Nicotinic receptors in chronic kidney disease

Tobacco smoking remains the most important modifiable risk factor for improving overall morbidity and mortality. In addition to being a risk factor for cancer, cardiovascular  and lung diseases, strong evidence from human and animal studies has demonstrated that cigarette smoking accelerates the progression of chronic kidney disease (CKD). Clinical studies have shown a strong association between cigarette smoking and worsening CKD in patients with diabetes mellitus, hypertension, polycystic kidney disease, and post kidney transplant. Nicotine, in addition to being responsible for the addictive properties of cigarette smoking, also has other important biological effects on a variety of organs and tissues. In humans, nicotine induces transitory increases in blood pressure accompanied by reductions in glomerular filtration rate and effective renal plasma flow. In animals, nicotine increases the severity of renal injury in subjects with diabetic nephropathy, CKD, and acute kidney injury (AKI). These effects of nicotine on the kidney are linked to increased generation of reactive oxygen species and activation of pro-fibrotic pathways. There are several nicotinic acetylcholine receptor (nAChR) subunits which are expressed in the normal kidney, and the specific blockade of  α7-subunit ameliorates the effects of nicotine in animal models with CKD. In summary, the clinical and experimental evidence indicates that nicotine, via the activation of specific nAChRs, is partly responsible for the deleterious effects of cigarette smoking in the progression of CKD.  Better understanding of these mechanisms may result in the development of novel strategies to ameliorate the effects of cigarette smoking in CKD.