Norma J. Ofsthun

Mineral Metabolism, Mortality, and Morbidity in Maintenance Hemodialysis

Mortality rates in ESRD are unacceptably high. Disorders of mineral metabolism (hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism) are potentially modifiable. For determining associations among disorders of mineral metabolism, mortality, and morbidity in hemodialysis patients, data on 40,538 hemodialysis patients with at least one determination of serum phosphorus and calcium during the last 3 mo of 1997 were analyzed. Unadjusted, case mix-adjusted, and multivariable-adjusted relative risks of death were calculated for categories of serum phosphorus, calcium, calcium x phosphorus product, and intact parathyroid hormone (PTH) using proportional hazards regression. Also determined was whether disorders of mineral metabolism were associated with all-cause, cardiovascular, infection-related, fracture-related, and vascular access-related hospitalization. After adjustment for case mix and laboratory variables, serum phosphorus concentrations >5.0 mg/dl were associated with an increased relative risk of death (1.07, 1.25, 1.43, 1.67, and 2.02 for serum phosphorus 5.0 to 6.0, 6.0 to 7.0, 7.0 to 8.0, 8.0 to 9.0, and >/=9.0 mg/dl). Higher adjusted serum calcium concentrations were also associated with an increased risk of death, even when examined within narrow ranges of serum phosphorus. Moderate to severe hyperparathyroidism (PTH concentrations >/=600 pg/ml) was associated with an increase in the relative risk of death, whereas more modest increases in PTH were not. When examined collectively, the population attributable risk percentage for disorders of mineral metabolism was 17.5%, owing largely to the high prevalence of hyperphosphatemia. Hyperphosphatemia and hyperparathyroidism were significantly associated with all-cause, cardiovascular, and fracture-related hospitalization. Disorders of mineral metabolism are independently associated with mortality and morbidity associated with cardiovascular disease and fracture in hemodialysis patients.

Survival with Three-Times Weekly In-Center Nocturnal Versus Conventional Hemodialysis

Whether the duration of hemodialysis treatments improves outcomes remains controversial. Here, we evaluated survival and clinical changes associated with converting from conventional hemodialysis (mean=3.75 h/treatment) to in-center nocturnal hemodialysis (mean=7.85 h/treatment). All 959 consecutive patients who initiated nocturnal hemodialysis for the first time in 77 Fresenius Medical Care facilities during 2006 and 2007 were eligible. We used Cox models to compare risk for mortality during 2 years of follow-up in a 1:3 propensity score-matched cohort of 746 nocturnal and 2062 control patients on conventional hemodialysis. Two-year mortality was 19% among nocturnal hemodialysis patients compared with 27% among conventional patients. Nocturnal hemodialysis associated with a 25% reduction in the risk for death after adjustment for age, body mass index, and dialysis vintage (hazard ratio=0.75, 95% confidence interval=0.61-0.91, P=0.004). With respect to clinical features, interdialytic weight gain, albumin, hemoglobin, dialysis dose, and calcium increased on nocturnal therapy, whereas postdialysis weight, predialysis systolic blood pressure, ultrafiltration rate, phosphorus, and white blood cell count declined (all P<0.001). In summary, notwithstanding the possibility of residual selection bias, conversion to treatment with nocturnal hemodialysis associates with favorable clinical features, laboratory biomarkers, and improved survival compared with propensity score-matched controls. The potential impact of extended treatment time on clinical outcomes while maintaining a three times per week hemodialysis schedule requires evaluation in future clinical trials.

Outcomes Associated with In-Center Nocturnal Hemodialysis from a Large Multicenter Program

BACKGROUND AND OBJECTIVES The objective of this study was to evaluate epidemiology and outcomes of a large in-center nocturnal hemodialysis (INHD) program. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This case-control study compared patients who were on thrice-weekly INHD from 56 Fresenius Medical Care, North America facilities with conventional hemodialysis patients from 244 facilities within the surrounding geographic area. All INHD cases and conventional hemodialysis control subjects who were active as of January 1, 2007, were followed until December 31, 2007, for evaluation of mortality and hospitalization. RESULTS As of January 1, 2007, 655 patients had been on INHD for 51 +/- 73 d. Patients were younger, there were more male and black patients, and vintage was longer, but they had less diabetes compared with 15,334 control subjects. Unadjusted hazard ratio was 0.59 for mortality and 0.76 for hospitalization. After adjustment for case mix and access type, only hospitalization remained significant. Fewer INHD patients were hospitalized (48 versus 59%) with a normalized rate of 9.6 versus 13.5 hospital days per patient-year. INHD patients had greater interdialytic weight gains but lower BP. At baseline, hemoglobin values were similar, whereas albumin and phosphorus values favored INHD. Mean equilibrated Kt/V was higher in INHD patients related to longer treatment time, despite lower blood and dialysate flow rates. CONCLUSIONS Patients who were on INHD exhibited excellent quality indicators, with better survival and lower hospitalization rates. The relative contributions of patient selection versus effect of therapy on outcomes remain to be elucidated in prospective clinical trials.

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.

Antibody response to Engerix‐B® and Recombivax‐HB® hepatitis B vaccination in end‐stage renal disease

Recombivax‐HB® (REC) and Engerix‐B® (ENG) are FDA‐approved vaccines for hepatitis B virus (HBV) in end‐stage renal disease (ESRD). This study compares antibody response rates between them in routine clinical practice. Patients completing the recommended 40 μg dose of REC (3 doses) or ENG (4 doses) between January 1, 2000 to April 30, 2003 were eligible. Patients with prior positive HBV surface antigen (HBsAg) or antibody (HBsAb) test results were excluded. The conversion rate and persistence of protective titer (HBsAb titer≥10 IU/mL) were tracked for 1 year. A supplemental analysis of a one‐to‐one matched patient sample was also performed. REC patients (N=885) were older, had longer dialysis vintage, and had a larger proportion of whites than ENG patients (N=13,661). Cumulative conversion response was greater in ENG (58%) than REC (40%) at 1 year (p<0.0001). The odds ratio for response to ENG compared with REC was 1.96 (95% limits: 1.56, 2.45; p<0.0001) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V. Persistent protective HBsAb after 1 year was 77% (ENG) vs. 53% (REC). HBsAg was positive in 208 ENG patients (1.5%) with all but 1 because of transient, vaccine‐related antigenemia. The difference in conversion response favoring ENG persisted in a one‐to‐one sample matched for age, gender, race, modality, and dialysis vintage. The study found higher seroconversion response to ENG compared with REC at several time points up to 1 year. Protective HBsAb disappeared in 23–47% of patients 1 year later, validating CDC recommendations to re‐test HBsAb yearly. The observed difference in response rates may be related to the extra ENG dose given at the second month (0, 1, 2, 6 regimen). The study raises a hypothesis that requires confirmation in a prospective clinical trial.

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.

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.

Limitations of Membrane Structure and Dialyzer Design on Large Solute Removal in Dialysis

Accessible online at: www.karger.com/journals/bpu This paper reviews the limitations of membrane structure and dialyzer design on large solute removal in dialysis using beta-2-microglobulin as an example of an inadequately removed large solute. Three mechanisms of solute removal – diffusion, convection, and adsorption – will be discussed. In each case, the trade-offs between transport characteristics and other (manufacturing and clinical) issues will be discussed. Three possible ways to improve large solute removal are: (1) to improve membrane structure; (2) to improve dialyzer design; (3) to improve therapy. This paper will be limited to (1) and (2). In another paper in this volume, Ronco [1] discusses the use of hemodiafiltration as an example of an improved therapy.

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.

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.