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

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.

Hyperglycemia Induces Inflammatory Response of Human Macrophages to CD163-Mediated Scavenging of Hemoglobin-Haptoglobin Complexes.

Hyperglycemia, a hallmark of diabetes, can induce inflammatory programming of macrophages. The macrophage scavenger receptor CD163 internalizes and degrades hemoglobin-haptoglobin (Hb-Hp) complexes built due to intravascular hemolysis. Clinical studies have demonstrated a correlation between impaired scavenging of Hb-Hp complexes via CD163 and diabetic vascular complications. Our aim was to identify whether hyperglycemia is able to amplify inflammation via Hb-Hp complex interactions with the immune system. M(IFNγ), M(IL-4), and control M0 macrophages were differentiated out of primary human monocytes in normo- (5 mM) and hyperglycemic (25 mM) conditions. CD163 gene expression was decreased 5.53 times in M(IFNγ) with a further decrease of 1.99 times in hyperglycemia. Hyperglycemia suppressed CD163 surface expression in M(IFNγ) (1.43 times). Flow cytometry demonstrated no impairment of Hb-Hp uptake in hyperglycemia. However, hyperglycemia induced an inflammatory response of M(IFNγ) to Hb-Hp1-1 and Hb-Hp2-2 uptake with different dynamics. Hb-Hp1-1 uptake stimulated IL-6 release (3.03 times) after 6 h but suppressed secretion (5.78 times) after 24 h. Contrarily, Hb-Hp2-2 uptake did not affect IL-6 release after 6h but increased secretion after 24 h (3.06 times). Our data show that hyperglycemia induces an inflammatory response of innate immune cells to Hb-Hp1-1 and Hb-Hp2-2 uptake, converting the silent Hb-Hp complex clearance that prevents vascular damage into an inflammatory process, hereby increasing the susceptibility of diabetic patients to vascular complications.