Kidney Health Initiative ESKD Data Standards Project.

The end-stage kidney disease (ESKD) Data Standards Project was launched by the Kidney Health Initiative (KHI) with the goal of standardizing dialysis-related measurements for research use. KHI is a public-private partnership between the American Society of Nephrology, US Food and Drug Administration, and organizations with an interest in kidney disease. KHI promotes safe and effective patient-centered therapies for people with kidney disease. In 2018, KHI established a workgroup with expertise in nephrology, nursing, quality management, ESKD data, organizational management, and clinical research. The workgroup identified 5 topic areas and 8 specific measures for the development of standards on the basis of the existing ESKD Measurement Specification Manual published by the Centers for Medicare & Medicaid Services. The topic areas were ultrafiltration rate, vascular access, dialysis small solute clearance (3 data standards), hospitalization (2 data standards), and mortality. The research standards were approved by the workgroup, reviewed by external reviewers, and opened to public comment. The data standards attempt to achieve balance between brevity and completeness in the face of knowledge gaps. The ESKD Data Standards are publicly available on the KHI website (https://khi.asn-online.org/projects/project.aspx?ID=78).

Conversion from Intravenous Vitamin D Analogs to Oral Calcitriol in Patients Receiving Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: In the United States, intravenous vitamin D analogs are the first-line therapy for management of secondary hyperparathyroidism in hemodialysis patients. Outside the United States, oral calcitriol (1,25-dihydroxyvitamin D3) is routinely used. We examined standard laboratory parameters of patients on in-center hemodialysis receiving intravenous vitamin D who switched to oral calcitriol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study of adult patients treated within Fresenius Kidney Care clinics. During a 6-month period (December 2013 to May 2014), we identified patients on an intravenous vitamin D analog (doxercalciferol or paricalcitol) who switched to oral calcitriol and matched them to patients receiving an intravenous vitamin D analog. Mean serum calcium, phosphate, and intact parathyroid hormone (iPTH) concentrations were examined for up to 12 months of follow-up. We used Poisson and Cox proportional hazards regression models to examine hospitalization and survival rates. The primary analysis was conducted as intention-to-treat; secondary analyses included an as-treated evaluation. RESULTS: A total of 2280 patients who switched to oral calcitriol were matched to 2280 patients receiving intravenous vitamin D. Compared with patients on intravenous vitamin D, mean calcium and phosphate levels in the oral calcitriol group were lower after the change to oral calcitriol. In contrast, iPTH levels were higher in the oral calcitriol group. At 12 months, the percentage of patients with composite laboratories in target range (calcium <10 mg/dl, phosphate 3.0-5.5 mg/dl, and iPTH 150-600 pg/ml) were comparable between groups (45% versus 45%; P=0.96). Hospital admissions, length of hospital stay, and survival were comparable between groups. An as-treated analysis and excluding those receiving cinacalcet did not reveal significant between-group differences. CONCLUSIONS: Among patients receiving in-center hemodialysis who were switched to oral calcitriol versus those on an intravenous vitamin D analog, the aggregate of all mineral and bone laboratory parameters in range was largely similar between groups.

Mortality and Hospitalizations among Sickle Cell Disease Patients with End-Stage Kidney Disease Initiating Dialysis.

