A multicenter descriptive analysis of anemia management in hemodialysis patients and its association with quality of life.

BACKGROUND: Appropriate management of anemia in patients with hemodialysis (HD) involves the administration of iron supplementation and erythropoietin-stimulating agents (ESAs), in addition to monitoring the response. This study aimed to evaluate the treatment of anemia in patients with HD and describe the factors associated with it and its effect on health-related quality of life (HRQOL). METHODS: The study was cross-sectional in design. The patients were included from three dialysis centers in Palestine from June to September 2018. The data collection instrument consisted of two portions; the initial portion contained demographic and clinical information on the patients, while the second consisted of the European Quality of Life 5-Dimension Scale (EQ-5D-5 L) and the visual analog scale EQ (EQ-VAS). RESULTS: The study included 226 patients. Their mean age (± SD) was 57 ± 13.9 years. The mean level of hemoglobin (Hb) (± SD) was 10.63 ± 1.71 g/dl, and 34.1% of the patients had a Hb level of 10-11.5 g/dl. All patients who required iron supplementation received it intravenously with a dose of 100 mg of iron sucrose. Almost 86.7% of the patients received darbepoetin alfa intravenously at 0.45 mcg/kg a week, and 24% had a Hb level > 11.5 g/dl. There were significant associations between the level of Hb and the number of comorbid diseases and the ESA that was received. However, other demographics and clinical factors did not significantly affect Hb levels. Certain variables, such as exercise, were a predictor of a higher quality of life. It should be noted that there is a significant impact of a low Hb value on the EQ-VAS scale. CONCLUSIONS: Our study found that more than half of the patients had a Hb level below the recommended goal of Kidney Disease Improving Global Outcomes (KDIGO). Furthermore, a significant association was found between patients' Hb level and HRQOL. Therefore, the appropriate treatment of anemia in patients with HD should be followed by adherence to the guideline recommendations, which consequently improves the HRQOL of HD patients, in addition to obtaining optimal therapy.

Association between serum phosphate levels and anemia in non-dialysis patients with chronic kidney disease: a retrospective cross-sectional study from the Fuji City CKD Network.

BACKGROUND: Patients with chronic kidney disease (CKD) present high mortality and morbidity rates despite the availability of various therapies. Although CKD-mineral and bone disorder (MBD) and renal anemia are important factors in patients with CKD, only few studies have analyzed the relationship between them. Therefore, this study aimed to evaluate the relationship between CKD-MBD and anemia in patients with CKD who did not receive erythropoiesis-stimulating agent or iron therapies. METHODS: This retrospective cross-sectional study included patients with CKD aged ≥ 20 years with estimated glomerular filtration rate (eGFR) categories G2a to G5 who were referred to the Fuji City General Hospital between April 2018 and July 2019. The exclusion criterion was ongoing treatment for CKD-MBD and/or anemia. RESULTS: The data of 300 patients with CKD were analyzed in this study. The median age of patients was 71 (range, 56.5-79) years. The median eGFR was 34 (range, 20-48) mL/min/1.73 m2, and the mean hemoglobin (Hb) level was 12.7 g/dL (standard deviation, 2.3), which decreased as the CKD stage increased. In a multivariate linear regression analysis of anemia-related factors, including age, renal function (eGFR), nutritional status, inflammation, and iron dynamics (serum iron level, total iron-binding capacity, ferritin levels), the serum phosphate levels were significantly associated with the Hb levels (coefficient [95% confidence interval], -0.73 [-1.1, -0.35]; P < 0.001). Subgroup analysis revealed a robust association between serum phosphate levels and Hb levels in the low-ferritin (coefficient [95% confidence interval], -0.94 [-1.53, -0.35]; P = 0.002) and advanced CKD groups (coefficient [95% confidence interval], -0.89 [-1.37, -0.41]; P < 0.001). CONCLUSIONS: We found an association between high serum phosphate levels and low Hb levels in patients with CKD not receiving treatment for anemia. These results underscore the possibility of a mechanistic overlap between CKD-MBD and anemia.

Synthesis and biological evaluation of (4-hydroxy-2-(substitued sulfonamido)pyrimidine-5-carbonyl)glycines as oral erythropoietin secretagogues.

