Antiphospholipid syndrome (APS) is a devastating autoimmune disease and in renal transplant recipients may result in allograft thrombosis or in extra-renal manifestation, mostly venous thromboembolism. There are many non- and immune risk factors affecting renal allograft in recipients with APS. However, renal allograft outcome in recipients with APS without APS nephropathy remains unknown. Aim: The aim of the study was to assess renal allograft function and survival in recipients with APS. Methods: Retrospective, multicenter study included 19 adult renal recipients with definite APS (primary or lupus-related) from three Polish transplant centers. Renal allograft function was assessed using serum creatinine concentration (SCr1) at 3rd month post-transplant and at the end of the observation (SCr2) and glomerular filtration rate (GFR) was estimated based on modification of diet in renal disease (MDRD) formula. General linear model was used to assess 12 month GFR change over time. Kaplan-Meier curves and restricted mean survival time were used for allograft survival. Matched control group consisted of 21 stable renal recipients without history of thrombosis and without anticoagulation/antiplatelet treatment. Results: The study group differs in induction therapy (p = 0.019), high-urgency procedure (p = 0.04), proteinuria (p = 0.0058), primary disease (lupus) (p < 0.0001), re-transplantation in primary APS (p = 0.0046) and shorter time since engraftment to SCr2 (p = 0.016). Primary APS was more often diagnosed post-transplant (p = 0.0005). Allograft biopsy revealed thrombotic microangiopathy (TMA) with acute rejection (AR) or isolated AR vs AR or chronic rejection in controls but did not reach significance (p = 0.054). Renal allograft function was inferior in the study group but did not reach significance: mean SCr2 (mg/dL) was 2.18 ± 1.41 and 1.5 ± 0.68 in controls, respectively, p = 0.27; mean GFR2 (ml/min/1.73m²) was 39.9 ± 20.83 and 51.23 ± 19.03, respectively, p = 0.102. Renal allograft duration was inferior in patients with APS and was (in years) 11.22 ± 1.44 vs. 14.36 ± 0.42, respectively, p = 0.037, in patients with primary APS (p = 0.021), in patients with APS diagnosed post-transplant (p = 0.012) but not in lupus-related APS (p = ns). Fifteen year renal allograft survival was inferior in APS vs. controls (73,86% vs. 90.48%, respectively, p = 0.049). Conclusions: Recipients with APS are at higher risk for allograft loss due to immune and non-immune causes. Renal allograft survival was inferior in recipients with APS and renal function remains impaired but stable.

The complement system is the primary defense mechanism against pathogens, acting through opsonization, the membrane attack complex, and classical, lectin, or alternative pathways. These pathways result in the production of key complement components, including C3a (complement component), C5a, and C3b, which recruit inflammatory cells. Complement dysregulation leads to renal disease through the overproduction of anaphylatoxins or inappropriate formation of the membrane attack complex. The levels of complement components have been shown to be useful as predictive markers in acute kidney injury, especially in conditions of alternative pathway activation, and in diseases of immune complex pathology such as lupus nephritis and IgA nephropathy. Genetic defects in complement regulatory proteins result in diseases such as C3 glomerulopathy or atypical hemolytic uremic syndrome, in which uncontrolled C3 convertase activity results in renal failure. Therapeutic interventions targeting complement components, including eculizumab or pegcetacoplan, improve patient outcomes in atypical hemolytic uremic syndrome and C3 glomerulopathy, respectively, while other interventions improve renal function in IgA nephropathy. These findings underscore the dual role of the complement system, which is not only implicated in the progression of renal diseases but also provides the potential for the development of therapeutic interventions for the treatment of various forms of nephropathy.