BACKGROUND: Sickle cell disease (SCD) is the most common inherited hematological disorder and a well-described risk factor for end-stage kidney disease (ESKD). Mortality and hospitalizations among patients with SCD who develop ESKD remain understudied. Furthermore, prior studies focused only on SCD patients where ESKD was caused by SCD. We aimed to describe mortality and hospitalization risk in all SCD patients initiating dialysis and explore risk factors for mortality and hospitalization. METHODS: We performed a national observational cohort study of African American ESKD patients initiating dialysis (2000-2014) in facilities affiliated with a large dialysis provider. SCD was identified by diagnosis codes and matched to a reference population (non-SCD) by age, sex, dialysis initiation year, and geographic region of care. Sensitivity analyses were conducted by restricting to patients where SCD was recorded as the cause of ESKD. RESULTS: We identified 504 SCD patients (mean age: 47 ± 14 years; 48% females) and 1,425 reference patients (mean age: 46 ± 14 years; 49% females). The median follow-up was 2.4 (IQR 1.0-4.5) years. Compared to the reference, SCD was associated with higher mortality risk (hazard ratio 1.66; 95% confidence interval [CI]: 1.36-2.03) and higher hospitalization rates (incidence rate ratio 2.12; 95% CI: 1.88-2.38) in multivariable analyses. Exploratory multivariable mortality risk models showed the largest mortality risk attenuation with the addition of time-varying hemoglobin and high-dose erythropoietin, but the association of SCD with mortality remained significant. Sensitivity analyses (restricted to ESKD caused by SCD) also showed significant associations between SCD and mortality and hospitalizations, but with larger effect estimates. High-dose erythropoietin was associated with the highest risk for mortality and hospitalization in SCD. CONCLUSIONS: Among ESKD patients, SCD is associated with a higher risk for mortality and hospitalization, particularly in patients where SCD is identified as the cause of ESKD.

One-Year Historical Cohort Study of the Phosphate Binder Sucroferric Oxyhydroxide in Patients on Maintenance Hemodialysis.

OBJECTIVE: The high pill burden of many phosphate binders (PBs) may contribute to increased prevalence of hyperphosphatemia and poor nutritional status observed among patients undergoing maintenance hemodialysis therapy. We examined the real-world effectiveness of sucroferric oxyhydroxide (SO), a PB with low pill burden, in managing serum phosphorus in patients with prevalent hemodialysis over a 1-year period. DESIGN: Historical cohort analyses of de-identified electronic medical records. SUBJECTS: In-center hemodialysis patients switched from another PB to SO therapy as part of routine care with 12 months of uninterrupted SO prescriptions recorded, and documented serum phosphorus levels were eligible for inclusion. Clinical data were extracted from a pharmacy service, FreseniusRx, database and Fresenius Kidney Care clinical data warehouse. MAIN OUTCOME MEASURES: Comparisons were made between the 91-day period before SO initiation (i.e., baseline) and the 4 consecutive 91-day intervals of SO treatment (Q1-Q4). Clinical measures included achievement of target phosphorus levels (≤5.5 mg/dL) and mean number of PB pills/day. RESULTS: Among 530 analyzed patients, the proportion achieving target serum phosphorus levels increased by >100% 1 year after switching to SO therapy, that is, from 17.7% at baseline to 24.5%, 30.5%, 36.4%, and 36.0% at Q1 through Q4, respectively (P < .0001 for all). Reductions in serum phosphorus were observed at all follow-up timepoints (P < .0001), irrespective of baseline PB. From a mean baseline PB pill burden of 8.5 pills/day, patients experienced an average 50% pill burden reduction during SO treatment (P < .0001). Phosphorus-attuned albumin and phosphorus-attuned protein intake (normalized protein catabolic rate) improved significantly after transition to SO (P < .0001). The effectiveness of SO was evident in prespecified subgroups of interest (i.e., black/African-American patients, Hispanic/Latino patients, and women). CONCLUSION: Among patients on hemodialysis, switching to SO resulted in a 2-fold greater likelihood of achieving target phosphorus levels while halving daily PB pill burden. Increases in phosphorus-attuned albumin and protein intake suggest improved nutritional status.

Association of Smoking Status With Mortality and Hospitalization in Hemodialysis Patients.

