Efficacy and Safety of Vibegron for Persistent Symptoms of Overactive Bladder in Men Being Pharmacologically Treated for Benign Prostatic Hyperplasia: Results From the Phase 3 Randomized Controlled COURAGE Trial.

PURPOSE: Efficacy and safety of vibegron, a ß3-adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial. MATERIALS AND METHODS: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs). RESULTS: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%). CONCLUSIONS: In this trial, vibegron met all primary and secondary end points, and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi.

Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and infections by other filamentous fungi from the SECURE clinical trial. Two hundred thirty-one patients who received the clinical dosing regimen and had exposure parameters were included in the analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included all-cause mortality through day 42 in the intent-to-treat (ITT) and modified ITT populations, data review committee (DRC)-adjudicated overall response at end of treatment (EOT), and DRC-adjudicated clinical response at EOT. The safety endpoints analyzed were elevated or abnormal alanine aminotransferase, increased aspartate aminotransferase, and a combination of the two. The endpoints were analyzed using logistic regression models. No statistically significant relationship (P > 0.05) was found between isavuconazole exposure and either efficacy or safety endpoints. The lack of association between exposure and efficacy indicates that the isavuconazole exposures achieved by clinical dosing were appropriate for treating the infecting organisms in the SECURE study and that increases in alanine or aspartate aminotransferase were not related to increase in exposures. Without a clear relationship, there is no current clinical evidence for recommending routine therapeutic drug monitoring for isavuconazole.

Phase I trial to investigate the effect of renal impairment on isavuconazole pharmacokinetics.

PURPOSE: The purpose of the study is to evaluate the effect of renal impairment (RI) and end-stage renal disease (ESRD) on the pharmacokinetics (PK) of isavuconazole and the inactive cleavage product, BAL8728. METHODS: A single intravenous dose of the prodrug isavuconazonium sulfate (372 mg, equivalent to 200 mg isavuconazole and 75 mg of BAL8728 cleavage product) was administered to healthy controls (parts 1 and 2) and participants with mild, moderate, or severe RI (part 2) or ESRD (part 1); ESRD participants received two doses of 200 mg isavuconazole, 1 h post-dialysis (day 1) and prior to dialysis (day 15). Plasma PK parameters for isavuconazole included maximum concentration (C max), area under the concentration-time curve (AUC) from time of dose to 72 h (AUC72), AUC extrapolated to infinity (AUC∞), AUC to last measurable concentration (AUClast), half-life (t ½ h), volume of distribution (V z), and total clearance (CL), for the healthy control group versus those with mild, moderate, or severe RI or ESRD. RESULTS: Isavuconazole C max values were 4% higher in mild RI and 7, 14, and 21% lower in participants with moderate RI, severe RI, or ESRD versus the healthy control group, respectively. When hemodialysis occurred post-dose (day 15), participants with ESRD had a 30% increase in AUC72 for isavuconazole in parallel with reduction of extracellular volume induced by dialysis. Exposure (AUC∞ and AUClast) was not significantly different for participants with mild, moderate, or severe RI versus healthy controls although there was considerable variability. The t1/2 (day 1) was 125.5 ± 63.6 h (healthy control group), 204.5 ± 82.6 h (ESRD group) in part 1, and 140.5 ± 77.7 h (healthy control group), 117.0 ± 66.2 h (mild RI), 158.5 ± 56.4 h (moderate RI), and 145.8 ± 65.8 L/h (severe RI) in part 2. CL was 2.4 ± 0.8 L/h (healthy control group) and 2.9 ± 1.3 L/h (ESRD group) in part 1 and 2.4 ± 1.2 L/h (healthy control group), 2.5 ± 1.0 L/h (mild RI), 2.2 ± 0.8 L/h (moderate RI), and 2.4 ± 0.8 L/h (severe RI) in part 2. The V z was 382.6 ± 150.6 L in the healthy control group and 735.6 ± 277.3 L in ESRD patients on day 1 in part 1 of the study. In part 2 of the study, V z was 410.8 ± 89.7 L in the healthy control group, 341.6 ± 72.3 L in mild RI, 509.1 ± 262.2 L in moderate RI, and 439.4 L in severe RI. CONCLUSIONS: Based on the findings of this study, dose adjustments of isavuconazole are unlikely to be required in individuals with RI or in those with ESRD who receive hemodialysis.

Population Pharmacokinetics of Isavuconazole in Subjects with Mild or Moderate Hepatic Impairment.

