Heart Failure and Edema Costs in Patiromer and SZC Users.

BACKGROUND: Previous work suggested differences between patients taking patiromer or sodium zirconium cyclosilicate (SZC) in real-world risk of heart failure (HF) hospitalizations and edema hospitalizations or emergency department (ED) visits (edema events). We further investigated these differences to assess economic importance. Retrospective study using published event rates and mean costs derived from Optum's de-identified Clinformatics® Data Mart (CDM) Database. METHODS: We designed a model to estimate adjusted economic offsets that combined respective patiromer and SZC HF hospitalization (25.1 and 35.8; difference 10.7 [95% confidence interval [CI]2: 2.6-18.8]) and edema event (3.4 and 7.1; difference 3.6 [95% CI: 1.7-7.1]) rates/100 person-years from the original published work with costs from our parallel data extract spanning 2019-2021, adjusted to 2021 US dollars. RESULTS: In a base case of mean HF hospitalization, edema event, and 30-count potassium-binder prescription costs from our data extract, the estimated mean savings with patiromer was $1,428 per person per year (PPPY; 95% CI: -$1,508 to $4,652). Respective costs PPPY for patiromer vs SZC were $8,526 vs $12,622 (difference $4,096 [95% CI: $1,160-$7,320]) for HF hospitalization and edema events, and $10,649 vs $7,981 (difference -$2,668) for potassium binders, totaling $19,175 for patiromer vs $20,603 for SZC. CONCLUSION: With differing drug costs, hospitalization and ED costs offset this difference when event rates were numerically small. Model outcomes were driven by HF hospitalization cost and least influenced by edema ED visit cost. A limitation was that the CDM data extract may differ from the original work.

Sex Differences in Cardiovascular Outcomes in Patients With Kidney Failure.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. METHODS AND RESULTS: We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all-cause death using adjusted time-to-event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person-years (95% CI, 231-233), with a higher rate in women than in men (248 per thousand person-years [95% CI, 247-250] versus 219 per thousand person-years [95% CI, 217-220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13-1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15-1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28-1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99-1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88-0.90]) and a lower risk of all-cause death than men (HR, 0.96 [95% CI, 0.95-0.97]). CONCLUSIONS: Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality.

A clinical score to predict recovery in end-stage kidney disease due to acute kidney injury.

Background: Acute kidney injury (AKI) is a major contributor to end-stage kidney disease (ESKD). About one-third of patients with ESKD due to AKI recover kidney function. However, the inability to accurately predict recovery leads to improper triage of clinical monitoring and impacts the quality of care in ESKD. Methods: Using data from the United States Renal Data System from 2005 to 2014 (n = 22 922), we developed a clinical score to predict kidney recovery within 90 days and within 12 months after dialysis initiation in patients with ESKD due to AKI. Multivariable logistic regressions were used to examine the effect of various covariates on the primary outcome of kidney recovery to develop the scoring system. The resulting logistic parameter estimates were transformed into integer point totals by doubling and rounding the estimates. Internal validation was performed. Results: Twenty-four percent and 34% of patients with ESKD due to AKI recovered kidney function within 90 days and 12 months, respectively. Factors contributing to points in the two scoring systems were similar but not identical, and included age, race/ethnicity, body mass index, congestive heart failure, cancer, amputation, functional status, hemoglobin and prior nephrology care. Three score categories of increasing recovery were formed: low score (0-6), medium score (7-9) and high score (10-12), which exhibited 90-day recovery rates of 12%, 26% and 57%. For the 12-month scores, the low, medium and high groups consisted of scores 0-5, 6-8 and 9-11, with 12-month recovery rates of 16%, 33% and 62%, respectively. The internal validation assessment showed no overfitting of the models. Conclusion: A clinical score derived from information available at incident dialysis predicts renal recovery at 90 days and 12 months in patients with presumed ESKD due to AKI. The score can help triage appropriate monitoring to facilitate recovery and begin planning long-term dialysis care for others.

Evaluation of longer- vs short-term use of patiromer on health care resource utilization in the patiromer longer-term use evaluation (VALUE) study.

