Trimetazidine Decreases Risk of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease

Nadkarni, Girish N.; Konstantinidis, Ioannis; Patel, Achint; Yacoub, Rabi; Kumbala, Damodar; Patel, Rajan A.G.; Annapureddy, Narender; Pakanati, Krishna Chaitanya; Simoes, Priya; Javed, Fawad; Benjo, Alexandre

doi:10.1177/1074248415573320

Cited by 27 publications

(17 citation statements)

References 35 publications

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“…In our updated meta-analysis, we found that TMZ can significantly reduce the incidence of CIN, which is consistent with the findings from the study by Nadkarni et al [15] In addition, our results showed that TMZ can also reduce postoperative serum creatinine levels, including the Scr levels after 24 hours, 48 hours, and 7 days. As we all know, the level of Scr is 1 of the important indicators reflecting the changes of renal function; the decrease of Scr level suggests the function of kidney is better.…”

Section: Discussionsupporting

confidence: 91%

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Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency

Lü

et al. 2017

Medicine

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Background:With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to people's physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. However, the study did not include patients from other countries and speaking different languages. So we conducted this study to update the previous meta-analysis that investigated the effects of TMZ on prevention of CIN in patients with renal insufficiency, and provided some theoretical reference for clinical.Methods:By searching PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, VIP database, and Wang Fang database for randomized controlled trial, which is comparing TMZ versus conventional hydration for prevention of CIN. Two researchers independently screened literature, and then evaluated the quality of literature and extracted the relevant data. Stata 11.0 software was used for statistical analysis.Results:Finally, this updated review showed that 3 studies that were not included in the previous meta-analysis were included in our study (3 articles were published in the Chinese Journal, 1 study for CIN, 1 study for CIN, serum creatinine (Scr), and superoxide dismutase, 1 study for CIN and Scr), and 1 outcome (Scr) reflecting the change of renal function was additionally included in our study. Of the 932 studies, 6 randomized controlled trials met the criteria, including 377 patients in TMZ group and 387 patients in control group. This meta-analysis for all studies showed that TMZ can significantly reduce the incidence of CIN (relative risk 0.27, 95% confidence interval [CI] 0.16, 0.46, P = 0.000), and can decrease the level of Scr after operation, including Scr of postoperative 24 hours (standardized mean difference [SMD] −0.30, 95% CI −0.51, −0.09, P = 0.005), Scr of postoperative 48 hours (SMD −0.66, 95% CI −1.23, −0.10, P = 0.022), and Scr of postoperative 7 days (SMD −0.74, 95% CI −1.36, −0.11, P = 0.021). However, the Scr of postoperative 72 hours between TMZ group and control group has no statistical significance (P = 0.362).Conclusion:Our study showed that when comparing with conventional hydration, TMZ can significantly reduce the incidence of CIN and the level of postoperative Scr. Therefore, we could suggest that TMZ was superior to conventional hydration for the treatment of CIN in patients with renal insufficiency. However, due to the restriction of quality and number of included articles, it still needs to carry out multicenter, randomized, double-blind clinical trials to confirm this conclusion in the future.

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Section: Discussionsupporting

confidence: 91%

“…In 2015, Nadkarni et al [15] performed a meta-analysis in which a randomized controlled trial (RCT) investigated the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. From this study, we observed that TMZ could significantly reduce the incidence of CIN.…”

Section: Introductionmentioning

confidence: 99%

Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency

Lü

et al. 2017

Medicine

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“…Our observations indicate that other pharmacological agents may cooperate with NK1R inhibitors in protecting kidney cells in ischemia-like conditions ( Supplementary Figure 1). TMZ is a promising candidate nephroprotectant [68,69], and it may be warranted to explore a TMZ-Aprepitant combination as a way to enhance the protective effects of these drugs. Importantly, the lack of cooperation between maximally-effective doses of NK1R and PAK1 inhibitors does not necessarily rule out their concomitant use.…”

Section: Discussionmentioning

confidence: 99%

The role of PAK1 in the sensitivity of kidney epithelial cells to ischemia-like conditions

