Use of incremental peritoneal dialysis: impact on clinical outcomes and quality of life measure.

BACKGROUND: Incremental peritoneal dialysis (PD) can be defined as a PD prescription that is less than the standard, full dose prescription and is typically used for patients initiating PD with residual kidney function. It has been suggested that use of incremental peritoneal dialysis may help preserve residual kidney function and may offer better quality of life due to the lower treatment burden, however published evidence is limited. In this study we assessed the associations between incremental peritoneal dialysis use and both clinical outcomes and quality of life measures in a large cohort of incident peritoneal dialysis patients in the US. METHODS: We considered adult patients initiating peritoneal dialysis between 31 July, 2015 and 31 May, 2019 within a single dialysis organization. Patients with body weight < 40 kg, amputation, or an estimated glomerular filtration rate > 20 mL/min during the first 4 weeks on peritoneal dialysis were excluded. Patients were assigned to exposure groups based on peritoneal dialysis prescription during dialysis weeks 5-8. Incremental peritoneal dialysis was defined by treatment frequency, number of exchanges/day, and exchange volume (for continuous ambulatory peritoneal dialysis patients) or by treatment frequency and presence/absence of last fill (for automated peritoneal dialysis patients). Analyses were performed separately for continuous ambulatory peritoneal dialysis and automated peritoneal dialysis. For each analysis, incremental peritoneal dialysis patients were propensity score matched to eligible full-dose peritoneal dialysis patients. Patients were followed for a maximum of 12 months until censoring for loss to follow-up or study end. Outcomes were compared using Poisson models (mortality, hospitalization, peritoneal dialysis discontinuation), linear mixed models (estimated glomerular filtration rate), and paired t tests (KDQOL domain scores). RESULTS: Among continuous ambulatory peritoneal dialysis patients, compared to full-dose peritoneal dialysis, incremental peritoneal dialysis use was associated with better KDQOL scores on 3 domains: physical composite score (42.5 vs 37.7, p = 0.03), burden of kidney disease (60.2 vs 45.6, p = 0.003), effects of kidney disease (79.4 vs 72.3, p = 0.05). Hospitalization and mortality rates were numerically lower (0.77 vs 1.12 admits/pt-year, p = 0.09 and 5.0 vs 10.2 deaths/100 pt-years, p = 0.22), while no associations were found with estimated glomerular filtration rate or peritoneal dialysis discontinuation rate. Use of incremental peritoneal dialysis was not associated with any discernable effects on outcomes in automated peritoneal dialysis patients. CONCLUSION: These results suggest that there may be benefits of using incremental PD in the context of continuous ambulatory peritoneal dialysis, particularly with respect to quality of life as a prescription strategy when initiating peritoneal dialysis. While no significant benefits of incremental peritoneal dialysis were detected among patients initiating automated peritoneal dialysis, no detrimental effects of using incremental schedules were observed for either peritoneal dialysis type.

Comparative Effectiveness of mRNA-based BNT162b2 Vaccine versus Adenovirus Vector-Based Ad26.COV2.S Vaccine for the Prevention of COVID-19 among Dialysis Patients.