BACKGROUND: Studies suggest that continuous long-term use of patiromer by patients with hyperkalemia is associated with less health care resource utilization compared with not using potassium binders. OBJECTIVE: To retrospectively evaluate health care resource utilization and costs with longer-term adherent vs short-term use of patiromer. METHODS: Time-restricted extracts from Optum's de-identified Clinformatics® Data Mart Database (CDM; January 2016-May 2019) and Symphony Health (SHA; January 2016-September 2018) deidentified databases were analyzed. Both include participants enrolled in commercial and privatized public insurance programs (SHA includes some government programs). Both integrate health care claims data from medical and pharmacy claims. Patients aged 18 years or older with hyperkalemia and an index patiromer prescription were selected. Patiromer use was identified as short-term (<2 months) and any fill quantity or adherent longer-term with claims for at least 2 consecutive months and fill quantities of at least 80% of the total days. Groups were matched on multiple categorical covariates to control for demographic variables, baseline characteristics, and markers of disease severity. Random sampling without replacement was performed 50 times to identify 50 sets of patients matched from the short-term cohort to the longer-term cohort. Health care costs/charges and encounters were compared for a 6-month post-index period using t-tests. RESULTS: Of the CDM patients, 1,267 (40.2%) vs 1,887 (59.8%) and of the SHA patients, 2,234 (35.1%) vs 4,132 (64.9%) experienced longer-term vs short-term patiromer use, respectively. Patient sampling selected 242 and 485 patient-matched pairs from CDM and SHA databases, respectively. At 6 months post-index in longer-term vs short-term patiromer groups (P < 0.0001 for all differences shown), respective mean medical and prescription costs/charges were $42,000 vs $54,311 (-$12,311) and $6,816 vs $4,786 (+$2,030), respectively, for CDM patients and $75,147 vs $84,414 (-$9,267) and $4,689 vs $3,736 (+$953) for SHA patients. In the CDM database, medical costs were lower for longer-term vs short-term cohorts for end-stage renal disease services charges ($10,342 vs $14,976 [-$4,634]), inpatient charges ($15,789 vs $21,473 [-$5,684]), and office visit charges ($10,152 vs $13,152 [-$3,000]). Patient out-of-pocket costs ($658 vs $420 [+$238]) and total prescription charges ($6,158 vs $4,366 [+$1,792]) were higher for the longer-term cohort of CDM patients, with similar findings in the SHA dataset. CONCLUSIONS: Adherent, longer-term use of patiromer is associated with significantly lower medical costs offsetting higher prescription costs, driven by the largest changes in inpatient and clinic services at CDM and SHA, respectively. This illustrates an economic value of longer-term adherence to patiromer.

Definition, Staging, and Role of Biomarkers in Acute Kidney Injury in the Context of Cardiovascular Interventions.

Acute kidney injury (AKI) is a frequently occurring complication of cardiovascular interventions, and associated with adverse outcomes. Therefore, a clear definition of AKI is of paramount importance to enable timely recognition and treatment. Historically, changes in the serum creatinine and urine output have been used to define AKI, and the criteria have evolved over time with better understanding of the impact of AKI on the outcomes. However, the reliance on serum creatinine for these AKI definitions carries numerous limitations including delayed rise, inability to differentiate between hemodynamics versus structural injury and assay variability to name a few.

Social determinants of patiromer adherence and abandonment: An observational, retrospective, real-world claims analysis.

BACKGROUND: Hyperkalemia is a frequent and serious complication in chronic kidney disease (CKD) that can impede continuation of beneficial evidence-based therapies. Recently, novel therapies such as patiromer have been developed to treat chronic hyperkalemia, but their optimal utility hinges on adherence. Social determinants of health (SDOH) are critically important and can impact both medical conditions and treatment prescription adherence. This analysis examines SDOH and their influence on adherence to patiromer or abandonment of prescriptions for hyperkalemia treatment. METHODS: This was an observational, retrospective, real-world claims analysis of adults with patiromer prescriptions and 6- and 12-months pre- and post-index prescription data in Symphony Health's Dataverse during 2015-2020, and SDOH from census data. Subgroups included patients with heart failure (HF), hyperkalemia-confounding prescriptions, and any CKD stages. Adherence was defined as >80% of proportion of days covered (PDC) for ≥60 days and ≥6 months, and abandonment as a portion of reversed claims. Quasi-Poisson regression modeled the impact of independent variables on PDC. Abandonment models used logistic regression, controlling for similar factors and initial days' supply. Statistical significance was p<0.05. RESULTS: 48% of patients at 60 days and 25% at 6 months had a patiromer PDC >80%. Higher PDC was associated with older age, males, Medicare/Medicaid coverage, nephrologist prescribed, and those receiving renin-angiotensin-aldosterone system inhibitors. Lower PDC correlated with higher out-of-pocket cost, unemployment, poverty, disability, and any CKD stage with comorbid HF. PDC was better in regions with higher education and income. CONCLUSIONS: SDOH (unemployment, poverty, education, income) and health indicators (disability, comorbid CKD, HF) were associated with low PDC. Prescription abandonment was higher in patients with prescribed higher dose, higher out-of-pocket costs, those with disability, or designated White. Key demographic, social, and other factors play a role in drug adherence when treating life-threatening abnormalities such as hyperkalemia and may influence patient outcomes.

