Cannabinoids and the kidney: effects in health and disease

Consumption of cannabis and various related products (cannabinoids) for both medicinal and recreational use is gaining popularity. Furthermore, regulatory changes are fostering a cultural shift toward increasing liberalization of cannabis use, thereby increasing the likelihood of even larger numbers of individuals being exposed in the future. The two different types of receptors (CB1 and CB2) that are activated by the pharmacologically active ingredients of cannabis are found in numerous tissues, including the kidneys. Experimental studies suggest that stimulation of these receptors using pharmacologic agents or their naturally occurring ligands could have both deleterious and beneficial effects on the kidneys, depending on receptor distribution, type of renal insult, or the timing of the activation during acute or chronic states of kidney injury. To date, the mechanisms by which the CB1 or CB2 receptors are involved in the pathology of these renal conditions remain to be fully described. Furthermore, a better understanding of the impact of exocannabinoids and endocannabinoids on the renal system may lead to the development of new drugs to treat kidney disease and its complications. Given the increasing public health relevance of cannabis exposure, it is clear that more research is necessary to clarify the various physiological and pathophysiological effects of cannabis and related analogs on the kidney. This will help limit the deleterious effects of these substances while promoting their potential beneficial impact on renal function in various types of kidney diseases.

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Metformin: A Candidate Drug for Renal Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms20010042 ◽

2018 ◽

Vol 20 (1) ◽

pp. 42 ◽

Cited By ~ 14

Author(s):

Raphaëlle Corremans ◽

Benjamin A. Vervaet ◽

Patrick C. D’Haese ◽

Ellen Neven ◽

Anja Verhulst

Keyword(s):

Experimental Studies ◽

Kidney Injury ◽

Renal Diseases ◽

Molecular Signaling ◽

Health Issues ◽

Cellular Mechanisms ◽

Beneficial Effects ◽

Candidate Drug ◽

Beneficial Impact ◽

Socio Economic Impact

Over the past decades metformin has been the optimal first-line treatment for type 2 diabetes mellitus (T2DM). Only in the last few years, it has become increasingly clear that metformin exerts benign pleiotropic actions beyond its prescribed use and ongoing investigations focus on a putative beneficial impact of metformin on the kidney. Both acute kidney injury (AKI) and chronic kidney disease (CKD), two major renal health issues, often result in the need for renal replacement therapy (dialysis or transplantation) with a high socio-economic impact for the patients. Unfortunately, to date, effective treatment directly targeting the kidney is lacking. Metformin has been shown to exert beneficial effects on the kidney in various clinical trials and experimental studies performed in divergent rodent models representing different types of renal diseases going from AKI to CKD. Despite growing evidence on metformin as a candidate drug for renal diseases, in-depth research is imperative to unravel the molecular signaling pathways responsible for metformin’s renoprotective actions. This review will discuss the current state-of-the-art literature on clinical and preclinical data, and put forward potential cellular mechanisms and molecular pathways by which metformin ameliorates AKI/CKD.

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Nephrotoxicity of Herbal Products in Europe—A Review of an Underestimated Problem of Nephrotoxicity of Herbal Products

International Journal of Molecular Sciences ◽

10.3390/ijms22084132 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4132

Author(s):

Katarzyna Kiliś-Pstrusińska ◽

Anna Wiela-Hojeńska

Keyword(s):

Kidney Diseases ◽

Herbal Medicines ◽

Kidney Injury ◽

Herbal Products ◽

Chronic Kidney Diseases ◽

European Origin ◽

Synthetic Drugs ◽

The Many ◽

Pharmacologically Active ◽

Traditional Chinese Herbal Medicines

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

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An Old Drug for a New Application: Potential Benefits of Sildenafil in Wound Healing

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3tc7v ◽

2012 ◽

Vol 15 (4) ◽

pp. 483 ◽

Cited By ~ 10

Author(s):

