Systemic Lupus Erythematosus Leading to Terminal Renal Failure and Excluding Patients from Kidney Allocation Due to Inadequate CDC-based Cross-Matching: Is There a Diagnostic Way out?

Systemic lupus erythematosus (SLE) is known to proceed to clinically relevant nephritis in more than 50% of patients and, in about 20% of these patients, to terminal renal failure. Thus, renal replacement therapy including kidney allografting is required for a considerable number of SLE-patients. For allografting patients’ donor-specific antibodies against HLA molecules of given donors (DSA) have to be excluded as preformed antibodies against these molecules represent the main cause for hyper-acute or acute rejections. In order to select recipients without these deleterious antibodies the complement-dependent cytotoxicity crossmatch (CDC-XM) assay was developed about forty years ago. Its negative pre-transplant outcome is currently regarded as the most important requirement for a successful kidney graft survival. During the last years several disadvantages of the CDC-based procedure have increasingly been discussed with respect to this assay’s high susceptibility to disruptive factors mainly leading to false positive outcomes. As is clearly shown by our case series this holds also true for the underlying disease SLE. We here present the data of SLE-patients initially destined for cadaver kidney donations. They all exhibited positive CDC-XM outcomes for the most part without known historical immunizing events. Furthermore, solid phase-based antibody screening and specification analyses did generally not show anti-HLA antibodies or antibodies directed against HLA-phenotypes of the corresponding donors thus leading to negative results of the so-called virtual crossmatch. Since exclusive virtual cross-matching is not allowed for the acceptance of allografting all of the positive CDC-XM assays were performed as reruns using alternative solid phase(ELISA-) based crossmatch assays. In best accordance with virtual cross-matching solid phase-based cross-matching did not exhibit DSA. Our data clearly demonstrate the benefit of alternative ELISA-based cross-matching to circumvent CDC-based artefacts and point on the urgent requirement to substitute the historical CDC-based procedure at least for this group of patients.