Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r 2 =0.31, P,0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 mM [54.8-133.0 mM] for dialysis-dependent patients versus 3.3 mM [3.1-6.0 mM] for healthy controls; P,0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min-max] 71.2 mM [29.2-189.7 mM] pretransplant versus 11.4 mM [8.9-20.2 mM] posttransplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 mM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P,0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography. Patients with CKD have a high prevalence of cardiovascular comorbidities, which primarily contributes to the exceedingly high mortality in this group. 1,2 For example, the 5-year survival for ESRD patients receiving dialysis is approximately 35%, with .50% of the mortality in this group resulting directly from cardiovascular causes. 1 It is well established that CKD patients exhibit a disproportionate burden of atherosclerosis as compared with individuals having normal kidney function. [2][3][4][5] Furthermore, a higher prevalence of traditional risk factors for the development of atherosclerosis, such as hypertension, diabetes and hyperlipidemia, only partially accounts for the accelerated atherosclerosis in CKD patients, leading to the hypothesis that unique risk factors must be present in this population. 6,7

Despite a growing organ shortage in the United States, many deceased donor kidneys removed for transplantation are discarded. Kidney biopsy findings often play a role in these discards, although it is not clear whether biopsies reliably inform acceptance decisions. Therefore, we carried out a systematic review of the medical literature on the utility of both procurement and implantation biopsies for predicting posttransplant outcomes. Between January 1, 1994 and July 1, 2014, 47 studies were published in the English language literature that examined the association between pretransplant donor biopsy findings from 50 or more donors (with more than half being from deceased donors) and either posttransplant graft failure, delayed graft function, or graft function. In general, study quality was poor. All were retrospective or did not indicate if they were prospective. Results were heterogeneous, with authors as often as not concluding that biopsy results did not predict posttransplant outcomes. The percent glomerular sclerosis was most often examined, and failed to predict graft failure in 7 of 14 studies. Of 15 semiquantitative scoring systems proposed, none consistently predicted posttransplant outcomes across studies. Routine use of biopsies to help determine whether or not to transplant a kidney should be reexamined.

Background and objectives Patients receiving dialysis undergo parathyroidectomy to improve laboratory parameters in resistant hyperparathyroidism with the assumption that clinical outcomes will also improve. However, no randomized clinical trial data demonstrate the benefits of parathyroidectomy. This study aimed to evaluate clinical outcomes up to 1 year after parathyroidectomy in a nationwide sample of patients receiving hemodialysis.Design, setting, participants, & measurements Using data from the US Renal Data System, this study identified prevalent hemodialysis patients aged $18 years with Medicare as primary payers who underwent parathyroidectomy from 2007 to 2009. Baseline characteristics and comorbid conditions were assessed in the year preceding parathyroidectomy; clinical events were identified in the year preceding and the year after parathyroidectomy. After parathyroidectomy, patients were censored at death, loss of Medicare coverage, kidney transplant, change in dialysis modality, or 365 days. This study estimated cause-specific event rates for both periods and rate ratios comparing event rates in the postparathyroidectomy versus preparathyroidectomy periods.Results Of 4435 patients who underwent parathyroidectomy, 2.0% died during the parathyroidectomy hospitalization and the 30 days after discharge. During the 30 days after discharge, 23.8% of patients were rehospitalized; 29.3% of these patients required intensive care. In the year after parathyroidectomy, hospitalizations were higher by 39%, hospital days by 58%, intensive care unit admissions by 69%, and emergency room/ observation visits requiring hypocalcemia treatment by 20-fold compared with the preceding year. Causespecific hospitalizations were higher for acute myocardial infarction (rate ratio, 1.98; 95% confidence interval, 1.60 to 2.46) and dysrhythmia (rate ratio 1.4; 95% confidence interval1.16 to 1.78); fracture rates did not differ (rate ratio 0.82; 95% confidence interval 0.6 to 1.1).Conclusions Parathyroidectomy is associated with significant morbidity in the 30 days after hospital discharge and in the year after the procedure. Awareness of clinical events will assist in developing evidence-based risk/benefit determinations for the indication for parathyroidectomy.

Medicare is the federal health insurance program for individuals in the US who are aged ≥65 years, select individuals with disabilities aged <65 years, and individuals with end-stage renal disease. The Centers for Medicare and Medicaid Services grants researchers access to Medicare administrative claims databases for epidemiologic and health outcomes research. The data cover beneficiaries’ encounters with the health care system and receipt of therapeutic interventions, including medications, procedures, and services. Medicare data have been used to describe patterns of morbidity and mortality, describe burden of disease, compare effectiveness of pharmacologic therapies, examine cost of care, evaluate the effects of provider practices on the delivery of care and patient outcomes, and explore the health impacts of important Medicare policy changes. Considering that the vast majority of US citizens ≥65 years of age have Medicare insurance, analyses of Medicare data are now essential for understanding the provision of health care among older individuals in the US and are critical for providing real-world evidence to guide decision makers. This review is designed to provide researchers with a summary of Medicare data, including the types of data that are captured, and how they may be used in epidemiologic and health outcomes research. We highlight strengths, limitations, and key considerations when designing a study using Medicare data. Additionally, we illustrate the potential impact that Centers for Medicare and Medicaid Services policy changes may have on data collection, coding, and ultimately on findings derived from the data.