Erythropoietin (EPO) is the predominant regulating factor in erythropoiesis. Herein we describe the identification of (4-hydroxy-2-(substitued sulfonamido)pyrimidine-5-carbonyl) glycine-based oral EPO secretagogues. Most of these compounds obviously increased the EPO level in Hep3B cells by stabilizing the hypoxia-inducible factor-α (HIF-α). Furthermore, their potential inhibitory activities against HIF prolyl hydroxylase domain (PHD) revealed their function as PHD inhibitors in PHD-HIF pathway. Compound 6i, with a biphenyl substituent on the sulfonamido group, particularly increased plasma EPO level in mice and could serve as a candidate of EPO stimulating agent for anemia treatment.

Potential effective treatment of shortening continuous erythropoietin receptor activator treatment interval combined with iron supplementation in hemodialysis patients.

Our previous randomized controlled trial comparing the total dose of weekly versus biweekly continuous erythropoietin receptor activator (CERA) therapy to maintain optimal hemoglobin (Hb) levels showed no significant differences between the two therapies. This post-hoc analysis assessed whether the total dose of weekly versus biweekly CERA therapy to maintain Hb levels among HD patients differed among groups with or without iron supplementation. Of 107 patients, 40 received intravenous iron supplementation due to iron deficiency (iron group) and 67 did not (non-iron group). In the iron group, the weekly therapy tended to require a lower total CERA dose compared with the biweekly therapy (274 ± 274 vs 381 ± 223 µg/12 weeks, P = 0.051). Changes in circulating hepcidin levels, a negative regulator of intestinal iron uptake, after 2 weeks of CERA treatment were significantly lower in the weekly therapy compared with the biweekly therapy (-4.2 ± 6.3 vs 11.1 ± 7.3 ng/mL, P = 0.015). In the non-iron group, there were no significant differences in total CERA dose or changes in hepcidin levels between the two therapies. Shortening the CERA treatment interval combined with iron supplementation may lead to the more efficient treatment of HD patients with iron deficiency.

Erythropoietin-stimulating agent-resistant vitamin B6 deficiency anemia in a pediatric patient on hemodialysis.

BACKGROUND: Vitamin B6 is a rate-limiting coenzyme that plays an important role in the biosynthesis of heme and the incorporation of iron into protoporphyrin. Its deficiency is often seen in chronic kidney disease (CKD), particularly those requiring dialysis and following administration of erythropoietin-stimulating agent (ESA). CASE- DIAGNOSIS/TREATMENT: A 16-year-old African-American male with stage 5 CKD on chronic hemodialysis experienced a decrease in hemoglobin over a 3-month period from 11 to 6.5 g/dl while receiving ESA, resulting in multiple blood transfusions. His transferrin saturation was 41%, ferritin level 706 [80-388] ng/mL, mean corpuscular volume (MCV) 87 [78-98] µm3, corrected reticulocytes count 2.3% [0.2-1.8%], and vitamin B6 1.2 [5.3-46.7] µg/L. Bone marrow biopsy was normocellular (65%) with erythroid hyperplasia and rare dyserythropoiesis. Prussian blue staining showed increased iron storage. Supplemental vitamin B6 (100 mg daily) was initiated at hemoglobin 7.3 g/dL with correction of anemia. Eighteen months later, his hemoglobin is 11.7 g/dL, transferrin saturation 45%, with no additional blood transfusions. CONCLUSIONS: Vitamin B6 deficiency anemia should be considered in any pediatric patient on hemodialysis who does not respond to standard ESA and iron therapy.

A nurse prescriber-led protocol for anaemia management in established haemodialysis patients: A retrospective study.

