Franklin W. Maddux

Intradialytic hypotension: frequency, sources of variation and correlation with clinical outcome.

Intradialytic hypotension (IH) is a frequent complication of hemodialysis (HD) and is associated with increased patient mortality and cardiovascular events. We studied IH to determine its variability, correlates, and clinical impact in 13 outpatient HD facilities. Blood pressure was captured by machine download. IH was defined as >30 mmHg decrease in systolic blood pressure to <90 mmHg. Risk factors were assessed by logistic regression and hospitalization by Poisson regression. Time to death and first hospitalization were assessed using Kaplan–Meier analysis in patients completing >20 HD treatments. We studied IH in 44,801 treatments (Tx) in 1137 patients. IH was frequent (17.2% of treatments) and highly variable by patient (0–100% Tx) and dialysis facility (11.1–25.8% Tx). 25.1% of patients had no IH (0% Tx) and 16.2% had IH on >35% Tx. Increased IH frequency was associated with age, female gender, diabetes, Hispanic origin, longer end stage renal disease vintage, higher body mass index, higher ultrafiltration volume, the second and third weekly Tx, lower pre‐HD systolic blood pressure, higher difference between prescribed and achieved post‐HD weight, and higher dialysate temperature. Dialysis facility was an independent predictor of IH frequency. Patients with >35% IH treatments had poorer survival (P = 0.036), and more frequent and longer hospitalization (P = 0.04, P = 0.002, respectively) than patients without IH. In conclusion, IH frequency was highly variable, associated with individual facilities, patient and treatment characteristics, and correlated with mortality and hospitalization. Identifying practice patterns associated with IH coupled with routine reporting of IH will facilitate medical management and may result in the prevention of IH, decreased mortality, and decreased hospitalization.

Early Outcomes among Those Initiating Chronic Dialysis in the United States

BACKGROUND AND OBJECTIVES Approximately one million Americans initiated chronic dialysis over the past decade; the first-year mortality rate reported by the U.S. Renal Data System was 19.6% in 2007. This estimate has historically excluded the first 90 days of chronic dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS To characterize the mortality and hospitalization risks for patients starting chronic renal replacement therapy, we followed all patients initiating dialysis in 1733 facilities throughout the United States (n = 303,289). Mortality and hospitalizations within the first 90 days were compared with outcomes after this period, and the results were analyzed. Standard time-series analyses were used to depict the weekly risk estimates for each outcome. RESULTS Between 1997 and 2009, >300,000 patients initiated chronic dialysis and were followed for >35 million dialysis treatments; the highest risk for morbidity and mortality occurred in the first 2 weeks of treatment. The initial 2-week risk of death for a typical dialysis patient was 2.72-fold higher, and the risk of hospitalization was 1.95-fold higher when compared to a patient who survived the first year of chronic dialysis (week 53 after initiation). Similarly, over the first 90 days, the risk of mortality and hospitalization remained elevated. Thereafter, between days 91 and 365, these risks decreased considerably by more than half. Surviving these first weeks of dialysis was most associated with the type of vascular access. Initiating dialysis with a fistula was associated with a decreased early death risk by 61%, whereas peritoneal dialysis decreased the risk by 87%. CONCLUSIONS The first 2 weeks of chronic dialysis are associated with heightened mortality and hospitalization risks, which remain elevated over the ensuing 90 days.

Prevalence and Outcomes of Antimicrobial Treatment for Staphylococcus aureus Bacteremia in Outpatients with ESRD

Staphylococcus bacteremia is a common and life-threatening medical emergency, but it is treatable with appropriate antibiotic therapy. To identify opportunities that may reduce morbidity and mortality associated with S. aureus, we analyzed data from 293,094 chronic hemodialysis outpatients to characterize practices of antibiotic selection. In the study population, the overall rate of bacteremia was 15.4 per 100 outpatient-years; the incidence rate for methicillin-sensitive (MSSA) was 2.1 per 100 outpatient-years, and the incidence rate for methicillin-resistant (MRSA) S. aureus was 1.9 per 100 outpatient-years. One week after the collection of the index blood culture, 56.1% of outpatients with MSSA bacteremia were receiving vancomycin, and 16.7% of outpatients with MSSA were receiving cefazolin. Among MSSA-bacteremic patients who did not die or get hospitalized 1 week after blood culture collection, use of cefazolin was associated with a 38% lower risk for hospitalization or death compared with vancomycin (adjusted HR=0.62, 95% CI=0.46-0.84). In conclusion, vancomycin is commonly used to treat MSSA bacteremia in outpatients receiving chronic dialysis, but there may be more risk of treatment failure than observed among those individuals who receive a β-lactam antibiotic such as cefazolin.

