Perkins Robert M, Aboudara Matthew C, Uy Alice L, Olson Stephen W, Cushner Howard M, Yuan Christina M
Nephrology Service, Madigan Army Medical Center, Fort Lewis, WA 98431, USA.
Am J Kidney Dis. 2009 Apr;53(4):606-16. doi: 10.1053/j.ajkd.2008.11.026. Epub 2009 Feb 12.
Pentoxifylline is a nonspecific phosphodiesterase inhibitor with anti-inflammatory properties. It reduces proteinuria in patients with glomerular disease, although its impact on glomerular filtration rate (GFR) is unknown. We hypothesized that pentoxifylline would slow the estimated GFR decrease in patients with chronic kidney disease at high risk of progression.
Pilot randomized double-blind placebo-controlled trial.
SETTING & PARTICIPANTS: 40 outpatients with decreased GFR, hypertension, and proteinuria greater than 1 g/24 h currently treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or the combination and followed up in a nephrology clinic at a tertiary medical care facility.
Pentoxifylline, 400 mg twice daily, or matching placebo.
Difference in rates of estimated GFR change during the 1-year study period between the 2 groups.
Estimated GFR (4-variable Modification of Diet in Renal Disease Study equation) and proteinuria by 24-hour urine collection were assessed at baseline and 6 and 12 months after enrollment.
Baseline characteristics were similar between the 2 groups. At 1 year, the mean estimated GFR decrease was significantly less in the pentoxifylline group than the placebo group (-1.2 +/- 7.0 versus -7.2 +/- 8.2 mL/min/1.73 m2/y; mean difference, -6.0 mL/min/1.73 m2/y; 95% confidence interval, -11.4 to -0.6; P = 0.03). For pentoxifylline-treated participants, the mean estimated GFR decrease during treatment was slower compared with the year before study enrollment (-9.6 +/- 11.9 mL/min/1.73 m2/y; mean difference, -8.4 mL/min/1.73 m2/y; 95% confidence interval, -14.8 to -2.1; P = 0.01). Proteinuria was not different between the pentoxifylline and placebo groups at baseline, 6 months, or 1 year.
Small sample size and incomplete follow-up.
Pentoxifylline may slow the estimated GFR decrease in high-risk patients. This may be independent of its antiproteinuric properties and warrants further investigation.
己酮可可碱是一种具有抗炎特性的非特异性磷酸二酯酶抑制剂。它可降低肾小球疾病患者的蛋白尿,但其对肾小球滤过率(GFR)的影响尚不清楚。我们推测己酮可可碱会减缓慢性肾脏病进展高危患者的估计GFR下降。
前瞻性随机双盲安慰剂对照试验。
40例GFR降低、患有高血压且蛋白尿大于1g/24小时的门诊患者,目前正在接受血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂或两者联合治疗,并在一家三级医疗保健机构的肾脏病门诊接受随访。
己酮可可碱,每日两次,每次400mg,或匹配的安慰剂。
两组在1年研究期内估计GFR变化率的差异。
在基线以及入组后6个月和12个月时,通过24小时尿液收集评估估计GFR(肾脏病膳食改良研究方程的4变量法)和蛋白尿。
两组的基线特征相似。1年后,己酮可可碱组的平均估计GFR下降显著低于安慰剂组(-1.2±7.0对-7.2±8.2 mL/min/1.73m²/年;平均差异,-6.0 mL/min/1.73m²/年;95%置信区间,-11.4至-0.6;P = 0.03)。对于接受己酮可可碱治疗的参与者,治疗期间的平均估计GFR下降与研究入组前一年相比更慢(-9.6±11.9 mL/min/1.73m²/年;平均差异,-8.4 mL/min/1.73m²/年;95%置信区间,-14.8至-2.1;P = 0.01)。己酮可可碱组和安慰剂组在基线、6个月或1年时的蛋白尿无差异。
样本量小且随访不完全。
己酮可可碱可能会减缓高危患者的估计GFR下降。这可能与其抗蛋白尿特性无关,值得进一步研究。