“Nephropathy is the decline in kidney function. A promising treatment for numerous types of illness is using natural materials as natural chemical compounds. The inquiry was conducted to investigate cannabidiol (CBD) potential for renal syndrome protection. The five equal groups of fifty male Sprague-Dawley rats weighing 150 ± 25 g each were designed; group I received distilled water orally, while group II got an intraperitoneal injection of doxorubicin (18 mg/kg bwt). Group III received CBD (26 mg/kg bwt) orally, while group IV received 1 ml of CBD (26 mg/kg bwt) and group V received trimetazidine (10 mg/kg bwt), in addition to a single intraperitoneal dose of doxorubicin (18 mg/kg bwt) on the 11th day for both groups (IV, V). The administration of CBD (26 mg/kg bwt) led to a noticeable improvement in oxidative stress parameters (SOD and GSH) in rats by significantly lowering enzyme activity (ALT and AST), as well as serum creatinine and urea, IL-6, and MDA, confirming the anti-inflammatory accuracy of CBD linked to significant lowering to IL6R DNA frequency concentration in line with histopathology results. As a result of its anti-inflammatory and antioxidant capabilities, cannabidiol may have protective quality, and CBD medication could be related to controlling renal problems.”
“Cannabidiol (CBD) is thought to have multiple biological effects, including the ability to attenuate inflammatory processes. Cannabigerols (CBGA and its decarboxylated CBG molecule) have pharmacological profiles similar to CBD. The endocannabinoid system has recently emerged to contribute to kidney disease, however, the therapeutic properties of cannabinoids in kidney disease remain largely unknown. In this study, we determined whether CBD and CBGA can attenuate kidney damage in an acute kidney disease model induced by the chemotherapeutic cisplatin. In addition, we evaluated the anti-fibrosis effects of these cannabinoids in a chronic kidney disease model induced by unilateral ureteral obstruction (UUO). We find that CBGA, but not CBD, protects the kidney from cisplatin-induced nephrotoxicity. CBGA also strongly suppressed mRNA of inflammatory cytokines in cisplatin-induced nephropathy, whereas CBD treatment was only partially effective. Furthermore, both CBGA and CBD treatment significantly reduced apoptosis through inhibition of caspase-3 activity. In UUO kidneys, both CBGA and CBD strongly reduced renal fibrosis. Finally, we find that CBGA, but not CBD, has a potent inhibitory effect on the channel-kinase TRPM7. We conclude that CBGA and CBD possess reno-protective properties, with CBGA having a higher efficacy, likely due to its dual anti-inflammatory and anti-fibrotic effects paired with TRPM7 inhibition.”
“CBGA and CBD alone or in combination could be helpful as therapeutic options to treat chronic kidney disease with anti-inflammatory and anti-fibrotic properties and CBGA may be able to serve as an adjuvant for cisplatin chemotherapy.”
“Background: Cannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown.
Materials and Methods: Post hoc analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.S. centers during 2009-2015. Associations between self-reported cannabis consumption and the categorical and continuous outcomes were determined using multivariable Cox regression and linear mixed models, respectively.
Results: Over a mean follow-up of 4.5±1.8 years, 94 participants without chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2) who consumed cannabis had similar rates of annual eGFR decline versus 889 nonconsumers (mean difference=-0.02 mL/min/1.73 m2/year, p=0.9) and incident CKD (≥25% reduction in eGFR compared with the 3-month post-hospitalization measured eGFR and achieving CKD stage 3 or higher) (adjusted hazard ratio [aHR]=1.2; 95% confidence interval [CI]=0.7-2.0). Nineteen participants with CKD (eGFR <60 mL/min/1.73 m2) who consumed cannabis had more rapid eGFR decline versus 597 nonconsumers (mean difference=-1.3 mL/min/1.73 m2/year; p=0.02) that was not independently associated with an increased risk of CKD progression (≥50% reduction in eGFR compared with the 3-month post-hospitalization eGFR, reaching CKD stage 5, or receiving kidney replacement therapy) (aHR=1.6; 95% CI=0.7-3.5). Cannabis consumption was not associated with the rate of change in urine albumin to creatinine ratio (UACR) over time among those with (p=0.7) or without CKD (p=0.4).
Conclusions: Cannabis consumption did not adversely affect the kidney function of participants without CKD but was associated with a faster annual eGFR decline among participants with CKD. Cannabis consumption was not associated with changes in UACR over time, incident CKD, or progressive CKD regardless of baseline kidney function. Additional research is needed to investigate the kidney endocannabinoid system and the impact of cannabis use on kidney disease outcomes.”