Shadi Farsaie ◽

Hossein Khalili ◽

Iman Karimzadeh ◽

Simin Dashti-Khavidaki

Keyword(s):

Wound Healing ◽

Animal Studies ◽

Case Reports ◽

Experimental Studies ◽

Phosphodiesterase Inhibitor ◽

Cochrane Central Register ◽

Skin Damage ◽

Beneficial Effects ◽

Cochrane Database ◽

The Impact

Purpose: Several studies have evaluated the effects of sildenafil on the tissue repair and wound healing. In the present review, the impact of sildenafil on the wound healing in all available clinical and non-clinical (experimental) studies has been discussed. Methods: A literature search was performed using PubMed, Scopus, Medline, Embase, Cochrane central register of controlled trials and Cochrane database systematic reviews. Related articles indexed in Google Scholar were also included. Key words used as search terms were ‘phosphodiesterase inhibitor’, ‘sildenafil’, ‘skin’, ‘cutaneous’, ‘skin lesion’, ‘skin damage’, ‘wound’, and ‘wound healing’. No time limitation was considered in this review. Results: A total of 15 animal studies, 7 case reports, and 2 small clinical studies have reported the effects of sildenafil on the wound healing. The effects included skin flaps and grafts, anastomosis, systemic sclerosis and Raynaud's disease. Conclusions: The available data support the beneficial effects of sildenafil in improvement of tissue healing in various conditions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Acute Kidney Injury in Pregnancy: The Need for Higher Awareness. A Pragmatic Review Focused on What Could Be Improved in the Prevention and Care of Pregnancy-Related AKI, in the Year Dedicated to Women and Kidney Diseases

Journal of Clinical Medicine ◽

10.3390/jcm7100318 ◽

2018 ◽

Vol 7 (10) ◽

pp. 318 ◽

Cited By ~ 7

Author(s):

Giorgina Piccoli ◽

Elena Zakharova ◽

Rossella Attini ◽

Margarita Ibarra Hernandez ◽

Bianca Covella ◽

...

Keyword(s):

Acute Kidney Injury ◽

Kidney Diseases ◽

Kidney Injury ◽

Hypertensive Disorders Of Pregnancy ◽

Future Health ◽

Hypertensive Disorders ◽

Relevant Effect ◽

The Impact ◽

In Pregnancy

Pregnancy-related acute kidney injury (pAKI), preeclampsia (PE), and the hypertensive disorders of pregnancy are closely related conditions, which are, in turn, frequently linked to pre-existing and often non-diagnosed chronic kidney disease (CKD). The current literature and research mainly underline the effects of pregnancy complications on the offspring; this review strongly emphasizes the maternal health as well. These conditions not only negatively affect pregnancy outcomes, but have a relevant effect on the future health of affected mothers and their children. Therefore, dedicated diagnostic and follow-up programs are needed, for optimizing materno-foetal health and reducing the impact of pregnancy-related problems in the mothers and in the new generations. This narrative review, performed on the occasion of the 2018 World Kidney Day dedicated to women’s health, focuses on three aspects of the problem. Firstly, the risk of AKI in the hypertensive disorders of pregnancy (the risk is the highest in developing countries; however PE is the main cause of pregnancy related AKI worldwide). Secondly, the effect of AKI and the hypertensive disorders of pregnancy on the development of CKD in the mother and offspring: long-term risks are increased; the entity and the trajectories are still unknown. Thirdly, the role of CKD in the pathogenesis of AKI and the hypertensive disorders of pregnancy: CKD is a major risk factor and the most important element in the differential diagnosis; pregnancy is a precious occasion for early diagnosis of CKD. Higher awareness on the importance of AKI in pregnancy is needed to improve short and long term outcomes in mothers and children.

