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Biomarkers / Biomarker · Journal article
Annals of Medicine · August 18, 2026
Encouraging direction, but not yet definitive.
This single-center retrospective study of 256 IgAN patients found that elevated homocysteine levels are associated with more severe tubular atrophy/interstitial fibrosis, worse kidney function markers, and hypertension. However, the association was substantially attenuated after adjusting for renal function, and homocysteine's discriminative ability for tubulointerstitial fibrosis is only modest (AUC 0.756), limiting its value as a standalone prognostic tool.
Single-center retrospective cohort study. Patients with primary IgAN diagnosed at Zhongshan Hospital (Xiamen), Fudan University, between August 2018 and December 2023. Excluded: secondary IgAN (autoimmune, chronic hepatitis, malignancies), incomplete clinical or pathological data, renal biopsy with <10 glomeruli.. Intervention: Elevated homocysteine (≥hyperhomocysteinemia threshold, not precisely defined in excerpt). Compared with: Normal homocysteine levels. n = 256. Single center: Zhongshan Hospital (Xiamen), Fudan University, China.
32% of 256 IgAN patients had hyperhomocysteinemia; mean age 41.01 ± 12.83 years, 58.6% male HHcy patients showed higher rates of hypertension and increased serum creatinine, 24-hour urinary protein, urinary albumin-creatinine ratio, and cystatin C, with lower estimated glomerular filtration rate HHcy correlated significantly with severity of tubular/interstitial fibrosis with AUC = 0.756 (95% CI: 0.686–0.824, p 0.001) at exploratory cutoff 12.50 μmol/L
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Elevated homocysteine shows association with worse renal outcomes in IgAN, but its modest discriminative ability (AUC 0.756) and marked attenuation after adjusting for renal function suggest it should not be used as a standalone prognostic marker. Further prospective studies are needed to determine whether lowering homocysteine can modify disease progression.
Single-center retrospective study with clear associations between elevated homocysteine and renal pathology in IgAN, but modest discriminative ability (AUC 0.756) and attenuation after adjustment for renal function limit clinical utility.
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Elevated homocysteine shows association with worse renal outcomes in IgAN, but its modest discriminative ability (AUC 0.756) and marked attenuation after adjusting for renal function suggest it should not be used as a standalone prognostic marker. Further prospective studies are needed to determine whether lowering homocysteine can modify disease progression.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
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.
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