Wang Yan-Na, Xia Han, Song Zhuo-Ran, Zhou Xu-Jie, Zhang Hong
Renal Division, Peking University First Hospital, Beijing, China.
Peking University Institute of Nephrology, Beijing, China.
Front Med (Lausanne). 2022 Mar 7;9:812552. doi: 10.3389/fmed.2022.812552. eCollection 2022.
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 ( = 0.38, < 0.001), the proportion of ischemia originated glomerular sclerosis ( = 0.32, < 0.001), and the severity of tubular atrophy/interstitial fibrosis ( = 0.57, < 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; = 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.
高同型半胱氨酸血症(HHcy)在慢性肾脏病(CKD)患者中非常常见,并且与这些患者发生心血管事件及死亡的风险相关。然而,HHcy在CKD原发性病因中的患病率及其在肾脏疾病进展中的作用尚未完全明确。在本研究中,我们调查了221例IgA肾病(IgAN)患者和194例其他原发性肾小球疾病患者不同CKD阶段HHcy的患病率。我们还在一组365例IgAN患者中评估了同型半胱氨酸(Hcy)[校正估计肾小球滤过率(eGFR)后]与CKD进展事件(定义为终末期肾病或eGFR下降50%)之间的关联。IgAN、膜性肾病、微小病变病、局灶节段性肾小球硬化患者的HHcy患病率分别为67.9%(150/221)、53.5%(76/142)、51.5%(17/33)和42.1%(8/19)。Hcy/eGFR比值与IgAN的病理特征显著相关,包括全球肾小球硬化比例( = 0.38, < 0.001)、缺血性肾小球硬化比例( = 0.32, < 0.001)以及肾小管萎缩/间质纤维化的严重程度( = 0.57, < 0.001)。重要的是,Hcy/eGFR比值是CKD进展事件的独立危险因素(风险比,1.38;95%置信区间,1.13 - 1.68; = 0.002)。CKD进展事件的风险随Hcy/eGFR比值持续增加,但当Hcy/eGFR比值>1.79时达到平台期。我们的研究结果表明,升高的Hcy/eGFR比值可能是IgAN患者肾脏预后不良的早期标志物。