BACKGROUND: Studies have demonstrated that mRNA-based SARS-CoV-2 vaccines are highly effective among patients on dialysis. Because individual vaccines may be differentially available or acceptable to patients, it is important to understand comparative effectiveness relative to other vaccines, such those on the basis of adenovirus technologies. METHODS: In this retrospective study, we compared the clinical effectiveness of adenovirus vector-based Ad26.COV2.S (Janssen/Johnson & Johnson) to mRNA-based BNT162b2 (Pfizer/BioNTech) in a contemporary cohort of patients on dialysis. Patients who received a first BNT162b2 dose were matched 1:1 to Ad26.COV2.S recipients on the basis of date of first vaccine receipt, US state of residence, site of dialysis care (in-center versus home), history of COVID-19, and propensity score. The primary outcome was the comparative rate of COVID-19 diagnoses starting in the 7th week postvaccination. In a subset of consented patients who received Ad26.COV2.S, blood samples were collected ≥28 days after vaccination and anti-SARS-CoV-2 immunoglobulin G antibodies were measured. RESULTS: A total of 2572 matched pairs of patients qualified for analysis. Cumulative incidence rates of COVID-19 did not differ for BNT162b2 versus Ad26.COV2.S. No differences were observed in peri-COVID-19 hospitalizations and deaths among patients receiving BNT162b2 versus Ad26.COV2.S, who were diagnosed with COVID-19 during the at-risk period. Results were similar when excluding patients with a history of COVID-19, in subgroup analyses restricted to patients who completed the two-dose BNT162b2 regimen, and in patients receiving in-center hemodialysis. SARS-CoV-2 antibodies were detected in 59.4% of 244 patients who received Ad26.COV2.S. CONCLUSIONS: In a large real-world cohort of patients on dialysis, no difference was detected in clinical effectiveness of BNT162b2 and Ad26.COV2.S over the first 6 months postvaccination, despite an inconsistent antibody response to the latter.

Effect of ultrafiltration profiling on outcomes among maintenance hemodialysis patients: a pilot randomized crossover trial.

BACKGROUND: More rapid fluid removal during hemodialysis is associated with adverse cardiovascular outcomes and longer dialysis recovery times. The effect of ultrafiltration (UF) profiling, independent of concomitant sodium profiling, on markers of intradialytic hemodynamics and other outcomes has been inadequately studied. METHODS: Four-phase, blinded crossover trial. Participants (UF rates > 10 mL/h/kg) were assigned in random order to receive hemodialysis with UF profiling (constantly declining UF rate, intervention) vs. hemodialysis with conventional UF (control). Each 3-week 9-treatment period was followed by a 1-week 3-treatment washout period. Participants crossed into each study arm twice (2 phases/arm); 18 treatments per treatment type. The primary outcomes were intradialytic hypotension, pre- to post-dialysis troponin T change, and change from baseline in left ventricular global longitudinal strain. Other outcomes included intradialytic symptoms and blood volume measured-plasma refill (post-dialysis volume status measure), among others. Each participant served as their own control. RESULTS: On average, the 34 randomized patients (mean age 56 years, 24% female, mean dialysis vintage 6.3 years) had UF rates > 10 mL/h/kg in 56% of treatments during the screening period. All but 2 patients completed the 15-week study (prolonged hospitalization, kidney transplant). There was no significant difference in intradialytic hypotension, troponin T change, or left ventricular strain between hemodialysis with UF profiling and conventional UF. With UF profiling, participants had significantly lower odds of light-headedness and plasma refill compared to hemodialysis with conventional UF. CONCLUSIONS: Ultrafiltration (UF) profiling did not reduce the odds of treatment-related cardiac stress but did reduce the odds of light-headedness and post-dialysis hypervolemia. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03301740 (registered October 4, 2017).

Anemia and mortality in patients with nondialysis-dependent chronic kidney disease.

BACKGROUND: A combination of safety concerns and labeling changes impacted use of erythropoiesis-stimulating agents (ESAs) in renal anemia. Data regarding contemporary utilization in pre-dialysis chronic kidney disease (CKD) are lacking. METHODS: Electronic healthcare records and medical claims data of pre-dialysis CKD patients were aggregated from a large US managed care provider (2011-13). ESA use patterns, characteristics, and outcomes of ESA-treated/untreated patients were quantified. RESULTS: At baseline, 109/32,308 patients (0.3%) were ESA users. Treated patients were older, had more advanced CKD (58.8% vs 5.4% with stage 4/5 vs 3) and greater prevalence of comorbid diabetes, hypertension, heart failure, and peripheral vascular disease. An additional 266 patients initiated ESA: hemoglobin at initiation was 8-10 g/dL in 193 of these and >10 g/dL in the remainder; 61.7% had stage 4/5 CKD; prevalence of cardiovascular disease was high (50.8% heart failure; 25.2% prior myocardial infarction; 24.1% prior stroke). During follow-up, rates of death and cardiovascular events were higher in baseline ESA users and ESA naives versus non-users. CONCLUSIONS: ESA use in pre-dialysis CKD patients was exceedingly rare and directed disproportionately to older, sicker patients; these patients had high rates of death and cardiovascular events. These data provide context for contemporary use of ESA in pre-dialysis CKD.

