Consensus recommendations on fasting during Ramadan for patients with kidney disease: review of available evidence and a call for action (RaK Initiative).

Ramadan fasting (RF) involves abstaining from food and drink during daylight hours; it is obligatory for all healthy Muslims from the age of puberty. Although sick individuals are exempt from fasting, many will fast anyway. This article explores the impact of RF on individuals with kidney diseases through a comprehensive review of existing literature and consensus recommendations. This study was conducted by a multidisciplinary panel of experts.The recommendations aim to provide a structured approach to assess and manage fasting during Ramadan for patients with kidney diseases, empowering both healthcare providers and patients to make informed decisions while considering their unique circumstances.

The prevalence of cardiorenal anemia syndrome among patients with heart failure and its association with all-cause hospitalizations: a retrospective single-center study from the Middle East.

Background and aim: Little is known about the burden of cardiorenal syndrome (CRS) and cardiorenal anemia syndrome (CRAS) in the Middle East Region. Furthermore, whether the occurrence rates of CRAS differ across heart failure (HF) phenotypes is not widely investigated. We aimed to examine the prevalence of CRS and CRAS in patients with HF, compare characteristics of patients with CRAS-HFrEF vs. CRAS-HFpEF, and investigate anemia association with 1-year all-cause hospitalizations. Methods: HF patients who visited a multidisciplinary HF clinic at a single center between 10-2015 and 06-2022 (n = 968) were retrospectively included. Differences in rates of CRAS prevalence, and patients' characteristics of those with CRAS-HFrEF vs. CRAS-HFpEF were determined using appropriate testing methods. Generalized estimating equation (GEE) models were used to determine if anemia was associated with higher rates of hospitalization. Results: CRS was prevalent in 34.4% of subjects, while 25.3% had CRAS. CRAS prevalence rates among patients with HFpEF vs. HFrEF were comparable (27.2% vs. 24.2%, p = 0.3). Compared to patients with HFrEF-CRAS, those with HFpEF-CRAS were more likely females (p < 0.001), had a higher burden of hypertension (p = 0.01), and lower hemoglobin (p = 0.02). In an adjusted GEE model, anemia was associated with an average increase of 1.8 admissions in CRS patients (p = 0.015). Conclusion: In patients with HF, 1 in 3 patients presented with CRS, and 1 in 4 patients had CRAS. The prevalence of CRAS was comparable among those HFpEF and HFrEF. Anemia was associated with an increased rate of 1-year all-cause hospitalization in CRS patients.

Clinical outcomes of ceftolozane-tazobactam dosing in patients with sepsis undergoing renal replacement therapies.

Ceftolozane-tazobactam (C/T) recommended dosing in patients undergoing renal replacement therapies (RRT) is lacking evidence. The objective of this study was to evaluate the clinical outcomes of C/T dosing in patients on RRT. MATERIALS AND METHODS: A retrospective descriptive study conducted at our institution between May 1, 2017, and March 15, 2022. The primary endpoint was to determine the clinical cure for patients who received C/T for documented infection while on RRT. The secondary endpoints were the microbiologic cure, 30-day infection recurrence, and 30-day crude mortality. RESULTS: Of the 27 patients who met the inclusion criteria, 17 (63%) were males, median age was 69 (62 - 82) years, and weight 67 (57 - 79) kg. The majority of patients had pneumonia 19 (70.4%) followed by bacteremia 5 (18.5%). Multidrug resistant Pseudomonas spp. was the causative organism of infection in 22 subjects (81.5%). Clinical cure was achieved in 17 subjects (63%). Of the 14 subjects who had their culture repeated, 10 (71.4%) patients had microbiologic cure vs. 4 (28.5%) patients who had a microbiologic failure (p = 0.327). 30-day infection recurrence occurred in 6 (35.3%) patients of the clinical cure group and 2 (20%) patients in the clinical failure group (p = 0.362), while mortality occurred in 5 (29.4%) subjects vs. 7 (70%) in both groups, respectively (p = 0.049). The most frequently used doses of C/T were 1.5 g IV q8h while undergoing continuous venovenous hemodiafiltration and 0.75 g IV q8h while undergoing hemodialysis (p = 0.209). The median duration of therapy was 9 (4.5 - 13) days in the clinically cured group vs. 5 (3.75 - 5.5) days in those who had clinical failure (p = 0.038). There was no adverse event reported using these doses during the study period. CONCLUSION: The used doses of C/T in this study were higher than those approved by the U.S. FDA, while clinical success is uncertain. Larger outcomes and pharmacokinetics studies are needed to establish effective dosing and therapy duration.