Isavuconazole, administered as the prodrug isavuconazonium sulfate, was recently approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of adults with invasive aspergillosis and mucormycosis. The objective of this analysis was to develop a population pharmacokinetic model using NONMEM (version 7.2) for subjects with hepatic impairment, using intravenous and oral administration data from two hepatic studies, and to simulate concentration profiles to steady state, thus evaluating the need for dose adjustment. A two-compartment model with Weibull absorption function and first-order elimination process adequately described plasma isavuconazole concentrations. The population mean clearance in healthy subjects was 2.5 liters/h (5th and 95th percentiles: 2.0 and 3.1). The mean clearance values for subjects with mild and moderate hepatic impairment decreased approximately to 1.55 liters/h (5th and 95th percentiles: 1.3 and 1.8 liters/h) and 1.32 liters/h (5th and 95th percentiles: 1.05 and 1.35), respectively. Peripheral volume of distribution increased with body mass index. Simulations of mean concentration time profiles to steady state showed less than a 2-fold increase in mean trough concentrations for subjects with mild and moderate hepatic impairment compared with healthy subjects. After administration of the single dose, safety data for subjects with mild and moderate hepatic impairment were generally comparable to those for healthy subjects in both studies. Due to the <2-fold increase in trough concentrations and the established safety margin, dose adjustment appears to be unnecessary in subjects with mild or moderate hepatic impairment.

Comparison of the safety, tolerability, and pharmacokinetics of fidaxomicin in healthy Japanese and caucasian subjects.

BACKGROUND AND OBJECTIVES: Fidaxomicin treatment of Clostridium difficile infection is known to produce minimal systemic exposure, as the antibacterial (antibiotic) remains primarily in the gut. In this randomized, double-blind, placebo-controlled study, the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of fidaxomicin were evaluated in healthy Japanese and Caucasian subjects. METHODS: Thirty-six healthy subjects were randomly assigned in a 3:1 ratio to receive either fidaxomicin or placebo. Cohort 1 (100 mg) and Cohort 2 (200 mg) comprised 12 Japanese subjects each and Cohort 3 (200 mg) comprised 12 Caucasian subjects. Subjects received a single dose of the study drug on Day 1 and received multiple doses for 10 days after a wash-out period. RESULTS: After multiple 200 mg dosing of fidaxomicin, both mean maximum plasma concentrations (C max) in Japanese (8.7 ± 5.3 ng/mL) and Caucasian (7.0 ± 3.7 ng/mL) subjects and the area under the concentration-time curve (AUC) were higher in Japanese subjects (58.5 ± 36.7 ng·h/mL) than in Caucasian subjects (37.6 ± 15.7 ng·h/mL), although variation in both groups was large. The mean fecal concentrations of fidaxomicin in Japanese and Caucasian subjects were 2669 and 2181 µg/g, respectively. The possibly study drug-related adverse events were diarrhea (n = 1), feeling hot (n = 1), and hypersomnia (n = 2), which were mild in severity. CONCLUSIONS: In both Japanese and Caucasian subjects, fidaxomicin demonstrated similarly minimal systemic absorption, and was mainly excreted in feces. Fidaxomicin was safe and well-tolerated in all subjects.

Glucoregulatory hormones and choice of osmotic agent in peritoneal dialysis.

OBJECTIVE: The present study was performed to explore the range of effects of amino acid-based peritoneal dialysis (PD) solutions on glucoregulatory hormones in comparison with an osmotically equivalent glucose-based solution. ♢ METHODS: 13 adult nondiabetic patients on PD underwent 2 peritoneal dwells of 2 hours' duration with either 1.5% dextrose solution or 1.1% amino acid solution. Serial sampling for glucoregulatory hormones was done throughout the duration of the dwell. ♢ RESULTS: Instillation of the 1.5% dextrose solution resulted in a modest change in plasma glucose, paralleled by a small increase in plasma insulin levels and plasma insulin-like growth factor (IGF-1). Plasma glucagon was not changed and plasma growth hormone level declined. Instillation of the 1.1% amino acid solution resulted in an increase in plasma glucose, plasma insulin, plasma glucagon, and plasma IGF-1. Plasma growth hormone level declined. Both solutions led to an increase in plasma norepinephrine but no changes were observed in epinephrine or dopamine. ♢ CONCLUSIONS: Our observations suggest that the mere replacement of glucose by amino acids in PD solutions does not necessarily imply "glucose sparing" from the perspective of induction of a glucoregulatory hormonal response because of the aminogenic stimulation of secretion of multiple hormones.

Metabolic effects of incremental doses of intraperitoneal amino acids on automated peritoneal dialysis.

