The renal replacement therapy landscape in 2030: reducing the global cardiovascular burden in dialysis patients.

Despite the significant progress made in understanding chronic kidney disease and uraemic pathophysiology, use of advanced technology and implementation of new strategies in renal replacement therapy, the clinical outcomes of chronic kidney disease 5 dialysis patients remain suboptimal. Considering residual suboptimal medical needs of short intermittent dialysis, it is our medical duty to revisit standards of dialysis practice and propose new therapeutic options for improving the overall effectiveness of dialysis sessions and reduce the burden of stress induced by the therapy. Several themes arise to address the modifiable components of the therapy that are aimed at mitigating some of the cardiovascular risks in patients with end-stage kidney disease. Among them, five are of utmost importance and include: (i) enhancement of treatment efficiency and continuous monitoring of dialysis performances; (ii) prevention of dialysis-induced stress; (iii) precise handling of sodium and fluid balance; (iv) moving towards heparin-free dialysis; and (v) customizing electrolyte prescriptions. In summary, haemodialysis treatment in 2030 will be substantially more personalized to the patient, with a clear focus on cardioprotection, volume management, arrhythmia surveillance, avoidance of anticoagulation and the development of more dynamic systems to align the fluid and electrolyte needs of the patient on the day of the treatment to their particular circumstances.

Using more frequent haemodialysis to manage volume overload in dialysis patients with heart failure, obesity or pregnancy.

Managing dialysis in patients with heart failure, pregnancy or obesity is complex. More frequent haemodialysis 5-6 days/week in randomized clinical trials has shown benefits for controlling volume overload, blood pressure and phosphorus, reducing left ventricular hypertrophy (LVH), and improving patient tolerance to therapy. Therapy prescriptions were guided by volume of urea cleared, time-integrated fluid loading control and increased phosphate-ß2 microglobulin removal, with greater treatment frequency to address clinical efficacy targets. Case studies in all three categories show that treatment with more frequent haemodialysis in low-dialysate flow systems (Qd <200 mL/min, dialysate of 25-30 L/session, 5-7 days/week for 2.5-3.0 h/session) improves control of heart failure. In pregnancy, treatment 7 days/week with 30 L and 3 h/session of dialysis enabled successful delivery of infants at 32-34 weeks, with all doing well 2-5 years after birth. Obese patients with a body mass index (BMI) >35 achieved control of volume, blood pressure and uraemic symptoms compared to their prior 3 times/week in-centre haemodialysis. Greater application of more frequent haemodialysis should be considered, particularly in high-risk populations, to improve clinical care.

Partial and full deletion of nicotinic acetylcholine receptor α4 and ß2 subunits reduces sensitivity to acute nicotine administration and development of tolerance following chronic nicotine administration.

The diversity of nicotinic cholinergic receptor (nAChR) subunits underlies the complex responses to nicotine. Mice differing in the expression of α4 and ß2 subunits, which are most widely expressed in brain, were evaluated for the responses to acute nicotine administration on Y-maze crossings and rears, open-field locomotion and body temperature following chronic treatment with nicotine (0, 0.25, 1.0 and 4.0 mg/kg/h). Deletion or partial deletion of the α4, ß2 or both nAChR subunits reduced the sensitivity of mice to acute nicotine administration. This reduced sensitivity was gene dose-dependent. Modification of α4 subunit expression elicited a greater reduction in sensitivity than the modification of ß2 subunit expression. No measurable tolerance was observed for mice of any genotype following chronic treatment with 0.25 mg/kg/h nicotine. Modest tolerance was noted following treatment with 1.0 mg/kg/h. Greater tolerance was observed following treatment with 4.0 mg/kg/h. The extent of tolerance differed among the mice depending on genotype: wild-type (α4 and ß2) developed measurable tolerance for all four tests. Heterozygotes (α4, ß2 and α4/ß2) developed tolerance for only Y-maze crossings and body temperature. Null mutants (α4 and ß2) did not become tolerant. However, following chronic treatment with 4.0 mg/kg/h nicotine, wild type, α4 and α4 mice displayed increased Y-maze crossings following acute administration of 0.5 mg/kg nicotine that may reflect the activity of α6ß2*-nAChR. These results confirm the importance of the α4 and ß2 nAChR subunits in mediating acute and chronic effects of nicotine on locomotion and body temperature in the mouse.