Microbiologic outcomes of ceftazidime-avibactam dosing in patients with sepsis utilizing renal replacement therapies.

INTRODUCTION: The suggested dose of ceftazidime-avibactam (CEF/AVI) in patient with multidrug resistant organisms and utilizing renal replacement therapies (RRTs) is not validated in clinical studies. The objective of this study was to evaluate the microbiologic cure of bacteremia and pneumonia using the recommended CEF/AVI dosing in patients utilizing RRT. METHODS: A retrospective observational study conducted at our institution between September 15, 2018 and March 15, 2022. The primary end point was to determine the microbiologic cure. The secondary end points were the clinical cure, 30-day recurrence, 30-day all cause mortality. RESULTS: Fifty-six patients met the inclusion criteria, 36 (64.3%) were males, the median age was 69 (59.5-79.3) years, and the median weight was 69 (60-83.8) kg. Pneumonia represented 34 (60.7%) of infections. Microbiologic cure was achieved in 32 (57%) subjects. However, clinical cure was achieved in 23 (71.9%) patients in the microbiologic cure group versus 12 (50%) in the microbiologic failure group (p = 0.094). The 30-day recurrence occurred in 2 (6.3%) patients in the microbiologic cure group versus 3 (12.5%) in the microbiologic failure group (p = 0.673). Further, the 30-day all-cause mortality was 18 (56.3%) versus 10 (41.7%) in both groups respectively (p = 0.28). The most used dose in patients utilizing continuous veno-venous hemofiltration (CVVH) was 1.25 g q8h, while the dose was 1.25 g q24h in those who utilized intermittent hemodialysis (IHD). The multivariate logistic regression indicated that bacteremia (OR 41.5 [3.77-46]), Enterobacterales (OR 5.4 [1.04-27.9]), and the drug daily dose (OR 2.33 [1.15-4.72]) were independently associated with microbiologic cure. CONCLUSION: Microbiologic cure of ceftazidime-avibactam in patient utilizing CVVH and IHD is dependent on bacteremia diagnosis, the drug daily dose, and bacterial species. These findings need to be replicated in a larger prospective study, with no recommendations in those utilizing RRT.

Prevalence and management of hyperkalemia in chronic kidney disease and heart failure patients in the Gulf Cooperation Council (GCC).

Hyperkalemia is a frequent complication in patients with chronic kidney disease (CKD) or heart failure (HF) and associated with neuromuscular manifestations, changes in the electrocardiogram, and increased risk of mortality. While data on the prevalence and management of hyperkalemia in the gulf region are scarce, risk factors such as preference for potassium-rich foods (e.g., dates and dried fruits/vegetables), periods of intense fasting (e.g., Ramadan), and diabetes (an ancestor of CKD and HF) are common. Therefore, a panel of nephrologists and cardiologists from countries of the Gulf Cooperation Council (GCC) convened to collate and review available data on the prevalence, regional drivers, and current practice in the management of hyperkalemia in the region. Eventually, this review provides consensus recommendations on a balanced utilization of dietary and pharmacological options including new potassium binders for achieving and sustainably maintaining desirable serum potassium levels in countries of the GCC region. Alignment with regional habits and practice was a key aspect to facilitate the uptake of the recommendations into physicians' practice and patients' lives.

