Nathan W. Levin

Immunomodulating effects of vitamin D analogs in hemodialysis patients.

Apart from its well‐known functions in calcium homeostasis and parathyroid hormone regulation, 1,25‐(OH)2D3 and its synthetic analogs are being increasingly recognized for their potent antiproliferative, pro‐differentiative and immunomodulating activities. The effects of these drugs are exerted either via vitamin D receptor‐dependent genomic, or cell‐surface receptor‐mediated, non‐genomic pathways. Several vitamin D analogs with fewer hypercalcemic side effects have been developed for use in secondary hyperparathyroidism. These analogs may potentially improve treatment of autoimmune disorders and graft rejection, and in dialysis patients may open a new opportunity for amelioration of the chronic inflammatory status. It has recently been shown that hemodialysis (HD) patients treated with paricalcitol have lower total and cardiovascular mortality and morbidity rates and experience improved hospitalization outcomes compared with HD patients treated with calcitriol, suggesting a potential beneficial effect in chronic inflammation and the development of cardiovascular disease. Specific studies on the immunomodulating effects of vitamin D are needed in the HD population.

Differences in cardiovascular mortality rates among hemodialysis patients in the United States and Japan: The importance of background cardiovascular mortality

Mortality rates among hemodialysis patients differ greatly among the United States, Europe, and Japan and it has been hypothesized that this is mainly due to differences in practice patterns. Results from the international DOPPS study, however, indicate that differences in practice patterns among the United States, Japan, and Europe are small and not alone explanatory for the differences in mortality rates. Ethnic variability in predisposition to atherosclerotic cardiovascular disease in the general population may lead to significant differences in background cardiovascular mortality in the United States, Japan, and Europe. It is our hypothesis that cardiovascular mortality in dialysis patients is to a great extent dependent on cardiovascular background mortality of the general population. We are currently studying the relationship between all‐cause and cardiovascular death rates in countries worldwide using the WHO database. Preliminary data from 35 countries show that all‐cause and cardiovascular death rates differ significantly among regions, with Eastern European countries reporting four‐ to sevenfold higher death rates than Asian countries. A strong linear relationship between cardiovascular and all‐cause death rates is observed among these countries. The next step of our study will be to compare country‐specific cardiovascular death rates of dialysis populations with those of the respective general populations. Ethnic differences in cardiovascular morbidity and mortality may be explained by genetic variability based upon polymorphism of genes involved in the pathogenesis of atherosclerosis and myocardial infarction.

Salivary Urea Nitrogen as a Biomarker for Renal Dysfunction

Kidney disease is highly prevalent all over the world in acute and chronic forms. Patients with kidney dysfunction have a higher morbidity and mortality especially due to cardiovascular events. Biomarkers nowadays available for the assessment of renal function such as serum creatinine, cystatin C, and blood urea nitrogen are mostly laboratory dependent. Many studies have been conducted following the aim to determine biomarkers of kidney disease allowing early diagnosis, faster V. Calice-Silva (*) • R. Pecoits-Filho School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil e-mail: vivicalice@gmail.com; vivicalice@hotmail.com; r.pecoits@pucpr.br J.G. Raimann • P. Kotanko • N. Levin Renal Research Institute, New York, NY, USA e-mail: jochen.raimann@rriny.com; peter.kotanko@rriny.com; nwlevin3@gmail.com W. Wu Integrated Biomedical Technology, Elkhart, IN, USA e-mail: ibtbiomed@earthlink.net # Springer Science+Business Media Dordrecht 2015 V.B. Patel, V.R. Preedy (eds.), Biomarkers in Kidney Disease, DOI 10.1007/978-94-007-7743-9_32-1 1 treatment initiation, and consequent better outcomes. However, in many places worldwide there are a large number of patients affected by acute and chronic kidney disease without receiving adequate diagnosis or treatment. The presence of urea in the saliva was firstly described in 1841 and has since then been repeatedly studied as an indicator of renal function. While it can be measured by laboratory methods, a real advantage is found in it as a bedside methodology (e.g., as a dipstick), which allows early and cost-effective diagnosis in areas with limited resources. The aim is to review current evidence of the saliva as a general biomarker and more specifically salivary urea nitrogen as a noninvasive and useful biomarker of decreased kidney function.