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The prognostic value of hyperhomocysteinemia in IgA nephropathy
Di Wu1, Yingxin Rong1, Xinyue Wang1
1National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 305 East Zhongshan Road, Nanjing, 210016, China.
Insights
Hyperhomocysteinemia (HHcy) is linked to poorer kidney function and more severe pathology in IgA nephropathy (IgAN) patients. This condition independently predicts kidney failure, highlighting its significance in IgAN progression.
Area of Science:
- Nephrology
- Internal Medicine
- Clinical Research
Background:
- Hyperhomocysteinemia (HHcy) is common in chronic kidney disease (CKD).
- IgA nephropathy (IgAN) patients, especially in early CKD stages, frequently exhibit HHcy.
Purpose of the Study:
- To investigate the association between HHcy and renal outcomes in patients diagnosed with IgAN.
- To determine if HHcy is an independent risk factor for end-stage kidney disease (ESKD) in IgAN.
Main Methods:
- Evaluated 366 biopsy-proven IgAN patients, stratifying them into HHcy and normal Hcy groups.
- Assessed clinical and pathological features, including eGFR, proteinuria, and renal histology.
- Utilized multivariate Cox regression and Kaplan-Meier analysis to evaluate ESKD risk and renal survival.
Main Results:
- Patients with HHcy showed significantly worse renal function and more severe histopathological findings.
- HHcy was associated with higher rates of proteinuria, glomerulosclerosis, crescent lesions, and tubular injury.
- HHcy independently predicted ESKD (HR=4.008, P=0.036), with significantly poorer renal survival observed in the HHcy group (P<0.001).
Conclusions:
- Hyperhomocysteinemia is linked to diminished renal function and advanced pathological changes in IgAN.
- HHcy is an independent risk factor for kidney failure (ESKD) in patients with IgA nephropathy.
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.
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