Foot and Ankle Care by Podiatrists and Amputations in Patients With Diabetes and Kidney Failure.

Importance: Patients with kidney failure have an increased risk of diabetes-related foot complications. The benefit of regular foot and ankle care in this at-risk population is unknown. Objective: To investigate foot and ankle care by podiatrists and the outcomes of diabetic foot ulcers (DFUs) in patients with kidney failure. Design, Setting, and Participants: This retrospective cohort study included Medicare beneficiaries with type 2 diabetes receiving dialysis who had a new DFU diagnosis. The analysis of the calendar year 2016 to 2019 data from the United States Renal Data System was performed on June 15, 2023, with subsequent updates on December 11, 2023. Exposures: Foot and ankle care by podiatrists during 3 months prior to DFU diagnosis. Main Outcomes and Measures: The outcomes were a composite of death and/or major amputation, as well as major amputation alone. Kaplan-Meier analysis was used to estimate 2 to 3 years of amputation-free survival. Foot and ankle care by podiatrists and the composite outcome was examined using inverse probability-weighted Cox regression, while competing risk regression models were used for the analysis of amputation alone. Results: Among the 14 935 adult patients with kidney failure and a new DFU (mean [SD] age, 59.3 [12.7] years; 35.4% aged ≥65 years; 8284 men [55.4%]; Asian, 2.7%; Black/African American, 35.0%; Hispanic, 17.7%; White, 58.5%), 18.4% (n = 2736) received care by podiatrists in the 3 months before index DFU diagnosis. These patients were older, more likely to be male, and have more comorbidities than those without prior podiatrist visits. Over a mean (SD) 13.5 (12.0)-month follow-up, 70% of those with podiatric care experienced death and/or major amputation, compared with 74% in the nonpodiatric group. Survival probabilities at 36 months were 26.3% vs 22.8% (P < .001, unadjusted Kaplan-Meier survival analysis). In multivariate regression analysis, foot and ankle care was associated with an 11% lower likelihood of death and/or amputation (hazard ratio [HR], 0.89 95% CI, 0.84-0.93) and a 9% lower likelihood of major amputation (above or below knee) (HR, 0.91; 95% CI, 0.84-0.99) than those who did not. Conclusions and Relevance: The findings of this study suggest that patients with kidney failure at risk for DFUs who receive foot and ankle care from podiatrists may be associated with a reduced likelihood of diabetes-related amputations.

Predicting Early Death Among Elderly Dialysis Patients: Development and Validation of a Risk Score to Assist Shared Decision Making for Dialysis Initiation.

BACKGROUND: A shared decision-making tool could help elderly patients with advanced chronic kidney disease decide about initiating dialysis therapy. Because mortality may be high in the first few months after initiating dialysis therapy, incorporating early mortality predictors in such a tool would be important for an informed decision. Our objective is to derive and validate a predictive risk score for early mortality after initiating dialysis therapy. STUDY DESIGN: Retrospective observational cohort, with development and validation cohorts. SETTING & PARTICIPANTS: US Renal Data System and claims data from the Centers for Medicare & Medicaid Services for 69,441 (aged ≥67 years) patients with end-stage renal disease with a previous 2-year Medicare history who initiated dialysis therapy from January 1, 2009, to December 31, 2010. CANDIDATE PREDICTORS: Demographics, predialysis care, laboratory data, functional limitations, and medical history. OUTCOMES: All-cause mortality in the first 3 and 6 months. ANALYTICAL APPROACH: Predicted mortality by logistic regression. RESULTS: The simple risk score (total score, 0-9) included age (0-3 points), low albumin level, assistance with daily living, nursing home residence, cancer, heart failure, and hospitalization (1 point each), and showed area under the receiver operating characteristic curve (AUROC)=0.69 in the validation sample. A comprehensive risk score with additional predictors was also developed (with AUROC=0.72, high concordance between predicted vs observed risk). Mortality probabilities were estimated from these models, with the median score of 3 indicating 12% risk in 3 months and 20% in 6 months, and the highest scores (≥8) indicating 39% risk in 3 months and 55% in 6 months. LIMITATIONS: Patients who did not choose dialysis therapy and did not have a 2-year Medicare history were excluded. CONCLUSIONS: Routinely available information can be used by patients with chronic kidney disease, families, and their nephrologists to estimate the risk of early mortality after dialysis therapy initiation, which may facilitate informed decision making regarding treatment options.

