Kielstein Jan T, Heisterkamp Markus, Jing Jiaojiao, Nadal Jennifer, Schmid Matthias, Kronenberg Florian, Busch Martin, Sommerer Claudia, Lorenzen Johan M, Eckardt Kai-Uwe, Köttgen Anna
Medical Clinic V: Nephrology | Rheumatology | Blood Purification, Academic Teaching Hospital Braunschweig, Braunschweig, Germany.
Department of Nephrology, Hannover Medical School, Hannover, Germany.
Clin Kidney J. 2019 Nov 8;14(1):277-283. doi: 10.1093/ckj/sfz136. eCollection 2021 Jan.
Despite a plethora of studies on the effect of urate-lowering therapy (ULT) in patients with chronic kidney disease (CKD), current guidelines on the treatment of hyperuricaemia and gout vary, especially concerning the need for dose adjustment of allopurinol, whose main metabolite is accumulating with declining renal function. Data on allopurinol dosing and its relationship to renal function, co-medication and sex and the resulting urate level in large cohorts are missing.
We studied a subgroup of 2378 patients of the German Chronic Kidney Disease (GCKD) study to determine prescription patterns of ULT among CKD patients under nephrological care and the relationship of ULT dose to urate levels. Prescription and dosing of ULT were manually abstracted from the patient's paper charts at the baseline visit, in which all currently used medications and their dosing were recorded.
In this cohort, 39.6% were women, the mean estimated glomerular filtration rate (eGFR) was 51.3 ± 19.3 mL/min/1.73 m and the mean age was 59.0 ± 12.4 years. Of the 2378 examined patients, 666 (28.0%) received ULT. The dose of ULT was available for 572 patients. The main ULT agent was allopurinol (94.4%), followed by febuxostat (2.9%) and benzbromarone (2.6%). Of the 540 patients who used allopurinol with a reported daily dose, 480 had an eGFR <60 mL/min/1.73 m and 320 had an eGFR <45 mL/min/1.73 m, 31.5% of the latter ( = 101) received a dose >150 mg/day, the recommended maximal dose for this level of eGFR. The prescribed dose was not related to eGFR: the median eGFR for patients taking 100, 150 and 300 mg/day was 40 [interquartile range (IQR) 32-49], 43 (34-52) and 42 (35-54) mL/min/1.73 m, respectively. Patients with lower doses of allopurinol had higher serum urate levels than patients with higher (than recommended) allopurinol doses. Sex, alcohol intake, eGFR, use of diuretics and treatment with allopurinol were independent determinants of serum urate levels in multivariate regression analysis.
The most frequently used drug to lower serum urate levels in this CKD cohort was allopurinol. Even in patients regularly seen by nephrologists, the dose of allopurinol is often not adjusted to the current eGFR. Patients with higher ULT doses achieved better control of their serum urate levels. Lowering of serum urate in CKD patients requires balancing potential adverse effects of allopurinol with suboptimal control of serum urate levels.
尽管有大量关于降尿酸治疗（ULT）对慢性肾脏病（CKD）患者影响的研究，但目前关于高尿酸血症和痛风治疗的指南各不相同，尤其是在别嘌醇剂量调整方面，其主要代谢产物会随着肾功能下降而蓄积。关于大样本队列中别嘌醇给药及其与肾功能、合并用药、性别以及由此产生的尿酸水平之间关系的数据尚缺失。
我们研究了德国慢性肾脏病（GCKD）研究中的2378例患者亚组，以确定肾脏病护理下CKD患者的ULT处方模式以及ULT剂量与尿酸水平的关系。ULT的处方和剂量是在基线访视时从患者的纸质病历中手动提取的，病历中记录了所有当前使用的药物及其剂量。
在该队列中，39.6%为女性，平均估算肾小球滤过率（eGFR）为51.3±19.3 mL/min/1.73 m²，平均年龄为59.0±12.4岁。在2378例接受检查的患者中，666例（28.0%）接受了ULT。572例患者的ULT剂量可用。主要的ULT药物是别嘌醇（94.4%），其次是非布司他（2.9%）和苯溴马隆（2.6%）。在540例报告了每日剂量的使用别嘌醇的患者中，480例eGFR<60 mL/min/1.73 m²，320例eGFR<45 mL/min/1.73 m²，后者中31.5%（=101例）接受的剂量>150 mg/天，这是该eGFR水平推荐的最大剂量。规定剂量与eGFR无关：服用100、150和300 mg/天的患者的eGFR中位数分别为40[四分位间距（IQR）32 - 49]、43（34 - 52）和42（35 - 54）mL/min/1.73 m²。别嘌醇剂量较低的患者血清尿酸水平高于（高于推荐剂量的）别嘌醇剂量较高的患者。在多变量回归分析中，性别、酒精摄入量、eGFR、利尿剂的使用以及别嘌醇治疗是血清尿酸水平的独立决定因素。
在该CKD队列中，最常用于降低血清尿酸水平的药物是别嘌醇。即使在肾脏病医生定期诊治的患者中，别嘌醇剂量通常也未根据当前eGFR进行调整。ULT剂量较高的患者血清尿酸水平得到了更好的控制。降低CKD患者的血清尿酸需要在别嘌醇的潜在不良反应与血清尿酸水平控制不佳之间进行权衡。
