The Phosphate Binder Ferric Citrate and Mineral Metabolism and Inflammatory Markers in Maintenance Dialysis Patients: Results From Prespecified Analyses of a Randomized Clinical Trial.

BACKGROUND: Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. STUDY DESIGN: 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. SETTING & PARTICIPANTS: Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders. INTERVENTION: 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). OUTCOMES: Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. MEASUREMENTS: Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. RESULTS: There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25 mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95 mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1 pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. LIMITATIONS: Open-label study, few peritoneal dialysis patients. CONCLUSIONS: Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.

Reassessment of albumin as a nutritional marker in kidney disease.

The decision by nephrologists, renal dietitians, federal agencies, health care payers, large dialysis organizations, and the research community to embrace serum albumin as an important index of nutrition and clinical performance is based on numerous misconceptions. Patients with analbuminemia are not malnourished and individuals with simple malnutrition are rarely hypoalbuminemic. With the possible exception of kwashiorkor, a rare nutritional state, serum albumin is an unreliable marker of nutritional status. Furthermore, nutritional supplementation has not been clearly shown to raise levels of serum albumin. The use of serum albumin as a quality care index is also problematic. It has encouraged a reflexive reliance on expensive and unproven interventions such as dietary supplements and may lead to adverse selection of healthier patients by health care providers. The authors offer a rationale for considering albumin as a marker of illness rather than nutrition. Viewed in this manner, hypoalbuminemia may offer an opportunity to improve patient well-being by identifying and treating the underlying disorder.

SARS-CoV-2 Antibody Seroprevalence Among Maintenance Dialysis Patients in the United States.

RATIONALE & OBJECTIVE: Reported coronavirus disease 2019 (COVID-19) cases underestimate the actual number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Patients receiving maintenance dialysis are at high risk for COVID-19 and higher case rates have been reported relative to the general population. To better understand infection patterns, we performed a seroprevalence study among maintenance dialysis patients at a large dialysis organization in the United States. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: We measured immunoglobulin G antibodies in an institutional review board-approved study of remnant serum samples collected for routine laboratory screenings in a national sample of 12,932 maintenance dialysis patients (May 27 to July 1, 2020). EXPOSURE: State, sex, age, and race. OUTCOMES: Seropositivity; ratio of seropositivity to known COVID-19 case rate. ANALYTIC APPROACH: Seropositivity was calculated overall and by state, sex, age, and race. The ratio of seropositivity to known COVID-19 cases was calculated overall and by state. RESULTS: 747 (5.8%) samples were seropositive. Seroprevalence varied by state and was lowest in Kentucky (1.0%) and highest in New York (23.6%). Seroprevalence was similar among men and women. Among samples from patients younger than 70 years, 6.0% to 6.5% were seropositive; whereas 5.2% and 3.9% of samples from patients aged 70 to 79 and 80 years or older, respectively, were seropositive. Samples from Black and Hispanic patients were 7.3% and 7.7% positive, respectively, compared with 2.8% of samples from White patients. After adjustment, risk differences among racial groups were lower but not eliminated. During the study period, the known COVID-19 case rate was 3.3%. The ratio of seropositivity to known COVID-19 cases was 1.7. LIMITATIONS: Imperfect assay sensitivity; results represent infections occurring before July 2020; deidentification prevented comparison of antibodies to previous COVID-19 status for individual patients; may not generalize to patients dialyzing with other providers or in other countries. CONCLUSIONS: Seroprevalence was 5.8% among dialysis patients as of July 1, 2020. This indicates that the actual number of infections was 1.7 times greater than reported cases. This ratio is lower than reported in the general population, suggesting that there were fewer unknown infections among maintenance dialysis patients.

Management of chronic kidney disease mineral-bone disorder.

