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Rationale & Objective Previous studies of inflammation and anemia management in hemodialysis (HD) patients may be biased due to patient differences. We used a self-matched longitudinal design to test whether new inflammation, defined as an acute increase in C-reactive protein (CRP) level, reduces hemoglobin response to erythropoiesis-stimulating agent (ESA) treatment. Study Design Self-matched longitudinal design. Setting & Participants 3,568 new inflammation events, defined as CRP level > 10 mg/L following a 3-month period with CRP level ≤ 5 mg/L, were identified from 12,389 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018) in 10 countries in which CRP is routinely measured. Predictor “After” (vs “before”) observing a high CRP level. Outcomes Within-patient changes in hemoglobin level, ESA dose, and ESA hyporesponsiveness (hemoglobin 6,000 [Japan] or >8,000 [Europe] U/wk). Analytical Approach Linear mixed models and modified Poisson regression. Results Comparing before with after periods, mean hemoglobin level decreased from 11.2 to 10.9 g/dL (adjusted mean change, −0.26 g/dL), while mean ESA dose increased from 6,320 to 6,960 U/wk (adjusted relative change, 8.4%). The prevalence of ESA hyporesponsiveness increased from 7.6% to 12.3%. Both the unadjusted and adjusted prevalence ratios of ESA hyporesponsiveness were 1.68 (95% CI, 1.48-1.91). These associations were consistent in sensitivity analyses varying CRP thresholds and were stronger when the CRP level increase was sustained over the 3-month after period. Limitations Residual confounding by unmeasured time-varying risk factors for ESA hyporesponsiveness. Conclusions In the 3 months after HD patients experienced an increase in CRP levels, hemoglobin levels declined quickly, ESA doses increased, and the prevalence of ESA hyporesponsiveness increased appreciably. Routine CRP measurement could identify inflammation as a cause of worsened anemia. In turn, these findings speak to a potentially important role for anemia therapies that are less susceptible to the effects of inflammation., Graphical Abstract

Background Real-world incidence, clinical consequences, and healthcare resource utilization (HRU) of hyperkalemia (HK) remain poorly characterized, particularly in patients with specific comorbidities. Methods Data from the Clinical Practice Research Datalink and Hospital Episode Statistics databases were analyzed to determine incidence of an index HK event, subsequent clinical outcomes, and HRU in the English population. Factors associated with index HK in a primary care setting were also identified for those with an index HK event during the study period (2009–2013) and matched controls. Results The overall incidence rate of an index HK event was 2.9 per 100 person-years. Use of renin–angiotensin–aldosterone system inhibitors was strongly associated with HK (odds ratio, 13.6–15.9). Few patients (5.8%) had serum potassium (K+) retested ≤ 14 days following the index event; among those retested, 32% had HK. Following an index HK event, all-cause hospitalization, HK recurrence, and kidney function decline were the most common outcomes (incidence rates per 100 person-years: 14.1, 8.1, and 6.7, respectively), with higher rates in those with comorbidities or K+ > 6.0 mmol/L. Mortality and arrhythmia rates were higher among those with K+ > 6.0 mmol/L. Older age, comorbid diabetes mellitus, and mineralocorticoid receptor antagonist use were associated with HK recurrence. Relatively few patients received testing or prescriptions to treat HK following an event. Conclusions Severe index HK events were associated with adverse outcomes, including arrhythmia and mortality. Despite this, retesting following an index event was uncommon, and incidence of recurrence was much higher than that of the index event. Electronic supplementary material The online version of this article (10.1186/s12882-019-1250-0) contains supplementary material, which is available to authorized users.