Excess Deaths Attributable to Influenza-Like Illness in the ESRD Population.

BACKGROUND: Morbidity and mortality vary seasonally. Timing and severity of influenza seasons contribute to those patterns, especially among vulnerable populations such as patients with ESRD. However, the extent to which influenza-like illness (ILI), a syndrome comprising a range of potentially serious respiratory tract infections, contributes to mortality in patients with ESRD has not been quantified. METHODS: We used data from the Centers for Disease Control and Prevention (CDC) Outpatient Influenza-like Illness Surveillance Network and Centers for Medicare and Medicaid Services ESRD death data from 2000 to 2013. After addressing the increasing trend in deaths due to the growing prevalent ESRD population, we calculated quarterly relative mortality compared with average third-quarter (summer) death counts. We used linear regression models to assess the relationship between ILI data and mortality, separately for quarters 4 and 1 for each influenza season, and model parameter estimates to predict seasonal mortality counts and calculate excess ILI-associated deaths. RESULTS: An estimated 1% absolute increase in quarterly ILI was associated with a 1.5% increase in relative mortality for quarter 4 and a 2.0% increase for quarter 1. The average number of annual deaths potentially attributable to ILI was substantial, about 1100 deaths per year. CONCLUSIONS: We found an association between community ILI activity and seasonal variation in all-cause mortality in patients with ESRD, with ILI likely contributing to >1000 deaths annually. Surveillance efforts, such as timely reporting to the CDC of ILI activity within dialysis units during influenza season, may help focus attention on high-risk periods for this vulnerable population.

Contemporary Trends in Clinical Outcomes among Dialysis Patients with Medicare Coverage.

BACKGROUND: The dialysis patient population in the United States continues to grow. Trends in rates of death and hospitalization among dialysis patients have important consequences for outpatient dialysis capacity and Medicare spending. OBJECTIVES: To estimate contemporary trends in rates of death and hospitalization among dialysis patients in the United States, overall and within subgroups. METHODS: We used Medicare Limited Data Sets (100% sample) in 2014-2017 to estimate trends in rates of death and hospitalization among dialysis patients with Medicare Parts A and B enrollment. We used seasonal autoregressive integrated moving average models to identify secular trends in the incidence of outcomes. RESULTS: There were 631,075 unique patients; 222,924 deaths; and 1,876,779 hospital admissions. Weekly risks of both death and hospitalization exhibited strong seasonality. However, overall weekly risks of death were 34.9, 35.4, 35.2, and 35.7 deaths per 10,000 patients in 2014-2017, respectively (p = 0.47, from a likelihood ratio test of secular trend). The overall weekly risk of hospitalization was 3.08, 3.05, 3.11, and 3.11% in 2014, 2015, 2016, and 2017, respectively (p = 0.30). There were significant secular trends in risk of death in subgroups defined by black race and residency in South Atlantic states (p < 0.05). There were also secular trends in risk of hospitalization in subgroups defined by age 20-44 years, concurrent enrollment in Medicaid, and residency in South Central states. CONCLUSION: For the first time since the beginning of this century, rates of both death and hospitalization among dialysis patients with Medicare fee-for-service coverage have stagnated. The reasons for this change are unknown and require detailed assessment. Persistent lack of change in clinical outcomes may alter the future expectations about dialysis patient population growth.

Effect of dialysate potassium and lactate on serum potassium and bicarbonate concentrations during daily hemodialysis at low dialysate flow rates.