Polypharmacy in cardiorenal syndrome patients.

Cardiorenal syndrome (CRS) is a term defined as complex interactions between concomitant cardiac and renal dysfunction in which disease of one organ initiates, perpetuates, and/or accelerates the decline in the other. It accounts for a third of presentations with heart failure and is associated with poor clinical outcomes. Polypharmacy (defined as using five or more medications) is common in CRS patients and is associated with worst clinical outcomes. The risk for polypharmacy increases to several fold with associated comorbidities, poses risks to the overall health of the patient, and enhances non-compliance to essential medications. Deprescribing non-essential medications, coordination between multiple specialties to mitigate the risk of polypharmacy, pharmacist- and nurse-led clinics to improve adherence to medications, use of polypills and telemonitoring are various methods to reduce polypharmacy. In this paper, we highlight different strategies to prevent polypharmacy and improve compliance and adherence to essential medications.

Urinary tract infections in hemodialysis patients-The controversy of antimicrobial drug urine concentrations.

BACKGROUND: Major infectious diseases societies recommend the use of antimicrobials that achieve high-urinary concentrations to treat urinary tract infection (UTI), which is a concept of little relevance to the oliguric and anuric hemodialysis (HD) dependent population. Outcome studies in this population are more relevant, but unfortunately scarce. We sought to investigate the impact of different antimicrobials on clinical and microbiologic outcomes in HD dependent population. METHODS: A retrospective observational study conducted at our quaternary care hospital between May 2015 and December 2019. We included all HD dependent adults diagnosed with UTIs. Our primary end points were clinical and microbiologic cure. Our secondary end points were 90-day recurrence and mortality. RESULTS: Fifty-six patients were included in the study with 33 (58.9%) females, mean age of 69.9 ± 11.6 years, and mean body mass index of 27.7 ± 7.8 kg/m2 . Thirty-six subjects of the sample (64.3%) were anuric. Ninety-one percent of the patients achieved clinical cure. Out of those who had repeat cultures, 90.7% achieved microbiologic cure. Clinical and microbiologic cure rates were not significantly different between the oliguric and anuric groups. The 90-day recurrence rate was 11.1% and mortality was 19%, none of them was related to UTI. CONCLUSION: Our findings demonstrate high rate of clinical and microbiologic cure in the treatment of oliguric and anuric HD dependent patients. We suggest that drug development and treatment societies to consider clinical and microbiologic outcomes in conjunction with achievable urinary concentration when making recommendations for the treatment of UTI.

Nocardial Infection in the Early Period after Kidney Transplantation.

Patients with solid organ transplant have weaker immune system and can develop opportunistic infections. Prophylactic antimicrobials can help lower that risk but do not prevent it completely. High index of suspicion increases the chance of diagnosing rare opportunistic infections in immunocompromised patients and helps early and effective treatment. We present a unique case of a patient who developed pneumonia from Nocardia early after kidney transplant despite being on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. He was diagnosed and treated early which helped improving his outcome. We discuss incidence, risk factors, and treatment of nocardiosis post kidney transplant.

Clinical and Haemodynamic Effects of Arteriovenous Shunts in Patients with Heart Failure with Preserved Ejection Fraction.

The arteriovenous shunt (AVS) is the most commonly used vascular access in patients receiving regular haemodialysis. The AVS may have a significant haemodynamic impact on patients with heart failure. Many studies have sought to understand the effect of AVS creation or closure on heart structure and functions, most of which use non-invasive methods, such as echocardiography or cardiac MRI. Data are mainly focused on heart failure with reduced ejection fraction and there are limited data on heart failure with preserved ejection fraction. The presence of an AVS has a significant haemodynamic impact on the cardiovascular system and it is a common cause of high-output cardiac failure. Given that most studies to date use non-invasive methods, invasive assessment of the haemodynamic effects of the AVS using a right heart catheter may provide additional valuable information.