AIM AND OBJECTIVE: To evaluate the impact of a nurse prescriber-led protocol compared to a traditional physician-led nonprotocol-based approach had on maintaining targeted haemoglobin levels in patients on maintenance haemodialysis. BACKGROUND: Anaemia is a common complication of chronic kidney disease and has a profound impact on the patients' well-being. Current practices place a greater emphasis on the decision-making role of nurses in renal anaemia management. The introduction of nurse prescribing in this area is a relatively new concept. DESIGN: A retrospective cohort design, covering an eight-month period pre- and post introduction of a nurse prescriber-led anaemia protocol; study adheres to the STROBE Statement. METHODS: Using a nonprobability convenience sample, data extracted from the medical records and electronic patient records system (eMed) related to 74 patients at a single outpatient haemodialysis centre located within an acute general teaching hospital. The primary outcome was patients' haemoglobin level pre- and post introduction of the protocol. Secondary outcomes included erythropoietin-stimulating agent and iron dosage, and serum ferritin and transferrin saturation levels. RESULTS: There were no statistically significant differences between pre- and post protocol serum haemoglobin level and erythropoietin-stimulating agent dosage. Under the management of the nurse prescriber, patients experienced a significant improvement in serum ferritin and transferrin saturation levels and required significantly less intravenous iron dosage. CONCLUSIONS: This study, the first of its kind, found that patients receiving haemodialysis experience a significant improvement in iron indices while receiving a significantly lower amount of intravenous iron when managed by a nurse prescriber. Furthermore, the nurse prescribers' decision-making capacity is as effective as a physician-led nonprotocol-based approach in achieving haemoglobin target levels. RELEVANCE TO CLINICAL PRACTICE: Nurse prescribers have a role in implementing a safe, standardised and sustained approach to anaemia management in outpatient haemodialysis settings without compromising patient care.

The Role of Big Data in the Development and Evaluation of US Dialysis Care.

Rapid growth in electronic communications and digitalization, combined with advances in data management, analysis, and storage, have led to an era of "Big Data." The Social Security Amendments of 1972 turned end-stage renal disease (ESRD) care into a single-payer system for most patients requiring dialysis in the United States. As a result, there are few areas of medicine that have been as influenced by Big Data as dialysis care, for which Medicare's large administrative data sets have had a central role in the evaluation and development of public policy for several decades. In the 1970/1980s, Medicare data helped identify concerning trends in costs, access to dialysis care, and quality of care delivered. As the research community and policymakers made Medicare's administrative data increasingly accessible for investigation, analyses of Medicare claims have had a large role in facilitating policy synthesis and refinement. Efforts to address the skyrocketing cost of injectable drugs in the 1990s and 2000s exemplify this expanded role of Big Data. Although there are opportunities for large government and nongovernmental administrative data sets to continue serving a critical role in the evaluation and development of ESRD policies, it is important to understand challenges and limitations associated with their use.

Using dynamic treatment regimes to understand erythropoietin-stimulating agent hyporesponsiveness.

BACKGROUND: Erythropoietin-stimulating agent hyporesponsiveness (ESAH) is associated with increased cardiovascular mortality in patients with end-stage renal disease (ESRD) on hemodialysis. Dynamic treatment regimes (DTR), a clinical decision support (CDS) tool that guides the prescription of specific therapies in response to variations in patient states, have been used to guide treatment for chronic illnesses that require frequent monitoring and therapy changes. Our objective is to explore the role of utilizing a DTR to reduce ESAH in pediatric hemodialysis patients. METHODS: Retrospective analysis of ESRD patients on hemodialysis who received ESAs. Dosing was adjusted using a locally developed protocol designed to target a hemoglobin between 10 and 12 g/dl. Analyzing this protocol as a DTR, we assessed adherence to the protocol over time measuring how the hyporesponse index (ESA dose/hemoglobin value) changed due to varying levels of adherence. RESULTS: Eighteen patients met study criteria. Median hemoglobin was 11.4 g/dl (range 6.1-15.4), and median weekly ESA dose (darbepoetin-equivalent) was 0.4 mcg/kg/dose (range 0-2.1). Full adherence to the DTR was identified in 266 (71%) of the 4-week periods, with a median average adherence score of 0.80 (range 0.63-0.91). As adherence to the DTR improved, ESAH decreased. During the last 12 weeks, 13 out of 18 patients had lower average ESA/hemoglobin ratio than the first 12 weeks. CONCLUSIONS: A DTR appears to be well-suited to the treatment of anemia in ESRD and reduces ESAH. Our work shows the potential of DTRs to drive the development and evaluation of clinical practice guidelines.

Improving Erythropoiesis Stimulating Agent Hyporesponsiveness in Hemodialysis Patients: The Role of Hepcidin and Hemodiafiltration Online.