“Background: Cytokine release syndrome, also termed “cytokine storm,” is the leading cause of morbidity and mortality among patients with various conditions such as sepsis. While cytokine storm is associated with multiple organ damage, acute cardiac and renal injury represents a hallmark of cytokine storm. Since recent reports have suggested that cannabidiol (CBD) may assist in the treatment of inflammatory diseases, our objective was to examine the effect of CBD on cytokine storm-induced cardiac and renal injury using the lipopolysaccharide (LPS)-induced sepsis mouse model.
Materials and Methods: At 8 weeks of age, mice were randomly assigned to receive CBD (15 mg/kg) or vehicle one hour before a single injection of either phosphate-buffered saline or LPS (10 mg/kg) for an additional 24 h.
Results: Our results show that CBD improves cardiac function and reduces renal injury in a mouse model of cytokine storm. Moreover, our data indicate that CBD significantly reduces systemic and renal inflammation to contribute to the improvements observed in a cytokine storm-model of cardiac and renal injury.
Conclusions: Overall, the findings of this study suggest that CBD could be repurposed to reduce morbidity in patients with cytokine storm particularly in severe infections such as sepsis.”
“Background: Legislation of cannabis use has been approved in many European and North American countries. Its impact on urological cancers is unclear. This study was conducted to explore the association between cannabis use and the risk of urological cancers.
Methods: We identified 151,945 individuals with information on cannabis use in the UK Biobank from 2006 to 2010. Crude and age-standardized incidence ratios of different urological cancers were evaluated in the entire cohort and subgroups. Cox regression was performed for survival analysis.
Results: Previous use of cannabis was a significant protective factor for renal cell carcinoma (HR = 0.61, 95%CI:0.40-0.93, p = 0.021) and prostate cancer (HR = 0.82, 95%CI:0.73-0.93, p = 0.002) in multivariable analysis. The association between previous cannabis use and both renal cell carcinoma and bladder cancer was only observed in females (HRRCC = 0.42, 95%CI:0.19-0.94, p = 0.034; HRBCa = 0.43, 95%CI:0.21-0.86, p = 0.018) but not in men. There was no significant association between cannabis use and testicular cancer incidence. Mendelian randomization demonstrated a potential causal effect of cannabis use on a lower incidence of renal cell carcinoma.
Conclusions: Previous use of cannabis was associated with a lower risk of bladder cancer, renal cell carcinoma, and prostate cancer. The inverse association between cannabis and both renal cell carcinoma and bladder cancer was only found in females but not in males.”
“Cannabis, also known as marijuana, is the most used substance derived from Cannabis Sativa which can be used for recreational or medical purposes. Some evidence also suggested that cannabinoids might induce apoptosis of cancer cells and inhibit oncogenesis, indicating a potential treatment effect”
“Previous Cannabis Use Linked to Lower Risk of Some Genitourinary Cancers”
“Ethnopharmacological relevance: Cannabis sativa L. is among numerous medicinal plants widely used in traditional medicine in treating various ailments including kidney diseases.
Aims: The protective effect of C. sativa on oxidative stress, cholinergic and purinergic dysfunctions, and dysregulated glucogenic activities were investigated in oxidative injured kidney (Vero) cell lines.
Methods: Fixed Vero cells were treated with sequential extracts (hexane, dichloromethane [DCM] and ethanol) of C. sativa leaves for 48 h before subjecting to MTT assay. Vero cells were further incubated with FeSO4 for 30 minutes, following pretreatment with C. sativa extracts for 25 minutes. Normal control consisted of Vero cells not treated with the extracts and/or FeSO4, while untreated (negative) control consisted of cells treated with only FeSO4.
Results: MTT assay revealed the extracts were slightly cytotoxic at the highest concentrations (250 μg/mL). There was a significant depletion in glutathione level and catalase activity on induction of oxidative stress, with significant elevation in malondialdehyde level, acetylcholinesterase, ATPase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase and glycogen phosphorylase activities. These activities and levels were significantly reversed following pretreatment with C. sativa extracts.
Conclusion: These results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells.”
“Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage.
Accumulating proofs demonstrates that the endocannabinoid system (ECS) may provide a promising access for treatment strategy of renal IRI associated AKI.
In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation.
Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.”
“Cannabis (marijuana, weed, pot, ganja, Mary Jane) is the most commonly used federally illicit drug in the United States.
The present review provides an overview of cannabis and cannabinoids with relevance to the practice of nephrology so that clinicians can best take care of patients.
Cannabis may have medicinal benefits for treating symptoms of advanced chronic kidney disease (CKD) and end-stage renal disease including as a pain adjuvant potentially reducing the need for opioids.
Cannabis does not seem to affect kidney function in healthy individuals. However, renal function should be closely monitored in those with CKD, the lowest effective dose should be used, and smoking should be avoided. Cannabis use may delay transplant candidate listing or contribute to ineligibility.