Net Budgetary Impact of Ferric Citrate as a First-Line Phosphate Binder for the Treatment of Hyperphosphatemia: A Markov Microsimulation Model.

Ferric citrate (FC) has demonstrated efficacy as a phosphate binder and reduces the requirements for erythropoiesis-stimulating agents (ESAs) and intravenous (IV) iron in dialysis patients. We developed a net budgetary impact model to evaluate FC vs. other phosphate binders from the vantage of a large dialysis provider. We used a Markov microsimulation model to simulate mutually referential longitudinal effects between serum phosphate and phosphate binder dose; categories of these defined health states. Health states probabilistically determined treatment attendance and utilization of ESA and IV iron. We derived model inputs from a retrospective analysis of incident phosphate binder users from a large dialysis organization (January 2011-June 2013) and incorporated treatment effects of FC from a phase III trial. The model was run over a 1-year time horizon. We considered fixed costs of providing dialysis; costs of administering ESA and IV iron; and payment rates for dialysis, ESAs, and IV iron. In the base-case model, FC had a net budgetary impact (savings) of +US$213,223/year per 100 patients treated vs. standard of care. One-way sensitivity analyses showed a net budgetary impact of up to +US$316,296/year per 100 patients treated when higher hemoglobin levels observed with FC translated into a 30% additional ESA dose reduction, and up to +US$223,281/year per 100 patients treated when effects on missed treatment rates were varied. Two-way sensitivity analyses in which acquisition costs for ESA and IV iron were varied showed a net budgetary impact of +US$104,840 to +US$213,223/year per 100 patients treated. FC as a first-line phosphate binder would likely yield substantive savings vs. standard of care under current reimbursement.

The effect of altitude on erythropoiesis-stimulating agent dose, hemoglobin level, and mortality in hemodialysis patients.

Residence at higher altitude has been associated with improved anemia parameters and lower mortality rates among end-stage renal disease (ESRD) patients. However, these associations were observed prior to the 2011 shift in erythropoiesis-stimulating agent (ESA) dosing. To determine the impact of altitude on contemporary ESRD patients, a retrospective observational analysis was conducted in which patients were ascribed to one of four altitude categories as of 1 Jan 2012 and outcomes were assessed during 2012. Associations between altitude category and outcomes were estimated using generalized linear mixed models, adjusted for covariates that differed at baseline. Patients at higher altitude were less likely to receive ESA treatment, and dose was 723 U/treatment (95 % confidence interval [CI]: 544, 834) lower in the highest altitude category compared to the lowest category. The proportion of patients using IV iron decreased with increasing altitude category. Patients in the highest two categories had greater mean hemoglobin values (+0.15 and +0.23 g/dL) than the lowest. Mortality was lower for patients in the highest altitude category compared to those in the lowest (incidence rate ratio 0.73; 95 % CI: 0.63, 0.88), although their rate of missed dialysis treatments was slightly higher. This study confirms that, in the context of current anemia management practices, high altitude is associated with higher hemoglobin and lower mortality, despite lower utilization of ESA and IV iron.

Spectrum and Burden of Erythropoiesis-Stimulating Agent Hyporesponsiveness Among Contemporary Hemodialysis Patients.