Hyporesponsiveness to erythropoietin stimulating agents (ESAs) is a condition associated with increased mortality. Even after identifying the condition, the causes are difficult to treat and only partially reversible in end-stage renal disease patients. Thus, the role of more recent hemodialysis (HD) techniques in improving such conditions is an emerging issue. However, major randomized clinical trials have not confirmed the results of smaller observational studies in which online hemodiafiltration has shown some efficacy in improving patients' response to ESAs. In our interpretation, these findings are not in contrast, but they can be explained by a better understanding of the interactions between HD and ESAs on iron mobilization, first of all through the role of hepcidin. The kinetics of hepcidin removal through HD combined with the action of selected ESAs may help the clinician in prescribing the best association between HD treatment and ESAs to overcome hyporesponsiveness.

Residual renal function in chronic dialysis is not associated with reduced erythropoietin-stimulating agent dose requirements: a cross-sectional study.

BACKGROUND: Anaemia is a very common problem in patients with end-stage kidney disease (ESKD) and the use of erythropoietin-stimulating agents (ESA) has revolutionised its treatment. Residual renal function (RRF) is associated with a reduction in ESA resistance and mortality in chronic dialysis. The primary aim was to establish whether RRF has an association with ESA dose requirements in ESKD patients receiving chronic dialysis. METHODS: A single center, cross-sectional study involving 100 chronic dialysis patients was conducted from December 2015 to May 2016. Participants were divided into two groups depending on presence of RRF, which was defined as a 24-h urine sample volume of ≥ 100 ml. Erythropoietin resistance index [ERI = total weekly ESA dose (IU)/weight (kg)/haemoglobin concentration (g/dL] was used as a measure of ESA dose requirements. RESULTS: There was no difference in ERI between those with RRF as compared to those without (9.5 versus 11.0, respectively; P = 0.45). Also, ERI did not differ between those receiving haemodialysis as compared with peritoneal dialysis (10.8 versus 10.2, respectively; P = 0.84) or in those using renin-angiotensin system (RAS) blockers as compared with no RAS blocker use (11.6 versus 9.2, respectively; P = 0.10). Lower ERI was evident for those with cystic kidney disease as compared to those with other causes of ESKD (6.9 versus 16.5, respectively; P = 0.32) although this did not reach statistical significance. Higher ERI was found in those with evidence of systemic inflammation as compared to those without (16.5 versus 9.5, respectively; P = 0.003). CONCLUSIONS: There was no association between RRF and ESA dose requirements, irrespective of dialysis modality, RAS blocker use, primary renal disease or hyperparathyroidism.

Home Therapy to Reduce Office Visits for Patients with Chronic Kidney Disease and Anemia.

Anemia is a common complication of chronic kidney disease (CKD) and a predictor of increased mortality. This project integrated erythropoietin-stimulating agent (ESA) with CKD care under one practice setting, co-managing anemia with CKD while reducing frequency of office visits in a rural setting. Patients self-administered their weekly dosage of erythropoietin with monthly follow-ups. As a result, office visits decreased by 56% for patients with CKD Stage 4 and by 54% for patients with CKD Stage 5.

Fixed dose of long-acting erythropoietic stimulating agents at higher frequency improves appetite, reduces inflammation and corrects anaemia in patients on haemodialysis.

Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 µg once monthly for 2 months, 50 µg twice monthly for 2 months and then 100 µg once monthly for two months. The effectiveness was determined by comparing haematocrit, nutritional status (serum protein and albumin) and inflammatory markers (tumour necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 and Hepcidin) at the beginning of the study with those at the end of the study. Forty-seven out of 67 patients completed the trial. At the end, haematocrit was significantly higher (34.51 vs 33.22%, P=.004), levels of inflammatory markers were significantly lower (TNF-α (30.71 vs 35.67 ng/mL, P=.007), IL-6 (5.12 vs 7.95 ng/mL, P=.033), hepcidin (60.39 vs 74.39 ng/mL, P=.002)), blood glucose levels were significantly lower (112.40 vs 139.02 mg/dL, P=.003) and albumin was significantly higher (4.11 vs 3.98, P=.001). Patients with a better than average response had a lower initial number of red blood cells (3.3 vs 3.6 × 10(6) /mm(3) , P=.025) and a lower IL-1 (3.8 vs 12.9 ng/mL, P=.01). They also had significantly lower blood glucose levels at the end. (91.3 vs 124.0 mg/dL, P=.03). We demonstrate that a fixed monthly dose of CERA at a twice monthly dosing schedule improves nutrition, reduces the inflammation and corrects anaemia in patients on haemodialysis. This finding may provide a new strategy for treating CKD-related anaemia.

