Prevalence of Chronic Atrial Fibrillation in Dialysis Patients

Background: Atrial fibrillation (AF) is reported to be common in patients on maintenance dialysis, but estimates of prevalence vary substantially. To date, no Medicare claims-based approach has been employed to rigorously assess prevalence of chronic AF. Methods: A novel database was created to identify patients undergoing maintenance dialysis who were dually-eligible for Medicare and Medicaid for at least 3 months in 2004-05. A Medicare claims-based algorithm was used to generate a plausible range of chronic AF prevalences using four approaches. Poisson analysis was employed to determine the demographic, functional status, comorbidity, and other factors, as assessed by the Medical Evidence Form, associated with chronic AF. Results: Of 102,748 dually-eligible individuals for whom data was complete, 21,540 (21.0%) had at least one claim for non-perioperative AF. Raw percentages (irrespective of length of follow-up time) of individuals with chronic AF ranged from 9.8% (using the most inclusive strategy) to 4.6% (the most exclusive); intermediate approaches led to closely-clustered estimates of 8.1% and 6.4%. The intermediate approaches demonstrated chronic AF prevalence to range from 64.2 (95% confidence intervals, 62.9 - 65.5) to 50.4 (49.2 - 51.7) per 1000 patient-years. Age 60 years, male sex, Caucasian race, body mass index 30 kg/m2, and inability to ambulate were associated with chronic AF; hypertension as a comorbidity was inversely associated with AF. Occurrence of AF was roughly 10 times greater in the youngest patients when compared to similar individuals not on dialysis. Conclusions: A linked Medicare-Medicaid database, together with a claims-based diagnostic algorithm, was used to generate prevalence estimates for chronic AF in dually-eligible dialysis patients. As expected, AF is far more common than in the non-dialysis population

Treatment of secondary hyperparathyroidism in kidney disease: what we know and do not know about use of calcimimetics and vitamin D analogs

There is a growing understanding of the pathophysiology of secondary hyperparathyroidism (SHPT) and a recent emergence of new agents for SHPT treatment in patients with advanced kidney disease. At the same time, appreciation that mineral metabolic derangements promote vascular calcification and contribute to excess mortality, along with recognition of potentially important “non-classical” actions of vitamin D, have prompted the nephrology community to reexamine the use of various SHPT treatments, such as activated vitamin D sterols, phosphate binders, and calcimimetics. In this review, the evidence for treatment of SHPT with calcimimetics and vitamin D analogs is evaluated, with particular consideration given to recent clinical trials that have reported encouraging findings with cinacalcet use. Additionally, several controversies in the pathogenesis and treatment of SHPT are explored. The proposition that calcitriol deficiency is a true pathological state is challenged, the relative importance of the vitamin D receptor and the calcium sensing receptor in parathyroid gland function is summarized, and the potential relevance of non-classical actions of vitamin D for patients with advanced renal disease is examined. Taken collectively, the balance of evidence now supports a treatment paradigm in which calcimimetics are the most appropriate primary treatment for SHPT in the majority of end stage renal disease patients, but which nevertheless acknowledges an important role for modest doses of activated vitamin D sterols

Impact of a modified data capture period on Liu comorbidity index scores in Medicare enrollees initiating chronic dialysis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: The Liu Comorbidity Index uses the United States Renal Data System (USRDS) to quantify comorbidity in chronic dialysis patients, capturing baseline comorbidities from days 91 through 270 after dialysis initiation. The 270 day survival requirement results in sample size reductions and potential survivor bias. An earlier and shorter time-frame for data capture could be beneficial, if sufficiently similar comorbidity information could be ascertained. Methods: USRDS data were used in a retrospective observational study of 70,114 Medicare- and Medicaid-eligible persons who initiated chronic dialysis during the years 2000–2005. The Liu index was modified by changing the baseline comorbidity capture period to days 1–90 after dialysis initiation for persons continuously enrolled in Medicare. The scores resulting from the original and the modified comorbidity indices were compared, and the impact on sample size was calculated. Results: The original Liu comorbidity index could be calculated for 75% of the sample, but the remaining 25% did not survive to 270 days. Among 52,937 individuals for whom both scores could be calculated, the mean scores for the original and the modified index were 7.4 ± 4.0 and 6.4 ± 3.6 points, respectively, on a 24-point scale. The most commonly calculated difference between scores was zero, occurring in 44% of patients. Greater comorbidity was found in those who died before 270 days. Conclusions: A modified version of the Liu comorbidity index captures the majority of comorbidity in persons who are Medicare-enrolled at the time of chronic dialysis initiation. This modification reduces sample size losses and facilitates inclusion of a sicker portion of the population in whom early mortality is common. Keywords: Comorbidity, Kidney failure, Chronic, Renal dialysis, Epidemiologic research desig

Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults

Risk of chronic kidney disease (CKD) is influenced by environmental and genetic factors and increases sharply in individuals 70 years and older. Polygenic scores (PGS) for kidney disease-related traits have shown promise but require validation in well-characterized cohorts. Here, we assessed the performance of recently developed PGSs for CKD-related traits in a longitudinal cohort of healthy older individuals enrolled in the Australian ASPREE randomized controlled trial of daily low-dose aspirin with CKD risk at baseline and longitudinally. Among 11,813 genotyped participants aged 70 years or more with baseline eGFR measures, we tested associations between PGSs and measured eGFR at baseline, clinical phenotype of CKD, and longitudinal rate of eGFR decline spanning up to six years of follow-up per participant. A PGS for eGFR was associated with baseline eGFR, with a significant decrease of 3.9 mL/min/1.73m2 (95% confidence interval -4.17 to -3.68) per standard deviation (SD) increase of the PGS. This PGS, as well as a PGS for CKD stage 3 were both associated with higher risk of baseline CKD stage 3 in cross-sectional analysis (Odds Ratio 1.75 per SD, 95% confidence interval 1.66-1.85, and Odds Ratio 1.51 per SD, 95% confidence interval 1.43-1.59, respectively). Longitudinally, two separate PGSs for eGFR slope were associated with significant kidney function decline during follow-up. Thus, our study demonstrates that kidney function has a considerable genetic component in older adults, and that new PGSs for kidney disease-related phenotypes may have potential utility for CKD risk prediction in advanced age

Ad-CD40L mobilizes CD4 T cells for the treatment of brainstem tumors

Diffuse Midline Glioma, formerly Diffuse Intrinsic Pontine Glioma (DIPG), is the deadliest pediatric brainstem tumor with median survival of less than one year. Here, we investigated 1) whether direct delivery of adenovirus expressing CD40L (Ad-CD40L) to brainstem tumors would induce immune-mediated tumor clearance and, 2) if so, whether therapy would be associated with a manageable toxicity due to immune-mediated inflammation in the brainstem. Methods Syngeneic gliomas in the brainstems of immune competent mice were treated with Ad-CD40L and survival, toxicity and immune profiles determined. A clinically translatable vector, whose replication would be tightly restricted to tumor cells, rAd-Δ24-CD40L, was tested in human patient-derived Diffuse Midline Gliomas and immunocompetent models. Results Expression of Ad-CD40L restricted to brainstem gliomas by pre-infection induced complete rejection, associated with immune cell infiltration, of which CD4+ T cells were critical for therapy. Direct intra-tumoral injection of Ad-CD40L into established brainstem tumors improved survival and induced some complete cures but with some acute toxicity. RNA-seq analysis showed that Ad-CD40L therapy induced neuroinflammatory immune responses associated with IL-6, IL-1β and TNF-α. Therefore, to generate a vector whose replication, and transgene expression, would be tightly restricted to tumor cells, we constructed rAd-Δ24-CD40L, the backbone of which has already entered clinical trials for Diffuse Midline Glioma. Direct intra-tumoral injection of rAd-Δ24-CD40L, with systemic blockade of IL-6 and IL-1β, generated significant numbers of cures with readily manageable toxicity. Conclusions Virus-mediated delivery of CD40L has the potential to be effective in treating Diffuse Midline Gliomas without obligatory neuroinflammation-associated toxicity

Association of 25-hydroxyvitamin D deficiency with NT-pro BNP levels in patients with acute myocardial infarction: a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Nutritional vitamin D deficiency is an emerging risk factor for acute myocardial infarction (AMI) and heart failure. The association of 25-hydroxyvitamin D levels with N-terminal pro B-type natriuretic peptide (NT-proBNP), a robust prognostic marker for post-AMI mortality and heart failure, is unknown and could illuminate a potential pathway for adverse outcomes among post-AMI patients with 25-hydroxyvitamin D deficiency.</p> <p>Methods</p> <p>In a cross-sectional analysis, we studied 238 AMI patients from 21 U.S. centers to test the association of nutritional vitamin D (25-hydroxyvitamin D [25(OH)D]) deficiency with NT-proBNP levels. Levels of 25(OH)D levels were categorized as normal (≥30 ng/mL), insufficient (>20 - <30 ng/mL), deficient (>10 - ≤20 ng/mL), or severely deficient (≤10 ng/mL).</p> <p>Results</p> <p>Low 25(OH)D levels were found in 95.7% of AMI patients. No significant trends for higher mean baseline log NT-proBNP levels in severely deficient (6.9 ± 1.3 pg/mL), deficient (6.9 ± 1.2 pg/mL), and insufficient (6.9 ± 0.9 pg/ml) groups were observed as compared with patients having normal (6.1 ± 1.7 pg/mL) levels, <it>P </it>= 0.17. Findings were similar in the subset of patients who had follow-up NT-proBNP levels drawn at one month. In multivariate regression modeling, after adjusting for multiple covariates, 25(OH)D was not associated with NT-proBNP.</p> <p>Conclusions</p> <p>Potential associations between nutritional vitamin D deficiency and prognosis in the setting of AMI are unlikely to be mediated through NT-proBNP pathways. Future studies should examine other mechanisms, such as inflammation and vascular calcification, by which 25(OH)D deficiency could mediate adverse outcomes post-AMI.</p

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...