Background and Aims Elevated albuminuria in patients with chronic kidney disease (CKD) is associated with increased risks of CKD progression, cardiovascular events and all-cause death. In the DAPA-CKD study, dapagliflozin significantly reduced the risk of all-cause death in patients with elevated albuminuria compared with placebo (hazard ratio: 0.69; 95% confidence interval 0.53–0.88). To assess the cost-effectiveness of new treatments, decision makers require survival estimates over a longer period than that of a typical clinical trial, usually over a lifetime time horizon. A formal elicitation process is currently underway to obtain estimates of long-term survival of patients with albuminuric CKD from clinical experts. Their responses will be used to validate extrapolations of all-cause mortality data from DAPA-CKD, which could inform cost-effectiveness analyses for dapagliflozin. Method Targeted literature searches were conducted to collate data on all-cause mortality in patients with CKD and elevated albuminuria. Clinical trials and observational studies were included if they involved non-dialysis-dependent patients with CKD aged 18 years and over, had more than 500 participants per study arm and reported incidence of all-cause death and/or all-cause mortality/survival Kaplan–Meier (KM) curves. To estimate long-term survival, KM curves were extrapolated to 20 years by calculating standard mortality ratios (SMRs) using age- and sex-adjusted general-population lifetable data. Study and patient characteristics and mortality data from relevant studies were provided to clinical experts to inform their judgements in a formal elicitation process. After receiving training on the elicitation process, six leading disease area experts were invited to complete the elicitation survey using an Excel-based tool, which consisted of 10 calibration questions, and three questions regarding the survival of patients in the placebo arm of the DAPA-CKD study at 10 and 20 years. The elicited estimates will be weighted and aggregated using Cooke’s method. Results Literature searches identified 13 relevant articles (seven clinical trials and six observational studies), with a range of 1094 to 5674 participants. Mean age varied across studies (range: 55–70 years). Where reported, median follow-up was 9–144 months, and mean estimated glomerular filtration rate (eGFR) at baseline was 22.4–56.3 mL/min/1.73 m2. Five studies exclusively included patients with type 2 diabetes (T2D). The incidence of all-cause death was reported in nine studies and was 1.5–9.4 deaths per 100 patient-years, with the highest incidence observed in a study reporting data for patients with CKD stage 4 and 5 (8.0 and 9.4 deaths per 100 patient-years, respectively). Nine studies provided KM curves; from these, estimated survival at 2 years ranged from 86% (study population mean age 67 years, eGFR < 15 mL/min/1.73 m2) to 98% (study population mean age 58 years, mean eGFR 46.2 mL/min/1.73 m2). The SMR-extrapolated survival at 10 and 20 years was 36–80% and 2–69%, respectively. The ranges defined by the expert judgements collected to date for survival at 10 and 20 years are in line with the variability of the extrapolated KM survival curves. The elicitation process is ongoing and therefore, to avoid biasing the judgements that remain to be collected, preliminary results are not reported here. Results of the expert elicitation will be presented in full at the congress. Conclusion Initial results from the survey calibration questions suggest that the expert elicitation process provides expert judgements that are both informative and precise. The elicitation of survival estimates for patients with CKD and elevated albuminuria at 10 and 20 years will provide greater insight than extrapolated data alone, and will increase the validity of long-term survival projections for dapagliflozin cost-effectiveness analyses.

Background In patients on dialysis with anemia, avoiding red blood cell transfusions is preferable. We sought to develop and validate a novel transfusion prediction risk score for patients receiving maintenance hemodialysis. Methods This retrospective cohort study used United States Renal Data System data to create a model development cohort (patients who were point prevalent and on hemodialysis on November 1, 2012) and a validation cohort (patients who were point prevalent and on hemodialysis on August 1, 2013). We characterized comorbidity, inflammatory conditions, hospitalizations, anemia and anemia management, iron parameters, intravenous iron use, and vitamin D use during a 6-month baseline period to predict subsequent 3-month transfusion risk. We used logistic least absolute shrinkage and selection operator regression. In an exploratory analysis, model results were used to calculate a score to predict 6- and 12-month hospitalization and mortality. Results Variables most predictive of transfusion were prior transfusion, hemoglobin, ferritin, and number of hospital days in the baseline period. The resulting c-statistic in the validation cohort was 0.74, indicating relatively good predictive power. The score was associated with a significantly increased risk of subsequent mortality (hazard ratios 1.0, 1.22, 1.26, 1.54, 1.71, grouped from lowest to highest score), but not with hospitalization. Conclusions We developed a transfusion prediction risk score with good performance characteristics that was associated with mortality. This score could be further developed into a clinically useful application, allowing clinicians to identify patients on hemodialysis most likely to benefit from a timely, proactive anemia treatment approach, with the goal of avoiding red blood cell transfusions and attendant risks of adverse clinical outcomes.

Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.

Diabetes plays an important role in the complex relationship between chronic kidney disease (CKD) and cardiovascular disease. This retrospective observational study compared the influence of estimated glomerular filtration rate (eGFR) and proteinuria on the risk of major adverse cardiovascular event (MACE; myocardial infarction or stroke) in CKD patients with and without diabetes. Data were from a linked database of UK electronic health records. Individuals with CKD and no prior MACE were classified as type 1 diabetes (T1DM; n = 164), type 2 diabetes (T2DM; n = 9,711), and non-diabetes (non-DM; n = 75,789). Monthly updated time-dependent Cox proportional hazard models were constructed to calculate adjusted hazard ratios (aHRs) for progression to MACE from first record of abnormal eGFR or proteinuria (index date). In non-DM, aHRs (95% CIs) by baseline eGFR category (referent G2) were G1: 0.70 (0.55–0.90), G3a: 1.28 (1.20–1.35), G3b: 1.64 (1.52–1.76), G4: 2.19 (1.98–2.43), and G5: 3.12 (2.44–3.99), and by proteinuria category (referent A1) were A2: 1.13 (1.00–1.28), A2/3 (severity indeterminable): 1.58 (1.28–1.95), and A3: 1.64 (1.38–1.95). In T2DM, aHRs were G1: 0.98 (0.72–1.32), G3a: 1.18 (1.03–1.34), G3b: 1.31 (1.12–1.54), G4: 1.87 (1.53–2.29), G5: 2.87 (1.82–4.52), A2: 1.22 (1.04–1.42), A2/3: 1.45 (1.17–1.79), and A3: 1.82 (1.53–2.16). Low numbers in T1DM precluded analysis. Modelling T2DM and non-DM together, aHRs were, respectively, G1: 3.23 (2.38–4.40) and 0.70 (0.55–0.89); G2: 3.18 (2.73–3.70) and 1.00 (referent); G3a: 3.65 (3.13–4.25) and 1.28 (1.21–1.36); G3b: 4.01 (3.40–4.74) and 1.65 (1.54–1.77); G4: 5.78 (4.70–7.10) and 2.21 (2.00–2.45); G5: 9.00 (5.71–14.18) and 3.14 (2.46–4.00). In conclusion, reduced eGFR and proteinuria were independently associated with increased risk of MACE regardless of diabetes status. However, the risk of MACE in the same eGFR state was 4.6–2.4 times higher in T2DM than in non-DM.

Whether and how anemia treatment with erythropoiesis stimulating agents (ESAs) before hemodialysis initiation may be associated with lower mortality after dialysis initiation is unknown. We compared all-cause and cardiovascular mortality in two groups of patients who experienced distinct anemia treatment patterns with ESAs before and after hemodialysis initiation. This retrospective cohort analysis included patients initiating hemodialysis April 1, 2012-June 30, 2013, identified from United States Renal Data System end-stage renal disease (ESRD) and pre-ESRD files. Patients treated with ESAs before and after hemodialysis initiation who maintained Hb ≥ 9.0 g/dL throughout (comparator group, n = 3662) were compared with patients with Hb < 9.0 g/dL before hemodialysis initiation (with or without ESAs) whose levels increased with ESAs after hemodialysis initiation (referent group, n = 4461). Cox proportional hazards models were used to calculate the hazard ratio of all-cause and cardiovascular mortality after hemodialysis initiation. Of 20,454 patients, 4855 (23.7%) had Hb < 9.0 g/dL upon hemodialysis initiation; of these 4855, 26.6% received ESAs before initiation. Comparator group Hb levels increased from 8.2 ± 0.8 mg/dL upon initiation to 10.9 ± 1.2 with ESAs afterward. Comparator patients were more likely than referent patients to be younger (76.3 ± 6.7 versus 77.2 ± 6.9 years), male (51.5% versus 49.8%), and black (24.6% versus 18.6%). Risk of all-cause mortality was lower for the comparator group versus the referent group at 3 (HR 0.83, 95% CI 0.68-1.00, P = 0.052), 6 (0.86, 0.74-1.00, P = 0.047), and 12 (0.88, 0.78-0.99, P = 0.036) months. The pattern was similar for cardiovascular mortality. Hb ≥ 9.0 with ESAs before and after hemodialysis initiation was generally associated with lower post-initiation all-cause and cardiovascular mortality compared with predialysis Hb < 9.0 g/dL in patients whose Hb levels subsequently improved with ESAs after hemodialysis initiation.

