Cannabinoids and the kidney: effects in health and disease

Abstract

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.

Keywords: acute kidney injury; cannabis; chronic kidney disease; endocannabinoid system; kidney.

Fig. 1.

Prevalence of cannabis use worldwide in 2014. Modified from United Nations Office on Drugs and Crime, United Nations Office on Drugs and Crime. http://www.unodc.org/wdr2016/field/1.2.2._Prevalence_cannabis.pdf, accessed on March 27, 2017.

Fig. 2.

Percentage marijuana use during the past 12 mo among people aged ≥12 yr, overall and by age group. Modified from National Survey on Drug Use and Health Data. https://www.cdc.gov/mmwr/volumes/65/ss/ss6511a1.htm, accessed on March 27, 2017.

Fig. 3.

Cannabinoid receptor signaling in renal glomerular and tubular epithelial cells. Cannabinoid 1 (CB₁) receptor activation activates distinct pathways in the podocytes/mesangial cells of the glomerulus (A), proximal tubule (B), and thick ascending limb of Henle (C). ROS, reactive oxygen species; NOX, NADPH oxidase; CARM1, coactivator-associated arginine methyltransferase 1; AMPK, 5′ AMP-activated protein kinase; ERK, extracellular signal-regulated kinase; PPARγ, peroxisome proliferator-activated receptor gamma; IL-1β, interleukin-1β; SOCS3, suppressor of cytokine signaling 3; ICAM-1, intercellular adhesion molecule 1; TNF-α, tumor necrosis factor-α; NO, nitric oxide; NOS, nitric oxide synthase; iNOS, inducible nitric oxide synthase; TGF-β, transforming growth factor-β; CCR2, C-C motif chemokine receptor 2; PARP, poly ADP ribose polymerase; BK, bradykinin receptor; AT-1, angiotensin type 1 receptor; PKC, protein kinase C; PKA, protein kinase A; PA, palmitic acid; PLA₂, phospholipase A₂; BV, blood vessels; TRPV1, transient receptor potential vanilloid 1; DAG, diacylglycerol; PIP2, phosphatidylinositol 4,5-bisphosphate; IP₃, inositol 1,4,5-trisphosphate.