BACKGROUND: Observational studies of hemodialysis patients treated thrice weekly have shown that serum and dialysate potassium and bicarbonate concentrations are associated with patient outcomes. The effect of more frequent hemodialysis on serum potassium and bicarbonate concentrations has rarely been studied, especially for treatments at low dialysate flow rate. METHODS: These post-hoc analyses evaluated data from patients who transferred from in-center hemodialysis (HD) to daily HD at low dialysate flow rates during the FREEDOM Study. The primary outcomes were the change in predialysis serum potassium and bicarbonate concentrations after transfer from in-center HD (mean during the last 3 months) to daily HD (mean during the first 3 months). RESULTS: After transfer from in-center HD to daily HD (data from 345 patients, 51 ± 15 years of age, mean ± standard deviation), predialysis serum potassium decreased (P < 0.001) by approximately 0.4 mEq/L when dialysate potassium concentration during daily HD was 1 mEq/L; no change occurred when dialysate potassium concentration during daily HD was 2 mEq/L. After transfer from in-center HD to daily HD (data from 284 patients, 51 ± 15 years of age), predialysis serum bicarbonate concentration decreased (P = 0.0022) by 1.0 ± 3.3 mEq/L when dialysate lactate concentration was 40 mEq/L but increased (P < 0.001) by 2.5 ± 3.5 mEq/L when dialysate lactate concentration was 45 mEq/L. These relationships were dependent on serum potassium and bicarbonate concentrations during in-center HD. CONCLUSIONS: Control of serum potassium and bicarbonate concentrations during daily HD at low dialysate flow rates is readily achievable; the choice of dialysate potassium and lactate concentration can be informed when transfer is from in-center HD to daily HD.

Insights From the 2016 Peer Kidney Care Initiative Report: Still a Ways to Go to Improve Care for Dialysis Patients.

Although outcomes improved during the past decade for patients receiving maintenance dialysis, gains were few in certain key areas, as highlighted in the 2016 Peer Kidney Care Initiative Report. Overall incidence rates of dialysis therapy initiation in adults remained relatively stable (∼42 per 100,000 US population, 2009-2013), but rates varied more than 2-fold, from 26 to 54, across US geographic regions. Hospitalization rates in incident patients decreased from 261 hospitalizations per 100 patient-years in 2003 to 207 in 2012, but observation stay rates increased from 40 to 67, attenuating the decline in hospitalizations by half. Decreases in prevalent patient hospitalizations for heart failure, from 15.6 per 100 patient-years in 2004 to 9.5 in 2013, were partially offset by increases in hospitalizations for volume overload, from 3.0 in 2004 to 6.1 in 2013. Prevalent patient rates of hospitalizations for arrhythmias (∼4.6 per 100 patient-years) did not improve during the past decade, whereas sudden cardiac death as a proportion of total cardiovascular deaths increased from 53% to 73%. Hospitalization rates for pneumonia/influenza, at about 8.3 per 100 patient-years in prevalent patients, did not decrease during this period, while hospitalization rates for bacteremia/sepsis increased from 8.6 to 12.0. If decreases in mortality rates are to be sustained, novel approaches to these challenges will be required.

Identifying High-Risk Individuals for Chronic Kidney Disease: Results of the CHERISH Community Demonstration Project.

BACKGROUND: Most people with chronic kidney disease (CKD) are not aware of their condition. OBJECTIVES: To assess screening criteria in identifying a population with or at high risk for CKD and to determine their level of control of CKD risk factors. METHOD: CKD Health Evaluation Risk Information Sharing (CHERISH), a demonstration project of the Centers for Disease Control and Prevention, hosted screenings at 2 community locations in each of 4 states. People with diabetes, hypertension, or aged ≥50 years were eligible to participate. In addition to CKD, screening included testing and measures of hemoglobin A1C, blood pressure, and lipids. -Results: In this targeted population, among 894 people screened, CKD prevalence was 34%. Of participants with diabetes, 61% had A1C < 7%; of those with hypertension, 23% had blood pressure < 130/80 mm Hg; and of those with high cholesterol, 22% had low-density lipoprotein < 100 mg/dL. CONCLUSIONS: Using targeted selection criteria and simple clinical measures, CHERISH successfully identified a population with a high CKD prevalence and with poor control of CKD risk factors. CHERISH may prove helpful to state and local programs in implementing CKD detection programs in their communities.

Association between adjuvant chemotherapy and risk of acute kidney injury in elderly women diagnosed with early-stage breast cancer.