Rationale and study design of a randomized controlled trial to assess the effects of maintaining hemoglobin levels using darbepoetin alfa on prevention of development of end-stage kidney disease in non-diabetic CKD patients (PREDICT Trial).

BACKGROUND: Anemia associated with high mortality is a common complication of chronic kidney disease (CKD). Target hemoglobin (Hb) levels for CKD treatment remain controversial: Recent guidelines recommend a maximum of 13 g/dL to avoid increased risk of CVD. However, some smaller studies show slower progression of renal function loss with high Hb targets. Recently, darbepoetin alfa targeting Hb 11-13 g/dL was reported to improve renal composite outcome of Japanese patients compared with a low Hb group maintained at 9.0-11.0 g/dL using epoetin alfa (HR 0.66; 95% CI 0.47-0.93). The high Hb group showed significant reduction of left ventricular mass index and improved quality of life. Sub-analysis revealed greater beneficial effects in non-diabetic stage 5 CKD patients. This randomized controlled trial, PREDICT, aims to confirm the impact of targeting Hb levels of 11-13 g/dL using darbepoetin alfa with reference to a low Hb target of 9-11 g/dL. METHODS: We calculated the number of subjects (N = 440) necessary to detect a statistically significant level of α = 0.05 (two-sided) and statistical power of 80% for a minimum follow-up period of 2 years on the basis of a previous study. RESULTS: The study enrolled 498 non-diabetic Japanese patients with eGFR 8-20 mL/min/1.73 m(2). The primary outcome is a composite renal endpoint (starting chronic dialysis, transplantation, eGFR 6 mL/min/1.73 m(2) or less, 50% decrease in eGFR). Average follow-up period is 2 years and the study ends in 2016. CONCLUSION: PREDICT will determine the optimum target Hb for Japanese patients with non-diabetic CKD. (ClinicalTrials.gov No. NCT01581073).

Protocol of a randomized controlled trial of an erythropoietin stimulating agent decision aid for anemia treatment in kidney disease.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are commonly used for the treatment of anemia due to chronic kidney disease (CKD) and end stage renal disease (ESRD). Patients often lack an understanding of the potential risks and benefits of ESAs, despite government mandated education on this topic. Decision aids are tools commonly used to discuss important information in health care settings. To address this knowledge gap, we designed this study to evaluate the effectiveness of a novel ESA decision aid at promoting informed shared decision making (ISDM) between patients and providers related to ESA use for CKD- and ESRD-related anemia. METHODS: Using the principles of informed shared decision making theory, we designed and piloted an ESA decision aid intended to increase CKD and ESRD patient understanding of the potential risks and benefits of ESAs. Informed by the findings during development, the ESA decision aid was modified and finalized for testing. We will perform a randomized clinical trial to assess if administration of the ESA decision aid improves patient understanding of the risks and benefits of ESA use compared to control patients receiving standard care. Participants with either CKD or ESRD and who are receiving ESAs will be eligible for participation. The primary outcome is patients' score on the Patient Anemia Knowledge in Kidney Disease (PAKKD) survey assessed at enrollment and 3 months after. Secondary outcomes include decisional conflict related to ESAs, and patient satisfaction with provider communication. DISCUSSION: The Anemia Risk Communication for patients with Kidney Disease (ARC-KD) study will assess the effectiveness of a novel ESA decision aid to improve patient understanding of ESA use to manage CKD- and ESRD-related anemia. This decision aid is the first resource targeted to improve patient understanding of anemia management in the kidney health context. With the increasing options available for anemia management, this will serve as an important foundation to evolve in the future to optimize anemia-related shared decision making. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01992926 . Registered 11/14/2013.

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.

Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy.