Temporal Trends in Brain-Death Organ Donation in Asia: Results From the Global Observatory on Donation and Transplantation.

BACKGROUND: Organ shortage is the main limiting factor for further dissemination of organ transplantation therapies; implementation of brain-death (BD) criteria for organ donation purposes is essential for overcoming this limitation. Investigating and characterizing the effects of this intervention on organ availability and subsequent orthotopic organ transplantation in Asia, the world's most populous continent, should shed light on a global issue. The aim of this study was to describe temporal trends in brain-death donors (BDDs) and deceased-donor transplants (DDTs) in the Asian continent. METHODS: We used data from the Global Observatory on Donation and Transplantation (GODT), the world's most comprehensive source of data relating to organ donation and transplantation activities. Available data on the number of BDDs and DDTs in 48 Asian countries was collated and analyzed for the years 2000-2019. RESULTS: The number of BDDs in Asia increased progressively, from 25 BBDs in 2000 to 5357 in 2019. The number of DDTs increased concomitantly, albeit with an initial decline between 2004 and 2008, with an exponential increase in the number of kidney and liver transplants, followed by heart and lung transplants. Data from the latest year with complete data (2019) demonstrated 25,557 deceased-donor organs were transplanted, representing a >3-fold increase in the number of transplanted organs compared with the nadir in 2008. CONCLUSION: Although the Asian continent has noticed a rapid increase in BD transplantation activities during the past 2 decades, it is self-evident that further dissemination and adoption of BD donation are fundamental to reducing organ shortage gap.

Linagliptin in the Management of Type 2 Diabetes Mellitus After Kidney Transplant.

BACKGROUND: The incidence and prevalence of end-stage renal disease (ESRD) is increasing. The most common cause of ESRD is diabetes mellitus (DM). Kidney transplantation offers better quality of life and survival for patients with ESRD. Because of the use of immunosuppressive therapy and steroids post-kidney transplantation, the patients are at an increased risk for the development of posttransplant DM (PTDM). Management of DM after transplantation (whether pre-existing or transplant related) remains a challenge. Multiple treatment options are currently available to manage PTDM. Those medications have good safety and efficacy record in the general population and in patients with mild degrees of kidney disease. METHODS: We conducted a retrospective single center analysis of safety and efficacy of linagliptin post-kidney transplantation. The study was approved by the institutional review board. We collected data (demographics, laboratory tests, and any symptoms or hospitalizations) for 42 patients for a period of 12 months. RESULTS: All 42 patients received linagliptin throughout the study period. Patients' average age was 62 years. Twenty-three were women and all were of Middle Eastern descent and had kidney transplants on average of 25 months when they were included in the study. Nineteen patients had DM before the transplant, and the rest had PTDM. Eighteen patients were on metformin and 15 were on insulin, whereas the rest were not on any other medications at the start of the study. Baseline average creatinine was 1.5 mg/dL (132.9 mmol/L) and glycated hemoglobin (HbA1c) was 8.2 g/dL at the start of the study, whereas creatinine was 1.6 mg/dL (138.5 mmol/L) and HbA1c was 7.4 g/dL at the end. HbA1c dropped 0.8 on average within 3 months of starting linagliptin and remained at the same level for the rest of the study. Urine protein did not change significantly throughout the study. Three patients developed acute myocardial infarction during the study, and a fourth one was hospitalized with an opportunistic infection. Two patients had urinary tract infections. Adverse effects were minimal. No allergic reactions, hypoglycemia, or acute pancreatitis episodes were reported. The average weight and body mass index did not change throughout the study. None of the patients stopped the medication. CONCLUSIONS: In this retrospective analysis, linagliptin seems to be safe and efficacious after kidney transplantation. It can be considered as a treatment option to manage DM after transplantation.

Severe Acute Kidney Injury in Critically Ill Patients with COVID-19 Admitted to ICU: Incidence, Risk Factors, and Outcomes.