Hyperphosphatemia is highly prevalent among patients with end-stage kidney disease and is a major risk factor for cardiovascular disease and mortality. The contemporary management of hyperphosphatemia consists of oral phosphate binders for maintenance of normal serum phosphorus levels. Although several phosphate binders are currently available, limitations related to tolerability, safety, effectiveness, cost and pill burden have prompted the development of newer agents. Ferric-based compounds have been recognized to reduce phosphate absorption since the 1930s. In this manuscript, we review the recently available data on the use of ferric citrate with a focus on human studies that have led to its approval as a phosphate binder by the US FDA.

Background: A phase II open-label study was conducted in hemodialysis patients evaluating the short-term safety, tolerability, and iron absorption with ferric citrate when used as a phosphate binder. Methods: Enrollment occurred in two periods. Period 1 recruited patients taking 6–15 pills/day of binder with phosphorus of ≥2.5 mg/dl. Period 2 recruited patients taking ≥12 pills/day of binder with phosphorus of ≥3.5 mg/dl. Participants with ferritin ≥1,000 µg/l or transferrin iron saturation (TSAT) ≥50% at screening were excluded. Subjects discontinued their previous binders and started 4.5 g/day of ferric citrate (period 1) or 6 g/day (period 2) and were titrated for 4 weeks to maintain a phosphorus of 3.5–5.5 mg/dl. Chemistries and complete blood count were obtained weekly and a gastrointestinal questionnaire was administered at drug initiation and final visit. Iron therapy was permitted if the ferritin was Results: Fifty-five subjects were enrolled. Four serious adverse events were reported; none were related to the study drug. Findings from the gastrointestinal questionnaire included stool discoloration (69%), constipation (15%), and bloating (7%). Mean iron parameters at the beginning of the study were ferritin 554 ± 296 µg/l, iron 68 ± 21 µg/dl, and iron saturation 30 ± 7.8%. At the end of study, mean ferritin was 609 ± 340 µg/l (p = 0.02), iron 75 ± 27 µg/dl (p = 0.04), and TSAT was 35 ± 13% (p = 0.001). Mean phosphorus and calcium levels were unchanged from baseline at the end of study. Conclusion: Ferric citrate was well tolerated by patients after 4 weeks with no significant clinical or biochemical adverse events related to exposure.

Patients with end-stage renal disease (ESRD) are at risk of prolonged radiation exposure during therapy with radioactive iodine (131I) because it is normally renally excreted. However, 131I is dialyzable and exposure can be monitored with a standard Geiger counter during dialysis. We present two cases of thyroid carcinoma in patients with ESRD who were treated successfully with 131I while continuing chronic hemodialysis (HD). In each case, single HD treatments of 3 and 4 hours performed approximately 20 hours after the administration of 131I resulted in an 80% and 70% reduction in total body radiation levels, respectively. In both cases, Geiger counter measurements after HD following 131I administration revealed levels less than 3 mR/hr, allowing safe discharge from the hospital in a timely manner. All contaminated waste was disposed of by the hospital's Department of Radiation Safety. Postdialysis monitoring revealed no residual radiation contamination of the HD machine or radiation exposure to the dialysis staff. Hemodialyzer reuse was suspended until monitoring demonstrated no appreciable evidence of radioactivity in these spent supplies. HD is a critical aspect in the treatment of patients with ESRD receiving 131I and can safely be administered with close planning between the HD staff and the staff of radiation safety.