RATIONALE & OBJECTIVE: The relationship between tobacco smoking and comorbid condition outcomes in hemodialysis (HD) patients is not well understood. This study examined the association of tobacco smoking status with hospitalization and mortality in HD patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult HD patients at 2,223 US dialysis centers with HD vintage of 30 days or less who completed a tobacco smoking status survey as part of standard care between April 2013 and June 2015. PREDICTOR: Tobacco smoking category: never smoked, currently living with smoker, former smoker, moderate smoker (<1 pack per day), or heavy smoker (≥1 pack per day). OUTCOMES: Death and hospital admissions within 2 years of the tobacco smoking survey. ANALYTICAL APPROACH: Kaplan-Meier analysis and Cox proportional hazards regression for time to death; cumulative incidence function and Cox proportional hazards regression for time to first hospitalization; negative-binomial regression for number of hospitalizations. RESULTS: Of 22,230 patients studied, 13% were active smokers. Mortality probabilities increased with greater exposure to smoking (17%, 22%, 23%, and 27% for never, moderate, former, and heavy smokers, respectively; P<0.001), as did incidence rates for first hospitalization (23%, 27%, 27%, and 30%, respectively; P<0.001). Compared to never smoked, heavy smokers had the highest mortality rate (HR for heavy smokers, 1.41 [95% CI, 1.18-1.69]; HR for moderate smokers, 1.39 [95% CI, 1.24-1.55]; HR for former smokers, 1.19 [95% CI, 1.11-1.28]). Living with a smoker was not associated with mortality (HR, 0.93; 95% CI, 0.72-1.22). HRs for first hospitalization followed similar patterns. The incidence rate of mortality for active smokers with diabetes was 173.7/1,000 patient-years and 103.5/1,000 patient-years for those who never smoked (incidence rate ratio, 1.68; P<0.001). LIMITATIONS: Self-reported survey without detailed history of smoking/cessation. CONCLUSIONS: Risks for death and hospitalization are elevated among HD patients who smoke, being highest among younger individuals and those with diabetes. Second-hand smoke was not associated with poor clinical outcomes.

Real-World Scenario Improvements in Serum Phosphorus Levels and Pill Burden in Peritoneal Dialysis Patients Treated with Sucroferric Oxyhydroxide.

BACKGROUND: A database analysis was conducted to assess the effectiveness of sucroferric oxyhydroxide (SO) on lowering serum phosphorus and phosphate binder (PB) pill burden among adult peritoneal dialysis (PD) patients prescribed SO as part of routine care. METHODS: Adult PD patients (n = 258) prescribed SO through a renal pharmacy service were analyzed. Baseline was 3 months before SO prescription. SO-treated follow-up was for 6 months or until either a new PB was prescribed, SO was not refilled, PD modality changed, or patient was discharged. In-range serum phosphorus was defined as ≤5.5 mg/dL. RESULTS: At baseline, mean serum phosphorus was 6.59 mg/dL with 10 prescribed PB pills/day. The proportion of patients achieving in-range serum phosphorus increased by 72% from baseline to month 6. Prescribed PB pills/day decreased by 57% (10 at baseline to 4.3 at SO follow-up, p < 0.0001). The mean length of SO follow-up was 5.1 months; SO follow-up ended for 38, 27, and 50 patients at months 4, 5, and 6, respectively, due to no further PB fills, and for 10, 11, and 4 patients at months 4, 5, and 6, respectively, due to another PB prescribed. In patients with baseline serum phosphorus >5.5 mg/dL who achieved in-range serum phosphorus during SO follow-up for ≥1 quarter, a notable improvement in serum phosphorus (6.54 to 5.10 mg/dL, p < 0.0001) was observed, and there was a 53% reduction in PB pill burden (9.9 to 4.7, p < 0.0001). CONCLUSION: Among PD patients prescribed SO as part of routine care, improvements in serum phosphorus control and >50% reduction in PB pills/day were observed.

Real-world effectiveness of sucroferric oxyhydroxide in patients on chronic hemodialysis: A retrospective analysis of pharmacy data
.

AIMS: Hyperphosphatemia has been associated with an increased risk of mortality in patients with end-stage renal disease. We sought to assess the real-world effectiveness of sucroferric oxyhydroxide (SO), an iron-based phosphate binder (PB), in control of serum phosphorus levels, and to determine the associated pill burden in hemodialysis patients. MATERIALS AND METHODS: Adult, in-center hemodialysis patients first prescribed SO through a renal pharmacy service as part of routine clinical care between April 1, 2014 and March 31, 2015 were included in the analysis. The proportion of patients with phosphorus levels ≤ 5.5 mg/dL and the mean prescribed PB pills/day were compared between baseline (3 months prior to SO) and SO follow-up at 3 (SO 1 - 3) and 6 months (SO 4 - 6). Mineral bone disease markers, hemoglobin, iron indices, and erythropoiesis-stimulating agents and intravenous iron use were assessed. RESULTS: At baseline, all patients (n = 1,029) were prescribed PB, and 13.9% had mean serum phosphorus ≤ 5.5 mg/dL. Comparing baseline to SO 1 - 3, the mean prescribed PB pills/day declined from 9.6 to 3.8 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 13.9 to 26.1% (+88%). Comparing baseline to SO 4 - 6 (n = 424), the mean prescribed PB pills/day declined from 9.7 to 4.0 pills/day (p < 0.001), and the proportion of patients with serum phosphorus ≤ 5.5 mg/dL increased from 15.6 to 30.4% (+95%). CONCLUSIONS: Prescription of SO was associated with an increase in the proportion of patients achieving serum phosphorus levels ≤ 5.5 mg/dL along with fewer prescribed PB pills/day.
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Anemia management in patients receiving chronic hemodialysis.