BACKGROUND: Hemodialysis patients with erythropoiesis-stimulating agent (ESA) hyporesponsiveness have been a topic of active research. However, there have been no studies of ESA hyporesponsiveness among US patients following the dramatic change in anemia management that resulted from the 2011 changes in ESA product labeling and bundling of dialysis remuneration. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: We studied prevalent hemodialysis patients treated at a large dialysis organization in calendar years 2012 to 2013 (N=98,972). PREDICTOR: ESA hyporesponsiveness, defined as 2 consecutive hemoglobin measurements < 10g/dL (every other week) with contemporaneous ESA dose > 7,700U/treatment. Patients with ESA hyporesponsiveness were identified during the first quarter of 2012 and followed up through 2013 using intention-to-treat principles. OUTCOMES: Associations between the study exposure (ESA hyporesponsiveness) and mortality, missed hemodialysis treatments, ESA and iron use, and hemoglobin levels were determined using generalized estimating equations adjusting for imbalanced baseline covariates. RESULTS: At baseline, 12,361 (12.5%) patients were identified as having ESA hyporesponsiveness. The mean hemoglobin level among patients with ESA hyporesponsiveness was ∼1g/dL lower than in patients without ESA hyporesponsiveness at baseline, narrowing over follow-up to 0.4g/dL. Initially, mean ESA use was approximately 3-fold greater for patients with ESA hyporesponsiveness than for those without ESA hyporesponsiveness, decreasing to 2-fold greater at study end; iron use and missed hemodialysis treatment rates were also greater among patients with ESA hyporesponsiveness throughout. ESA hyporesponsiveness was associated with enhanced mortality risk versus non-ESA hyporesponsiveness: adjusted incidence rate ratios were estimated at 2.24 (95% CI, 1.93-2.60) in the second quarter, gradually decreasing to 1.48 (95% CI, 1.18-1.84) by study end. LIMITATIONS: It is possible that an alternative ESA hyporesponsiveness definition may be optimal. As such, the associations we observed may be conservative estimates of true relationships. CONCLUSIONS: When using a contemporary definition at one point in time, ESA hyporesponsiveness was potently and persistently associated with greater mortality, greater iron and ESA use, and lower hemoglobin levels compared to non-ESA hyporesponsiveness.

Comparative Effectiveness of Dialyzers: A Longitudinal, Propensity Score-Matched Study of Incident Hemodialysis Patients.

Differences in dialyzer design may have consequences for patient outcomes. We evaluated the comparative effectiveness of commonly used dialyzers with respect to measures of dialysis treatment, anemia management, inflammation, and dialyzer clotting. Patients receiving hemodialysis between January 1, 2009, and December 31, 2013, and using polyarylethersulfone-polyvinylpyrrolidone (PAS-PVP; Polyflux Revaclear) or polysulfone (PS; Optiflux 160 or Optiflux 180) dialyzers were followed for 1 year or until end of study or censoring for dialyzer switch, modality change, or loss to follow-up. For each comparison, eligible patients were propensity score-matched 1:1 on a range of baseline characteristics. Outcomes were assessed using generalized linear mixed models. Dialysis adequacy was similar in both dialyzer groups. Erythropoiesis-stimulating agent (ESA) doses were lower for patients using PAS-PVP versus patients using PS-160 (difference range: 75-589 units/treatment; statistically significant in months 1-5 and 7) and for patients using PAS-PVP versus patients using PS-180 (difference range: 27-591 unit/treatment; statistically significant in months 1-9). Intravenous iron doses trended lower for patients using PAS-PVP versus patients using PS, but hemoglobin concentrations were equivalent. In conclusion, use of PAS-PVP versus PS dialyzers was associated with equivalent dialysis adequacy, lower ESA doses, modestly lower Intravenous iron doses, and equivalent hemoglobin concentrations.

Characterization of chronic and acute ESA hyporesponse: a retrospective cohort study of hemodialysis patients.

