Association of elevated homocysteine levels with renal pathology and function in patients with IgA nephropathy: a single-center retrospective study

Abstract

Abstract Background The role of homocysteine (Hcy) in immunoglobulin A nephropathy (IgAN) remains unclear. This study investigates the association between Hcy levels, clinical symptoms, and pathological changes in patients with IgAN to elucidate Hcy’s clinical significance. Methods 256 IgAN patients were included and categorized into two groups : normal Hcy and hyperhomocysteinemia (HHcy). Clinical and pathological characteristics were compared between these groups. Logistic regression was used to analyze the association between clinicopathological factors and Hcy levels, while the predictive capability of Hcy for renal tubular atrophy/interstitial fibrosis was evaluated using receiver operating characteristic (ROC) curve analysis. Results The average age of participants was 41.01 ± 12.83 years; 58.6% were male, and 32% had HHcy. Patients with HHcy showed higher rates of hypertension and increased levels of serum creatinine, 24-hour urinary protein, urinary albumin-creatinine ratio, retinol-binding protein, cystatin C, urinary neutrophil gelatinase-associated lipocalin, beta2-microglobulin, serum potassium, serum phosphate, and parathyroid hormone. They also exhibited more severe tubular atrophy/interstitial fibrosis. In contrast, they had lower estimated glomerular filtration rate, hemoglobin, and HDL cholesterol levels. No significant differences were observed in mesangial hypercellularity, endocapillary hypercellularity, focal segmental glomerulosclerosis, and crescents scores between the groups. Hcy levels correlated significantly with the severity of tubular/interstitial fibrosis, serving as a modest predictor with an exploratory optimal cutoff value of 12.50 μmol/L [AUC = 0.756 (95% CI: 0.686–0.824, p < 0.001)]. Conclusions Elevated Hcy levels are associated with pathological severity and worse kidney function in IgAN patients. However, this association was largely attenuated after adjusting for renal function, and the AUC of 0.756 indicates only modest discriminative ability. Hcy should be used together with other clinical and pathological markers, not as a standalone prognostic tool. Whether lowering Hcy levels can modify IgAN progression remains to be determined in prospective studies.