Direct-Acting Oral Anticoagulants as Prophylaxis Against Thromboembolism in the Nephrotic Syndrome

We report 2 cases of apixaban use as prophylaxis against thromboembolism in the nephrotic syndrome (NS), and review the existing literature on direct-acting oral anticoagulant (DOAC) use in this scenario. Our cases appear to be the first reported use of apixaban as prophylaxis against thromboembolism in NS. We report our systematic review of the existing literature on direct-acting oral anticoagulant (DOAC) use in NS, and discuss theoretical issues relevant to their therapeutic use in this clinical scenario. We searched electronic databases such as OVID, EMBASE, PubMed, and CENTRAL, DARE. The search to identify studies and the application of inclusion and exclusion criteria was performed in duplicate independently. We identified 1 pilot randomized study, 3 case reports, and 3 conference proceedings abstracts relating to DOAC use in NS. These reports all pertain to the treatment of clinically evident thrombosis in NS with rivaroxaban, edoxaban, and dabigatran rather than prophylaxis against thrombosis. Although the existing literature on DOAC use in NS is limited, initial preliminary experience appears promising. Keywords: anticoagulation, DOAC, nephrotic, thrombosi

The influence of socioeconomic status on allograft and patient survival following kidney transplantation: Socioeconomic status and transplant outcome

Aim: Whether socioeconomic status confers worse outcomes after kidney transplantation is unknown. Its influence on allograft and patient survival following kidney transplantation in Ireland was examined. Methods: A retrospective, observational cohort study of adult deceased-donor first kidney transplant recipients from 1990 to 2009 was performed. Those with a valid Irish postal address were assigned a socioeconomic status score based on the Pobal Hasse-Pratschke deprivation index and compared in quartiles. Cox proportional hazards models and Kaplan–Meier survival analysis were used to investigate any significant association of socioeconomic status with patient and allograft outcomes. Results: A total of 1944 eligible kidney transplant recipients were identified. The median follow-up time was 8.2 years (interquartile range 4.4–13.3 years). Socioeconomic status was not associated with uncensored or death-censored allograft survival (hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.99–1.00, P = 0.33 and HR 1.0, 95% CI 0.99–1.00, P = 0.37, respectively). Patient survival was not associated with socioeconomic status quartile (HR 1.0, 95% CI 0.93–1.08, P = 0.88). There was no significant difference among quartiles for uncensored or death-censored allograft survival at 5 and 10 years. Conclusion: There was no socioeconomic disparity in allograft or patient outcomes following kidney transplantation, which may be partly attribut- able to the Irish healthcare model. This may give further impetus to calls in other jurisdictions for universal healthcare and medication coverage for kidney transplant recipients

Plot of odds ratios (with 95% confidence interval) of orthostatic hypotension (OH) at 30, 60, 90 and 110 seconds post active stand for each antihypertensive agent.

<p>Each point estimate represents the fully adjusted odds of OH for a particular antihypertensive agent compared to the odds of OH for the reference group. Individuals receiving beta-blocker therapy had an approximately three-fold increased odds of OH at each time point compared to untreated participants. The odds ratios for the other three agents were not statistically significant (error bounds cross the reference line). CCB, calcium channel blocker; RAAS, renin-angiotensin-aldosterone-system.</p

Fully adjusted estimate (95% confidence interval) of mean difference in diastolic blood pressure (y-axis) at each 10-second interval during the active stand (x-axis).

<p>As in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146156#pone.0146156.g002" target="_blank">Fig 2</a>, each antihypertensive agent was compared to untreated grade 1 hypertension. The confidence interval for the beta-blocker group did not overlap the point estimate for the reference group. The confidence intervals for the other antihypertensive agents consistently overlapped the point estimate for the reference group. CCB, calcium channel blocker; DBP, diastolic blood pressure; RAAS, renin-angiotensin-aldosterone-system.</p

Common variants in mendelian kidney disease genes and their association with renal function

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency <5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research