BACKGROUND: Some patients with chronic kidney disease do not respond adequately to erythropoiesis-stimulating agent (ESA) treatment; these patients are referred to as ESA hyporesponders. There is no widely accepted contemporary definition for chronic ESA hyporesponse. The study objective was to propose and validate an operational definition for chronic ESA hyporesponse. METHODS: This was a retrospective cohort study using electronic health care records. Participants were anemic hemodialysis patients treated during February 2012 and were followed for 15 months. Patients' ESA response (responders) or lack of response (chronic and acute hyporesponders) based on longitudinal patterns of ESA dose and hemoglobin level was assessed. Persistence of hyporesponse, longitudinal iron measures, transfusion rates, and mortality rates were analyzed. Frequency of blood transfusions (monthly) and death rates (quarterly) were calculated. Log normalized serum ferritin concentration was analyzed. RESULTS: Of 97,677 eligible patients, 6632 had acute hyporesponsiveness (ESA responsiveness restituted in ≤ 4 months) and 3086 had chronic hyporesponsiveness (lack of ESA response for > 4 months). Over months 1-4 among chronic hyporesponders, mean serum ferritin (722-785 ng/mL) and transferrin saturation (TSAT; 26.76 %-27.08 %) were constant, while acute hyporesponsive patients experienced increased ferritin (654-760 ng/mL) and TSAT (25.71-30.88 %) levels. Compared to ESA responders (0.19-0.30 %), chronic hyporesponders were transfused 7-times (1.20-2.17 %) more frequently over follow-up. Quarterly mortality was greatest in chronic ESA hyporesponders (2.98-5.48 %), followed by acute ESA hyporesponders (2.17-3.30 %) and ESA responders (1.43-2.49 %). With consistence over the study, chronic hyporesponders died more frequently than patients in the other study cohorts. CONCLUSIONS: Findings indicate that 4 months of continuous ESA hyporesponsiveness can be used to differentiate acute from chronic hyporesponsiveness. This definition of chronic hyporesponsiveness is supported by outcome data showing higher mortality and transfusion rates in chronic hyporesponders compared to acute hyporesponders.

Hypomagnesemia and Mortality in Incident Hemodialysis Patients.

BACKGROUND: In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown. STUDY DESIGN: We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures. SETTING & PARTICIPANTS: 9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011. PREDICTOR: Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ≥2.4mg/dL). OUTCOME: All-cause mortality. RESULTS: 2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0mg/dL were 1.39 (95% CI, 1.23-1.58; P<0.001) and 1.20 (95% CI, 1.06-1.36; P=0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5g/dL) and magnesium level < 2.0mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; P=0.004), whereas patients with high serum albumin levels (≥3.5g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 [P≤0.001] for magnesium < 2.0 and ≥2.0mg/dL, respectively; reference: albumin < 3.5g/dL and magnesium ≥ 2.0mg/dL). LIMITATIONS: Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Lower serum magnesium levels are associated with higher mortality in HD patients, including those with hypoalbuminemia. Interventional studies are warranted to examine whether correction of hypomagnesemia ameliorates adverse outcomes in this population.

Association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use prior to major elective surgery and the risk of acute dialysis.

BACKGROUND: Some studies but not others suggest angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use prior to major surgery associates with a higher risk of postoperative acute kidney injury (AKI) and death. METHODS: We conducted a large population-based retrospective cohort study of patients aged 66 years or older who received major elective surgery in 118 hospitals in Ontario, Canada from 1995 to 2010 (n = 237,208). We grouped the cohort into ACEi/ARB users (n = 101,494) and non-users (n = 135,714) according to whether the patient filled at least one prescription for an ACEi or ARB (or not) in the 120 days prior to surgery. Our study outcomes were acute kidney injury treated with dialysis (AKI-D) within 14 days of surgery and all-cause mortality within 90 days of surgery. RESULTS: After adjusting for potential confounders, preoperative ACEi/ARB use versus non-use was associated with 17% lower risk of post-operative AKI-D (adjusted relative risk (RR): 0.83; 95% confidence interval (CI): 0.71 to 0.98) and 9% lower risk of all-cause mortality (adjusted RR: 0.91; 95% CI: 0.87 to 0.95). Propensity score matched analyses provided similar results. The association between ACEi/ARB and AKI-D was significantly modified by the presence of preoperative chronic kidney disease (CKD) (P value for interaction < 0.001) with the observed association evident only in patients with CKD (CKD - adjusted RR: 0.62; 95% CI: 0.50 to 0.78 versus No CKD: adjusted RR: 1.00; 95% CI: 0.81 to 1.24). CONCLUSIONS: In this cohort study, preoperative ACEi/ARB use versus non-use was associated with a lower risk of AKI-D, and the association was primarily evident in patients with CKD. Large, multi-centre randomized trials are needed to inform optimal ACEi/ARB use in the peri-operative setting.

