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己酮可可碱、慢性肾脏病(CKD)进展和心血管死亡率:一项随机临床试验的长期随访。

Pentoxifylline, progression of chronic kidney disease (CKD) and cardiovascular mortality: long-term follow-up of a randomized clinical trial.

机构信息

Nephrology Department, Hospital General Universitario Gregorio Marañón, C/Dr Esquerdo 46, 28007, Madrid, Spain.

Spanish Kidney Research Network (REDINREN), FEDER FUND, Madrid, Spain.

出版信息

J Nephrol. 2019 Aug;32(4):581-587. doi: 10.1007/s40620-019-00607-0. Epub 2019 Apr 4.

Abstract

BACKGROUND

Pentoxifylline could reduce proteinuria and slow renal disease progression. We previously conducted a single-blind, randomized, controlled trial that showed that pentoxifylline decreases inflammatory markers and stabilizes renal function.

SETTING AND PARTICIPANTS

91 participants (46 in the pentoxifylline group and 45 in the control group) followed up for 7 additional years.

STUDY DESIGN

Post hoc analysis of a long-term follow-up after completion of the 12-months trial.

INTERVENTION

Pentoxifylline treatment (400 mg/twice a day) or standard treatment.

OUTCOME

Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥ 50% decrease in estimated glomerular filtration rate) and cardiovascular mortality.

RESULTS

During follow-up, a renal event was recorded in 24 patients from control group (13 initiated dialysis therapy and serum creatinine doubled in 11) and 11 patients from PTF group (7 initiated dialysis and serum creatinine doubled in 4) (log Rank: 5.822, p = 0.016). The possible protector effect of PTF was more significant in albuminuric patients and was independently of diabetes mellitus presence. Treatment with PTF reduced the renal events by 35% compared to the control group in a Cox model adjusted for diabetes mellitus, albuminuria and basal renal function (HR 0.65 (0.45-0.94), p = 0.022). Cardiovascular mortality was significantly reduced in PTF treatment (2 patients vs. 10 in control group) (log Rank 5.0977, p = 0.024). PTF treatment reduced cardiovascular mortality in 55% adjusted for diabetes mellitus and age (HR 0.45 (0.21-0.98), p = 0.044) (Table 3).

LIMITATIONS

Small sample size, single center, not double blind and post hoc follow-up analysis.

CONCLUSIONS

Long-term treatment with pentoxifylline may slow the rate of progression of kidney disease and reduce cardiovascular risk.

摘要

背景

己酮可可碱可减少蛋白尿并减缓肾脏疾病的进展。我们之前进行了一项单盲、随机、对照试验,结果表明己酮可可碱可降低炎症标志物并稳定肾功能。

设置和参与者

91 名参与者(己酮可可碱组 46 名,对照组 45 名)随访 7 年。

研究设计

完成 12 个月试验后的长期随访事后分析。

干预措施

己酮可可碱治疗(400mg/每天两次)或标准治疗。

结局

肾脏事件(定义为开始透析治疗和/或血清肌酐翻倍和/或估计肾小球滤过率下降≥50%)和心血管死亡率。

结果

随访期间,对照组有 24 例患者(13 例开始透析治疗,11 例血清肌酐翻倍)和 PTF 组 11 例患者(4 例开始透析治疗,血清肌酐翻倍)发生肾脏事件(对数秩检验:5.822,p=0.016)。PTF 的可能保护作用在白蛋白尿患者中更为显著,且独立于糖尿病的存在。在调整了糖尿病、白蛋白尿和基础肾功能的 Cox 模型中,与对照组相比,PTF 治疗将肾脏事件减少了 35%(HR 0.65(0.45-0.94),p=0.022)。PTF 治疗组心血管死亡率显著降低(2 例 vs. 对照组 10 例)(对数秩检验 5.0977,p=0.024)。PTF 治疗将心血管死亡率降低了 55%,调整了糖尿病和年龄因素(HR 0.45(0.21-0.98),p=0.044)(表 3)。

局限性

样本量小、单中心、非双盲和事后随访分析。

结论

长期使用己酮可可碱可能会减缓肾脏疾病的进展速度,并降低心血管风险。

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