BACKGROUND: The use of amino acid (AA) dialysate to ameliorate protein-energy malnutrition has been limited by adverse metabolic effects. OBJECTIVE: We undertook this study to examine the acute metabolic effects of escalating doses of AAs delivered with lactate/bicarbonate dialysate on automated peritoneal dialysis (APD). PATIENTS AND METHODS: 12 APD patients were treated with conventional lactate-buffered dialysate (week 1), followed by lactate/bicarbonate-buffered dialysate (week 2), then 2 - 2.5 L 1.1% AA solution were added (week 3), and then an additional 2 - 2.5 L 1.1% AA were added (week 4). The primary outcomes were change in serum bicarbonate and pH, change in protein catabolic rate (PCR), and change in normalized ultrafiltration (milliliters/gram of carbohydrate infused). RESULTS: Serum bicarbonate rose from week 1 to week 2 (28.9 +/- 3.2 vs 26.9 +/- 4.1 mmol/L, p = 0.03). Addition of one bag of AAs led to a decline in plasma bicarbonate (26.9 +/- 2.1 vs 28.9 +/- 3.2 mmol/L, p < 0.01), which was further magnified by the addition of the second bag of AAs (23.8 +/- 2.7 vs 26.9 +/- 2.1 mmol/L, p < 0.01). Serum bicarbonate fell significantly by week 4 compared to week 1 (23.8 +/- 2.7 vs 26.9 +/- 3.2 mmol/L, p < 0.01) although there was no significant change in venous pH or PCR when week 4 was compared to week 1. Normalized ultrafiltration was stable for the first 3 weeks but rose significantly in week 4 compared to week 1 (5.32 +/- 2.30 vs 4.14 +/- 1.58 mL/g, p = 0.03). CONCLUSIONS: Higher doses of AAs mixed with newer bicarbonate/lactate dialysate on APD result in a small decrease in serum bicarbonate but improved normalized ultrafiltration. This merits further study as both a nutritional supplement and a glucose-sparing strategy.

Health-related quality of life in CKD Patients: correlates and evolution over time.

BACKGROUND AND OBJECTIVES: Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time. DESIGN AND SETTING: A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument. RESULTS: Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 +/- 10.2; female: 37.7 +/- 10.8; P < 0.0001; diabetic: 37.3 +/- 10.6; nondiabetic: 41.6 +/- 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 +/- 9.7; no: 40.3 +/- 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 +/- 10.0; no: 40.2 +/- 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities. CONCLUSIONS: These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.

Health-related quality of life and hemoglobin levels in chronic kidney disease patients.

BACKGROUND: The relationship between quality of life (QofL) and anemia has been the subject of recent debates; it has been suggested that the QofL changes associated with the treatment of anemia of chronic kidney disease (CKD) or ESRD patients should not be used in making decisions to treat anemia in CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study examines the relationship between Kidney Disease Quality of Life (KDQofL) questionnaire domains and hemoglobin (Hgb) levels in 1200 patients with stage 3, 4, and 5 CKD followed in seven centers. QofL measures were compared in a stepwise fashion for hemoglobin levels of <11, 11 to <12, 12 to <13, and > or =13. ANOVA was used to examine the relationship between QofL scores and Hgb level, age, CKD stage, and albumin level; a history of diabetes, congestive heart failure, or myocardial infarction; use of erythropoetic-stimulating agents (ESA); and the interaction of hemoglobin level and ESA. RESULTS: The results demonstrate that with increasing Hgb levels there is a statistically significant increase in all four physical domains, the energy/vitality domain, and the physical composite score of the SF-36, and the general health score on the kidney disease component of the questionnaire. The most dramatic improvements in these various domains occurred between the <11 and the 11 to 12 group. CONCLUSIONS: Higher Hgb levels are associated with improved QofL domains of the KDQofL questionnaire. These findings have implications for the care of CKD patients in terms of the initiation of and the Hgb target of ESA therapy.

A prospective evaluation of renal replacement therapy modality eligibility.