Guiding principles and checklist for population-based quality metrics.

The Centers for Medicare and Medicaid Services oversees the ESRD Quality Incentive Program to ensure that the highest quality of health care is provided by outpatient dialysis facilities that treat patients with ESRD. To that end, Centers for Medicare and Medicaid Services uses clinical performance measures to evaluate quality of care under a pay-for-performance or value-based purchasing model. Now more than ever, the ESRD therapeutic area serves as the vanguard of health care delivery. By translating medical evidence into clinical performance measures, the ESRD Prospective Payment System became the first disease-specific sector using the pay-for-performance model. A major challenge for the creation and implementation of clinical performance measures is the adjustments that are necessary to transition from taking care of individual patients to managing the care of patient populations. The National Quality Forum and others have developed effective and appropriate population-based clinical performance measures quality metrics that can be aggregated at the physician, hospital, dialysis facility, nursing home, or surgery center level. Clinical performance measures considered for endorsement by the National Quality Forum are evaluated using five key criteria: evidence, performance gap, and priority (impact); reliability; validity; feasibility; and usability and use. We have developed a checklist of special considerations for clinical performance measure development according to these National Quality Forum criteria. Although the checklist is focused on ESRD, it could also have broad application to chronic disease states, where health care delivery organizations seek to enhance quality, safety, and efficiency of their services. Clinical performance measures are likely to become the norm for tracking performance for health care insurers. Thus, it is critical that the methodologies used to develop such metrics serve the payer and the provider and most importantly, reflect what represents the best care to improve patient outcomes.

Early trends from the Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS).

BACKGROUND: Launched in January 2011, the prospective payment system (PPS) for the US Medicare End-Stage Renal Disease Program bundled payment for services previously reimbursed independently. Small dialysis organizations may be particularly susceptible to the financial implications of the PPS. The ongoing Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS) was designed to describe trends in care and outcomes over the period of PPS implementation. This report details early results between October 2010 and June 2011. STUDY DESIGN: Prospective observational cohort study of patients from a sample of 51 small dialysis organizations. SETTING & PARTICIPANTS: 1,873 adult hemodialysis and peritoneal dialysis patients. OUTCOMES: Secular trends in processes of care, anemia, metabolic bone disease management, and red blood cell transfusions. MEASUREMENTS: Facility-level data are collected quarterly. Patient characteristics were collected at enrollment and scheduled intervals thereafter. Clinical outcomes are collected on an ongoing basis. RESULTS: Over time, no significant changes were observed in patient to staff ratios. There was a temporal trend toward greater use of peritoneal dialysis (from 2.4% to 3.6%; P = 0.09). Use of cinacalcet, phosphate binders, and oral vitamin D increased; intravenous (IV) vitamin D use decreased (P for trend for all <0.001). Parathyroid hormone levels increased (from 273 to 324 pg/dL; P < 0.001). Erythropoiesis-stimulating agent doses decreased (P < 0.001 for IV epoetin alfa and IV darbepoetin alfa), particularly high doses. Mean hemoglobin levels decreased (P < 0.001), the percentage of patients with hemoglobin levels <10 g/dL increased (from 12.7% to 16.8%), and transfusion rates increased (from 14.3 to 19.6/100 person-years; P = 0.1). Changes in anemia management were more pronounced for African American patients. LIMITATIONS: Limited data were available for the prebundle period. Secular trends may be subject to the ecologic fallacy and are not causal in nature. CONCLUSIONS: In the period after PPS implementation, IV vitamin D use decreased, use of oral therapies for metabolic bone disease increased, erythropoiesis-stimulating agent use and hemoglobin levels decreased, and transfusion rates increased numerically.

Impact of uremia on human adipose tissue phenotype.