Anemia treatment in hemodialysis-dependent (HDD) CKD patients involves adequate supply of iron and an erythropoiesis-stimulating agent (ESA). Despite widespread usage of these agents, there is no generally accepted "standard dosing algorithm" for treating anemia in HDD-CKD patients. The new anemia Quality Incentive Program (QIP) introduced by the Centers for Medicare & Medicaid Services represents a motivation to standardize and harmonize iron and ESA regimens with interactive electronic algorithms and novel modes of deliveries for IV iron and ESA doses. In addition, quality assessment and performance improvement programs at dialysis facilities include achieving measurable improvement in health outcomes, healthcare cost, and reductions in medical errors. Thus, the Corporate Medical Advisory Board for Fresenius Medical Services (FMS) is evaluating an anemia algorithm that will be incorporated into the automated workflow of a new clinical system at FMS clinics. In the future, such systems might communicate with medication pumps incorporated into state-of-the-art HD machines, thereby eliminating manual data entry of medication orders and other potential errors related to data entry or administration of medications such as ESA and IV iron. In addition, the CritLine III TQA Monitor, which allows real-time blood volume, oxygen, and anemia monitoring during HD in acute and chronic settings, may become an integrated diagnostic tool to improve volume and anemia management through better fluid management and ESA dose adjustment algorithms. These novel interactive electronic algorithms, delivery and monitoring methods, and data transfer may be integrated in the Pharmatech process to meet patient-specific anemia therapy.

Application of kinetic modeling to mineral metabolism management.

Patients with CKD face many consequences of renal failure, including disorders of bone and mineral metabolism. The current approach to management of these mineral metabolism issues lacks comprehensive quantitative assessment, so a kinetic modeling program has been designed to quantify intake and removal of phosphorus and calcium, as well as provide recommendations for treatment and prescriptions based on total mass balance and serum concentrations. This program is known as phosphorus kinetic modeling or PKM. The modeling program and associated graphical reports have been developed as a tool for clinicians in the management of mineral metabolism in CKD patients.

International Quotidian Dialysis Registry: Annual report 2010.

The International Quotidian Dialysis Registry (IQDR) is a global initiative designed to study practices and outcomes associated with the use of hemodialysis (HD) regimens of increased frequency and/or duration. The IQDR grew out of the initiative that lead to the randomized prospective studies of nocturnal HD and short hours daily dialysis vs. conventional thrice weekly HD that are conducted by the Frequent Hemodialysis Network sponsored by the National Institutes of Health. These 2 separate studies are drawing to a close and the first results are expected to be reported later this year. These studies use surrogate outcomes for their primary endpoints as they are not powered to look at outcomes of mortality and hospitalization. The IQDR attempts to aggregate long-term follow-up data from centers utilizing alternative HD regimens worldwide and will have adequate statistical power to examine those important outcomes. To date, the IQDR has enrolled patients from Canada, the United States, Australia, New Zealand, and France and has linked with commercial databases and national registries. This sixth annual report of the IQDR describes: (1) An update on the governance structure; (2) The recommendations made at the first general meetings of the IQDR Scientific Committee and Advisory Board; (3) The status of those recommendations; (4) A summary of current data sources and participating registries; (5) The status of recruitment to date; (6) The creation of a specific Canadian IQDR data set and; (7) The current research agenda.