BACKGROUND: Patient eligibility for renal replacement therapy (RRT) modalities is frequently debated, but little prospective data are available from large patient cohorts. METHODS: We prospectively evaluated medical and psychosocial eligibility for the three RRT modalities in patients with chronic kidney disease (CKD) stages III-V who were enrolled in an ongoing prospective cohort study conducted at seven North American nephrology practices. RESULTS: Ninety-eight percent of patients were considered medically eligible for haemodialysis (HD), 87% of patients were assessed as medically eligible for peritoneal dialysis (PD) and 54% of patients were judged medically eligible for transplant. Age was the leading cause of non-eligibility for both PD and transplant. Anatomical concerns (adhesions, hernias) were the second most frequent concern for PD eligibility followed by weight. Weight was also a concern for transplant eligibility. The proportion of patients medically eligible for RRT did not vary by CKD stage. There was, however, significant inter-centre variation in the proportion of patients medically eligible for PD and transplant. Ninety-five percent of patients were considered psychosocially eligible for HD, 83% of patients were assessed as psychosocially eligible for PD and 71% of patients were judged psychosocially eligible for transplant. The percentage of patients who were assessed as having neither medical nor psychosocial contraindications for RRT was 95% for HD, 78% for PD and 53% for transplant. CONCLUSIONS: Most CKD patients are considered by their medical care providers to be suitable for PD. Enhanced patient education, promotion of home dialysis for suitable patients and empowerment of patient choice are expected to augment growth of home dialysis modalities.

Perceived knowledge among patients cared for by nephrologists about chronic kidney disease and end-stage renal disease therapies.

The need to educate patients in order to enable them to participate in making appropriate choices for all therapeutic options in end stage renal disease would seem obvious yet there are many barriers to providing such information. We measured 'perceived knowledge' of the therapeutic options for end stage renal disease in a cohort of patients with chronic kidney disease in established treatment programs. A self administered questionnaire was given to 676 patients with stage 3-5 chronic kidney disease as part of the CRIOS study designed to identify trends in practice patterns and outcomes over a 4 year period. The median patient age was 66, about three-fourths were Caucasian and almost half were diabetic. When patients were asked to rate their level of knowledge, about one-third reported limited or no understanding of their chronic kidney disease and no awareness regarding their treatment options. A significant and substantial number of patients indicated they had no familiarity with transplant, hemodialysis, and continuous ambulatory or automated peritoneal dialysis. Perceived knowledge improved with the progression of kidney disease and frequency of nephrology visits; however, only about half of patients with 4 or more nephrology appointments in the prior year reported knowing of hemodialysis, continuous ambulatory peritoneal dialysis or transplant. Age, gender and disease had no impact on levels of patient knowledge, but African-Americans reported having significantly less understanding than Asians or Caucasians. These findings suggest that the lack of perception concerning the treatment options chronic kidney and end stage renal disease reflects, in part, problems with the education of patients by nephrologists and not a lack of referral of these patients to nephrologists for care. The discrepancy of perceived knowledge between African-Americans and other races needs special attention.

Predictive value of brain natriuretic peptides in patients on peritoneal dialysis: results from the ADEMEX trial.

BACKGROUND AND OBJECTIVES: Natriuretic peptides have been suggested to be of value in risk stratification in dialysis patients. Data in patients on peritoneal dialysis remain limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients of the ADEMEX trial (ADEquacy of peritoneal dialysis in MEXico) were randomized to a control group [standard 4 x 2L continuous ambulatory peritoneal dialysis (CAPD); n = 484] and an intervention group (CAPD with a target creatinine clearance > or =60 L/wk/1.73 m(2); n = 481). Natriuretic peptides were measured at baseline and correlated with other parameters as well as evaluated for effects on patient outcomes. RESULTS: Control group and intervention group were comparable at baseline with respect to all measured parameters. Baseline values of natriuretic peptides were elevated and correlated significantly with levels of residual renal function but not with body size or diabetes. Baseline values of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) but not proANP(1-30), proANP(31-67), or proANP(1-98) were independently highly predictive of overall survival and cardiovascular mortality. Volume removal was also significantly correlated with patient survival. CONCLUSIONS: NT-proBNP have a significant predictive value for survival of CAPD patients and may be of value in guiding risk stratification and potentially targeted therapeutic interventions.

Comparison between bicarbonate/lactate and standard lactate dialysis solution in peritoneal transport and ultrafiltration: a prospective, crossover single-dwell study.

