Shardlow Adam, McIntyre Natasha J, Fluck Richard J, McIntyre Christopher W, Taal Maarten W
Renal Medicine, Royal Derby Hospital, Derby, UK.
Division of Medical Sciences and Graduate Entry Medicine, Centre for Kidney Research and Innovation, School of Medicine, The University of Nottingham, Royal Derby Hospital, Derby, UK.
BMJ Open. 2017 Aug 23;7(8):e016528. doi: 10.1136/bmjopen-2017-016528.
Vitamin D deficiency, elevated fibroblast growth factor 23 (FGF23) and elevated parathyroid hormone (PTH) have each been associated with increased mortality in people with chronic kidney disease (CKD). Previous studies have focused on the effects of FGF23 in relatively advanced CKD. This study aims to assess whether FGF23 is similarly a risk factor in people with early CKD, and how this risk compares to that associated with vitamin D deficiency or elevated PTH.
Prospective cohort study.
Thirty-two primary care practices.
One thousand six hundred and sixty-four people who met Kidney Disease: Improving Global Outcomes (KDIGO) definitions for CKD stage 3 (two measurements of estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m at least 90 days apart) prior to study recruitment.
All-cause mortality over the period of study follow-up and progression of CKD defined as a 25% fall in eGFR and a drop in GFR category, or an increase in albuminuria category.
Two hundred and eighty-nine participants died during the follow-up period. Vitamin D deficiency (HR 1.62, 95% CI 1.01 to 2.58) and elevated PTH (HR 1.42, 95% CI 1.09 to 1.84) were independently associated with all-cause mortality. FGF23 was associated with all-cause mortality in univariable but not multivariable analysis. Fully adjusted multivariable models of CKD progression showed no association with FGF23, vitamin D status or PTH.
In this cohort of predominantly older people with CKD stage 3 and low risk of progression, vitamin D deficiency and elevated PTH were independent risk factors for all-cause mortality but elevated FGF23 was not. While FGF23 may have a role as a risk marker in high-risk populations managed in secondary care, our data suggest that it may not be as important in CKD stage 3, managed in primary care.
National Institute for Health Research Clinical Research Portfolio Study Number 6632.
维生素D缺乏、成纤维细胞生长因子23（FGF23）升高和甲状旁腺激素（PTH）升高均与慢性肾脏病（CKD）患者死亡率增加相关。既往研究主要关注FGF23在相对晚期CKD中的作用。本研究旨在评估FGF23在早期CKD患者中是否同样为危险因素，以及该风险与维生素D缺乏或PTH升高相关风险相比如何。
前瞻性队列研究。
32家初级保健机构。
1664名在研究招募前符合肾脏病改善全球预后（KDIGO）CKD 3期定义（两次估算肾小球滤过率（eGFR）测量值在30至60 mL/min/1.73 m²之间，间隔至少90天）的患者。
研究随访期间的全因死亡率以及CKD进展，定义为eGFR下降25%、肾小球滤过率类别降低或蛋白尿类别增加。
289名参与者在随访期间死亡。维生素D缺乏（风险比[HR] 1.62，95%置信区间[CI] 1.01至2.58）和PTH升高（HR 1.42，95% CI 1.09至1.84）与全因死亡率独立相关。FGF23在单变量分析中与全因死亡率相关，但在多变量分析中不相关。CKD进展的完全调整多变量模型显示与FGF23、维生素D状态或PTH无关。
在这个以老年CKD 3期患者为主且进展风险较低的队列中，维生素D缺乏和PTH升高是全因死亡率的独立危险因素，但FGF23升高不是。虽然FGF23可能在二级保健管理的高危人群中作为风险标志物发挥作用，但我们的数据表明，在初级保健管理的CKD 3期中，它可能不那么重要。
英国国家卫生研究院临床研究注册库研究编号6632。