BACKGROUND: Recognition of adipose-related signaling in surgery is increasing, although direct interrogation of human adipose has been sparse. Few scenarios rival uremia for health impact. We hypothesized that adipose from uremic patients holds a relatively higher adipose-derived hormone and proinflammatory adipokine signature; we simultaneously evaluated the impact of clinical parameters on adipose phenotype. MATERIALS AND METHODS: Adipose was harvested from surgical patients. Histology and protein analyses were completed for select mediators. RESULTS: In the overall cohort of 71 patients, the mean age was 63.4 y; 46.4% of patients had diabetes mellitus, 49.2% had hyperlipidemia, and 53.5% had coronary artery disease. Compared with nonuremic patients, uremic patients had one-tenth of the levels of leptin (P < 0.001), one-third of the levels of adiponectin (P < 0.001), and threefold higher levels of resistin (P < 0.001). Females had sixfold higher levels of leptin, 1.5-fold higher levels of adiponectin, and twofold higher levels of tumor necrosis factor alpha but equivalent resistin. There were differences in mediators when stratified by age. In both the obese and nonobese strata, we observed a concordant pattern of association (magnitude or significance) of uremia and leptin, adiponectin, and resistin. No differentials in other mediators emerged on body mass index stratification. Multiple regression analysis for leptin, adiponectin, and resistin (with age, gender, and uremia as independent variables) showed uremia as the highest independent predictor of all the three mediators. CONCLUSIONS: Advanced chronic kidney disease is associated with perturbations in adipose-derived hormones (leptin, adiponectin, and resistin). Adipose adiponectin and leptin (in contrast to reported plasma levels) were lower in uremic patients; there is an inverse correlation between adipose resistin and renal function. Compared with other clinical parameters including body mass index, uremia dominates overall in determining adipose phenotype, highlighting the complex biological interplay between uremia and adipose biology.

Preoperative statin use and postoperative acute kidney injury.

BACKGROUND: Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. METHODS: We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression. RESULTS: Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58-0.95) to 0.80 (0.71-0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery. CONCLUSIONS: Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.

Association of smoking with cardiovascular and infection-related morbidity and mortality in chronic hemodialysis.

BACKGROUND AND OBJECTIVES: Smoking is common in the hemodialysis population and is associated with increased all-cause mortality and development of cardiovascular disease. Cause-specific outcomes have not yet been examined in detail. This study investigated the association of baseline smoking status with all-cause, cardiovascular, and infection-related morbidity and mortality in patients undergoing long-term hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Post hoc analysis of the HEMO Study in patients with available comorbidity, clinical, and nutritional data. Cox proportional hazards regression models were fit to estimate the association of smoking status with mortality. Poisson and negative binomial regression models were fit to estimate the association of smoking status with hospitalization rate. RESULTS: Complete data were available for 1842 individuals (44% male, 63% black, 45% diabetic). Mean age was 58 ± 14 years. At baseline, 17% were current smokers and 32% were former smokers. After case-mix adjustment, compared with never smoking, current smoking was associated with greater infection-related mortality (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.32-3.10) and all-cause mortality (HR, 1.44; 95% CI, 1.16-1.79) and greater cardiovascular (incidence rate ratio [IRR], 1.49; 95% CI, 1.22-1.82), infection-related (IRR, 1.35; 95% CI, 1.11-1.64) and all-cause (IRR, 1.43; 95% CI, 1.24-1.65) hospitalization rates. The population attributable fraction (i.e., fraction of observed deaths that may have been avoided) was 5.3% for current smokers versus never-smokers and 2.1% for current versus former smokers. CONCLUSIONS: Active smoking is prevalent in the chronic hemodialysis population and is associated with greater all-cause, cardiovascular, and infection-related morbidity and mortality.

High rate of fistula placement in a cohort of dialysis patients in a single payer system.

