Category Archives: Kidney Disease

Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay.

Posted on by
Reply

Transplantation Proceedings Home

“Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs.

Benefits in chronic pain treatment with cannabidiol (CBD) have been reported.

This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain.

RESULTS:

We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change.

CONCLUSIONS:

During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.”

https://www.ncbi.nlm.nih.gov/pubmed/29579828

http://www.transplantation-proceedings.org/article/S0041-1345(17)30962-4/fulltext

Marijuana Use and Renal Function Among US Adults.

Posted on by
Reply

The American Journal of Medicine Home

“In recent years, the number of states that have legalized medical marijuana or retail sales has increased, bringing potential changes of marijuana use pattern among the general population. However, health effects of acute and chronic marijuana use on many relevant health outcomes, including renal function, remain largely unexamined.

In this study, we aimed to assess the association between recent and past marijuana use and renal function.

CONCLUSIONS:

We did not observe any clinically significant association between current or past self-reported marijuana use and measures of kidney function.”

https://www.ncbi.nlm.nih.gov/pubmed/29291894

http://www.amjmed.com/article/S0002-9343(17)31193-2/fulltext

“No link between current or previous marijuana use and kidney disease, say researchers” https://www.sciencedaily.com/releases/2018/03/180301125051.htm

“Marijuana Doesn’t Seem to Harm the Kidneys” https://www.webmd.com/mental-health/addiction/news/20180306/marijuana-doesnt-seem-to-harm-the-kidneys

“”Our research provides some reassuring evidence suggesting that there is no detrimental effect of infrequent, relatively light use of marijuana on kidney function among healthy adults under age 60,”” https://consumer.healthday.com/general-health-information-16/illicit-drugs-news-217/marijuana-doesn-t-seem-to-harm-the-kidneys-731632.html

“Pot Won’t Harm Healthy Young People’s Kidneys, Study Suggests”  https://www.medicinenet.com/script/main/art.asp?articlekey=206375

Cannabinoid Receptors in Diabetic Kidney Disease.

Posted on by
Reply

 Current Diabetes Reports

“The purpose of this review is to examine and summarize studies assessing the relevance of the endocannabinoid system (ECS) in diabetic kidney disease (DKD).

Endocannabinoids and endocannabinoid receptors of type 1 (CB1R) and of type 2 (CB2R) are present in the normal kidney. Expression of CB1R and CB2R is altered in experimental DKD.

Studies in experimental animals and cultured kidney cells show a beneficial effect of peripheral CB1R blockade and CB2R activation in DKD and an even greater efficacy of a combined treatment.

Preclinical studies confirm that both CB1R and CB2R are implicated in the pathogenesis of DKD and may represent novel targets for treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/29399721

https://link.springer.com/article/10.1007%2Fs11892-018-0975-7 

Selective cannabinoid 2 receptor stimulation reduces tubular epithelial cell damage following renal ischemia-reperfusion injury.

Posted on by
Reply

Journal of Pharmacology and Experimental Therapeutics “Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with increased rates of mortality. Currently, therapies to treat AKI are not available, so identification of new targets which, upon diagnosis of AKI, can be modulated to ameliorate renal damage is essential.

In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295, was designed, synthesized, and tested in vitro and in silico.

These data suggests that selective CB2 receptor activation could be a potential therapeutic target in the treatment for AKI.”

https://www.ncbi.nlm.nih.gov/pubmed/29187590

http://jpet.aspetjournals.org/content/early/2017/11/29/jpet.117.245522

Modulation of Renal GLUT2 by the Cannabinoid-1 Receptor: Implications for the Treatment of Diabetic Nephropathy.

Posted on by
Reply

Related image

“Altered glucose reabsorption via the facilitative glucose transporter 2 (GLUT2) during diabetes may lead to renal proximal tubule cell (RPTC) injury, inflammation, and interstitial fibrosis. These pathologies are also triggered by activating the cannabinoid-1 receptor (CB1R), which contributes to the development of diabetic nephropathy (DN). However, the link between CB1R and GLUT2 remains to be determined. Here, we show that chronic peripheral CB1R blockade or genetically inactivating CB1Rs in the RPTCs ameliorated diabetes-induced renal structural and functional changes, kidney inflammation, and tubulointerstitial fibrosis in mice. Inhibition of CB1R also downregulated GLUT2 expression, affected the dynamic translocation of GLUT2 to the brush border membrane of RPTCs, and reduced glucose reabsorption. Thus, targeting peripheral CB1R or inhibiting GLUT2 dynamics in RPTCs has the potential to treat and ameliorate DN. These findings may support the rationale for the clinical testing of peripherally restricted CB1R antagonists or the development of novel renal-specific GLUT2 inhibitors against DN.”

https://www.ncbi.nlm.nih.gov/pubmed/29030466

http://jasn.asnjournals.org/content/early/2017/10/12/ASN.2017040371

Cannabinoid receptor 2 as a novel target for promotion of renal cell carcinoma prognosis and progression.