PURPOSE: We studied elderly Medicare enrollees newly diagnosed with early-stage breast cancer to examine the association between adjuvant chemotherapy and acute kidney injury (AKI). METHODS: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort study including women diagnosed with stages I-III breast cancer at ages 66-89 years between 1992 and 2007. We performed one-to-one matching on time-dependent propensity score on the day of adjuvant chemotherapy initiation within 6 months after the first cancer-directed surgery based on the estimated probability of chemotherapy initiation at each day for each patient, using a Cox proportional hazards model. We estimated the cumulative incidence of AKI using Kaplan-Meier methods. We used Cox proportional hazards models to evaluate the association between chemotherapy and the risk of AKI, and compared the risk among major chemotherapy types. RESULTS: The study included 28,048 women. The 6-month cumulative incidence of AKI was 0.80% for chemotherapy-treated patients, compared with 0.30% for untreated patients (P < 0.001). Adjuvant chemotherapy was associated with a nearly threefold increased risk of AKI [hazard ratio (HR) 2.73; 95% CI 1.8-4.1]. Compared with anthracycline-based chemotherapy, the HRs (95% CIs) were 1.66 (0.94-2.91), 0.88 (0.53-1.47), and 1.15 (0.57-2.32) for taxane-based, CMF, and other chemotherapy, respectively. CONCLUSION: Our findings showed that adjuvant chemotherapy was associated with increased risk of AKI in elderly women diagnosed with early-stage breast cancer. The risk seemed to vary by regimen type, but the differences were not statistically significant.

Association of Serum Potassium with All-Cause Mortality in Patients with and without Heart Failure, Chronic Kidney Disease, and/or Diabetes.

BACKGROUND: The relationship between serum potassium, mortality, and conditions commonly associated with dyskalemias, such as heart failure (HF), chronic kidney disease (CKD), and/or diabetes mellitus (DM) is largely unknown. METHODS: We reviewed electronic medical record data from a geographically diverse population (n = 911,698) receiving medical care, determined the distribution of serum potassium, and the relationship between an index potassium value and mortality over an 18-month period in those with and without HF, CKD, and/or DM. We examined the association between all-cause mortality and potassium using a cubic spline regression analysis in the total population, a control group, and in HF, CKD, DM, and a combined cohort. RESULTS: 27.6% had a potassium <4.0 mEq/L, and 5.7% had a value ≥5.0 mEq/L. A U-shaped association was noted between serum potassium and mortality in all groups, with lowest all-cause mortality in controls with potassium values between 4.0 and <5.0 mEq/L. All-cause mortality rates per index potassium between 2.5 and 8.0 mEq/L were consistently greater with HF 22%, CKD 16.6%, and DM 6.6% vs. controls 1.2%, and highest in the combined cohort 29.7%. Higher mortality rates were noted in those aged ≥65 vs. 50-64 years. In an adjusted model, all-cause mortality was significantly elevated for every 0.1 mEq/L change in potassium <4.0 mEq/L and ≥5.0 mEq/L. Diuretics and renin-angiotensin-aldosterone system inhibitors were related to hypokalemia and hyperkalemia respectively. CONCLUSION: Mortality risk progressively increased with dyskalemia and was differentially greater in those with HF, CKD, or DM.

Use of prophylactic growth factors and antimicrobials in elderly patients with cancer: a review of the Medicare database.

PURPOSE: Growth factors and antimicrobials can reduce complications of chemotherapy-induced myelosuppression. Their prophylactic use in elderly patients is important given the associated comorbidity in this age group. There is a developing trend by payers to include supportive care agents in chemotherapy care bundles, which could affect clinical practice. We examined whether the febrile neutropenia (FN) risk categories can be used to describe utilization in the Centers for Medicare & Medicaid fee-for-service system in older adults. METHODS: We conducted a retrospective cohort study using the Medicare 20% sample data to describe growth factor and antimicrobial use patterns in patients receiving chemotherapy for breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL). RESULTS: The highest percentage of patients receiving granulocyte colony-stimulating factor (GCSF) within the first 5 days of a chemotherapy cycle were on high-FN-risk regimens, particularly for cycle 1 (73.7%, breast cancer; 61.5%, NHL) and cycle 2 (75.9%, breast cancer; 77.5%, NHL). Chemotherapy regimens for lung cancer are less myelotoxic, and growth factor use was more likely with latter cycles. Antibiotic use was lower at 15% within a cycle and appeared to be in response to complications. CONCLUSION: Practitioners use GCSF and antibiotics for elderly patients treated with potentially toxic chemotherapy, while comorbidity burden plays a role for patients treated with less myelotoxic regimens. The complexity of these choices in clinical practice should be considered in the proposed reimbursement changes being piloted by Medicare and private insurance companies seeking treatment cost reductions, as altered use could affect safety and efficacy.

Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform.

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005-2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: -0.24 [-0.08 to -0.37] for stroke, -2.43 [-1.35 to -3.70] for VTE, and -0.77 [-0.28 to -1.27] for heart failure), although non-ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.

The incidence, prevalence, and outcomes of glomerulonephritis derived from a large retrospective analysis.

The incidence and period prevalence of glomerulonephritis (GN) with resultant rates of death and end-stage renal disease (ESRD) in the United States are unknown. Therefore, we assessed the presumptive burden of GN in a 20% Medicare sample, 5,442,495 individuals, and an Optum Clinformatics Employer Group Health Plan sample of 13,712,946 individuals. GN was established using International Classification of Diseases, Ninth Revision, Clinical Modification claims-based algorithms. Outcomes were all-cause mortality and ESRD rates. Cox proportional hazards modeling was used to determine factors associated with outcomes in incident patients. For secondary (systemic immunologic disease) and primary GN, respectively, incidence rates per 100,000 patient-years were 134 (95% CI: 132-136) and 57 (56-58) in the Medicare cohort, and 10 (9-10) and 20 (19-21) in the health plan cohort. Period prevalence per 100,000 individuals was 917 (909-952) and 306 (302-311) in Medicare and 52 (51-54) and 70 (68-71) in the health plan. Death rates in incident Medicare patients were 3.9-fold higher for secondary and 2.7-fold higher for primary GN compared with no GN. ESRD rates were typically 1 to 2 orders of magnitude higher compared with no GN. In the Medicare cohort, women with incident secondary GN were less likely than men to progress to ESRD (hazard ratio: 0.70; 95% CI: 0.62-0.80) and death (0.82; 0.79-0.86). Black patients were more likely than white patients to progress to ESRD (secondary GN, 1.56; 1.31-1.85; primary GN, 1.57; 1.35-1.83), but not to death. Thus, in the United States, GN based on health claims data is associated with increased likelihood of progression to ESRD and death.

Understanding kidney care needs and implementation strategies in low- and middle-income countries: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

Evidence-based cinical practice guidelines improve delivery of uniform care to patients with and at risk of developing kidney disease, thereby reducing disease burden and improving outcomes. These guidelines are not well-integrated into care delivery systems in most low- and middle-income countries (LMICs). The KDIGO Controversies Conference on Implementation Strategies in LMIC reviewed the current state of knowledge in order to define a road map to improve the implementation of guideline-based kidney care in LMICs. An international group of multidisciplinary experts in nephrology, epidemiology, health economics, implementation science, health systems, policy, and research identified key issues related to guideline implementation. The issues examined included the current kidney disease burden in the context of health systems in LMIC, arguments for developing policies to implement guideline-based care, innovations to improve kidney care, and the process of guideline adaptation to suit local needs. This executive summary serves as a resource to guide future work, including a pathway for adapting existing guidelines in different geographical regions.

Mortality, Hospitalization, and Technique Failure in Daily Home Hemodialysis and Matched Peritoneal Dialysis Patients: A Matched Cohort Study.