Anaphylaxis and Hypotension after Administration of Peginesatide

This letter describes serious adverse events (three fatal cardiorespiratory arrests and two grade 4 anaphylaxis and hypotension events) related to the administration of peginesatide during surveillance in patients undergoing dialysis. As a result, the drug was removed from the market.

Accountable Care Organizations and ESRD: The Time Has Come

Accountable care organizations (ACOs) are a newly proposed vehicle for improving or maintaining high-quality patient care while controlling costs. They are meant to achieve the goals of the Medicare Shared Savings Program mandated by the Patient Protection and Affordable Care Act (PPACA) of 2010. ACOs are voluntary groups of hospitals, physicians, and health care teams that provide care for a defined group of Medicare beneficiaries and assume responsibility for providing high-quality care through defined quality measures at a cost below what would have been expected. If an ACO succeeds in achieving both the quality measures and reduced costs, the ACO will share in Medicares cost savings. Health care for patients with end-stage renal disease is complex due to multiple patient comorbid conditions, expensive, and often poorly coordinated. Due to the unique needs of patients with end-stage renal disease receiving dialysis, ACOs may be unable to provide the highly specialized quality care these patients require. We discuss the benefits and risks of a renal-focused ACO for dialysis patients, as well as the kidney communitys prior experience with an ACO-like demonstration project.

Dialysate Potassium, Serum Potassium, Mortality, and Arrhythmia Events in Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study (DOPPS)

BACKGROUND Sudden death is a leading cause of death in patients on maintenance hemodialysis therapy. During hemodialysis sessions, the gradient between serum and dialysate levels results in rapid electrolyte shifts, which may contribute to arrhythmias and sudden death. Controversies exist about the optimal electrolyte concentration in the dialysate; specifically, it is unclear whether patient outcomes differ among those treated with a dialysate potassium concentration of 3 mEq/L compared to 2 mEq/L. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 55,183 patients from 20 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). PREDICTOR Dialysate potassium concentration at study entry. OUTCOMES Cox regression was used to estimate the association between dialysate potassium concentration and both all-cause mortality and an arrhythmia composite outcome (arrhythmia-related hospitalization or sudden death), adjusting for potential confounders. RESULTS During a median follow-up of 16.5 months, 24% of patients died and 7% had an arrhythmia composite outcome. No meaningful difference in clinical outcomes was observed for patients treated with a dialysate potassium concentration of 3 versus 2 mEq/L (adjusted HRs were 0.96 [95% CI, 0.91-1.01] for mortality and 0.98 [95% CI, 0.88-1.08] for arrhythmia composite). Results were similar across predialysis serum potassium levels. As in prior studies, higher serum potassium level was associated with adverse outcomes. However, dialysate potassium concentration had only minimal impact on serum potassium level measured predialysis (+0.09 [95% CI, 0.05-0.14] mEq/L serum potassium per 1 mEq/L greater dialysate potassium concentration). LIMITATIONS Data were not available for delivered (vs prescribed) dialysate potassium concentration and postdialysis serum potassium level; possible unmeasured confounding. CONCLUSIONS In combination, these results suggest that approaches other than altering dialysate potassium concentration (eg, education on dietary potassium sources and prescription of potassium-binding medications) may merit further attention to reduce risks associated with high serum potassium levels.

A Nationally Representative Study of Calcific Uremic Arteriolopathy Risk Factors

Accurate identification of risk factors for calcific uremic arteriolopathy (CUA) is necessary to develop preventive strategies for this morbid disease. We investigated whether baseline factors recorded at hemodialysis initiation would identify patients at risk for future CUA in a matched case-control study using data from a large dialysis organization. Hemodialysis patients with newly diagnosed CUA (n=1030) between January 1, 2010, and December 31, 2014, were matched by age, sex, and race in a 1:2 ratio to hemodialysis patients without CUA (n=2060). Mean ages for patients and controls were 54 and 55 years, respectively; 67% of participants were women and 49% were white. Median duration between hemodialysis initiation and subsequent CUA development was 925 days (interquartile range, 273-2185 days). In multivariable conditional logistic regression analyses, diabetes mellitus; higher body mass index; higher levels of serum calcium, phosphorous, and parathyroid hormone; and nutritional vitamin D, cinacalcet, and warfarin treatments were associated with increased odds of subsequent CUA development. Compared with patients with diabetes receiving no insulin injections, those receiving insulin injections had a dose-response increase in the odds of CUA involving lower abdomen and/or upper thigh areas (odds ratio, 1.49; 95% confidence interval, 1.03 to 2.51 for one or two injections per day; odds ratio, 1.88; 95% confidence interval, 1.30 to 3.43 for 3 injections per day; odds ratio, 3.74; 95% confidence interval, 2.28 to 6.25 for more than three injections per day), suggesting a dose-effect relationship between recurrent skin trauma and CUA risk. The presence of risk factors months to years before CUA development observed in this study will direct the design of preventive strategies and inform CUA pathobiology.

