Novel Findings May Improve Kidney Injury Outcomes

Interestingly, acetylcholine is also expressed in non-neuronal cells. However, its expression in the kidney was not known until this study. Additional key findings from this study include: The podocyte—a specialized epithelial cell playing a major role in the glomerular filtration barrier—is one of the sources of acetylcholine production. In glomerular disease there is an increase in acetylcholine and upregulation of choline acetyltransferase (ChAT)—the enzyme that catalyzes the biosynthesis of acetylcholine from acetyl CoA and choline. Acetylcholine/ChAT production can be induced in podocytes.

“Our studies support a role of podocyte-acetylcholine as an important endogenous anti-inflammatory and endothelial defensive factor that can be regulated and provides protection in GN,” said Truong. The anti-GBM GN is a severe kidney inflammation model in which the glomerular microvascular network is disrupted. Using this model, Truong and his team demonstrated that acetylcholine protects against kidney injury by reducing the expression of cytokines and chemokines. According to Truong, “In addition to controlling the filtration barrier, podocytes also orchestrate the local intraglomerular anti-inflammatory response and protection of the endothelium by releasing acetylcholine, which inhibits cytokine/chemokine production and maintains endothelial integrity. We also identified a novel role for podocyte acetylcholine as a protectant in GN, which may lead to innovative, non-immunosuppressive approaches for treating glomerular diseases.” Furthermore, Truong’s study suggests a protective effect of acetylcholine in human diseases, based on the microarray of human kidney samples that show higher ChAT expression in CKD patients as compared to normal subjects and for Alzheimer’s disease patients who receive cholinesterase inhibitors have lesser chances of CKD progression, myocardial infarction, and cardiovascular death. CKD is rarely diagnosed in the early stages. Once CKD develops, its progression is irreversible. Hence, therapies aimed at modulating the inflammation-related mechanisms in CKD can be the key to effective clinical interventions. “We’ve learned that the stimulation of acetylcholine in the kidney is feasible with current medications,” noted Truong. “Also targeting the cholinergic system—an endogenous protective pathway—could be associated with fewer side effects compared with nonspecific immunosuppressive drugs used to treat GN.”