International Quotidian Dialysis Registry: annual report 2009.

The International Quotidian Dialysis Registry (IQDR) is a global initiative designed to study practices and outcomes associated with the use of hemodialysis regimens of increased frequency and/or duration. Several small studies suggest that compared with conventional hemodialysis (HD), short-daily, nocturnal, and long conventional HD regimens may improve surrogate endpoints and quality of life. However, methodologically robust comparisons on hard outcomes are sorely lacking. The IQDR represents the first-ever attempt to aggregate long-term follow-up data from centers utilizing alternative HD regimens worldwide, and will have adequate statistical power to examine the effects of these regimens on multiple clinical endpoints, including mortality. To date, the IQDR has enrolled patients from Canada, the United States, Australia, and New Zealand, with plans in place to begin linking with additional commercial databases and national registries. This fifth annual report of the IQDR describes (1) a proposed governance structure that will facilitate international collaboration, stakeholder input and funding; (2) data sources and participating registries; (3) recruitment to date and patient baseline characteristics; and (4) an agenda for future research.

Home hemodialysis: a comparison of in-center and home hemodialysis therapy in a cohort of successful home hemodialysis patients.

We retrospectively evaluated 29 patients dialyzed for 6 months in-center on Fresenius 2008H or 2008K dialysis machines followed by 6 months at home using the Fresenius 2008K@home to determine the safety and efficacy of home hemodialysis (HHD) using the 2008K@home. Patients who initiated HHD were identified from order records and qualified for inclusion if they had available records and a minimum of three pre- and postdialysis blood urea nitrogen measurements during each period. Dialysis adequacy (mean standard weekly Kt/V) remained stable during the in-center (IC; 2.3 +/- 0.7 start, 2.3 +/- 0.7 end) and home periods (2.4 +/- 0.6 start, 2.5 +/- 0.7 end). During the home period, the percentage of delivered/prescribed single pool Kt/V was 96% +/- 12%; delivered/prescribed treatment time 98% +/- 10%; delivered/prescribed blood flow 95% +/- 7%, and delivered/prescribed dialysate flow was 99% +/- 8%. Twelve patients had 69 adverse events (5.84/100 treatments) IC and 18 patients had 40 (3.34/100 treatments) at home. No deaths were reported. In conclusion, a group of successful HHD patients received their prescribed hemodialysis therapy with the same or better adequacy as provided IC with no increase in adverse events. This demonstrates that selected patients can deliver HHD as safely and effectively as when receiving hemodialysis IC.

The International Quotidian Dialysis Registry: Annual report 2008.

Alternative hemodialysis (HD) schedules, including short-daily and nocturnal HD, continue to proliferate, with the hope of offering improved patient outcomes. Three nights per week and every other night, nocturnal HD are now being provided to more patients worldwide, both at home and in-center. However, alternative HD schedules are still experimental in most centers, and studies establishing the efficacy of these therapies with respect to major clinical outcomes are needed. Endorsed by the National Institutes of Health, the International Quotidian Dialysis Registry is an international collaboration that was established in 2002 to prospectively study large numbers of patients treated with alternate HD schedules. The Registry will ultimately allow alternate HD modalities to be compared to conventional thrice-weekly HD with respect to clinical endpoints, including mortality, using a prospective cohort study. To date, the Registry has enrolled 182, 1193, and 740 subjects from Canada, the United States, and Australia, respectively. This report is the fourth annual update and describes recruitment progress, baseline characteristics of enrolled patients, and worldwide prescription patterns.

Impact of the change in CMS billing rules for erythropoietin on hemoglobin outcomes in dialysis patients.

On April 1, 2006, new Centers for Medicare and Medicaid Services (CMS) rules for billing erythropoietin (EPO) for dialysis patients went into effect. Two key provisions of the rules were to cap the dose for a single patient at 500,000 IU/month and to mandate a 25% reduction in dose for patients whose latest hemoglobin (HGB) or hematocrit (HCT) in the prior month exceeded 13 g/dl or 39%, respectively. The purpose of this article is to document the effect of the rules change on HGB outcomes in a single large dialysis provider whose computer system was modified to enforce the rules. HGB and EPO doses for 5 months following the implementation were analyzed retrospectively. The most noteworthy observation is that while the rule appears to have reduced the percentage of patients with an HGB of >13 g/dl slightly, it has also increased the percentage of patients with HGB in the medically undesirable range of <11 g/dl.

