Abstract / Summary
Abstract Background New-onset diabetes after transplantation (NODAT) represents a frequent metabolic sequela of kidney transplantation that amplifies cardiovascular risk and compromises allograft survival. Angiopoietin-like protein 6 (ANGPTL6; angiopoietin-related growth factor) is a hepatokine implicated in energy homeostasis, endothelial repair, and angiogenesis, and dysregulated circulating concentrations have been documented in obesity, metabolic syndrome, and type 2 diabetes mellitus. Its behaviour in NODAT has not previously been characterised. Objective To compare serum ANGPTL6 concentrations between kidney transplant recipients who developed NODAT and those who remained normoglycaemic, and to evaluate ANGPTL6 as a candidate biomarker of post-transplant metabolic and vascular dysregulation. Methods We conducted a retrospective, registry-based comparative study of 308 kidney transplant recipients (NODAT, n = 153; normoglycaemic transplant controls, n = 155) drawn from a national transplant registry cohort, whom we previously characterised immunogenetically. Serum ANGPTL6 was quantified by validated sandwich enzyme-linked immunosorbent assay in duplicate (intra- and inter-assay coefficients of variation < 10%). Between-group comparisons employed independent-samples t-tests; effect magnitude was expressed as Cohen's d; outliers were screened by z-scores and boxplot inspection. Results Mean serum ANGPTL6 was significantly higher in recipients with NODAT than in normoglycaemic controls (75,135.33 ± 16,012.22 vs 69,974.87 ± 14,954.01 pg/mL; mean difference 5,160 pg/mL, 95% CI 1,699–8,622; Cohen's d = 0.33; p = 0.001) (Table 2, Fig. 1). The elevation was distributional rather than driven by extreme values, with outliers exceeding 90,000 pg/mL confined predominantly to the NODAT group. Sex, age, and immunosuppressive regimen did not materially modify ANGPTL6 concentrations. Conclusion Serum ANGPTL6 is significantly elevated in NODAT, independent of immunosuppressive regimen, and may represent the hepatokine component of an immune–vascular–metabolic axis linking Th1 activation, angiopoietin imbalance, and post-transplant metabolic failure. ANGPTL6 warrants evaluation within longitudinal, multi-marker risk models for NODAT.