Chronic kidney disease mineral-bone disorder (CKD-MBD) is a systemic disorder of abnormal serum levels of mineral-related biochemistries, abnormal bone, and extraskeletal calcification. Although we have gained understanding on how these components are interrelated, our therapeutic tools remain focused on only one aspect of CKD-MBD at a time. However, the management of these disorders is also interrelated; treatments may help one aspect of the disorder but cause or accelerate another. As such, management remains a major challenge to nephrologists and requires balancing risk and benefit of the various available therapies. Our challenge for the decade ahead is to determine which combinations of therapy can be used safely together to prevent morbidity and mortality in CKD. Furthermore, the pathophysiology that sets these events into motion begins well before the onset of ESRD. Future therapies and guidelines should, therefore, also emphasize the need for earlier detection and management of CKD, shaped by the results of valid clinical trials.

Managing hyperphosphatemia in patients with chronic kidney disease on dialysis with ferric citrate: latest evidence and clinical usefulness.

Ferric citrate is a novel phosphate binder that allows the simultaneous treatment of hyperphosphatemia and iron deficiency in patients being treated for end-stage renal disease with hemodialysis (HD). Multiple clinical trials in HD patients have uniformly and consistently demonstrated the efficacy of the drug in controlling hyperphosphatemia with a good safety profile, leading the US Food and Drug Administration in 2014 to approve its use for that indication. A concurrent beneficial effect, while using ferric citrate as a phosphate binder, is its salutary effect in HD patients with iron deficiency being treated with an erythropoietin-stimulating agent (ESA) in restoring iron that becomes available for reversing chronic kidney disease (CKD)-related anemia. Ferric citrate has also been shown in several studies to diminish the need for intravenous iron treatment and to reduce the requirement for ESA. Ferric citrate is thus a preferred phosphate binder that helps resolve CKD-related mineral bone disease and iron-deficiency anemia.

Nephrologists' professional ethics in dialysis practices.

Although the number of incidents is unknown, professional quality-oriented renal organizations have become aware of an increased number of complaints regarding nephrologists who approach patients with the purpose of influencing patients to change nephrologists or dialysis facilities (hereinafter referred to as patient solicitation). This development prompted the Forum of ESRD Networks and the Renal Physicians Association to publish a policy statement on professionalism and ethics in medical practice as these concepts relate to patient solicitation. Also common but not new is the practice of nephrologists trying to recruit their own patients to a new dialysis unit in which they have a financial interest. This paper presents two illustrative cases and provides an ethical framework for analyzing patient solicitation and physician conflict of interest. This work concludes that, in the absence of objective data that medical treatment is better elsewhere, nephrologists who attempt to influence patients to change nephrologists or dialysis facilities fall short of accepted ethical standards pertaining to professional conduct, particularly with regard to the physician-patient relationship, informed consent, continuity of care, and conflict of interest.

Making measures count.

An abundance of available laboratory information has led in part to the establishment of quantitative performance goals that use serum albumin, hemoglobin, Kt/V, and bone mineral indices to track quality of medical care and even physician reimbursement. As we look to the future, the next generation of measures should should more specifically reflect efforts to improve more fundamental outcomes, such as mortality, hospitalization, and quality of life. In this essay we address the important question of how clinicians can translate rich sources of quantitative data into a service that makes a difference in our patients' lives; a way to distinguish exemplary from ordinary care; a means to support continuous improvement in our care patterns individually and as part of larger, integrated health care systems all while avoiding prematurely advocating flawed quality measures. We also offer a pathway for how future quality measures can be developed. Our ultimate goal is to individualize quantitative assessments and by doing so encourage more meaningful, patient-oriented care that will lead to improved outcomes, greater physician job satisfaction, and wiser allocation of scarce resources.

Satisfaction with renal replacement therapy and education: the American Association of Kidney Patients survey.

