Associations Between Elevated Anticardiolipin IgG, Thrombocytopenia, and Combined Diabetes–Hypertension Etiology in Hemodialysis Patients

Background: Elevated anticardiolipin IgG (aCL IgG) has been reported in end-stage renal disease (ESRD), but its association with specific etiologies of kidney failure remains unexplored. The unique pathophysiology of diabetic–hypertensive nephropathy may be associated with a microenvironment that could potentially contribute to antiphospholipid antibody production and thrombotic complications. This study aimed to investigate whether aCL IgG elevation in hemodialysis (HD) patients is associated with combined diabetes–hypertension (DM + HTN) etiology and thrombocytopenia, thereby identifying a clinically distinct potential high-risk subgroup. In this hypothesis-generating study, we focused on within-HD patient comparisons rather than healthy controls. Methods: We enrolled 242 participants: 150 healthy controls (included only to establish local reference ranges) and 92 patients with maintenance HD. The study was conducted from 01 September to 20 November 2025 in Madinah, Saudi Arabia. Serum aCL IgG was measured by chemiluminescence immunoassay (positive ≥ 12 GPL units). Comprehensive hematological and biochemical parameters were analyzed. Multivariable logistic regression identified predictors of aCL positivity. Results: In the HD cohort, 21% demonstrated aCL positivity; this represents a substantially higher rate than the 2% observed in local healthy controls (p < 0.001). This elevation was not uniform across etiologies. Strikingly, 94.7% (18/19) of aCL-positive HD patients had DM + HTN aetiology, compared with only 17.8% of aCL-negative patients (p < 0.001). Thrombocytopenia was significantly more severe in aCL-positive patients (median platelets: 100 vs. 191 × 109/L, p < 0.001). In multivariable analysis, DM + HTN etiology (HTN-alone vs. DM + HTN odds ratio [OR]: 0.0013, 95% confidence interval [CI]: 0.00002–0.0999, p = 0.003; confirmed by Firth’s penalized logistic regression sensitivity analysis, and lower platelet count (OR: 0.92 per 1 × 109/L increase, 95% CI: 0.87–0.98, p = 0.006) independently predicted aCL positivity. Conclusions: These hypothesis-generating findings suggest a potential association between metabolic–vascular disease and antiphospholipid immunity in ESRD. Causality cannot be inferred from this cross-sectional design. At present, routine aCL screening is not recommended outside of research protocols; prospective studies are needed to confirm these associations.