Nicotine signaling and progression of chronic kidney disease in smokers

The deleterious health effects of cigarette smoking are far reaching, and it remains the most important modifiable risk factor for improving overall morbidity and mortality. In addition to being a risk factor for cancer, cardiovascular disease and lung disease, there is strong evidence, both from human and animal studies, demonstrating a role for cigarette smoking in the progression of chronic kidney disease (CKD). Clinical studies have shown a strong correlation between cigarette smoking and worsening CKD in patients with diabetes, hypertension, polycystic kidney disease, and post kidney transplant. Nicotine, in addition to its role in the addictive properties of cigarette smoking, has other biological effects via activation of non-neuronal nicotinic acetylcholine receptors (nAChRs). Several nAChR subunits are expressed in the normal kidney and blockade of the α7-nAChR subunit ameliorates the effects of nicotine in animal models of CKD. Nicotine increases the severity of renal injury in animal models including acute kidney injury, diabetes, acute nephritis and subtotal nephrectomy. The renal effects of nicotine are also linked to increased generation of reactive oxygen species and activation of pro-fibrotic pathways. In humans, nicotine induces transitory increases in blood pressure accompanied by reductions in glomerular filtration rate and effective renal plasma flow. In summary, clinical and experimental evidence indicate that nicotine is at least in part responsible for the deleterious effects of cigarette smoking in the progression of CKD. The mechanisms involved are the subject of active investigation and may result in novel strategies to ameliorate the effects of cigarette smoking in CKD.