Vascular calcification in chronic kidney disease associated with pathogenic variants in ABCC6.

Vascular calcification is prevalent in chronic kidney disease (CKD). Genetic causes of CKD account for 10-20% of adult-onset disease. Vascular calcification is thought to be one of the most important risk factors for increased cardiovascular morbidity and mortality in CKD patients and is detectable in 80% of patients with end stage kidney disease (ESKD). Despite the high prevalence of vascular calcification in CKD, no single gene cause has been described. We hypothesized that variants in vascular calcification genes may contribute to disease pathogenesis in CKD, particularly in families who exhibit a predominant vascular calcification phenotype. We developed a list of eight genes that are hypothesized to play a role in vascular calcification due to their involvement in the ectopic calcification pathway: ABCC6, ALPL, ANK1, ENPP1, NT5E, SLC29A1, SLC20A2, and S100A12. With this, we assessed exome data from 77 CKD patients, who remained unsolved following evaluation for all known monogenic causes of CKD. We also analyzed an independent cohort (Ontario Neurodegenerative Disease Research Initiative (ONDRI), n = 520) who were screened for variants in ABCC6 and compared this to a control cohort of healthy adults (n = 52). We identified two CKD families with heterozygous pathogenic variants (R1141X and A667fs) in ABCC6. We identified 10 participants from the ONDRI cohort with heterozygous pathogenic or likely pathogenic variant in ABCC6. Replication in a healthy control cohort did not reveal any variants. Our study provides preliminary data supporting the hypothesis that ABCC6 may play a role in vascular calcification in CKD. By screening CKD patients for genetic causes early in the diagnostic pathway, patients with genetic causes associated with vascular calcification can potentially be preventatively treated with new therapeutics with aims to decrease mortality.

"Drink at least 8 glasses of water a day to be healthy???".

The saying "drink at least 8 glasses of water per day to be healthy" has had little supporting evidence. The purpose of this article was to briefly introduce the role of hydration in health in order to explore in more detail recent observational studies of hyperhydration in chronic kidney disease (CKD) in man. The Modification of Diet in Renal Disease study initially noted a negative association between increasing urine output and progression of CKD that was absent when corrected for baseline variables. Recently, data from 2 different cross-sectional populations found those with the highest fluid intake had a significantly lower risk of CKD. In a longitudinal, community-based cohort study adjusted for baseline variables, decline in kidney function was significantly slower in those with higher versus lower baseline urine volume. These new and contradictory results underline the need for a randomized controlled study to test the hypothesis that increased fluid intake will slow renal decline.