BACKGROUND: Use of home dialysis is growing in the United States, but few direct comparisons of major clinical outcomes on daily home hemodialysis (HHD) versus peritoneal dialysis (PD) exist. STUDY DESIGN: Matched cohort study. SETTING & PARTICIPANTS: We matched 4,201 new HHD patients in 2007 to 2010 with 4,201 new PD patients from the US Renal Data System database. PREDICTOR: Daily HHD versus PD. OUTCOMES: Relative mortality, hospitalization, and technique failure. RESULTS: Mean time from end-stage renal disease onset to home dialysis therapy initiation was 44.6 months for HHD and 44.3 months for PD patients. In intention-to-treat analysis, HHD was associated with 20% lower risk for all-cause mortality (HR, 0.80; 95% CI, 0.73-0.87), 8% lower risk for all-cause hospitalization (HR, 0.92; 95% CI, 0.89-0.95), and 37% lower risk for technique failure (HR, 0.63; 95% CI, 0.58-0.68), all relative to PD. In the subset of 1,368 patients who initiated home dialysis therapy within 6 months of end-stage renal disease onset, HHD was associated with similar risk for all-cause mortality (HR, 0.95; 95% CI, 0.80-1.13), similar risk for all-cause hospitalization (HR, 0.96; 95% CI, 0.88-1.05), and 30% lower risk for technique failure (HR, 0.70; 95% CI, 0.60-0.82). Regarding hospitalization, risk comparisons favored HHD for cardiovascular disease and dialysis access infection and PD for bloodstream infection. LIMITATIONS: Matching unlikely to reduce confounding attributable to unmeasured factors, including residual kidney function; lack of data regarding dialysis frequency, duration, and dose in daily HHD patients and frequency and solution in PD patients; diagnosis codes used to classify admissions. CONCLUSIONS: These data suggest that relative to PD, daily HHD is associated with decreased mortality, hospitalization, and technique failure. However, risks for mortality and hospitalization were similar with these modalities in new dialysis patients. The interaction between modality and end-stage renal disease duration at home dialysis therapy initiation should be investigated further.

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

BACKGROUND: Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. PREDICTOR: Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. OUTCOMES: Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. MEASUREMENTS: Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. RESULTS: Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. LIMITATIONS: Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. CONCLUSIONS: Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates.

Changes in secondary hyperparathyroidism-related biochemical parameters and medication use following parathyroidectomy.

BACKGROUND: Little is known about changes in parathyroid hormone (PTH), calcium and phosphorous levels after parathyroidectomy in hemodialysis patients. We studied the effects of parathyroidectomy on these biochemical values in a large cohort of patients receiving maintenance hemodialysis. METHODS: This retrospective cohort study included patients identified in both the United States Renal Data System and the database of a large dialysis organization who underwent parathyroidectomy in 2007-09, were aged ≥ 18 years, had Medicare Parts A and B as primary payer and had received hemodialysis for ≥ 1 year pre-parathyroidectomy. Descriptive statistics were calculated for continuous variables; categorical variables were used to characterize the population and evaluate monthly laboratory and medication use; median values were calculated for laboratory measures. RESULTS: Among 1402 parathyroidectomy patients, mean age was 48.9 years, 52.4% were males, 58.8% were African American and mean dialysis duration was 7.5 years. Median PTH levels increased over the year before parathyroidectomy from 1039 to 1661 pg/mL and decreased afterward to 98 pg/mL at 1 month; levels remained ≥ 897 pg/mL for 10% of patients. Median calcium levels fell from 9.6 mg/dL before to 7.9 mg/dL 1 month after parathyroidectomy; levels were ≤ 7.1 mg/dL for 25% and remained ≤ 7.2 mg/dL for the lowest 25% at 3 months. Median phosphorous level was 6.8 mg/dL immediately before parathyroidectomy, decreased to 3.8 mg/dL immediately after and reached 5.8 mg/dL at 1 year. CONCLUSIONS: While PTH levels dropped after parathyroidectomy for most patients, surgery was sometimes ineffective in reducing levels and sometimes led to over-suppression. Hypocalcemia could be profound and long lasting, suggesting the need for prolonged vigilance.

Controlling confounding of treatment effects in administrative data in the presence of time-varying baseline confounders.