Posted on by
Reply

Journal of Cancer Research and Clinical Oncology

“Renal cell carcinoma (RCC) is the most common malignancy of urogenital system, and patients with RCC may face a poor prognosis. However, limited curable therapeutic options are currently available.

The aim of this study is to investigate the role of Cannabinoid receptor 2 (CB2) in RCC progression.

CB2 expression is functionally related to cellular proliferation, migration, and cell cycle of RCC cells.

Our data suggest that CB2 might be a potential therapeutic target for RCC.”

https://www.ncbi.nlm.nih.gov/pubmed/28993942
https://link.springer.com/article/10.1007%2Fs00432-017-2527-y

The role of cannabinoid receptors in renal diseases.

Posted on by
Reply

Image result for Curr Med Chem journal

“Chronic kidney disease (CKD) remains a major challenge for Public Health systems and corresponds to the replacement of renal functional tissue by extra-cellular matrix proteins such as collagens and fibronectin. There is no efficient treatment to date for CKD except nephroprotective strategies.

The cannabinoid system and more specifically the cannabinoid receptors 1 (CB1) and 2 (CB2) may represent a new therapeutic target in CKD.

Our review will first focus on the current state of knowledge regarding the cannabinoid system in normal renal physiology and in various experimental nephropathies, especially diabetes.  We will review the data obtained in models of diabetes and obesity as well as in nonmetabolic models of renal fibrosis and emphasizes the promising role of CB1 blockers and CB2 agonists in the development of renal disease and fibrosis. Next, we will review the current state of knowledge regarding the cellular pathways involved in renal fibrogenesis and renal injury.

Overall, this review will highlight the therapeutic potential of targeting the cannabinoid receptors in CKD and diabetes.”

https://www.ncbi.nlm.nih.gov/pubmed/28901271

Increased Renal 2-Arachidonoylglycerol Level Is Associated with Improved Renal Function in a Mouse Model of Acute Kidney Injury.

Posted on by
Reply

Mary Ann Liebert, Inc. publishers

“Acute kidney injury (AKI) is associated with a significantly increased risk of morbidity and mortality. Ischemia-reperfusion injury (IRI) is a major cause of AKI. In this study, we investigated the role of the endocannabinoid (EC) system in renal IRI using a well-established mouse model.

Results: Renal IRI was associated with significantly increased serum BUN and creatinine, increased tubular damage score, increased expression of renal markers of inflammation and oxidative stress and elevated renal 2-AG content. Pretreatment with JZL184 was associated with a significant increase in renal 2-AG content and there was also improved serum BUN, creatinine and tubular damage score. However, renal expression of inflammation and oxidative stress markers remained unchanged.

Conclusions: This is the first report documenting that renal IRI is associated with an increase in kidney 2-AG content. Further enhancement of 2-AG levels using JZL184 improved indices of renal function and histology, but did not lower renal expression of markers of inflammation and oxidative stress. Further studies are needed to determine the mechanisms responsible for the effects observed and the potential value of 2-AG as a therapeutic target in renal IRI.”

 https://www.ncbi.nlm.nih.gov/pubmed/28861493
http://online.liebertpub.com/doi/10.1089/can.2016.0013

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

Posted on by
Reply

Figure

“Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB1R) induces nephropathy, whereas CB1R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB1R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β-oxidation. Collectively, these findings indicate that renal proximal tubule cell CB1R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway.”

https://www.ncbi.nlm.nih.gov/pubmed/28860163

http://jasn.asnjournals.org/content/early/2017/08/30/ASN.2016101085

Targeting cannabinoid signaling for peritoneal dialysis-induced oxidative stress and fibrosis.

Posted on by
Reply

“Long-term exposure to bioincompatible peritoneal dialysis (PD) solutions frequently results in peritoneal fibrosis and ultrafiltration failure, which limits the life-long use of and leads to the cessation of PD therapy. Therefore, it is important to elucidate the pathogenesis of peritoneal fibrosis in order to design therapeutic strategies to prevent its occurrence. Peritoneal fibrosis is associated with a chronic inflammatory status as well as an elevated oxidative stress (OS) status. Beyond uremia per se, OS also results from chronic exposure to high glucose load, glucose degradation products, advanced glycation end products, and hypertonic stress. Therapy targeting the cannabinoid (CB) signaling pathway has been reported in several chronic inflammatory diseases with elevated OS. We recently reported that the intra-peritoneal administration of CB receptor ligands, including CB1 receptor antagonists and CB2receptor agonists, ameliorated dialysis-related peritoneal fibrosis. As targeting the CB signaling pathway has been reported to be beneficial in attenuating the processes of several chronic inflammatory diseases, we reviewed the interaction among the cannabinoid system, inflammation, and OS, through which clinicians ultimately aim to prolong the peritoneal survival of PD patients.”

https://www.ncbi.nlm.nih.gov/pubmed/28540200

http://www.wjgnet.com/2220-6124/full/v6/i3/111.htm