Renal Division, Department of Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, Taiwan.
Graduate Institute of Physiology, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Section 1, Taipei, Taiwan.
J Biomed Sci. 2017 Nov 13;24(1):84. doi: 10.1186/s12929-017-0390-4.
Blood pressure control with renin-angiotensin system (RAS) blockade has remained the gold standard for treating patients with proteinuric chronic kidney disease (CKD) up to date. Nevertheless, RAS blockade slows but does not halt the progression of kidney disease, thus highlighting the need to search for additional therapeutic approaches. The nonselective phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) is an old drug that exhibits prominent anti-inflammatory, anti-proliferative and anti-fibrotic activities both in vitro and in vivo. Studies in human subjects have shown that PTX monotherapy decreases urinary protein excretion, and add-on therapy of PTX to background RAS blockade additively reduces proteinuria in patients with CKD of various etiology. More recent studies find that PTX combined with RAS blockade delays the decline of glomerular filtration rate in diabetic patients with mild to moderate CKD, and reduces the risk of end-stage renal disease in diabetic and non-diabetic patients in late stage of CKD with high proteinuria levels. In this review, we update the clinical trial results of PTX as monotherapy, or in conjunction or in comparison with RAS blockade on patients with proteinuria and CKD, and propose a mechanistic scheme explaining the renoprotective activities of this drug.
迄今为止，肾素-血管紧张素系统（RAS）阻滞剂控制血压一直是治疗蛋白尿性慢性肾脏病（CKD）患者的金标准。然而，RAS 阻滞剂虽然可以减缓但不能阻止肾脏疾病的进展，因此需要寻找额外的治疗方法。非选择性磷酸二酯酶（PDE）抑制剂己酮可可碱（PTX）是一种老药，在体外和体内均具有显著的抗炎、抗增殖和抗纤维化作用。在人体研究中，PTX 单药治疗可降低尿蛋白排泄，PTX 附加治疗与 RAS 阻滞剂联合治疗可使不同病因 CKD 患者的蛋白尿进一步减少。最近的研究发现，PTX 联合 RAS 阻滞剂可延缓轻度至中度 CKD 糖尿病患者肾小球滤过率的下降，并降低伴有大量蛋白尿的晚期 CKD 糖尿病和非糖尿病患者终末期肾病的风险。在这篇综述中，我们更新了 PTX 作为单药治疗，或与 RAS 阻滞剂联合或比较治疗蛋白尿和 CKD 患者的临床试验结果，并提出了一个解释该药物肾保护作用的机制方案。