PURPOSE: Confounding, a concern in nonexperimental research using administrative claims, is nearly ubiquitous in claims-based pharmacoepidemiology studies. A fixed-length look-back window for assessing comorbidity from claims is common, but it may be advantageous to use all historical claims. We assessed how the strength of association between a baseline-identified condition and subsequent mortality varied by when the condition was measured and investigated methods to control for confounding. METHODS: For Medicare beneficiaries undergoing maintenance hemodialysis on 1 January 2008 (n = 222 343), we searched all Medicare claims, 1 January 2001 to 31 December 2007, for four conditions representing chronic and acute diseases, and classified claims by number of months preceding the index date. We used proportional hazard models to estimate the association between time of condition and subsequent mortality. We simulated a confounded comorbidity-exposure relationship and investigated an alternative method of adjustment when the association between the condition and mortality varied by proximity to follow-up start. RESULTS: The magnitude of the mortality hazard ratio estimates for each condition investigated decreased toward unity as time increased between index date and most recent manifestation of the condition. Simulation showed more biased estimates of exposure-outcome associations if proximity to follow-up start was not considered. CONCLUSIONS: Using all-available claims information during a baseline period, we found that for all conditions investigated, the association between a comorbid condition and subsequent mortality varied considerably depending on when the condition was measured. Improved confounding control may be achieved by considering the timing of claims relative to follow-up start.

Co-trending of parathyroid hormone and phosphate in patients receiving hemodialysis.

AIM: The objective of this study was to examine the time-varying relationship of chronic kidney disease-mineral bone disorder (CKD-MBD) related biochemical parameters (parathyroid hormone (PTH), calcium, phosphate) over a 12-month period. MATERIAL AND METHODS: Using data from a large US provider of dialysis services from 2010 through 2012, we constructed a cohort of adult patients receiving in-center hemodialysis who had biochemical parameters measured at both baseline and 12 months of follow-up. We used descriptive statistics to assess the overall distributions of the biochemical parameters at both measurements, to examine how patients transitioned between categories for each biochemical parameter, and to evaluate how the biochemical parameters changed with respect to each other. RESULTS: Among the 132,087 patients included in our analyses, the cross-sectional distributions for the combined categories of 150 - < 300 and 300 - < 600 pg/mL for PTH between the two measurements remained unchanged (67% of patients). For calcium and phosphate, the distributions across all categories also remained largely unchanged. Considering within-patient changes over time. however, a majority (74%) of patients who initially had a PTH < 150 pg/mL transitioned to a higher category, while a majority (56%) of patients who initially had a PTH > 600 pg/mL transitioned to a lower category. We observed that phosphate values on average directly trended with PTH values over the follow-up period. CONCLUSION: We found that while calcium showed relatively little variation, parallel bidirectional variation in PTH and phosphate over time was quite common among adult patients receiving hemodialysis. Optimal control of phosphate is likely to be dependent not only on consistent adherence to dietary restrictions and phosphate binders, but may additionally rely on adequate and sustained control of PTH.

Patient characteristics, disease burden, and medication use in stage 4 - 5 chronic kidney disease patients.

AIMS: We aimed to assess demographic characteristics, comorbidity and hospitalization burdens, laboratory abnormalities, and patterns of chronic kidney disease (CKD)-related medication use in a large cohort of patients with CKD stage 4 - 5. METHODS: In a retrospective cohort analysis, the Medicare 5% sample and Truven MarketScan employer group health plan databases were used to examine patients aged ≥ 65 and < 65 years, respectively. CKD was determined by ≥ 1 inpatient or ≥ 2 outpatient claims with relevant ICD-9-CM diagnosis codes during the 1-year baseline period. The follow-up period was 1 year from day 91 after the index date RESULTS: In the Medicare data, 12,930 (1.1%) CKD stage 4 - 5 patients were identified. Mean age was 79.2 ± 7.4 years; 56.1% were women and 83.1% white; 46.8% had atherosclerotic heart disease, and 36.9% congestive heart failure; 37.9% were hospitalized within 1 year. In the MarketScan data, 6,010 (0.04%) patients were identified. Mean age was 55.2 ± 8.8 years; 48.0% were women; 21.4% were hospitalized within 1 year. Heart failure was the leading cause of hospitalization for both groups. Parathyroid hormone levels were > 300 pg/mL for 39.1% of MarketScan patients, but only 20.9% received activated vitamin D. ESAs were administered to 28.2% of MarketScan patients with iron saturation < 30% and to 7.7% with hemoglobin > 11.5% and saturation ≥ 30%. CONCLUSIONS: Comorbidity burdens and hospitalization rates were high for patients with advanced, non-dialysis requiring CKD. While hyperparathyroidism and anemia were common, appropriate medication use was not optimal, suggesting opportunities for improved care.