Plasma D-dimer as a potential predictor of progression in IgA nephropathy: a cohort study

Abstract

Introduction Coagulation disorders play a key role in chronic kidney disease, and the formation or elevation of plasma D-dimer levels reflects activation of the coagulation system. However, its relationship with the severity and progression of kidney disease in IgA nephropathy (IgAN) remains unclear. Methods We assessed 1818 patients with IgAN diagnosed between 2002 and 2019 at the First Affiliated Hospital, Zhejiang University School of Medicine. Plasma D-dimer levels were measured at the time of the renal biopsy. The association between plasma D-dimer levels and kidney disease progression events, defined as a 50% decline in eGFR and end-stage kidney disease (ESKD), was tested using restricted cubic splines and Cox proportional hazard models. Results The median plasma D-dimer level was 220 (170–388.5) µg/L FEU, which was significantly higher than healthy controls 170 (170–202) µg/L FEU. Plasma D-dimer levels were positively correlated with proteinuria ( r = 0.211, p < 0.001) and serum galactose-deficient IgA1 ( r = 0.226, p = 0.004) and negatively correlated with eGFR (r=-0.127, p < 0.001) and Oxford T ( p < 0.001) and C ( p = 0.004) scores. After a median follow-up of 25.67 (13.03–47.44) months, 126 (6.93%) patients experienced composite kidney disease progression events. Higher plasma D-dimer levels were associated with an increased risk of kidney disease progression events (hazard ratio, 1.73; 95% confidence interval [95% CI], 1.40–2.23) per ln-transformed plasma D-dimer ( p < 0.001), after adjustment for sex, age, proteinuria, Mean arterial pressure (MAP) and Oxford classification scores. In reference to the first tertile of plasma D-dimer, hazard ratios were 1.48 (95% CI, 0.76–2.88) for the second tertile, 3.03 (95% CI, 1.58–5.82) for the third tertile. Conclusions High plasma D-dimer levels were associated with the progression of kidney disease severity in IgA nephropathy.