Objectives: The management of patients undergoing bilateral nephrectomy for renal cancer presents significant challenges, particularly in addressing hypotension, anemia, and tumor recurrence during hemodialysis. Case presentation: A patient diagnosed with renal clear cell carcinoma in 2009 was followed until his demise in June 2022, with detailed documentation of symptoms, signs, laboratory results, diagnosis, and treatment. In the presented case, post-nephrectomy, the patient experienced frequent hypotension and anemia during dialysis, improving with erythropoietin-stimulating agents and subsequently with rosuvastatin. Later, multiple metastases were detected, correlating with normalized blood pressure and hemoglobin. Literature review: A literature search up to September 2023 was also conducted, gathering data on hypotension, anemia, and tumor recurrence post-nephrectomy. Literature analysis of six cases revealed a 100% tumor recurrence rate in elderly patients (>50 years). Conclusion: Treatment of anemia in bilateral nephrectomy patients warrants consideration of medication-induced tumor recurrence, highlighting early kidney transplantation to avoid adverse reactions like hypotension.

Association of malnutrition-inflammation complex and responsiveness to erythropoiesis-stimulating agents in long-term hemodialysis patients.

BACKGROUND: Protein-energy wasting, inflammation and refractory anemia are common in long-term hemodialysis patients. A decreased responsiveness to erythropoiesis-stimulating agents (ESA) is often the cause of the refractory anemia. We hypothesized that the malnutrition-inflammation complex is an independent predictor of decreased responsiveness to ESAs in hemodialysis patients. METHODS: This cohort study of 754 hemodialysis patients was examined for an association between inflammatory and nutritional markers, including the malnutrition-inflammation score (MIS) and responsiveness to ESA. Cubic spline models were fitted to verify found associations. RESULTS: The mean (±SD) age of patients was 54 ± 15 years, 53% were diabetic and 32% blacks. MIS was worse in the highest quartile of ESAs responsiveness index (ERI, ESA dose divided by hemoglobin) when compared with 1st quartile (6.5 ± 4.5 versus 4.4 ± 3.4; P < 0.001). Both C-reactive protein (log CRP) (ß = 0.19) and interleukin-6 (log IL-6) (ß = 0.32) were strong and independent predictors of ERI using multivariate linear regression. Serum albumin (ß = -0.30) and prealbumin levels (ß = -0.14) were inversely associated with ERI. Each 1 SD higher MIS, higher CRP and lower albumin were associated with 86, 44 and 97% higher likelihood of having highest versus three lowest ERI quartiles in fully adjusted models [odds ratio (and 95% confidence interval) of 1.86 (1.31-2.85), 1.44 (1.08-1.92) and 1.97 (1.41-2.78)], respectively. Cubic splines confirmed the continuous and incremental nature of these associations. CONCLUSIONS: Malnutrition-inflammation complex is an incremental predictor of poor responsiveness to ESAs in hemodialysis patients. Further studies are needed to assess whether modulating inflammatory or nutritional processes can improve anemia management.

Physician Compliance With a Computerized Clinical Decision Support System for Anemia Management of Patients With End-stage Kidney Disease on Hemodialysis: Retrospective Electronic Health Record Observational Study.