Adherence Barriers to Chronic Dialysis in the United States

Hemodialysis patients often do not attend their scheduled treatment session. We investigated factors associated with missed appointments and whether such nonadherence poses significant harm to patients and increases overall health care utilization in an observational analysis of 44 million hemodialysis treatments for 182,536 patients with ESRD in the United States. We assessed the risk of hospitalization, emergency room visit, or intensive-coronary care unit (ICU-CCU) admission in the 2 days after a missed treatment relative to the risk for patients who received hemodialysis. Over the 5-year study period, the average missed treatment rate was 7.1 days per patient-year. In covariate adjusted logistic regression, the risk of hospitalization (odds ratio [OR], 3.98; 95% confidence interval [95% CI], 3.93 to 4.04), emergency room visit (OR, 2.00; 95% CI, 1.87 to 2.14), or ICU-CCU admission (OR, 3.89; 95% CI, 3.81 to 3.96) increased significantly after a missed treatment. Overall, 0.9 missed treatment days per year associated with suboptimal transportation to dialysis, inclement weather, holidays, psychiatric illness, pain, and gastrointestinal upset. These barriers also associated with excess hospitalization (5.6 more events per patient-year), emergency room visits (1.1 more visits), and ICU-CCU admissions (0.8 more admissions). In conclusion, poor adherence to hemodialysis treatments may be a substantial roadblock to achieving better patient outcomes. Addressing systemic and patient barriers that impede access to hemodialysis care may decrease missed appointments and reduce patient morbidity.

PD First: Peritoneal Dialysis as the Default Transition to Dialysis Therapy

Peritoneal dialysis (PD) and in‐center hemodialysis (HD) are accepted as clinically equivalent dialysis modalities, yet in‐center HD is the predominant renal replacement therapy (RRT) modality offered to new end‐stage renal disease (ESRD) patients in the United States and most other industrialized nations. This predominance has little to do with clinical outcomes, patient choice, cost, or quality of life. It has been driven by ease of HD initiation, physician experience and training, inadequate pre‐ESRD patient education, ample in‐center HD capacity, and lack of adequate infrastructure for PD‐related care. As compared with in‐center HD, PD is a widely applicable, yet underutilized modality of RRT that provides comparable clinical outcomes, superior quality of life measures, significant cost savings, and many other unmeasured advantages. A “PD First” approach not only has advantages for patients but also physicians, healthcare systems, and society. In this review, we will summarize evidence demonstrating that PD should be the default modality when new ESRD patients are transitioning to dialysis therapy when preemptive transplantation is not an option and highlight the essential infrastructural requirements to allow for a “PD First” model.

No difference in bleeding risk between subcutaneous enoxaparin and heparin for thromboprophylaxis in end-stage renal disease

Enoxaparin, a low-molecular-weight form of heparin, is not approved for use in dialysis patients in the United States, because it is eliminated through the kidneys and could therefore accumulate and cause inadvertent bleeding. Accordingly, it is unknown if enoxaparin is as safe to prescribe as subcutaneous heparin for thromboprophylaxis in patients with chronic renal failure. Here we conducted a retrospective comparative effectiveness study in a large population of chronic maintenance dialysis patients initiated with subcutaneous injections of enoxaparin or heparin for thromboprophylaxis. The primary study end point was hospitalization or death related to bleeding, with a secondary end point of venous thromboembolism. Among 7721 dialysis patients started on subcutaneous enoxaparin or heparin at doses for thromboprophylaxis, the crude rate for bleeding requiring hospitalization or resulting in death was 15.2 (95% confidence interval (CI) 12.7-18.2) events per 100 patient-years in the enoxaparin group, which did not differ from the heparin group in which the crude rate was 16.2 (95% CI 14.0-18.7) events per 100 patient-years. In risk factor-adjusted Poisson models, enoxaparin was not associated with more bleeding in comparison to heparin (risk ratio, 0.98; 95% CI 0.78-1.23). The risk of venous thromboembolism was not associatively worse with enoxaparin (risk ratio, 0.77; 95% CI 0.49-1.22). Thus, in dialysis patients, daily enoxaparin for thromboprophylaxis was not associated with increased serious bleeding or less effective compared to subcutaneous heparin.