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Hope and Stress Resilience

10.1093/oxfordhb/9780199399314.013.26 ◽

2017 ◽

Author(s):

Anthony D. Ong ◽

Taylor Standiford ◽

Saarang Deshpande

Keyword(s):

Psychological Functioning ◽

Experimental Studies ◽

Well Being ◽

Protective Effects ◽

Cross Sectional ◽

Phenomenological Experience ◽

Direct Association ◽

Beneficial Impact ◽

The Impact ◽

Clinical Populations

A sizeable literature has implicated hopelessness in the phenomenological experience of various mood disorders, vulnerability to psychopathology, and overall poor psychological functioning. By contrast, how hope contributes to resilience and well-being has been understudied. This systematic review integrates findings from cross-sectional, longitudinal, ambulatory, and experimental studies that investigate the impact of hope and well-being outcomes in both healthy and clinical populations. Although the literature is not without theoretical gaps and methodological inconsistencies, the pattern of findings suggests that aggregate or trait measures of hope provide the most consistent evidence of a direct association between hope and well-being in healthy and clinical populations. More limited empirical data exists on the protective effects of hope. The chapter concludes that more rigorous and theoretically informed research is needed before firm conclusions can be drawn about the possible beneficial impact of hope on well-being.

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ANTIOXIDANT POTENTIAL OF ADEMETIONINE IN GENTAMICINE NEPHROPATHY PROGRESSION

Актуальні проблеми сучасної медицини Вісник Української медичної стоматологічної академії ◽

10.31718/2077-1096.20.1.8 ◽

2020 ◽

Vol 20 (1) ◽

pp. 8-12

Author(s):

V.M. Drachuk ◽

I. I. Zamorskiy ◽

O. M. Horoshko

Keyword(s):

Glutathione Peroxidase ◽

Experimental Studies ◽

Kidney Injury ◽

Thiobarbituric Acid ◽

Oxidative Modification ◽

Antioxidant Potential ◽

Amino Acid Derivative ◽

New Therapies ◽

Sh Groups ◽

The Impact

Acute kidney injury has been globally considered as a serious medical issue. Its incidence rate is increasing over the years despite the introduction of new therapies, the cause of which is often a side effect to drugs, or due to the impact of toxins, trauma. Nephrotoxicity is one of the most important side effects of aminoglycoside antibiotics, and on gentamicin, in particular. Despite rigorous patient monitoring, this type of nephrotoxicity appears in 10–30% of therapeutic courses. Therefore, searching for new therapies, which would be able to prevent or decrease toxic kidney injury during the treatment with aminoglycosides is quite relevant. Ademetionine is an amino acid derivative, which possesses various effects such as antioxidant, membrane stabilizing, anti-inflammatory and regenerative. Aim of the research is to study an antioxidative activity of ademetionine in conditions of gentamicin nephropathy progression in rats. Materials and methods. Research was conducted on non-linear mature white rats weighting 130-180 g, randomly divided into 3 groups (n = 7): I group included intact control animals, II group included rodents with gentamicin nephropathy (injection of 4% Gentamicin sulphate solution in a dosage of 80 mg/kg for 6 days), III group involved the rats receiving ademetionine («Abbott SpA», Italy) in a dosage of 20 mg/kg. Peroxidation processes in blood and kidneys were evaluated by the content of active products that react with thiobarbituric acid and oxidative modification of proteins levels, antioxidant defence was assessed by catalase and glutathione peroxidase activity, SH-groups and ceruloplasmin content. Results. In the course of experimental studies on the model of gentamicin nephropathy, the expressive antioxidant activity of ademetionine was proven: it was demonstrated by reducing the intensity of lipid peroxidation (a decrease in the content of active products that react with thiobarbituric acid) and proteins (a decrease in the content of oxidative modified proteins) in the blood and kidney homogenate, next with increased activity of the enzymatic link of antioxidant protection (glutathione peroxidase and catalase) and non-enzymatic (ceruloplasmin and compounds with SH-groups). The antioxidant potential of ademetionine has been confirmed by an increase in the antioxidant-prooxidant index in kidney tissue and a significant decrease in the index of oxidative stress in the blood of treated animals. Conclusion. Thus, the results of experimental studies indicate the antioxidative effect of ademetionine in modelled gentamicin nephropathy, and point out the necessity of further studying its potential nephroprotectective properties.

