, both hepatocytes and liver-resident antigen-presenting cells are capable of activating na€ ıve T cells (30)(31)(32).…”

“…Recent evidence suggests that, in multiorgan transplantation, the liver allograft can also provide immunoprotection for the simultaneously transplanted organs (7,8). For example, the incidence of long-term alloimmune-mediated injury in the kidney allografts of simultaneous liver-kidney transplant recipients is lower than that in solitary kidney transplant recipients (9). A few small studies have demonstrated that the incidence of early heart allograft rejection is also reduced in simultaneous heart-liver transplant recipients (10,11).…”

Liver transplantation: Rejection and tolerance

“…In multiorgan transplantations, the liver allograft appears to provide a protective effect to simultaneously transplanted organs from the same deceased donor. For example, in simultaneous liver‐kidney transplantation, the incidences of biopsy‐proven kidney AMR and TCMR are lower than those seen after solitary kidney transplantation in a matched cohort . After simultaneous liver‐heart transplantation, the incidence of heart AMR had a 3‐fold decrease .…”

Deletion of donor-reactive T cell clones after human liver transplant

“…appears to provide immunoprotection compared with single heart 8 or kidney [9][10][11] grafts, suggesting the liver allograft may promote systemic suppression of the antidonor response. appears to provide immunoprotection compared with single heart 8 or kidney [9][10][11] grafts, suggesting the liver allograft may promote systemic suppression of the antidonor response.…”