Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients

Abstract

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb^® ABO columns to reusable non-antigen-specific Immunosorba^® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

Keywords: ABO-incompatible kidney transplantation; complications; immunoadsorption; infections; mortality.

FIGURE 1

Study profile. 138 patients received ABO-incompatible living kidney transplantation after desensitization using different immunoadsorption columns. ABOi, ABO-incompatible; IA, immunoadsorption; KTx, kidney transplantation.

FIGURE 2

Severe infectious complications during the first year after ABO-incompatible kidney transplantation. Shown are absolute numbers and percentages for each IA group for severe infectious complications during the first year after ABOi KTx. Grey blocks indicate patients desensitized with antigen-specific IA (sIA); white blocks represent patients receiving non-antigen-specific IA (nsIA). The incidence of severe infections was compared using a two-tailed Fisher’s exact test (sIA vs. nsIA: 7 (8.6%) vs. 16 (28.6%), p = 0.004).

FIGURE 3

Cumulative incidence of infectious complications after ABO-incompatible kidney transplantation. (A) Time period until the occurrence of the first infection after transplantation according to IA modality. nsIA: non-antigen-specific immunoadsorption; sIA: antigen-specific immunoadsorption, (B) Cumulative incidence of any infectious complication after KTx for the whole cohort. (C) Estimation of 1-year cumulative incidence of any post-transplant infection. “cuminc”: cumulative incidence. (D) Time period until the occurrence of the first severe infection after KTx according to IA modality. nsIA: non-antigen-specific immunoadsorption; sIA, antigen-specific immunoadsorption, (E) Cumulative incidence of severe infectious complications after KTx for the whole cohort. (F) Estimation of 1-year cumulative incidence of severe post-transplant infections. A severe infection required the detection of pathogens in the blood stream or a SOFA score ≥2. To estimate the cumulative cause-specific infection-free survival, the Aalen-Johansen estimate was used; Gray’s test was then used to test for a difference between cause-specific survival functions.

FIGURE 4

Severe infectious complications after ABO-incompatible kidney transplantation. (A) Focus of severe infection, (B) Focus of blood culture pathogens. A severe infection was defined as the detection of pathogens in the blood stream or a SOFA score ≥2. p-values are estimated with a two-tailed Fisher’s exact test. *Denotes statistical significance between antigen-specific IA and non-antigen-specific IA (**p < 0.01).

FIGURE 5

Regression coefficient plot visualizing the relative hazard of postoperative severe infections during the first year after ABO-incompatible kidney transplantation. Provided are parameter estimates with 95% confidence limits. IA, ASA category, age >50 years and recipient sex were included as categorical variables. ASA, American Association of Anesthesiologists; IA, immunoadsorption.

FIGURE 6

Patient survival during the first 2 years after ABOi kidney transplantation. Data are shown for 81 patients receiving sIA and 57 patients receiving nsIA. To display the time period until the occurrence of patient death during the first 2 years after kidney transplantation via Kaplan-Meier graph, a log-rank test was utilized. nsIA, non-antigen-specific immunoadsorption; sIA, antigen-specific immunoadsorption.