The epidemiology of systolic blood pressure and death risk in hemodialysis patients.

BACKGROUND: This study compares the associations of predialysis systolic blood pressure (SBP) with mortality risk in both incident and prevalent hemodialysis (HD) cohorts by using both conventional and time-varying Cox analyses, thus addressing limitations of prior studies. METHODS: A total of 56,338 incident patients starting HD therapy during 1997 to 2001 and 69,590 prevalent HD patients on January 1, 2002, were grouped into the following categories: (1) SBP less than 120 mm Hg, (2) 120 < or = SBP < 140 mm Hg, (3) 140 < or = SBP < 160 mm Hg, (4) 160 < or = SBP < 180 mm Hg, (5) 180 < or = SBP < 200 mm Hg, and (6) SBP of 200 mm Hg or greater. Conventional and time-varying models evaluated 1-year and 3-year (incident patients only) survival. RESULTS: Nine percent and 26.0% of incident patients and 5.7% and 20.1% of prevalent patients were in categories 1 and 2, respectively. Their associated 1-year hazard ratios (HRs) were 2.63 to 3.68 and 1.57 to 1.68 compared with category 4, the reference group. HRs for categories 3, 5, and 6 were not different from category 4. Time-varying models magnified category 1 and 2 HRs to 5.54 to 7.42 and 1.92 to 2.21, such that 25% to 35% of patients in the target SBP range (< 140 mm Hg) had the greatest risk. A "reversed J-shaped" risk profile emerged in the time-varying models, with very high SBP (category 6) associated with HRs of 1.52 to 1.55, but only 1% of patients were in category 6. Three-year outcomes were similar. CONCLUSION: Epidemiological characteristics of predialysis SBP consistently differ from those in the general population despite different analytic perspectives. The data suggest a need for greater investigative, diagnostic, and therapeutic focus on HD patients with normal and prehypertensive blood pressure ranges.

Epoetin alfa use in patients with ESRD: an analysis of recent US prescribing patterns and hemoglobin outcomes.

BACKGROUND: It is unknown to what degree physicians adjust erythropoietin doses to achieve hemoglobin levels (11.0 to 12.0 g/dL [110 to 120 g/L]) recommended by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) for patients with end-stage renal disease receiving hemodialysis. Our objective is to examine epoetin alfa prescribing patterns for achieving the target hemoglobin level range in this population. METHODS: Monthly hemoglobin levels and epoetin alfa doses from 2 large databases were retrospectively analyzed. One data set comprised 31,267 patients from the Fresenius Medical Care-North America (FMC-NA) database, and the other comprised 128,761 patients based on claims for Medicare services. RESULTS: Longitudinal evaluation of the FMC-NA data set showed that hemoglobin levels in patients administered epoetin alfa cycled in and out of the NKF-K/DOQI hemoglobin target range, and doses were decreased in 98.8% of patients with persistent hemoglobin levels greater than 12.0 g/dL (> 120 g/L). Hemoglobin levels in patients from the Medicare data set that initially were outside the target range migrated into the range with epoetin alfa dose titration. FMC-NA patients with a 3-month average hemoglobin level less than 11.0 g/dL (< 110 g/L) were administered significantly greater epoetin alfa doses than those with average hemoglobin levels greater than 12.0 g/dL (> 120 g/L; 21,838 versus 13,503 U/wk; P < 0.0001). Less than 0.4% of patients administered epoetin alfa were persistently anemic (hemoglobin < 11.0 g/dL [< 110 g/L]) and were administered persistently high doses (> 30,000 U/wk), but failed to respond with a 0.5-g/dL or greater (> or = 5-g/L) increase in hemoglobin levels. CONCLUSION: In these analyses, few hemodialysis patients experienced persistent anemia while being administered high epoetin alfa doses. Physicians appeared to appropriately adjust doses to achieve hemoglobin levels recommended by the NKF-K/DOQI guidelines.