Erythropoiesis-stimulating agent use among non-dialysis-dependent CKD patients before and after the trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) using a large US health plan database.

BACKGROUND: In a landmark study, TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) examined the use of erythropoiesis-stimulating agent (ESA) therapy to treat anemia among patients with chronic kidney disease (CKD) and found no benefit compared to placebo. STUDY DESIGN: A retrospective observational design was used to determine the impact of TREAT on clinical practice. SETTING & PARTICIPANTS: A large US health plan database with more than 1.2 million claims for patients with non-dialysis-dependent CKD stages 3 and 4. FACTOR: ESA prescribing 2 years before and after publication of TREAT. OUTCOMES: Rate of ESA prescribing for ESA-naive and -prevalent cohorts. MEASUREMENTS: (1) Monthly ESA prescribing in the 2 years before and after publication of TREAT (ordinary least squares regression), (2) adjusted likelihood of prescribing ESA after TREAT (clustered logistic regression), and (3) probability of receiving ESA therapy based on anemia status (χ(2) test). RESULTS: For patients with CKD stage 3, the proportion prescribed ESA therapy declined from 17% pre-TREAT to 11% post-TREAT (a 38% decline), and for those with CKD stage 4, from 34% to 27% (a 22% decline). Prescribing of ESA therapy was declining even before TREAT, but the decline accelerated in the post-TREAT period (stage 3: change of slope, -0.08 [P<0.001]; stage 4: change of slope, -0.16 [P<0.001]). ESA prescribing declined after TREAT regardless of anemia status; among patients with hemoglobin levels <10g/dL, only 25% of patients with CKD stage 3 and 33% of patients with stage 4 were prescribed ESAs 2 years after TREAT, a notable 50% decline. After adjusting for all covariates, the probability of prescribing ESAs was 35% lower during the 2-year period after versus before publication of TREAT (OR, 0.65; 95% CI, 0.63-0.67). LIMITATIONS: The cumulative effect of adverse safety concerns in the period before TREAT also influenced physician prescribing of ESA therapy and could not be separated from the influence of TREAT. CONCLUSIONS: TREAT appears to be a watershed study that was followed by a marked decline in ESA prescribing for patients with CKD.

Dialysis chains and placement on the waiting list for a cadaveric kidney transplant.

BACKGROUND: The proliferation of multi-unit for-profit dialysis chains in the ESRD industry has raised concerns for patient quality of care including access to renal transplantation therapy (RTT). The effect of dialysis facility chain status on RTT is unknown. METHODS: Data from the United States Renal Data System were used to identify 4,465 dialysis facilities and 56,714 dialysis patients who started hemodialysis in 2006. Patients were followed from initiation of hemodialysis in 2006 to placement on the renal transplant waiting list or to December 31, 2009. The role of dialysis facility chain status (affiliation, size, and ownership) on placement on the renal transplant waiting list was evaluated by multi-level mixed-effect regression models that account for clustering within facilities. RESULTS: Patients from for-profit chain facilities, compared to nonprofit chain facilities, were 13% (95% CI 0.77-0.98) less likely to be waitlisted. In contrast, among nonchains, facility ownership did not influence likelihood of being waitlisted. There was also a marginally significant difference in waiting list placement by chain size: large chains compared with mid or small chains were 8% (95% CI 0.84-1.00) less likely to place patients on the waiting list. After adjustment for patient and facility characteristics, dialysis facility chain affiliation (chain-affiliated or not) was not found to be independently associated with the likelihood of placement on the transplant waitlist. CONCLUSION: Dialysis chain affiliation expands previously observed ownership-related differences in placement on the waiting list. For-profit ownership of dialysis chain facilities appears to be a significant impediment to access to renal transplants.

Organizational status of dialysis facilities and patient outcome: does higher injectable medication use mediate increased mortality?

OBJECTIVE: Examine the mediating effect of injectable drugs in the relationship between dialysis facility organizational status and patient mortality. STUDY SETTING: Medicare dialysis population. STUDY DESIGN: Data from the U.S. Renal Data System (USRDS) were used to identify 3,884 freestanding dialysis facilities and 37,942 Medicare patients incident to end-stage renal disease (ESRD) in 2006. The role of injectable medications was evaluated during a 2-year follow-up period by mediational analyses using mixed-effect regression models. DATA COLLECTION: USRDS data were matched with Dialysis Facility Report data from Centers for Medicare and Medicaid Services (CMS) and census data. PRINCIPAL FINDINGS: There was a strong association found between organizational status and use of injectable drugs. Large for-profit chains used significantly higher injectable medications compared with nonprofit chains and independent facilities. However, the relationship between facility organizational status and patient mortality was not found to be mediated through the higher use of injectable drugs. CONCLUSIONS: Large for-profit chain facilities administered higher IV epoetin, iron, and vitamin D dosages, but this did not result in improved survival. Given the associated costs and lack of a survival benefit, the overuse of injectable medications among the U.S. dialysis patients will likely end under the recent bundling of injectable medications without jeopardizing patient outcomes.

