No abstract

Cigarette smoking is the major cause of preventable morbidity and mortality in the United States. It is a major risk factor for atherosclerotic vascular disease and recently was identified as an important risk factor in the progression of chronic kidney disease. Several compounds in cigarette smoke, including nicotine and reactive aldehydes (eg, acrolein), have been implicated as mediators of endothelial dysfunction and atherosclerosis in smokers. In addition, studies have demonstrated that nicotine induces endothelial dysfunction in humans and accelerates atherosclerosis in animals. Large clinical trials have suggested that cigarette smoking is a risk factor for progression of chronic kidney disease in diabetics and nondiabetics, and in polycystic kidney disease, lupus nephritis, and IgA nephropathy. Recent studies suggest that nicotine has powerful mitogenic effects and induces extracellular matrix production in human mesangial cells via reactive oxygen species generation. These effects of nicotine may play a major role in the pathogenic mechanisms that mediate the deleterious effects of smoking in renal disease.

Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Individualization of treatment with P-binders and combinations of anti-parathyroid agents may improve biochemical control with lower incidence of undesirable effects. Isolated biochemical parameters do not accurately reflect calcium or P load or bone activity and do not stratify high cardiovascular risk patients with CKD. Initial guidance is provided on reasonable therapeutic strategies which consider the presence of CVC. This part reflects that although there is not an absolute evidence, many studies point to the need to improve P imbalance while trying to, at least, avoid progression of CVC by restriction of Ca-based P-binders if economically feasible. The availability of new drugs (i.e. inhibitors of intestinal transporters), and studies including early CKD should ultimately lead to clearer and more cost/effective clinical targets for CKD-MBD.

Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Here, initial guidance to control hyperparathyroidism is provided, taking into account the presence/absence of CVC. We include also measures for patients at risk of adynamic bone disease or suffering from calciphylaxis. Many epidemiological studies (relating to vitamin D) and thorough analyses of recent randomized clinical trials (of cinacalcet) point towards benefits of attempting to improve biochemical parameters while trying to, at least, avoid progression of CVC by more rational use of intestinal P-binders and low-dose vitamin D derivatives and/or calcimimetics. This approach does not seem to be far away from significantly improving hard-outcomes, at least in the dialysis population. The availability of new drugs and the performance of randomized clinical trials should ultimately lead to define earlier, clearer, and more cost-effective patient stratification and biochemical targets with consequent significant clinical improvements.