中国非透析慢性肾脏病患者高磷血症的流行病学概况及其预后分析

Epidemiological status and prognostic analysis of hyperphosphatemia in non-dialysis chronic kidney disease patients in China

目的了解中国成人非透析慢性肾脏病(chronic kidney disease,CKD)患者高磷血症的患病率和降磷药物使用率,探索高磷血症及降磷治疗与临床结局的相关性。方法该研究为大型回顾性、多中心队列研究,研究人群来源于中国肾脏病大数据协作网,纳入2013—2020年诊断为CKD的≥18岁的非透析且有血磷检测结果的首次住院患者。高磷血症定义为住院期间首次检测的血磷>1.45 mmol/L,正常血磷定义为0.97 mmol/L≤血磷≤1.45 mmol/L。使用Cox回归模型分析高磷血症与全因死亡、心血管事件死亡和CKD进展的关系,以及使用降磷药物与全因死亡和心血管事件死亡的关系。结果该研究共纳入157987例有血磷检测结果的成人非透析CKD患者,年龄60(47,72)岁,男性91453例(57.89%),估算肾小球滤过率为63.49(39.12,92.90)ml·min^(-1)·(1.73 m^(2))^(-1),常见的合并症为高脂血症84497例(53.48%)、高血压58818例(37.23%)和心力衰竭42686例(27.02%)。高磷血症的患病率为14.83%(23431/157987)。在合并高磷血症的CKD 3~5期患者中,降磷药物的使用率为13.34%(3962/29705)。多因素Cox回归分析结果显示,在64662例随访时间≥90 d的患者中,随访时间为3.3(1.5,5.4)年,高磷血症与全因死亡(高磷血症/正常血磷,HR=1.13,95%CI 1.06~1.22,P=0.001)及心血管事件死亡(高磷血症/正常血磷,HR=1.28,95%CI 1.04~1.56,P=0.018)风险增加均显著相关。在47581例随访时间≥90 d且基线估算肾小球滤过率>30 ml·min^(-1)·(1.73 m^(2))^(-1)的患者中,随访时间为1.8(0.9,3.2)年,高磷血症与CKD进展风险增加显著相关(高磷血症/正常血磷,HR=1.08,95%CI 1.00~1.17,P=0.038)。在8856例有死亡随访资料且有高磷血症患者中,随访时间为3.3(1.5,5.4)年,使用降磷药物与全因死亡(HR=0.88,95%CI 0.82~0.95,P<0.001)和心血管事件死亡(HR=0.84,95%CI 0.72~0.97,P=0.022)风险降低均显著相关。结论中国成人非透析CKD患者高磷血症患病率较高,但降磷药物使用率较低。高磷血症是非透析CKD患者全因死亡、心血管事件死亡及肾功能进展的独立危险因素,使用降磷药物可能降低上述风险。定期监测非透析CKD患者血磷水平并对高磷血症患者启动降磷治疗可能有利于改善其临床预后。

Objective To elucidate the prevalence of hyperphosphatemia and utilization rate of phosphorus-lowering drugs in adult non-dialysis chronic kidney disease(CKD)patients in China,and explore the relationship between hyperphosphatemia,phosphate-lowering therapy,and clinical outcomes.Methods It was a large retrospective and multicenter cohort study.The study subjects were sourced from the China Renal Data System.The first-time hospitalized patients aged 18 years old and above and diagnosed with CKD who did not enter dialysis and having serum phosphorus test results from 2013 to 2020 were included.Hyperphosphatemia was defined as an initial serum phosphorus level exceeding 1.45 mmol/L during hospitalization,and normal serum phosphorus was defined as 0.97 mmol/L≤serum phosphorus≤1.45 mmol/L.Cox regression model was employed to assess the association of hyperphosphatemia with all-cause mortality,cardiovascular mortality,and CKD progression as well as the association of phosphorus-lowering therapy with all-cause mortality and cardiovascular mortality.Results A total of 157987 adult non-dialysis CKD patients with serum phosphorus test results were included in the study,with age of 60(47,72)years old and 91453 males(57.89%).The estimated glomerular filtration rate was 63.49(39.12,92.90)ml·min^(-1)·(1.73 m^(2))^(-1).The common comorbidities included hyperlipidemia(53.48%,84497/157987),hypertension(37.23%,58818/157987)and heart failure(27.02%,42686/157987).The prevalence of hyperphosphatemia was 14.83%(23431/157987).Among CKD stage 3-5 patients with hyperphosphatemia,the utilization rate of phosphate-lowering medications was 13.34%(3962/29705).Multivariate Cox regression analysis showed that among 64662 patients with≥90 days of follow-up[3.3(1.5,5.4)years],hyperphosphatemia was significantly correlated with an increased risk of all-cause mortality and cardiovascular mortality(hyperphosphatemia/normal serum phosphorus,HR=1.13,95%CI 1.06-1.22,P=0.001;HR=1.28,95%CI 1.04-1.56,P=0.018,respectively).Among 47581 patients with≥90 days of follow-up[1.8(0.9,3.2)years]and baseline estimated glomerular filtration rate>30 ml·min^(-1)·(1.73 m^(2))^(-1),hyperphosphatemia was significantly correlated with an increased risk of CKD progression(hyperphosphatemia/normal serum phosphorus,HR=1.08,95%CI 1.00-1.17,P=0.038).Among 8856 patients with follow-up data of death[3.3(1.5,5.4)years]and hyperphosphatemia,phosphate-lowering medication use was significantly correlated with a reduced risk of all-cause mortality(HR=0.88,95%CI 0.82-0.95,P<0.001)and cardiovascular mortality(HR=0.84,95%CI 0.72-0.97,P=0.022).Conclusions The prevalence of hyperphosphatemia is high among Chinese adult non-dialysis CKD patients,but the utilization rate of phosphate-lowering medications remains low.Hyperphosphatemia is an independent risk factor of all-cause mortality,cardiovascular mortality,and kidney function progression,while phosphate-lowering medications may mitigate these risks in non-dialysis CKD patients.Regular monitoring of serum phosphorus level for non-dialysis CKD patients,and initiating phosphate-lowering therapy for hyperphosphatemia patients may positively improve clinical outcomes.