Cannabidiol (CBD) has recently exploded in popularity. Although generally well tolerated, safe without significant side effects, and effective for a variety of neurological and psychiatric conditions, consumers have easy access to a wide range of unregulated CBD products, some with inaccurate labeling and false health claims. Importantly, CBD may raise tacrolimus levels.
Patients and healthcare professionals have little guidance or evidence regarding the impact of cannabis use on people with kidney disease. This knowledge gap will remain as long as federal regulations remain prohibitively restrictive towards prospective research.”
“As patients who receive cannabidiol (CBD) may have co-existing renal morbidities, it is important to understand whether dose adjustments are necessary to mitigate the risk of exposure-related toxicity. This study was conducted to evaluate the pharmacokinetics, safety, and tolerability of CBD in patients with renal impairment.
The pharmacokinetics and safety of a single oral 200 mg dose of a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (Epidiolex® in the USA; 100 mg/mL) were assessed in subjects with mild, moderate, or severe renal impairment (n = 8/group) relative to matched subjects with normal renal function (n = 8). Blood samples were collected until 48 h post-dose and evaluated by liquid chromatography with tandem mass spectrometry. Analysis of variance was used to compare primary pharmacokinetic parameters (maximum measured plasma concentration [Cmax], oral clearance of drug from plasma [CL/F], renal clearance [CLR], area under the plasma concentration-time curve [AUC] from time zero to last measurable concentration [AUCt], and AUC from time zero to infinity [AUC∞]); descriptive analysis was used for secondary pharmacokinetic parameters (time to Cmax [tmax], terminal [elimination] half-life [t½], cumulative amount excreted from time zero to the last quantifiable sample [Aelast], and fraction of the systemically available drug excreted into the urine [fe]).
No statistically significant differences were observed in Cmax, AUCt, AUC∞, or tmax values between subjects with mild, moderate, or severe renal impairment and subjects with normal renal function for CBD or its major metabolites, 7-carboxy-CBD (7-COOH-CBD) and 7-hydroxy-CBD (7-OH-CBD), and minor metabolite, 6-hydroxy-CBD (6-OH-CBD); geometric mean ratio for Cmax values ranged from 0.68 to 1.35. No differences were observed for other secondary parameters (Aelast and fe). CBD, 7-COOH-CBD, 7-OH-CBD, and 6-OH-CBD were highly protein bound (> 90%); binding was similar in all subject groups. Urine analysis for CBD recorded no appreciable amount, and thus no urinary pharmacokinetic parameters could be derived. Adverse events (AEs) affected two subjects; all five AEs were mild in severity and resolved during the trial. There were no serious AEs or discontinuations due to AEs. Laboratory, physical examination, vital sign, and 12-lead electrocardiogram findings were not clinically significant.
Renal impairment had no effect on the metabolism of CBD after a single oral 200 mg dose. CBD was generally well tolerated in subjects with varying degrees of renal function.”
“Renal impairment status had no effect on CBD pharmacokinetics following a single oral 200 mg dose, with no statistically significant effects on Cmax, AUCt, AUC∞, or tmax. CBD was generally well tolerated; there were no serious or severe AEs, and no new safety concerns were identified.”
“Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease characterized by the rapid decline of kidney function. Herein, we explored the therapeutic potential of targeting the cannabinoid 2 receptor (CB2-R) utilizing a commonly used mouse model of liver fibrosis and hepatorenal syndrome (HRS), induced by bile duct ligation (BDL).
We found that liver injury triggered marked inflammation and oxidative stress also in the kidneys of BDL-operated mice. We detected pronounced histopathological alterations with tubular injury paralleled with increased inflammation, oxidative/nitrative stress and fibrotic remodeling both in hepatic and renal tissues as well as endothelial activation and markedly impaired renal microcirculation. This was accompanied by increased CB2-R expression in both liver and the kidney tissues of diseased animals. A selective CB2-R agonist, HU-910, markedly decreased numerous markers of inflammation, oxidative stress and fibrosis both in the liver and in the kidneys. HU-910 also attenuated markers of kidney injury and improved the impaired renal microcirculation in BDL-operated mice.
Our results suggest that oxidative stress, inflammation and microvascular dysfunction are key events in the pathogenesis of BDL-associated renal failure. Furthermore, we demonstrate that targeting the CB2-R by selective agonists may represent a promising new avenue to treat HRS by attenuating tissue and vascular inflammation, oxidative stress, fibrosis and consequent microcirculatory dysfunction in the kidneys.”
“Bile duct ligation (BDL) causes hepatorenal syndrome (HRS). Oxidative damage/inflammation drives liver and kidney injury following BDL. Cannabinoid-2 receptor (CB2-R) activation attenuates hepatic damage in BDL. CB2-R activation mitigates the renal inflammation and oxidative damage in BDL. CB2-R activation attenuates renal microcirculatory dysfunction in BDL.”