High doses of epoetin do not lower mortality and cardiovascular risk among elderly hemodialysis patients with diabetes.

A randomized trial had suggested that high doses of erythropoiesis-stimulating agents (ESAs) might increase the risk of cardiovascular outcomes in predialysis diabetic patients. To evaluate this risk in diabetic patients receiving dialysis, we used data from 35,593 elderly Medicare patients on hemodialysis in the US Renal Data System of whom 19,034 were diabetic. A pooled logistic model was used to estimate the monthly probability of mortality and a composite cardiovascular end point. Inverse probability weighting was used to adjust for measured time-dependent confounding by indication, estimated separately for diabetic and non-diabetic cohorts. The adjusted 9-month mortality risk, significantly different between an ESA dose of 45,000 and 15,000 U/week, was 13% among diabetics and 5% among non-diabetics. In diabetic patients, the hazard ratio (HR) for more than 40,000 U/week was 1.32 for all-cause mortality and 1.26 for a composite end point of death and cardiovascular events compared with patients receiving 20,000 to 30,000 U/week. The corresponding HRs in non-diabetic patients were 1.06 and 1.10, respectively. A smaller effect of dose was found in non-diabetic patients. Thus, higher ESA doses, which are often necessary to achieve high hemoglobin levels, are not beneficial, and possibly harmful, to diabetic patients receiving dialysis. Our findings support a Food and Drug Administration advisory recommending that the lowest possible ESA dose be used to treat hemodialysis patients.

The effect of dialysis chains on mortality among patients receiving hemodialysis.

OBJECTIVE: To examine the association between dialysis facility chain affiliation and patient mortality. STUDY SETTING: Medicare dialysis population. STUDY DESIGN: Data from the United States Renal Data System (USRDS) were used to identify 3,601 free-standing dialysis facilities and 34,914 Medicare patients' incidence to end-stage renal disease (ESRD) in 2004. Mixed-effect regression models were used to estimate patient mortality by dialysis facility chain and profit status during the 2-year follow-up. DATA COLLECTION: USRDS data were matched with facility, cost, and census data. PRINCIPAL FINDINGS: Of the five largest dialysis chains, the lowest mortality risk was observed among patients dialyzed at nonprofit (NP) Chain 5 facilities. Compared with Chain 5, hazard ratios were 19 percent higher (95 percent CI 1.06-1.34) and 24 percent higher (95 percent CI 1.10-1.40) for patients dialyzed at for-profit (FP) Chain 1 and Chain 2 facilities, respectively. In addition, patients at FP facilities had a 13 percent higher risk of mortality than those in NP facilities (95 percent CI 1.06-1.22). CONCLUSIONS: Large chain affiliation is an independent risk factor for ESRD mortality in the United States. Given the movement toward further consolidation of large FP chains, reasons behind the increase in mortality require scrutiny.

Factors influencing route of administration for epoetin treatment among hemodialysis patients in the United States.

BACKGROUND: Published clinical guidelines advocate subcutaneous (SC) administration for epoetin therapy, although this is practiced among only 7% of all hemodialysis patients. Despite this disparity, few studies have examined factors associated with route of epoetin administration in hemodialysis patients. METHODS: Data from the Centers for Medicare & Medicaid Services End-Stage Renal Disease Clinical Performance Measures Project were used to identify 13,854 patients receiving hemodialysis in 3,069 dialysis facilities from October to December in 1999 and 2000. Unadjusted associations were examined by using t-test and chi-square test. Adjusted associations were estimated by using generalized estimating equations to control for clustering of patients within the same dialysis facility. RESULTS: In the United States, use of the SC route of epoetin administration varies widely across the country. After adjusting for patient sociodemographics and comorbidities, the greatest rates of SC therapy are found in the Midwest and West, in providers not affiliated with chains, and in hospital-based and not-for-profit freestanding units. Previous exposure to SC administration (as a predialysis or peritoneal dialysis patient) predicted subsequent SC use, for-profit and large chains were significantly less likely to use SC administration, and increased use of injectable drugs overall (to maximize income) was associated with less SC use. CONCLUSION: In addition to regional variation in SC use, study findings indicate that physician decision making for epoetin administration route is influenced primarily by type of ownership and financial incentives. Adherence to published clinical guidelines was not a consistent predictor of SC use. Given the similar effectiveness, but significantly decreased dose associated with SC epoetin, these findings suggest an enormous opportunity for cost savings for the Medicare program.

