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Plasma Homocysteine as a Potential Marker of Early Renal Function Decline in IgA Nephropathy
Yan-Na Wang1,2,3,4, Han Xia5, Zhuo-Ran Song1,2,3,4
1Renal Division, Peking University First Hospital, Beijing, China.
Insights
Hyperhomocysteinemia (HHcy) is common in chronic kidney disease (CKD). Elevated homocysteine (Hcy) levels, adjusted for estimated glomerular filtration rate (eGFR), are linked to kidney disease progression and are an independent risk factor for CKD progression events in IgA nephropathy patients.
Area of Science:
- Nephrology
- Clinical Chemistry
- Cardiovascular Medicine
Background:
- Hyperhomocysteinemia (HHcy) is prevalent in chronic kidney disease (CKD) patients, associated with cardiovascular risks.
- The role of HHcy in the progression of primary kidney diseases remains unclear.
- Understanding HHcy prevalence and impact is crucial for managing CKD progression.
Purpose of the Study:
- To determine HHcy prevalence across different stages of CKD in IgA nephropathy (IgAN) and other primary glomerular diseases.
- To assess the association between homocysteine (Hcy)/estimated glomerular filtration rate (eGFR) ratio and kidney disease progression in IgAN.
- To identify Hcy/eGFR ratio as a potential early marker for adverse renal outcomes.
Main Methods:
- Investigated HHcy prevalence in 221 IgAN patients and 194 patients with other primary glomerular diseases.
- Evaluated the association of the Hcy/eGFR ratio with CKD progression events (ESKD or 50% eGFR decline) in 365 IgAN patients.
- Utilized statistical analysis, including hazard ratios and confidence intervals, to determine risk factors.
Main Results:
- HHcy prevalence varied across primary glomerular diseases, notably high in IgAN (67.9%).
- The Hcy/eGFR ratio correlated significantly with IgAN pathological features like glomerulosclerosis and tubular atrophy/interstitial fibrosis.
- The Hcy/eGFR ratio independently predicted CKD progression events, with risk increasing up to a ratio of 1.79.
Conclusions:
- Elevated Hcy/eGFR ratio is common in IgAN and associated with kidney damage.
- The Hcy/eGFR ratio serves as an independent risk factor for CKD progression in IgAN.
- An elevated Hcy/eGFR ratio may indicate a poor renal outcome in IgA nephropathy patients.
Abstract:
Hyperhomocysteinemia (HHcy) is very common among patients with chronic kidney disease (CKD), and related to the risk of cardiovascular events and mortality in these patients. However, the prevalence of HHcy in primary causes of CKD and its role in kidney disease progression are not well-understood. In this study, we investigated the prevalence of HHcy in different CKD stages in 221 patients with IgA nephropathy (IgAN) and 194 patients with other primary glomerular diseases. We also evaluated the association of homocysteine (Hcy) [after adjusted for estimated glomerular filtration rate (eGFR)] with CKD progression event, defined as ESKD or 50% decline in eGFR, in a cohort of 365 patients with IgAN. The prevalence of HHcy was 67.9% (150/221), 53.5% (76/142), 51.5% (17/33), and 42.1% (8/19) in patients with IgAN, membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, respectively. The Hcy/eGFR ratio was significantly associated with pathologic features of IgAN, including the proportion of global glomerulosclerosis (r = 0.38, p < 0.001), the proportion of ischemia originated glomerular sclerosis (r = 0.32, p < 0.001), and the severity of tubular atrophy/interstitial fibrosis (r = 0.57, p < 0.001). Importantly, Hcy/eGFR ratio was an independent risk factor for CKD progression event (hazard ratio, 1.38; 95% confidence interval, 1.13-1.68; p = 0.002). The risk of CKD progression events continuously increased with the Hcy/eGFR ratio, but reached a plateau when Hcy/eGFR ratio was >1.79. Our findings suggest that elevated Hcy/eGFR ratio may be an early marker of poor renal outcome in IgAN.
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