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Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression

American Journal of Nephrology ◽

10.1159/000475890 ◽

2017 ◽

Vol 45 (6) ◽

pp. 473-483 ◽

Cited By ~ 59

Author(s):

Masahiro Nezu ◽

Norio Suzuki ◽

Masayuki Yamamoto

Keyword(s):

Oxidative Stress ◽

Kidney Disease ◽

Kidney Diseases ◽

Kidney Injury ◽

Related Factor ◽

Renal Tubules ◽

Renal Protection ◽

Beneficial Effects ◽

Positive Effects ◽

Basic Studies

Background: Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor for the antioxidative stress response and it activates a variety of cytoprotective genes related to redox and detoxification. NRF2 activity is regulated by the oxidative-stress sensor molecule Kelch-like ECH-associated protein 1 (KEAP1) that induces proteasomal degradation of NRF2 through ubiquitinating NRF2 under unstressed conditions. Because oxidative stress is a major pathogenic and aggravating factor for kidney diseases, the KEAP1-NRF2 system has been proposed to be a therapeutic target for renal protection. Summary: Oxidative-stress molecules, such as reactive oxygen species, accumulate in the kidneys of animal models for acute kidney injury (AKI), in which NRF2 is transiently and slightly activated. Genetic or pharmacological enhancement of NRF2 activity in the renal tubules significantly ameliorates damage related to AKI and prevents AKI progression to chronic kidney disease (CKD) by reducing oxidative stress. These beneficial effects of NRF2 activation highlight the KEAP1-NRF2 system as an important target for kidney disease treatment. However, a phase-3 clinical trial of a KEAP1 inhibitor for patients with stage 4 CKD and type-2 diabetes mellitus (T2DM) was terminated due to the occurrence of cardiovascular events. Because recent basic studies have accumulated positive effects of KEAP1 inhibitors in moderate stages of CKD, phase-2 trials have been restarted. The data from the ongoing projects demonstrate that a KEAP1 inhibitor improves the glomerular filtration rate in patients with stage 3 CKD and T2DM without safety concerns. Key Message: The KEAP1-NRF2 system is one of the most promising therapeutic targets for kidney disease, and KEAP1 inhibitors could be part of critical therapies for kidney disease.

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The impact of anorexigenic peptides in experimental models of Alzheimer’s disease pathology

Journal of Endocrinology ◽

10.1530/joe-18-0532 ◽

2019 ◽

Vol 240 (2) ◽

pp. R47-R72 ◽

Cited By ~ 6

Author(s):

Lenka Maletínská ◽

Andrea Popelová ◽

Blanka Železná ◽

Michal Bencze ◽

Jaroslav Kuneš

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Energy Homeostasis ◽

Neurodegenerative Disorder ◽

Experimental Studies ◽

The Elderly ◽

Experimental Models ◽

New Drugs ◽

Neuroprotective Effects ◽

The Impact

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the elderly population. Numerous epidemiological and experimental studies have demonstrated that patients who suffer from obesity or type 2 diabetes mellitus have a higher risk of cognitive dysfunction and AD. Several recent studies demonstrated that food intake-lowering (anorexigenic) peptides have the potential to improve metabolic disorders and that they may also potentially be useful in the treatment of neurodegenerative diseases. In this review, the neuroprotective effects of anorexigenic peptides of both peripheral and central origins are discussed. Moreover, the role of leptin as a key modulator of energy homeostasis is discussed in relation to its interaction with anorexigenic peptides and their analogs in AD-like pathology. Although there is no perfect experimental model of human AD pathology, animal studies have already proven that anorexigenic peptides exhibit neuroprotective properties. This phenomenon is extremely important for the potential development of new drugs in view of the aging of the human population and of the significantly increasing incidence of AD.