BACKGROUND AND OBJECTIVES: This study was undertaken by the American Association of Kidney Patients (AAKP) to better understand ESRD patients' satisfaction with their current renal replacement therapy (RRT) and the education they received before initiating therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In addition to an open invitation on the AAKP website, nearly 9000 ESRD patients received invitations to complete the survey, which consisted of 46 questions. Satisfaction was measured on a 1 (extremely dissatisfied) to 7 (extremely satisfied) scale. RESULTS: Survey respondents were younger, more highly educated, and more likely to be white as well as employed as compared with the U.S. dialysis population. A total of 977 patients responded. Overall patient satisfaction with current RRT treatment varied from a low of 4.5 for in-center hemodialysis (ICHD) to a high of 6.1 in transplant (TX) patients. Peritoneal dialysis (PD) and home hemodialysis (HHD) mean scores were 5.2 and 5.5, respectively. PD, HHD, and TX patients' satisfaction scores were significantly higher than those of ICHD patients (P < 0.05). Approximately 31% of respondents felt that the therapies were not equally and fairly presented as treatment options, and 32% responded that they were not educated regarding HHD. CONCLUSIONS: ESRD patients are not uniformly advised about all possible treatment methods and hence were only moderately satisfied with their pretreatment education. Once on RRT, those on a home therapy or with a kidney TX are more satisfied than those with ICHD.

The internet as a tool for the renal community.

The Internet has impacted health care. With the introduction of the personal health record (PHR), patients have an opportunity to track their physician visits, medications, and laboratory values online in a pleasant and informative learning environment. The PHR is a secure, online, Internet-accessible method of storing and easily retrieving health information about one's medical history, physician visits, laboratory values, and medications. The American Association of Kidney Patients (AAKP) has taken the leadership role in developing a PHR for patients of the kidney community. There are several barriers that patients experience when using the Web for health resources. These include inaccurate or self-serving information and marketing statements that can be misleading and dangerous. Poorly written or inappropriate information for patients can be problematic, as can an abundance of extraneous information. For the most part, the public often has no way to judge what is and is not credible based on the context of the article alone. This article gives the reader a review of several Web resources that are available for patients and also for renal professionals. They are largely from large nonprofit organizations like the AAKP, National Kidney Foundation, Medical Education Institute, American Society of Nephrology, or The Nephron Information Center (nephron.com). This article also reviews sites from The National Kidney Disease Education Program, Hypertension-Dialysis and Clinical Nephrology, National Institute of Diabetes and Digestive and Kidney Diseases, and DaVita.

The Physician Quality Reporting Initiative: a practical approach to implementing quality reporting.

The Physician Quality Reporting Initiative (PQRI) is a voluntary program in which Medicare encourages eligible physicians in the United States to report on specific quality measures. This article is a case study of the implementation of PQRI reporting by Kidney Associates, a nephrology practice in Houston, TX. After reviewing and discussing 74 potential measures, the group narrowed the selection to 5 and chose 1 office measure and 2 dialysis measures. PQRI reporting was established through an Encounter Note template that forced a required entry for whether a patient was diabetic. For each diabetic, blood pressures were entered in the template and appropriate G-codes were created, which were then selected and linked with the diabetes International Classification of Diseases, Ninth Revision code and electronically submitted for billing. The dialysis measures were automatically selected from the urea reduction rate and hematocrit (hemoglobin x 3) measures that were received for each patient on a regular basis from a large dialysis chain. Software was developed to parse these data, evaluate them, and generate the appropriate G-codes. At the end of the billing cycle, these data were exported through a standard spreadsheet formatting along with the billing G codes, and claims were submitted. The system was cost-effective to implement, required minimal education, and achieved 100% cooperation through feedback education and rapid correction of systems issues. Kidney Associates was able to show that PQRI reporting is easy to implement with minimal expense and staff labor. Sharing these methods with other practices should facilitate the implementation of efficient reporting systems.

Static intra-access pressure ratio does not correlate with access blood flow.