Implementing a Health Utility Assessment Platform to Acquire Health Utilities in a Hemodialysis Outpatient Setting: Feasibility Study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) wait roughly 4 years for a kidney transplant. A potential way to reduce wait times is using hepatitis C virus (HCV)-viremic kidneys. OBJECTIVE: As preparation for developing a shared decision-making tool to assist patients with ESKD with the decision to accept an HCV-viremic kidney transplant, our initial goal was to assess the feasibility of using The Gambler II, a health utility assessment tool, in an ambulatory dialysis clinic setting. Our secondary goals were to collect health utilities for patients with ESKD and to explore whether the use of race-matched versus race-mismatched exemplars impacted the knowledge gained during the assessment process. METHODS: We used The Gambler II to elicit utilities for the following ESKD-related health states: hemodialysis, kidney transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney. We created race exemplar video clips describing these health states and randomly assigned patients into the race-matched or race-mismatched video arms. We obtained utilities for these 3 health states from each patient, and we evaluated knowledge about ESKD and HCV-associated health conditions with pre- and postintervention knowledge assessments. RESULTS: A total of 63 patients with hemodialysis from 4 outpatient Dialysis Center Inc sites completed the study. Mean adjusted standard gamble utilities for hemodialysis, transplant with HCV-unexposed kidney, and transplantation with HCV-viremic kidney were 82.5, 89, and 75.5, respectively. General group knowledge assessment scores improved by 10 points (P<.05) following utility assessment process. The use of race-matched exemplars had little effect on the results of the knowledge assessment of patients. CONCLUSIONS: Using The Gambler II to collect utilities for patients with ESKD in an ambulatory dialysis clinic setting proved feasible. In addition, educational information about health states provided as part of the utility assessment process tool improved patients' knowledge and understanding about ESKD-related health states and implications of organ transplantation with HCV-viremic kidneys. A wide variation in patient health state utilities reinforces the importance of incorporating patients' preferences into decisions regarding use of HCV-viremic kidneys for transplantation.

Incorporating Patients' Values and Preferences Into Decision Making About Transplantation of HCV-Naïve Recipients With Kidneys From HCV-Viremic Donors: A Feasibility Study.

Introduction. While use of (hepatitis C virus) HCV-viremic kidneys may result in net benefit for the average end-stage kidney disease (ESKD) patient awaiting transplantation, patients may have different values for ESKD-related health states. Thus, the best decision for any individual may be different depending on the balance of these factors. Our objective was to explore the feasibility of sampling health utilities from hemodialysis patients in order to perform patient-specific decision analyses considering various transplantation strategies. Study Design. We assessed utilities on a convenience sample of hemodialysis patients for health states including hemodialysis, and transplantation with either an HCV-uninfected kidney or an HCV-viremic kidney. We performed patient-specific decision analyses using each patient's age, race, gender, dialysis vintage, and utilities. We used a Markov state transition model considering strategies of continuing hemodialysis, transplantation with an HCV-unexposed kidney, and transplantation with an HCV-viremic kidney and HCV treatment. We interviewed 63 ESKD patients from four dialysis centers (Dialysis Clinic Inc., DCI) in the Cincinnati metropolitan area. Results. Utilities for ESKD-related health states varied widely from patient to patient. Mean values were highest for -transplantation with an HCV-uninfected kidney (0.89, SD: 0.18), and were 0.825 (SD: 0.231) and 0.755 (SD: 0.282), respectively, for hemodialysis and transplantation with an HCV-viremic kidney. Patient-specific decision analyses indicated 37 (59%) of the 63 ESKD patients in the cohort would have a net gain in quality-adjusted life years from transplantation of an HCV-viremic kidney, while 26 would have a net loss. Conclusions. It is feasible to gather dialysis patients' health state utilities and perform personalized decision analyses. This approach could be used in the future to guide shared decision-making discussions about transplantation strategies for ESKD patients.

Tobacco smoking induces metabolic reprogramming of renal cell carcinoma.