Background and objectives: Fibroblast growth factor-23 (FGF23) levels are elevated in ESRD and have been associated with adverse outcomes. The effects of various treatments for secondary hyperparathyroidism on FGF23 levels in ESRD have not been examined in a clinical trial.Design, setting, participants, & measurements: We assessed intact FGF23 levels in 91 subjects over the course of the ACHIEVE trial, which was designed to compare escalating doses of Cinacalcet plus fixed low-dose calcitriol analogs (Cinaclcet-D) with titration of calcitriol analogs alone (Flex-D) to suppress parathyroid hormone. Between-group and withingroup changes in log-transformed FGF23 levels were analyzed. Factors associated with change in FGF23 were assessed using a multiple regression model.Results: Intact FGF23 levels were markedly elevated in subjects at baseline. A statistically significant difference in percent change in log FGF23 levels was observed between treatment groups (P < 0.002). The Cinacalcet-D group had a significant decrease in percent change in log FGF23 levels (corrected P ‫؍‬ 0.021), whereas FGF23 levels trended toward an increase in the Flex-D group. Change in FGF23 level was significantly associated with changes in levels of phosphate (P < 0.0001) and calcium (P ‫؍‬ 0.0002) but not parathyroid hormone.Conclusions: Treatment with Cinacalcet plus low-dose calcitriol analogs results in lower FGF23 levels compared with a treatment regimen using calcitriol analogs alone in ESRD. The mechanisms underlying the differential effects of these treatment regimens on FGF23 levels and the clinical impact of these changes on FGF23 remain to be defined.

Background: Hyperkalemia is common in patients receiving maintenance hemodialysis. However, few studies have examined the association between serum potassium level and mortality. Methods: This study used annual cohorts of hemodialysis patients during 2007-2010. To determine hyperkalemia prevalence, monthly hyperkalemia was defined as serum potassium level ≥5.5 mEq/l; prevalence was calculated as a ratio of hyperkalemia episodes to follow-up time, reported separately by long and short interdialytic interval. To determine the impact of hyperkalemia on mortality, patients in the 2010 cohort were followed from first potassium measurement until death or a censoring event; hyperkalemia was defined, sequentially, by potassium levels 5.5-6.0 mEq/l at 0.1 mEq/l intervals. Time-dependent Cox proportional hazards modeling was used to estimate the association between hyperkalemia and mortality. Results: The 4 annual cohorts ranged from 28,774 to 36,888 patients. Mean age was approximately 63 years, about 56% were men, 51% were white and 44% had end-stage renal disease caused by diabetes. Hyperkalemia prevalence was consistently estimated at 16.3-16.8 events per 100 patient-months. Prevalence on the day after the long interdialytic interval was 2.0-2.4 times as high as on the day after the short interval. Hyperkalemia, when defined as serum potassium ≥5.7 mEq/l, was associated with all-cause mortality (adjusted hazards ratio (AHR) 1.13, 95% CI 1.01-1.28, p = 0.037, vs. <5.7 mEq/l) after adjustment. AHRs increased progressively as the hyperkalemia threshold increased, reaching 1.37 (95% CI 1.16-1.62, p < 0.0001) for ≥6.0 mEq/l. Conclusions: The long interdialytic interval was associated with increased likelihood of hyperkalemia. Hyperkalemia was associated with all-cause mortality beginning at serum potassium ≥5.7 mEq/l; mortality risk estimates increased ordinally through ≥6.0 mEq/l, suggesting a threshold at which serum potassium becomes substantially more dangerous.

Although water is essential for life, its use for medicinal purposes is not universally accepted. We performed a comprehensive review of the literature to determine where the evolving state of knowledge lies regarding the benefits of water as a therapy for renal diseases. In the past two decades, water has emerged as a potential therapeutic agent in nephrolithiasis, chronic kidney disease (CKD), and polycystic kidney disease (PKD) in particular. In nephrolithiasis, the benefit of drinking water beyond that demanded by thirst is a cornerstone of therapy for both primary and secondary disease. In CKD, recent observational studies suggest a strong, direct association between preservation of renal function and fluid intake. In PKD, increased water intake slows renal cyst growth in animals via direct vasopressin suppression, and pharmacologic blockade of renal vasopressin-V2 receptors has recently been shown to be efficacious in retarding cyst growth in PKD patients. Although evidence is lacking to support increased water intake in the general population, available evidence indicates that individuals who are at risk for nephrolithiasis as well as those with CKD and PKD may benefit from 3 to 4 l of urine output each day, a level of excretion that is likely to be safe.

Atrial fibrillation is an important comorbidity with substantial therapeutic implications in dialysis patients but its prevalence varies in different studies. We used a database that includes patients in the United States on hemodialysis who were eligible for government assistance with prescription drugs. We then used ICD-9 codes from billing claims in this database to identify patients with chronic atrial fibrillation. Multivariable logistic regression was used to determine adjusted prevalence odds ratios for associated factors. Of 63,884 individuals, the prevalence of chronic atrial fibrillation was 7%. The factors of age over 60 years, male, Caucasian, body mass index over 25 kg/m2, coronary artery disease, and heart failure were all significantly associated with chronic atrial fibrillation. Prevalence rates, particularly in younger patients, were far higher than those reported in an age group–matched nondialysis population. Thus, given its clinical impact, future efforts are needed to examine risk factors for adverse outcomes in chronic atrial fibrillation, and to identify appropriate management strategies for this disorder, as well as opportunities for quality improvement in this vulnerable population.