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Early versus late initiation of renal replacement therapy impacts mortality in septic patients with acute kidney injury: a meta-analysis

10.21203/rs.3.rs-16023/v1 ◽

2020 ◽

Author(s):

Chenglong Ge ◽

Yuan Jiang ◽

Qianyi Peng ◽

Yuhang Ai

Keyword(s):

Acute Kidney Injury ◽

Renal Replacement Therapy ◽

Replacement Therapy ◽

Meta Analysis ◽

Kidney Injury ◽

Cochrane Library ◽

Optimal Time ◽

Late Initiation ◽

Beneficial Impact ◽

The Impact

Abstract Background: Acute kidney injury (AKI) is a frequent complication in septic patients and increases in-hospital mortality. Our aim was to evaluate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in septic patients with acute kidney injury (AKI). Methods: Systematic review and meta-analysis were used in this study. We searched PubMed, EMBASE, MEDLINE and Cochrane Library. Results: Nine studies (two randomized controlled trials (RCTs) and seven retrospective cohorts) including 1694 patients were identified for detailed evaluation. This meta-analysis suggested that early RRT initiation within 48 hours (OR 0.30; 95% CI 0.20 to 0.45; I 2 0%) in septic patients with AKI reduced 28-day mortality (odds ratio (OR) 0.56; 95% confidence interval (CI) 0.37 to 0.86; I 2 73%), but intensive care unit (ICU) length of stay (LOS) (mean difference (MD) -1.49; 95% CI -3.65 to -0.67; I 2 53%), hospital LOS (MD -3.18; 95% CI -7.35 to 0.99; I 2 41%), the duration of RRT (MD -2.05; 95%CI -6.86 to 2.76; I 2 83%) and the duration of ventilation (MD 1.99; 95%CI -2.76 to 6.75; I 2 85%) were not influenced by the timing of RRT initiation. Conclusions: Early initiation of RRT within 48 hours in septic patients with AKI may have a beneficial impact on survival. However, this conclusion is based on heterogeneous trials of different quality and only two RCTs. Conclusive therapeutic recommendations regarding the optimal time to initiate RRT remain uncertain.

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Role of Macrophages and Related Cytokines in Kidney Disease

Frontiers in Medicine ◽

10.3389/fmed.2021.688060 ◽

2021 ◽

Vol 8 ◽

Author(s):

Elena Cantero-Navarro ◽

Sandra Rayego-Mateos ◽

Macarena Orejudo ◽

Lucía Tejedor-Santamaria ◽

Antonio Tejera-Muñoz ◽

...

Keyword(s):

Kidney Disease ◽

Immune Cells ◽

Kidney Diseases ◽

Experimental Studies ◽

Kidney Injury ◽

Chronic Inflammatory Disease ◽

Renal Diseases ◽

Circulating Cells ◽

Functional Homolog ◽

Nephron Loss

Inflammation is a key characteristic of kidney disease, but this immune response is two-faced. In the acute phase of kidney injury, there is an activation of the immune cells to fight against the insult, contributing to kidney repair and regeneration. However, in chronic kidney diseases (CKD), immune cells that infiltrate the kidney play a deleterious role, actively participating in disease progression, and contributing to nephron loss and fibrosis. Importantly, CKD is a chronic inflammatory disease. In early CKD stages, patients present sub-clinical inflammation, activation of immune circulating cells and therefore, anti-inflammatory strategies have been proposed as a common therapeutic target for renal diseases. Recent studies have highlighted the plasticity of immune cells and the complexity of their functions. Among immune cells, monocytes/macrophages play an important role in all steps of kidney injury. However, the phenotype characterization between human and mice immune cells showed different markers; therefore the extrapolation of experimental studies in mice could not reflect human renal diseases. Here we will review the current information about the characteristics of different macrophage phenotypes, mainly focused on macrophage-related cytokines, with special attention to the chemokine CCL18, and its murine functional homolog CCL8, and the macrophage marker CD163, and their role in kidney pathology.

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