Pentoxifylline for Proteinuria in Diabetic Kidney: A Meta-analysis

[Dr.Vad]

Am J Kidney Dis. 2008 Apr 21

The Effect of Pentoxifylline on Proteinuria in Diabetic Kidney Disease: A Meta-analysis.

McCormick BB, Sydor A, Akbari A, Fergusson D, Doucette S, Knoll G.

Division of Nephrology, Kidney Research Center, Ottawa Health Research Institute, Ottawa, Ontario, Canada; Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

BACKGROUND: Pentoxifylline is a potential therapeutic agent for diabetic kidney disease because it has anti-inflammatory, antifibrotic, and hemorheological properties. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING, POPULATION, & INTERVENTION: Adult patients with diabetic kidney disease who received oral pentoxifylline. SELECTION CRITERIA FOR STUDIES: We searched bibliographic databases for trials involving pentoxifylline that reported proteinuria, glomerular filtration rate, or blood pressure. OUTCOMES: The primary outcome measure was the effect of pentoxifylline on proteinuria stratified by whether pentoxifylline was compared with renin-angiotensin system blockade. RESULTS: 10 studies including a total of 476 participants with a median duration of 6 months were identified. Pentoxifylline significantly decreased proteinuria (weighted mean difference, -278 mg/d of protein; 95% confidence interval [CI], -398 to -159; P < 0.001) compared with placebo or usual care. Compared with captopril, the decrease in proteinuria with pentoxifylline was similar (weighted mean difference, 0 mg/d of protein; 95% CI, -17 to 18; P = 0.9). Secondary analysis showed that patients with microalbuminuria had a nonsignificant decrease in protein excretion (weighted mean difference, -87 mg/d; 95% CI, -201 to 27; P = 0.1), whereas those with overt proteinuria (protein > 300 mg/d) had a significant decrease (weighted mean difference, -502 mg/d; 95% CI, -805 to -198; P = 0.001). No significant changes in systolic or diastolic blood pressure or glomerular filtration rate were found. LIMITATIONS: Quality scores of studies were low, and there was significant heterogeneity. CONCLUSIONS: Available evidence suggests that pentoxifylline may decrease proteinuria in patients with diabetic nephropathy. To confirm these findings, large high-quality studies are required.

[o_udovichenko]

Большое спасибо за данные.
Вообще, у пентоксифилина есть ведь свои области применения, кое-где (лечение венозных язв и перемежающейся хромоты) он не бесполезен...
В любом случае, этот мета-анализ ценен для нас.

Правда, вот это смущает:
LIMITATIONS: Quality scores of studies were low, and there was significant heterogeneity.

Еще, по сути протеинурия - суррогатный параметр, долговременный эффект на прогрессирование диабетической нефропатии, насколько я понимаю, не оценивался. И вообще, исследования вряд ли были долговременными (хотя возможно, я ошибаюсь), и допустим, 3 мес приема препарата уменьшают протеинурию, а дальше что делать? Пожизненный прием 12 мес в году?

В общем, как правильно заметили авторы,
"To confirm these findings, large high-quality studies are required".

[Dr.Vad]

Согласен, что нетутя данных по результатам исследований, но эксперты в один голос рекомендуют снижать протеинурию, ибо от этого зависит и функция почек и ССЗ, напр:

The presence of proteinuria is a well-known risk factor for both the progression of renal disease and cardiovascular morbidity and mortality, and decreases in urine protein excretion level were associated with a slower decrease in renal function and decrease in risk of cardiovascular events.

Sarafidis PA, Khosla N, Bakris GL.
Antihypertensive therapy in the presence of proteinuria.
Am J Kidney Dis. 2007 Jan;49(1):12-26. Review.

Если на сартано-прилах уже получено целевое/оптимальное АД, а протеинурия все же высокая, то почему бы не добавить трентал?

В небольших группах пациентов это работает, а долгосрочные перспективы такого добавления (прогноз) естественно требуют больших клинических вливаний и наблюдений:

Diskin CJ, Stokes TJ, Dansby LM, Radcliff L, Carter TB.
Will the addition of pentoxifylline reduce proteinuria in patients with diabetic glomerulosclerosis refractory to maximal doses of both an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker?
J Nephrol. 2007 Jul-Aug;20(4):410-6.

Navarro JF, Mora C, Muros M, García J.
Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial.
J Am Soc Nephrol. 2005 Jul;16(7):2119-26.