2019

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Kidney ischemia, characterized by insufficient supply of oxygen and nutrients to renal epithelial cells, is the main cause of acute kidney injury and an important contributor to mortality world-wide. Earlier research implicated a G-protein coupled receptor (NK1R) in the death of kidney epithelial cells in ischemia-like conditions. P21-associated kinase 1 (PAK1) is involved in signalling by several G-proteins. We explored the consequences of PAK1 inhibition for cell survival under the conditions of reduced glucose and oxygen. Inhibition of PAK1 by RNA interference, expression of a dominant-negative mutant or treatment with small molecule inhibitors greatly reduced the death of cultured kidney epithelial cells. Similar protection was achieved by treating the cells with inhibitors of MEK1, in agreement with the prior reports on PAK1-MEK1 connection. Concomitant inhibition of NK1R and PAK1 offered no better protection than inhibition of NK1R alone, consistent with the two proteins being members of the same pathway. Furthermore, NK1R, PAK and MEK inhibitors reduced the induction of TRAIL in ischemia-like conditions. Considering the emerging role of TRAIL in ischemia-mediated cell death, this phenomenon may contribute to the protective effects of these small molecules. Our findings support further exploration of PAK and MEK inhibitors as possible agents to avert ischemic kidney injury. ARTICLE HISTORY

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“…Триметазидин, миокардиальный цитопротектор, хорошо известный антиангинальный и антиишемический препарат, включен на основании многоцентровых рандомизированных клинических исследований (РКИ) в российские и международные рекомендации по лечению не только различных форм ИБС, но и ХСН. Результаты последних РКИ и их мета-анализов представляют триметазидин как препарат, способный предотвращать и лечить контраст-индуцированную нефропатию (КИН) со значительным снижением скорости клубочковой фильтрации (СКФ) [4]. В экспериментальных исследованиях триметазидин предупреждал острое повреждение почек при шоке и сепсисе.…”

Section: Discussionunclassified

Trimetazidine Influence on Filtration and Tubulointerstitial Function of Kidneys in Ischemic Heart Disease Patients With Chronic Heart Failure and Renal Dysfunction

2018

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Цель. Оценка влияния триметазидина на показатели фильтрационной и тубулоинтерстициальной функций почек у больных стенокардией II-III функционального класса (ФК) на фоне стабильной хронической сердечной недостаточности (ХСН) II-III ФК в сочетании с хронической болезнью почек (ХБП) 3 стадии. Материал и методы. Обследовано 288 больных стабильной стенокардией II-III ФК, среди которых была выделена когорта из 162 (56,3%) больных ХСН II-III ФК. Среди них у 62 (38,3%) пациентов была зарегистрирована ХБП 3 стадии. Все больные ХСН и ХБП 3 стадии были рандомизированы на две равные группы в зависимости от вида медикаментозного вмешательства. Пациентам первой группы к стандартному лечению ХСН и ишемической болезнью сердца (ИБС), был добавлен препарат триметазидин (Предуктал МВ ® , фирмы Servier, Франция) 35 мг 1 раз в день утром, во второй группе пациенты лечились аналогично без применения триметазидина. Длительность лечения составила 6 месяцев. Для оценки функций почек определяли скорость клубочковой фильтрации (СКФ) (CKD-EPIcre), рассчитанную по креатинину сыворотки крови, цистатин С в крови и СКФ (CKD-EPIcys), рассчитанную по цистатину С, cоотношение альбумина к креатинину мочи в разовой порции (UACR), молекулы повреждения канальцев почек (KIM-1) в моче, тканевый ингибитор матриксных протеиназ 1 типа в крови (ТIMP-1). Результаты. Включение в стандартную терапию больных ИБС и ХСН в сочетании с ХБП 3 стадии триметазидина обеспечивает не только улучшение клинического течения заболеваний, увеличение толерантности к физической нагрузке, но и демонстрирует регресс нарушений функции почек по данным динамики снижения цистатина С (p=0,005), увеличения СКФ, рассчитанной по цистатину С (p=0,012), уменьшения UACR (p=0,002), KIM-1 (p<0,001), восстанавливает благоприятный коллагенолиз в интерстиции почек по результатам динамики снижения TIMP-1 (p<0,001). Заключение. Триметазидин проявляет нефропротективный эффект при включении его в терапию больных ИБС и ХСН в сочетании с ХБП 3 стадии. Этот эффект характеризуется улучшением фильтрационной функции, снижением экскреции альбумина с мочой, уменьшением канальцевых нарушений за счет подавления коллагенообразования в интерстиции почек.

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Trimetazidine Decreases Risk of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease

Abstract: The addition of TMZ to NS ± NAC significantly decreased the incidence of CIN in patients undergoing coronary angiography. In conclusion, TMZ could be considered as a potential tool for prevention of CIN in patients with renal dysfunction.

Cited by 27 publications

References 35 publications

Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency

Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency

The role of PAK1 in the sensitivity of kidney epithelial cells to ischemia-like conditions

Trimetazidine Influence on Filtration and Tubulointerstitial Function of Kidneys in Ischemic Heart Disease Patients With Chronic Heart Failure and Renal Dysfunction

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