Arteriovenous fistulas (AVFs) are considered superior to arteriovenous grafts and catheters. Nevertheless, AVF prevalence in the United States remains under the established target. The complication rates and financial cost of vascular access continue to rise and disproportionately contribute to the burgeoning health care costs. The relationship between financial incentives for a type of vascular access and rate of access placement is unclear. All chronic hemodialysis patients (n=99) receiving care at Philadelphia Veterans Affairs Medical Center as of August 1, 2008 were participants. Demographic characteristics, vascular access type, and nonrelative value unit compensation were assessed as predictors, and the vascular access prevalence rate, operative times, and frequency of access interventions were analyzed. A 73.7% AVF rate was achieved in this cohort of patients with 51.5% diabetes mellitus. The number of access procedures per patient per year remained constant over time. The Philadelphia Veterans Affairs Medical Center, a single payer system, achieved superior AVF prevalence and exceeded the national AVF target. Financial incentives for arteriovenous graft placement currently exist in the United States, as there is similar Medicare reimbursement for arteriovenous graft and basilic vein transposition, despite longer operative times for basilic vein transpositions. The high AVF prevalence at the Philadelphia Veterans Affairs Medical Center may be due to the VA nonrelative value unit-driven system that allows for interdisciplinary care, priority of AVFs, and frequent use of basilic vein transposition surgery, when appropriate. We have identified an important, hypothesis-generating example of a nonrelative value unit-based approach to vascular access yielding superior results with respect to patient care and cost.

A comparison of sodium phosphosoda purgative to polyethylene glycol bowel preparations prior to colonoscopy.

BACKGROUND AND OBJECTIVES: Successful colonoscopy is contingent upon adequate bowel preparation, which is often achieved using either an oral sodium phosphate preparation or a polyethylene glycol-based preparation. Comparison of the relative performance of these two classes of agents has been assessed only in the context of clinical trials (and with mixed findings). However, efficacy measured in clinical trials often is not reflective of effectiveness in clinical practice. We undertook this analysis to determine the relative clinical effectiveness of oral sodium phosphosoda versus polyethylene glycol in clinical practice. METHODS: Subjects (n=343) were selected from among patients receiving outpatient colonoscopy at our institution between January 2004 and February 2006. Demographic, biochemical, and comorbid disease data were abstracted from the electronic medical record. Colonoscopy preparation, indication, and preparation quality were abstracted from colonoscopy reports. RESULTS: As compared to subjects receiving polyethylene glycol, those receiving oral sodium phosphosoda had an adjusted odds ratio (OR) (95% confidence intervals [CIs]) for adequate/good/excellent bowel preparation quality of 2.23 (1.18--4.22) and an adjusted OR (95% CIs) for good/excellent bowel preparation of 2.24 (1.26--3.97). There was no interaction on the basis of colonoscopy indication. CONCLUSIONS: Oral sodium phosphate-based purgatives were associated with significantly better bowel preparation quality among outpatients at our center.

Association between oral sodium phosphate bowel preparations and kidney injury: a systematic review and meta-analysis.

BACKGROUND: Case reports and series have suggested an association between oral sodium phosphate bowel preparations and kidney injury. Results of analytic studies have been mixed. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Patients receiving sodium phosphate bowel preparations (or comparators) in anticipation of colonoscopy. SELECTION CRITERIA FOR STUDIES: Primary data reports of controlled studies of the effects of oral sodium phosphate versus comparator on kidney function. PREDICTOR: Receipt of oral sodium phosphate bowel purgative. OUTCOMES: Random-effects pooled odds ratio for kidney injury in oral sodium phosphate-treated patients. RESULTS: Seven studies met criteria for inclusion. Significant heterogeneity existed in the populations under study (colonoscopy indication, baseline kidney function, and demographics), methods used (control group and use of prophylactic hydration), definition of kidney injury used (timing and magnitude), and results observed. The pooled odds ratio for kidney injury in oral sodium phosphate-treated patients ranged from 1.08 (95% confidence interval, 0.71 to 1.62) to 1.22 (95% confidence interval, 0.77 to 1.92). No obvious study- or patient-level factors that explained interstudy heterogeneity were identified. LIMITATIONS: Few studies, each of limited quality. CONCLUSIONS: Based on existing data, it is not possible to discern whether there is an association between receipt of oral sodium phosphate and kidney injury. Future investigation should be aimed at clarifying this association and examining the roles of prophylactic hydration and baseline kidney function on any imposed risk. Future work would be greatly enhanced by a standardized definition of incident kidney injury.