Hematocrit was not validated as a surrogate end point for survival among epoetin-treated hemodialysis patients.

OBJECTIVE: To evaluate the use of hematocrit as a surrogate end point for survival among end-stage renal disease (ESRD) patients treated with epoetin. STUDY DESIGN AND SETTING: Using United States Renal Data System (USRDS) data, we conducted an observational prospective study to analyze the relationships among epoetin dose, hematocrit, and survival for 31,301 facility-based hemodialysis patients incident to ESRD therapy in 1998. To address our objective, we used criteria developed by Prentice based on results from a Cox regression model. RESULTS: Results indicate that hematocrit is inversely associated with epoetin dose. For the same epoetin treatment-related achieved hematocrit levels, there were widely varying treatment-related survival outcomes, thereby challenging a central criterion required to empirically validate a surrogate end point. CONCLUSION: Our results support earlier clinical trial and epidemiological data suggesting that hematocrit may not be a valid surrogate for survival among the epoetin-treated renal failure population. We hypothesize that hematocrit may not be in the causal pathway or that epoetin may have important mechanisms of action apart from increasing hematocrit. Effective treatment for anemia may therefore not be simply a matter of increasing hematocrit. This study has potential implications for revising the existing treatment guidelines for anemia management and selecting an appropriate treatment regimen.

Epoetin requirements predict mortality in hemodialysis patients.

BACKGROUND: Anemia is a frequent complication of end-stage renal disease. Poor responsiveness to epoetin therapy hampers the management of anemia. Escalating epoetin doses often are used to overcome epoetin resistance. The objective of this study is to examine the relationship between epoetin dose requirements and mortality. METHODS: Using United States Renal Data System administrative claims data, we conducted a retrospective cohort study of 94,569 prevalent hemodialysis patients in 2000 and 2001. A Cox proportional hazard regression analysis, adjusted for baseline variables, and a 5-knot cubic regression spline were used to model the dose-response relationship between epoetin and all-cause mortality. RESULTS: Significant interpatient variation exists in epoetin dose requirements to attain defined hematocrit levels. For every hematocrit cohort studied, patients administered higher doses of epoetin had significantly lower hematocrit values and greater mortality rates. Using the cubic spline function, a significant nonlinear relationship between increased epoetin dose and mortality was found regardless of hematocrit (P < 0.0001), with the steepest increase in relative risk for death found after the 72.5th dose percentile. CONCLUSION: Epoetin dose requirement is an independent predictor of total mortality in hemodialysis patients after adjustment for hematocrit. Poor responders who continue to have low hematocrit values despite the administration of high epoetin doses may not necessarily benefit from more epoetin, but perhaps should be considered for other adjunctive therapies. In contrast to conventional wisdom, this study suggests that epoetin dosing requirements could provide important prognostic information beyond that predicted by hematocrit alone.

Improved survival with higher hematocrits: where is the evidence?

The Centers for Medicare and Medicaid Services (CMS) is reviewing Medicare coverage policy for recombinant human erythropoietin (epoetin) therapy. CMS officials are concerned that "Medicare spending on EPO may be higher than necessary without resulting in optimal patient benefit." Approximately 190 end-stage renal disease (ESRD) patients die each day-a mortality rate that has remained essentially unchanged since 1994-despite improvements in the "adequacy of dialysis, vascular access, and anemia management". To date, the evidence cited in support of a survival benefit of epoetin confuses the relationship between treatment response and outcomes with a causal effect of epoetin. A variety of mechanisms may account for a non-causal association between hematocrit and mortality can occur. We conclude that there is no basis for inferring the survival benefits (or detriments) of increasing a patient's hematocrit by adjusting the dosing of epoetin. Furthermore, we note that caution is required in administering large doses of epoetin to unresponsive patients in order to achieve the target hematocrit. A better understanding of the epoetin/survival relationship, well-grounded in science, is needed to provide a basis for CMS to improve its current epoetin policies, and may help to improve patient mortality.