晚期慢性腎臟病患者中尿酸與慢性腎臟病惡化之相關性

Abstract

背景與目標： 雖然許多研究認為較高的尿酸和慢性腎臟病的發展有關，但目前對於尿酸是否會加速腎功能惡化仍有爭議；尤其在晚期慢性腎臟病患者中，高尿酸是否和慢性腎臟病惡化相關仍爭論不休。因此，本研究即是探討在晚期慢性腎臟病患者中，尿酸與慢性腎臟病惡化之相關性。 方法： 本研究包含5562位於2004至2016年進入”全民健康保險末期腎臟病前期病人照護與衛教計畫”之第3b、4及5期的慢性腎臟病患者，依其基準尿酸值高低分成五組，比較各組各種慢性腎臟病惡化的指標，包括: 全因死亡率、進入末期腎疾病 (包括血液透析、腹膜透析以及腎臟移植)、與基準相比兩倍以上之血清肌酸酐、以及與基準相比降低25%以上之腎絲球過濾率。所有病人皆持續追蹤直至死亡、進入透析或腎臟移植、或是2016年12月31日。我們進行Cox比例風險模型，並校正多種變項，包括：年齡、性別、基準腎絲球過濾率，糖尿病、高血壓、蛋白尿、身體質量指數、抽菸、喝酒、痛風、血色素、白蛋白、磷和三酸甘油脂。 結果： 在中位數為29個月的追蹤中，448位病人死亡、1118位病人進入末期腎疾病、1263位病人達到與基準相比兩倍以上之血清肌酸酐、以及2529位病人與基準相比降低25%以上之腎絲球過濾率。隨著基準尿酸值的增加，會增加全因死亡率、進入末期腎疾病的發生率、與基準相比兩倍以上之血清肌酸酐的發生率。與基準尿酸值最低的組別相比，基準尿酸值最高的組別校正後的全因死亡風險比為1.49 (95% 信賴區間：1.05-2.12，趨勢檢定：P=0.01)、進入末期腎疾病風險比為1.40 (95% 信賴區間：1.08-1.82，趨勢檢定：P=0.03)、以及與基準相比兩倍以上之血清肌酸酐風險比為1.44 (95% 信賴區間：1.11-1.85，趨勢檢定：P=0.01)。然而，與基準相比降低25%以上之腎絲球過濾率的風險比並未達統計顯著意義 (風險比：1.07，95% 信賴區間：0.91-1.26，趨勢檢定：P=1.00)。而在依據年齡、性別、糖尿病狀況、及慢性腎臟病分期分層後，尿酸對於各種慢性腎臟病惡化指標仍有一致的影響。 結論： 高尿酸血症和腎臟惡化的指標有相關性。然而，下降尿酸對於慢性腎臟病患者是否為保護因子，則需要更進一步的研究。

Background and Objectives: Although many studies have suggested an association between higher uric acid and the development of chronic kidney disease(CKD), it is controversial whether a higher uric acid was associated with a faster decline in renal function, especially in advanced CKD patients. The aim of this study was to investigate the association between uric acid and CKD progression in advanced CKD patients. Methods: We retrospectively recruited a cohort of 5562 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program in 2004 to 2016 with CKD stage 3b, stage 4, and stage 5. We classified participants on the basis of quintiles of serum uric acid concentrations and surveyed the association between uric acid and the outcomes about CKD progression that including all-cause mortality, incidence of end stage renal disease (ESRD, which was defined as renal replacement therapy including hemodialysis, peritoneal dialysis and renal transplantation), doubling of baseline serum creatinine and a 25% or greater drop in GFR (glomerular filtration rate) from baseline. All the patients were followed until reaching death, the initiation of dialysis, renal transplantation or being censored at date December 31, 2016. We adjusted Cox proportional hazard model by covariates including age, gender, baseline GFR, diabetes mellitus, hypertension, proteinuria, body mass index, smoking, drinking, gout, hemoglobin, albumin, phosphate and triglyceride. Results: During a median follow-up of 29 months, 448 patients died, 1118 patients entered ESRD, 1263 patients reached doubling of baseline serum creatinine, and 2529 patients dropped greater or equal to 25% GFR from the baseline. As uric acid levels increased, the incidence rate of all-cause mortality, ESRD, and doubling of baseline serum creatinine increased significantly. Compared with those in the lowest quintile of uric acid, participants in the highest quintile of uric acid has an adjusted hazard with 1.49 (95% CI: 1.05-2.12, test for trend: P=0.01) for all-cause mortality, 1.40 (95% CI: 1.08-1.82, test for trend: P=0.03) for ESRD, and 1.44 (95% CI: 1.11-1.85, test for trend: P=0.01) for doubling of baseline serum creatinine. However, the risk for a 25% or greater drop in GFR from the baseline was not significant (HR=1.07, 95% CI: 0.91-1.26, test for trend: P=1.00). A consistent effect was observed various stratified factors, including age, gender, diabetes mellitus and CKD stage. Conclusions: Our study clearly demonstrated that hyperuricemia was associated with composite renal progression outcomes. Further intervention studies for uric acid reduction as the protective role of CKD progression are warranted.