BACKGROUND: Access flow (Qa) measurement is recommended by Kidney Disease Outcomes Quality Initiative (K/DOQI) as the preferred method for access surveillance. Static intra-access pressure ratio (SIAPR) measurement is the second surveillance method of choice. The purpose of this prospective multicenter study was to investigate the relationship between SIAPR and Qa and to examine the premise upon which SIAPR surveillance is based-namely, that high SIAPR is a surrogate for low Qa associated with hemodynamically significant stenosis. METHODS: SIAPR and Qa (HD01; Transonic Systems, Inc., Ithaca, NY, USA) were simultaneously measured monthly in 242 patients [146 prosthetic arteriovenous bridge grafts (AVG), 96 autogenous arteriovenous fistulas (AVF)] from three centers. SIAPR was measured according to the K/DOQI protocol. RESULTS: There was no correlation between Qa and venous or arterial SIAPR in AVGs (R(2)= 0.0037 and R(2)= 0.006, respectively, N= 730), or in AVFs (R(2)= 0.0247 and R(2)= 0.0329, respectively, N= 431). Of the high SIAPR measurements in AVGs, 81% and 50% were associated with Qa > or =600 and Qa > or =1000 mL/min, respectively. Of the AVGs studied, 41% (60/146) had consistently high Qa > or =1000 mL/min. Seventy percent (42/60) of these high-Qa AVGs had at least two consecutive sessions with high SIAPR measurements, thereby meeting the K/DOQI SIAPR criteria for referral. In addition, 78% (14/18) of new AVGs with Qa > or =1000 mL/min, and 86% (6/7) of AVGs with the highest Qa (> or =2000 mL/min), had high SIAPR. As a result, these high-Qa AVGs, which represented the best functioning AVGs by K/DOQI Qa standards, were erroneously targeted for referral based on SIAPR measurements. CONCLUSION: SIAPR does not correlate with Qa or discriminate between high and low Qa. Therefore, because the utility of SIAPR surveillance for detection of clinically significant stenosis depends on a correlation with Qa, the current use of absolute K/DOQI SIAPR thresholds for intervention based on the presumption that such thresholds are indicative of low Qa is not justified, and should be discontinued. Studies need to be done to examine the utility of SIAPR for trend analysis.

Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compared to placebo and iron dextran.

BACKGROUND: Parenteral iron is often required by hemodialysis patients to maintain adequate iron stores. Until recently, the only available form of intravenous iron was iron dextran, which is associated with significant adverse reactions, including anaphylaxis and death. Sodium ferric gluconate complex (SFGC) was recently approved for use in the U.S. under FDA's priority drug review. This Phase IV study was designed to evaluate the safety of a single dose of intravenous SFGC as compared to placebo and a historical iron dextran control. METHODS: This multicenter, crossover, randomized, double blind, placebo-controlled prospective comparative study was performed in hemodialysis patients requiring at least 125 mg of elemental iron. The historical control was obtained from a meta-analysis of four publications examining outcomes in patients exposed to iron dextran. SFGC naïve patients were administered SFGC without a test dose, undiluted, at a rate of 125 mg over 10 minutes, and compared to placebo comprising bacteriostatic saline. RESULTS: A total of 2534 patients were enrolled. The incidence of drug intolerance (an adverse event precluding re-exposure) was significantly less [0.44%, confidence interval (CI) 0.21 to 0.71%] after SFGC as compared to the iron dextran control (2.47%, CI 1.87 to 3.07%, P < 0.0001), but higher than after placebo (0.1%, P = 0.02). There was no difference found between SFGC and placebo in serious adverse events. A single life-threatening event occurred after SFGC (0.04%, CI 0.00 to 0.22%), which was significantly less than following iron dextran (0.61%, CI 0.36 to 0.86%), P = 0.0001. CONCLUSION: SFGC is well tolerated when given by intravenous push without a test dose. SFGC has a significantly lower incidence of drug intolerance and life-threatening events as compared to previous studies using iron dextran. The routine use of iron dextran in hemodialysis patients should be discontinued.