BACKGROUND: Critically ill patients with COVID-19 are prone to develop severe acute kidney injury (AKI), defined as KDIGO (Kidney Disease Improving Global Outcomes) stages 2 or 3. However, data are limited in these patients. We aimed to report the incidence, risk factors, and prognostic impact of severe AKI in critically ill patients with COVID-19 admitted to the intensive care unit (ICU) for acute respiratory failure. METHODS: A retrospective monocenter study including adult patients with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection admitted to the ICU for acute respiratory failure. The primary outcome was to identify the incidence and risk factors associated with severe AKI (KDIGO stages 2 or 3). RESULTS: Overall, 110 COVID-19 patients were admitted. Among them, 77 (70%) required invasive mechanical ventilation (IMV), 66 (60%) received vasopressor support, and 9 (8.2%) needed extracorporeal membrane oxygenation (ECMO). Severe AKI occurred in 50 patients (45.4%). In multivariable logistic regression analysis, severe AKI was independently associated with age (odds ratio (OR) = 1.08 (95% CI (confidence interval): 1.03-1.14), p = 0.003), IMV (OR = 33.44 (95% CI: 2.20-507.77), p = 0.011), creatinine level on admission (OR = 1.04 (95% CI: 1.008-1.065), p = 0.012), and ECMO (OR = 11.42 (95% CI: 1.95-66.70), p = 0.007). Inflammatory (interleukin-6, C-reactive protein, and ferritin) or thrombotic (D-dimer and fibrinogen) markers were not associated with severe AKI after adjustment for potential confounders. Severe AKI was independently associated with hospital mortality (OR = 29.73 (95% CI: 4.10-215.77), p = 0.001) and longer hospital length of stay (subhazard ratio = 0.26 (95% CI: 0.14-0.51), p < 0.001). At the time of hospital discharge, 74.1% of patients with severe AKI who were discharged alive from the hospital recovered normal or baseline renal function. CONCLUSION: Severe AKI was common in critically ill patients with COVID-19 and was not associated with inflammatory or thrombotic markers. Severe AKI was an independent risk factor of hospital mortality and hospital length of stay, and it should be rapidly recognized during SARS-CoV-2 infection.

Ertapenem Neurotoxicity in Hemodialysis Patients-Safe and Effective Dosing Is Still Needed: A Retrospective Study and Literature Review.

BACKGROUND: The approved dosing of ertapenem in patients with chronic kidney disease stage 5 utilizing dialysis (CKD-5D) is 0.5 g intravenous daily. Several reports associated this dosing strategy with neurotoxicity. OBJECTIVE: The purpose of this study is to identify the incidence of neurotoxicity in this population and the risk factors associated with this toxicity. The secondary objective was to review the literature and discuss a safer/cost-effective dosing strategy based on available data. METHODS: A retrospective study was conducted screening all patients who received ertapenem and hemodialysis at our quaternary hospital between May 2015 and March 2019. Patients' demographics, comorbidities, concomitant drugs (known to induce neurotoxicity), and seizure history were collected. RESULTS: A total of 99 eligible patients were identified; 10 of them (10%) developed neurotoxicity. The patients who developed neurotoxicity were all male; mean age was 74 ± 9 years as compared with 68.9 ± 13 years in the sample. Bivariate relationships between all predictors and the seizures (dichotomously coded) were estimated to investigate the risk factors. The following were the significant predictors of seizures: male sex (17%; P = 0.014), dementia (27%; P = 0.012), and concomitant use of ß-lactams, aminoglycosides, or fluoroquinolones (19.6%; P = 0.042). CONCLUSION AND RELEVANCE: The currently approved ertapenem dose imposes a risk of developing neurotoxicity in patients with CKD-5D. Utilizing the published data in this population, alternative post-dialysis dosing strategies administered through dialysis access such as 1 g loading dose, followed by either 0.5 g (for the 48 hours interdialytic time) or 1 g (for the 72 hours interdialytic time) might warrant further investigation for efficacy and safety.