OBJECTIVE: It has been proposed that biocompatible bicarbonate/lactate based (Bic/Lac), physiologic-pH peritoneal dialysis (PD) solutions will be beneficial in long-term PD. However, we do not yet have detailed knowledge concerning the comparative physiology of buffer transport for these new solutions and their impact on underlying peritoneal transport of solutes and ultrafiltration (UF). The purpose of this study was to investigate the profile of buffer handling and peritoneal membrane transport characteristics during a single dwell of the new Bic/Lac-based versus standard lactate-based (Lac) PD solution. METHODS: In this prospective crossover study, we compared a 25 mmol/L bicarbonate/15 mmol/L lactate buffered, physiologic pH, low glucose degradation product (GDP) solution (Physioneal; Baxter Healthcare, McGaw Park, Illinois, USA) with a standard lactate buffered, acidic pH, conventional solution (Dianeal; Baxter). 18 patients underwent two peritoneal equilibration tests (PETs) with 2.5% Dianeal and 2.5% Physioneal separated by 1 week. Buffer transport, mass transfer area coefficients (MTACs), solute transport, and UF were determined for the two PETs. All bags were weighed by a nurse before instillation and after drainage to assess the net UF in each dwell. RESULTS: 18 patients that met the inclusion criteria were enrolled in this study. Whereas intraperitoneal pH remained constant at 7.52 +/- 0.11 throughout the dwell with the Bic/Lac solution, pH was still in the acidic range with the Lac solution after 1 hour (7.29 +/- 0.13, p < 0.001); this difference disappeared after the second hour of dwell. The MTACs for creatinine (10.68 +/- 3.66 vs 10.73 +/- 2.96 mL/minute/1.73 m(2), p > 0.05) and urea (27.94 +/- 10.50 vs 27.62 +/- 6.95 mL/min/1.73 m(2), p > 0.05), for Bic/Lac versus Lac respectively, did not differ between these two solutions; transport of glucose and other solutes was also similar. However, after a 4-hour dwell with Bic/Lac solution, net UF was significantly lower than that observed with Lac solution (274.2 +/- 223.3 mL vs 366.1 +/- 217.3 mL, p = 0.026). CONCLUSIONS: Compared to standard Lac-based solution, Bic/Lac based, pH neutral, low-GDP solution avoids intraperitoneal acidity. Peritoneal mass transport kinetics are similar for small solutes. Net UF is significantly lower with Bic/Lac solution; the mechanism for this is unclear.

Improving cycler prescriptions in peritoneal dialysis through informatic profiling.

Cycler-based dialysis is the most common form of peritoneal dialysis in the United States of America, accounting for more than two thirds of patients on the modality. The advent of modern cyclers has enhanced the accessibility of therapy-delivery data. Cyclers have transformed peritoneal dialysis from an unobserved home therapy into an observable home therapy on many levels. We will discuss 3 of these levels herein. The ability to profile prescription behavior at a population level with attention to fill volume, number of cycles used per night, and total time on the cycler will be analyzed. Insights into the dynamics of flow during cycler therapy and the concept of transition point will then be explored. Finally, we will review the impact on patient care of making the delivery of the dialysis prescription easily observable to the medical team. It is our contention that these 3 levels of profiling offer practical lessons to enhance delivery of care for patients on cycler-based peritoneal dialysis.

Impact of initial dialysis modality and modality switches on Medicare expenditures of end-stage renal disease patients.

BACKGROUND: The number of end-stage renal disease (ESRD) enrollees and Medicare expenditures have increased dramatically. Pathways and associated Medicare expenditures in ESRD treatment need to be examined to potentially improve the efficiency of care. METHODS: This study examines the impact of initial dialysis modality choice and subsequent modality switches on Medicare expenditure in a 3-year period. The Dialysis Morbidity and Mortality Study Wave 2 data by the United States Renal Data System (USRDS) is used along with the USRDS Core CD and USRDS claims data. RESULTS: A total of 3423 incident dialysis patients (approximately equal number of peritoneal dialysis and hemodialysis) were included in the analysis. Unadjusted average annual Medicare expenditure (in 2004 dollars) for peritoneal dialysis as first modality was 53,277 dollars(95% CI 50,626 dollars-55,927 dollars), and 72,189 dollars (95% CI 67,513 dollars-76,865 dollars) for hemodialysis. Compared to "hemodialysis, no switch" subgroup, "peritoneal dialysis, no switch" had a significantly lower annual expenditure (44,111 dollars vs. 72,185 dollars) (P < 0.001). "Peritoneal dialysis, with at least one switch" and "hemodialysis, with at least one switch" had a lower or similar annual expenditure of 66,639 dollars and 72,335 dollars, respectively. After adjusting for patient characteristics, annual Medicare expenditure was still significantly lower for patients with peritoneal dialysis as the initial modality (56,807 dollars vs. 68,253 dollars) (P < 0.001). Similarly, compared to "hemdialysis, no switch" subgroup, "peritoneal dialysis, no switch" and "peritoneal dialysis, with at least one switch" had a significantly lower total expenditure. Further analysis showed that time-to-first switch also independently impacted total expenditure. CONCLUSION: Initial modality choice (peritoneal dialysis or hemodialysis) and subsequent modality switches had significant implications for Medicare expenditure on ESRD treatments.