BACKGROUNDClear cell renal cell carcinoma (ccRCC) is the most common histologically defined renal cancer. However, it is not a uniform disease and includes several genetic subtypes with different prognoses. ccRCC is also characterized by distinctive metabolic reprogramming. Tobacco smoking (TS) is an established risk factor for ccRCC, with unknown effects on tumor pathobiology.METHODSWe investigated the landscape of ccRCCs and paired normal kidney tissues using integrated transcriptomic, metabolomic, and metallomic approaches in a cohort of white males who were long-term current smokers (LTS) or were never smokers (NS).RESULTSAll 3 Omics domains consistently identified a distinct metabolic subtype of ccRCCs in LTS, characterized by activation of oxidative phosphorylation (OXPHOS) coupled with reprogramming of the malate-aspartate shuttle and metabolism of aspartate, glutamate, glutamine, and histidine. Cadmium, copper, and inorganic arsenic accumulated in LTS tumors, showing redistribution among intracellular pools, including relocation of copper into the cytochrome c oxidase complex. A gene expression signature based on the LTS metabolic subtype provided prognostic stratification of The Cancer Genome Atlas ccRCC tumors that was independent of genomic alterations.CONCLUSIONThe work identified the TS-related metabolic subtype of ccRCC with vulnerabilities that can be exploited for precision medicine approaches targeting metabolic pathways. The results provided rationale for the development of metabolic biomarkers with diagnostic and prognostic applications using evaluation of OXPHOS status. The metallomic analysis revealed the role of disrupted metal homeostasis in ccRCC, highlighting the importance of studying effects of metals from e-cigarettes and environmental exposures.FUNDINGDepartment of Defense, Veteran Administration, NIH, ACS, and University of Cincinnati Cancer Institute.

Contraceptive Use Among Women With End-Stage Kidney Disease on Dialysis in the United States.

RATIONALE & OBJECTIVE: Although end-stage kidney disease (ESKD) adversely affects fertility, pregnancies can occur among women receiving dialysis. ESKD increases the risk for adverse pregnancy outcomes and little is known about contraceptive use in women undergoing dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using the US Renal Data System covering January 1, 2005, through December 31, 2014, we evaluated for each calendar year women who for the entire year were aged 15 to 44 years, receiving dialysis, and with Medicare as the primary payer. PREDICTORS: Age, race/ethnicity, and calendar year of prevalent ESKD. OUTCOME: Contraceptive use. ANALYTIC APPROACH: We determined rates of contraceptive use and used multivariable logistic regression to identify factors associated with contraceptive use. RESULTS: The study cohort included 35,732 women and represented 115,713 person-years. The rate of contraceptive use was 5.30% of person-years (95% CI, 5.17%-5.42%). Overall, contraceptive use increased from 2005 to 2014 (4.21%; 95% CI, 3.84%-4.59% vs 6.54%, 95% CI, 6.10%-6.99%). Compared with women aged 25 to 29 years, contraceptive use was higher in women aged 15 to 24 years (OR, 1.30; 95% CI, 1.18-1.43) and lower in women aged 30 to 34 years (OR, 0.74; 95% CI, 0.68-0.81), 35 to 39 years (OR, 0.46; 95% CI, 0.42-0.50), and 40 to 44 years (OR, 0.30; 95% CI, 0.27-0.34). Compared with White women, contraceptive use was higher in Black (OR, 1.12; 95% CI, 1.02-1.24) and Native American women (OR, 1.60; 95% CI, 1.25-2.05). Women with ESKD due to glomerulonephritis had a higher likelihood of contraceptive use than women with ESKD due to diabetes (OR, 1.22; 95% CI, 1.06-1.42). Women receiving peritoneal dialysis had a lower likelihood of contraceptive use than women receiving hemodialysis (OR, 0.85; 95% CI, 0.78-0.93). Compared with women without predialysis nephrology care, contraceptive use was higher in women who received predialysis nephrology care for 12 or fewer months (OR, 1.22; 95% CI, 1.09-1.37) and more than 12 months (OR, 1.33; 95% CI, 1.20-1.47). LIMITATIONS: Retrospective design and use of administrative data. CONCLUSIONS: Among women with ESKD undergoing dialysis, contraceptive use remains low at 5.30%. Younger age, Native American and Black race/ethnicity, ESKD due to glomerulonephritis, hemodialysis, and predialysis nephrology care are associated with a higher likelihood of contraceptive use. The study highlights the importance of prepregnancy counseling for contraceptive use in women receiving dialysis.