Tocilizumab Use in a Chronic Hemodialysis Patient for the Management of COVID-19-Associated Pneumonia and Acute Respiratory Distress Syndrome.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease. As of writing this article, there are over 4.4 million people affected by COVID-19, and unfortunately, 300,000 have succumbed to the infection. In this article, we address a particularly more susceptible group of the population of end-stage renal disease (ESRD) patients on dialysis who may potentially benefit from being treated with tocilizumab. The use of tocilizumab has not been reported widely in ESRD patients on dialysis to treat COVID-19. In this case report, we describe a patient with ESRD on hemodialysis who was admitted to the intensive care unit, with severe pneumonia secondary to COVID-19 infection. This patient was treated with tocilizumab 400 mg intravenous and had a favorable outcome with no apparent adverse events.

Use of Empagliflozin in Recipients of Kidney Transplant: A Report of 8 Cases.

Transplant teams face increasing challenges to manage diabetes following kidney transplantation. There is an increasing number of diabetics undergoing transplantation and there is an increased incidence of posttransplant diabetes mellitus (PTDM) due to a higher prevalence of obesity, increased use of steroids and calcineurin inhibitors, and the acceptance of older patients as potential candidates. The options for treating diabetes in the general population are expanding. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors is one of the new modalities of treatment. We report the cases of 8 patients who underwent kidney transplantation and were treated with the SGLT-2 inhibitor empagliflozin for their pre-existing diabetes or for the development of PTDM. They were followed for an average of 12 months. The average age of the patients was 42.5 years. All 8 patients were taking tacrolimus, mycophenolate, and prednisolone. Although creatinine increased slightly (from 88.5 mmol/L to 99.5 mmol/L) in the month after starting empagliflozin, it stabilized after that. Hemoglobin A1c decreased on average 0.85 g/dL. Urine protein decreased by 0.6 g per day and weight decreased on average 2.4 kg throughout the year. One patient discontinued the medication due to recurrent urinary tract infections.

Successful treatment of multidrug resistant Klebsiella pneumoniae using dual carbapenem regimen in immunocompromised patient.

This report describes a longitudinal case of immunocompromised patient post kidney transplant who was admitted to our institution repeatedly for treatment of various infections caused by multi-drug resistant Klebsiella pneumoniae. The patient was successfully treated with a combination of ertapenem/meropenem on multiple occasions despite the elevated MICs. Our observations corroborate previous preclinical studies and case reports showing the efficacy of double carbapenem regimens against resistant Enterobacteriaceae.

Insights into cardiorenal interactions in acute decompensated heart failure.

PURPOSE OF REVIEW: Acute decompensated heart failure (ADHF) is one of the biggest challenges in the management of chronic heart failure. Despite the advances in medical and device therapy, high readmission and mortality rates continue to be a burden on healthcare systems worldwide. One of the strongest predictors of adverse outcomes in ADHF is renal dysfunction, referred to as cardiorenal syndrome (CRS) type 1. This review discusses some of the recently introduced findings related to the pathophysiology, diagnosis, and management of this disorder. RECENT FINDINGS: There is a better understanding of the pathophysiology of ADHF and CRS. Systemic and intrarenal hemodynamic data provided a much deeper insight into various mechanisms of interaction between the heart and the kidney. Novel biomarkers have been discovered and developed recently to help diagnose and predict prognosis of CRS. Although there was optimism toward using ultrafiltration in treating ADHF with CRS, recent data did not support that, and management remains primarily driven by reversing ADHF hemodynamic and neurohormonal derangements. SUMMARY: ADHF with CRS carries poor prognosis and high mortality. There is a need for individual risk assessment and management. A dedicated experienced multidisciplinary team is needed to diagnose and manage patients with this problem. Different approaches are needed to address the complex elements of this disorder.

Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia.

BACKGROUND: Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia. METHODS: Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months. RESULTS: Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups. CONCLUSION: In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects.