montelukast and Kidney-Failure--Chronic

Uremic pruritus is one of the most common disabling symptoms in patients with end-stage renal disease. We aimed to study the effect of montelukast sodium for the treatment of uremic pruritus lasting more than 3 months in patients undergoing hemodialysis and compare it with placebo.. Eighty patients undergoing hemodialysis at 3 centers in Shiraz, Iran, were recruited to a randomized double-blinded controlled trial to receive 10 mg of montelukast or placebo, daily for 30 days. To assess the severity of pruritus, a visual analogue scale and the Detailed Pruritus Score, based on a combined score of severity and distribution of pruritus and sleep disturbance, were used. Sleep disturbance, severity, and distribution scores were added up to calculate the patients' final score at the start and the end of the study.. The mean reduction of visual analogue scale score was significantly greater in the montelukast group (2.73 ± 2.03) compared to that in the placebo group (5.47 ± 2.37, P < .001). Mean reduction in Detailed Pruritus Score was also greater in the montelukast group (3.24 ± 2.2 versus 6.44 ± 3.25, respectively, P < .001). The mean high-sensitivity C-reactive protein in the montelukast group decreased from 5.48 ± 3.86 µg/mL to 3.86 ± 3.58 µg/mL, while it increased in the placebo group from 6.69 ± 4.49 µg/mL to 8.14 ± 5.20 µg/mL.. Montelukast can be an add-on therapy in uremic pruritus, especially when pruritus is refractive to other treatments.

Topics: Acetates; Adult; C-Reactive Protein; Cyclopropanes; Drug Monitoring; Female; Humans; Kidney Failure, Chronic; Leukotriene Antagonists; Male; Middle Aged; Pruritus; Quinolines; Renal Dialysis; Sulfides; Treatment Outcome; Uremia

Uremic pruritus (UP) is a common and tormenting symptom in end-stage renal disease patients undergoing maintenance hemodialysis. An increasing number of studies have been published in recent years to support the effectiveness of montelukast for UP. We will conduct a comprehensive systematic review and meta-analysis to evaluate effectiveness of montelukast for UP in hemodialysis patients.. The following electronic databases were searched: Pubmed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. The range of publication time was from the inception of the database to December 2020. Two reviewers will independently conduct article selection, data collection, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Meta-analysis will be performed by Review Manager 5.3. The Cochrane Collaboration tool will be used to assess the risk of bias.. This study will provide a systematic synthesis of current published data to explore the effectiveness of montelukast for UP in hemodialysis patients.. This systematic review and meta-analysis will provide clinical evidence for the effectiveness of montelukast for UP in hemodialysis patients and inform our understanding of the value of montelukast in improving pruritus symptoms. This study will help clinicians, patients, and policy makers to make better decisions regarding the appropriate role of montelukast as a part of patient management routines.. INPLASY2020100043.

Topics: Acetates; Clinical Protocols; Cyclopropanes; Humans; Kidney Failure, Chronic; Leukotriene Antagonists; Meta-Analysis as Topic; Pruritus; Quinolines; Renal Dialysis; Sulfides; Systematic Reviews as Topic

Continuous ambulatory peritoneal dialysis (CAPD) induces structural changes in the peritoneal membrane such as fibrosis, vasculopathy and angioneogenesis with a reduction in ultrafiltration capacity. Leukotriene (LT) receptor antagonists have been found to be effective to prevent fibrosis in some nonperitoneal tissues. The aim of this study is to investigate the possible beneficial effect of montelukast, a LT receptor antagonist, on peritoneal membrane exposed to hypertonic peritoneal dialysis in uremic rats.. Of the 48 male, 5/6 nephrectomized Wistar rats 29 remained alive and were included in the study. These studied rats were divided into 3 groups: Group I (n=7) was the control group, Group II (n=8) was treated with 20 ml hypertonic PDF intraperitoneally daily and Group III was treated with montelukast and similar PDF treatment protocol. The morphological and functional changes in the peritoneal membrane as well as cytokine expression were compared between groups.. Submesothelial thickness and the severity of the degree of hyaline vasculapathy were more prominent in group III when compared to group I. There were no significant differences between group II and other groups in terms of submesothelial thickness and the severity of the degree of hyaline vasculapathy. Increased expressions of TGF-β and VEGF in parietal peritoneal membrane were found in group II and group III when compared to group I. The amount of TGF-β and VEGF expression were similar in group II and group III.. This study suggests that montelukast treatment does not prevent the peritoneal membrane from deleterious effects of hyperosmolar PDF in the uremic environment.

Topics: Acetates; Animals; Cyclopropanes; Cytokines; Fibrosis; Kidney Failure, Chronic; Leukotriene Antagonists; Male; Membranes; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Quinolines; Rats; Rats, Wistar; Sulfides; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species and cytokine release. We aimed to investigate the possible protective effect of montelukast, a CysLT1 receptor antagonist, against oxidative damage in a rat model of CRF, induced by 5/6 reduction of renal mass. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which received saline or montelukast (10mg/kg, i.p.) for 4 weeks. At the end of the 4 weeks, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen and lactate dehydrogenase (LDH) activity were measured in the serum samples, while leukotriene B(4), TNF-alpha, IL-1 beta, IL-6, total antioxidant capacity (AOC) and leukocyte apoptosis were assayed in plasma samples. Kidney, lung, heart and brain tissue samples were taken for the determination of tissue malondialdehyde (MDA), glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Oxidant-induced tissue fibrosis was determined by tissue collagen contents, and the extent of tissue injuries was analyzed microscopically. CRF caused significant decreases in tissue GSH and plasma AOC, which were accompanied with significant increases in MDA levels, MPO activities, and collagen contents of all the studied tissues, while the circulating levels of the pro-inflammatory mediators, LDH activity, creatinine and BUN were elevated. Montelukast treatment reversed all these biochemical indices, as well as histopathological alterations induced by CRF. Similarly, flow cytometric measurements revealed that leukocyte apoptosis was increased in CRF group, while montelukast reversed this effect. In conclusion, CRF-induced oxidative tissue injury occurs via the activation of pro-inflammatory mediators and by neutrophil infiltration into tissues, and that protective effects of montelukast on CRF-induced injury can be attributed to its ability to inhibit neutrophil infiltration and apoptosis, to balance oxidant-antioxidant status and to regulate the generation of pro-inflammatory mediators.

Topics: Acetates; Animals; Antioxidants; Apoptosis; Blood Urea Nitrogen; Collagen; Creatinine; Cyclopropanes; Glutathione; Interleukin-1beta; Interleukin-6; Kidney; Kidney Failure, Chronic; L-Lactate Dehydrogenase; Leukocytes; Leukotriene Antagonists; Lung; Male; Malondialdehyde; Membrane Proteins; Multiple Organ Failure; Quinolines; Random Allocation; Rats; Rats, Wistar; Receptors, Leukotriene; Sulfides; Tumor Necrosis Factor-alpha