BACKGROUND: Previous studies on clinical decision support systems (CDSSs) for the management of renal anemia in patients with end-stage kidney disease undergoing hemodialysis have previously focused solely on the effects of the CDSS. However, the role of physician compliance in the efficacy of the CDSS remains ill-defined. OBJECTIVE: We aimed to investigate whether physician compliance was an intermediate variable between the CDSS and the management outcomes of renal anemia. METHODS: We extracted the electronic health records of patients with end-stage kidney disease on hemodialysis at the Far Eastern Memorial Hospital Hemodialysis Center (FEMHHC) from 2016 to 2020. FEMHHC implemented a rule-based CDSS for the management of renal anemia in 2019. We compared the clinical outcomes of renal anemia between the pre- and post-CDSS periods using random intercept models. Hemoglobin levels of 10 to 12 g/dL were defined as the on-target range. Physician compliance was defined as the concordance of adjustments of the erythropoietin-stimulating agent (ESA) between the CDSS recommendations and the actual physician prescriptions. RESULTS: We included 717 eligible patients on hemodialysis (mean age 62.9, SD 11.6 years; male n=430, 59.9%) with a total of 36,091 hemoglobin measurements (average hemoglobin and on-target rate were 11.1, SD 1.4, g/dL and 59.9%, respectively). The on-target rate decreased from 61.3% (pre-CDSS) to 56.2% (post-CDSS) owing to a high hemoglobin percentage of >12 g/dL (pre: 21.5%; post: 29%). The failure rate (hemoglobin <10 g/dL) decreased from 17.2% (pre-CDSS) to 14.8% (post-CDSS). The average weekly ESA use of 5848 (SD 4211) units per week did not differ between phases. The overall concordance between CDSS recommendations and physician prescriptions was 62.3%. The CDSS concordance increased from 56.2% to 78.6%. In the adjusted random intercept model, the post-CDSS phase showed increased hemoglobin by 0.17 (95% CI 0.14-0.21) g/dL, weekly ESA by 264 (95% CI 158-371) units per week, and 3.4-fold (95% CI 3.1-3.6) increased concordance rate. However, the on-target rate (29%; odds ratio 0.71, 95% CI 0.66-0.75) and failure rate (16%; odds ratio 0.84, 95% CI 0.76-0.92) were reduced. After additional adjustments for concordance in the full models, increased hemoglobin and decreased on-target rate tended toward attenuation (from 0.17 to 0.13 g/dL and 0.71 to 0.73 g/dL, respectively). Increased ESA and decreased failure rate were completely mediated by physician compliance (from 264 to 50 units and 0.84 to 0.97, respectively). CONCLUSIONS: Our results confirmed that physician compliance was a complete intermediate factor accounting for the efficacy of the CDSS. The CDSS reduced failure rates of anemia management through physician compliance. Our study highlights the importance of optimizing physician compliance in the design and implementation of CDSSs to improve patient outcomes.

Erythropoietin-Stimulating Agent Hyporesponsiveness in Patients Living with Chronic Kidney Disease.

Background: Erythropoietin-stimulating agent (ESA) hyporesponsiveness is commonly observed in patients with anemia secondary to chronic kidney disease (CKD). Because of its complexity, a global consensus on how we should define ESA hyporesponsiveness remains unavailable. The reported prevalence and demographic information on ESA hyporesponsiveness within the CKD population are variable with no consensus definition. Summary: ESA hyporesponsiveness is defined as having no increase in hemoglobin concentration from baseline after the first month of treatment on appropriate weight-based dosing. The important factors associated with ESA hyporesponsiveness include absolute or functional iron deficiency, inflammation, and uremia. Hepcidin has been demonstrated to play an important role in this process. Mineral bone disease secondary to CKD and non-iron malnutrition among other factors are also associated with ESA hyporesponsiveness. There is continued debate toward determining a gold-standard treatment pathway to manage ESA hyporesponsiveness. The development of hypoxia-inducing factor-stabilizers brings new insights and opportunities in the management of ESA hyporesponsiveness. Key Message: Management of ESA hyporesponsiveness involves a comprehensive multidisciplinary team approach to address its risk factors. The progression of basic and clinical research on identifying risk factors and management of ESA hyporesponsiveness brings greater hope on finding solutions to eventually tackling one of the most difficult problems in the topic of anemia in CKD.

Comparison of the effects of weekly and biweekly intravenous CERA administration on erythropoiesis: A randomized controlled trial.

Although continuous erythropoietin receptor activators (CERAs) are widely used erythropoiesis-stimulating agents for correcting renal anemia in patients undergoing hemodialysis (HD), few reports have examined weekly CERA administration. In this randomized controlled trial, we compared the efficacy and changes in the parameters of iron metabolism and erythropoiesis between weekly and biweekly CERA administration. In total, 120 patients undergoing maintenance HD were randomized to the weekly or biweekly group. The primary end point was the total CERA dose needed to maintain the target hemoglobin (Hb) levels during a 12-week evaluation period. There was no significant difference in the total dose between the weekly and biweekly groups (median 175.0 [interquartile range (IQR) 93.8-337.5] µg/12 weeks vs. 300.0 [IQR 125.0-375.0] µg/12 weeks, P = .18). The mean Hb levels during the evaluation period were 10.9 ± 0.8 g/dL in the weekly group and 10.7 ± 0.8 g/dL in the biweekly group (P = .25). Weekly CERA administration was well tolerated. Weekly CERA administration similarly managed anemia as biweekly administration in patients undergoing HD.