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Purpose <p>Hyperhomocysteinemia (HHcy) is widely observed in chronic kidney disease (CKD) patients. In early CKD stages, HHcy is more prevalent in IgA nephropathy (IgAN) patients. Here, we investigated the relationship between HHcy and renal outcomes among patients with IgAN.</p> Methods <p>This study evaluated patients with IgAN who underwent diagnostic renal biopsies in the National Clinical Research Center of Kidney Diseases Jinling Hospital from October 2012 to June 2024. Patients were stratified into two groups based on serum homocysteine (Hcy) levels: an HHcy group and a normal Hcy group. A comprehensive comparison between groups was conducted, assessing clinical and pathological manifestations. The end point was end-stage kidney disease (ESKD). The impact of HHcy on renal outcomes was evaluated using multivariate Cox proportional hazards regression models and Kaplan–Meier survival analysis.</p> Results <p>This study enrolled 366 patients with biopsy-proven IgAN. The cohort had a median age of 37&#xa0;years, with 60.4% male, and a median serum Hcy level of 13.6&#xa0;μmol/L. HHcy was present at diagnosis in 145 patients (39.6%). IgAN patients with HHcy demonstrated significantly worse renal function and histopathological severity compared to those with normal Hcy levels. These manifestations included lower eGFR, higher proteinuria, more severe global glomerulosclerosis and crescent lesions, a higher incidence of T1/T2 lesions, and more severe acute and chronic tubular injury, ultimately culminating in a higher incidence of ESKD (all <i>P</i> &lt; 0.05). After a median follow-up of 42.5&#xa0;months, 38 patients (10.4%) progressed to end-stage kidney disease (ESKD), 33 of whom were in the HHcy group. On multivariate Cox regression analysis, HHcy was identified as an independent risk factor for ESKD in patients with IgAN (HR = 4.008, 95% CI 1.093–14.691, <i>P</i> = 0.036). Kaplan–Meier survival analysis demonstrated significantly poorer renal survival in the HHcy group (<i>P</i> &lt; 0.001).</p> Conclusion <p>Our findings suggest that hyperhomocysteinemia is associated with worse renal function and more severe renal pathological manifestations, and serves as an independent risk factor for kidney failure in IgAN.</p>

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The prognostic value of hyperhomocysteinemia in IgA nephropathy

  • 期刊论文

  • 发表日期：

    2025年12月11日

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  • Di Wu,
  • Yingxin Rong,
  • Xinyue Wang,
  • Ruifeng Zhang,
  • Jingjing Wang,
  • Haitao Zhang

摘要

Purpose

Hyperhomocysteinemia (HHcy) is widely observed in chronic kidney disease (CKD) patients. In early CKD stages, HHcy is more prevalent in IgA nephropathy (IgAN) patients. Here, we investigated the relationship between HHcy and renal outcomes among patients with IgAN.

Methods

This study evaluated patients with IgAN who underwent diagnostic renal biopsies in the National Clinical Research Center of Kidney Diseases Jinling Hospital from October 2012 to June 2024. Patients were stratified into two groups based on serum homocysteine (Hcy) levels: an HHcy group and a normal Hcy group. A comprehensive comparison between groups was conducted, assessing clinical and pathological manifestations. The end point was end-stage kidney disease (ESKD). The impact of HHcy on renal outcomes was evaluated using multivariate Cox proportional hazards regression models and Kaplan–Meier survival analysis.

Results

This study enrolled 366 patients with biopsy-proven IgAN. The cohort had a median age of 37 years, with 60.4% male, and a median serum Hcy level of 13.6 μmol/L. HHcy was present at diagnosis in 145 patients (39.6%). IgAN patients with HHcy demonstrated significantly worse renal function and histopathological severity compared to those with normal Hcy levels. These manifestations included lower eGFR, higher proteinuria, more severe global glomerulosclerosis and crescent lesions, a higher incidence of T1/T2 lesions, and more severe acute and chronic tubular injury, ultimately culminating in a higher incidence of ESKD (all P < 0.05). After a median follow-up of 42.5 months, 38 patients (10.4%) progressed to end-stage kidney disease (ESKD), 33 of whom were in the HHcy group. On multivariate Cox regression analysis, HHcy was identified as an independent risk factor for ESKD in patients with IgAN (HR = 4.008, 95% CI 1.093–14.691, P = 0.036). Kaplan–Meier survival analysis demonstrated significantly poorer renal survival in the HHcy group (P < 0.001).

Conclusion

Our findings suggest that hyperhomocysteinemia is associated with worse renal function and more severe renal pathological manifestations, and serves as an independent risk factor for kidney failure in IgAN.