Background Preclinical data suggest that cyclooxygenase 2 inhibitors decrease proteinuria and preserve glomerular structure in animal models of diabetic nephropathy. The objective of this study is to compare the efficacy and safety of celecoxib with placebo for decreasing proteinuria in patients with diabetic nephropathy. Study Design Placebo-controlled double-blinded crossover design. Setting & Participants 24 patients with type 1 or 2 diabetes mellitus, proteinuria with protein of 500 mg/d or greater, and serum creatinine level of 3.0 mg/dL or less. Intervention Patients were randomly assigned to: (1) 6 weeks of celecoxib followed by a 3-week washout period, followed by 6 weeks of placebo followed by another 3-week washout; or (2) 6 weeks of placebo followed by a 3-week washout, followed by 6 weeks of celecoxib followed by another 3-week washout period. All patients were administered quinapril, 20 to 40 mg/d, or irbesartan, 150 to 300 mg/d. All patients were administered aspirin, 81 mg/d. Outcomes & Measurements Proteinuria was assessed by means of protein-creatinine ratio. Data were analyzed using the mixed-effect statistical model. Results There was no significant difference in urinary proteinuria after 6 weeks of treatment with placebo or celecoxib (proteinuria ratio, celecoxib versus placebo, 1.041; 95% confidence interval, 0.846 to 1.282). Celecoxib had no significant effect on potassium or estimated glomerular filtration rate. Frequencies of adverse events were similar between the placebo and celecoxib treatments. Limitations This pilot study was not designed to evaluate the safety or long-term clinical effects of celecoxib. Conclusions Celecoxib, 200 mg/d, for 6 weeks did not alter proteinuria. Few adverse events were noted in this high-risk population.

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

Ferric citrate (Zerenex™, Keryx Biopharmaceuticals, Inc.), a phosphate binder drug candidate, recently completed a Phase III program confirming efficacy and demonstrating safety when used to treat hyperphosphatemia in patients with end-stage renal disease. Results of these trials demonstrate that ferric citrate effectively controls serum phosphorus and is well tolerated. Additionally, these studies demonstrate that ferric citrate improves iron parameters and reduces IV iron and erythropoietin stimulating agent utilization while maintaining hemoglobin levels. These unique features may further benefit the management of end-stage renal disease-related anemia.

Background.Roux-en-Y gastric bypass (RYGB) can result in calcium and vitamin D deficiency. Parathyroid surgery carries the risk of immediate and long-term hypocalcemia.Methods and Results.We describe a 54-year-old woman with history of end-stage renal disease and gastric bypass surgery who developed calciphylaxis requiring a 3.5-gland parathyroidectomy. Seven weeks later, she presented with weakness, perioral numbness, leg cramps, a positive Chvostek's sign, hypotension, prolonged QT-interval, and serum calcium of 5.4 mg/dL. Oral and intravenous calcium, calcitriol, and high calcium bath hemodialysis were given. She required 18 days of intravenous calcium and an outpatient maintenance regimen of calcitriol 6 mcg/day, calcium carbonate 8 grams/day, calcium citrate 1.2 grams/day, and ergocalciferol 50,000 IU/week.Conclusion.The patient's life-threatening prolonged hypocalcemia and large requirements of calcium and calcitriol were due to a combination of malabsorption, hypoparathyroidism, and renal failure. Special considerations should be given to bariatric surgery patients undergoing neck exploration.

Sclerosing encapsulating peritonitis (SEP) is a rare and dreaded complication that can occur in patients undergoing peritoneal dialysis (PD). Although risk factors have been identified, the diagnosis is difficult and is usually made late in the disease after extensive fibrosis of the peritoneal membrane has occurred, at which point therapy is often fruitless. The high mortality rate of SEP is due to complications resulting from recurrent bowel obstruction, malnutrition, and sepsis. We report three patients with signs and symptoms suggestive of SEP all of whom had normal abdominal CT scans. Nevertheless, each patient underwent diagnostic laparoscopy, which confirmed the clinical suspicion of SEP. In each case, the diagnosis was made before extensive peritoneal fibrosis had occurred allowing therapeutic intervention at an early stage. All three patients subsequently became asymptomatic and thrived. This clinical improvement was supported by the lack of progression to overt peritoneal fibrosis on repeat laparoscopy. We conclude that a high index of suspicion in conjunction with a low threshold for diagnostic laparoscopy may be an effective strategy to establish an early diagnosis and treatment regimen for SEP. Additionally, repeat laparoscopy can be used to guide the length of therapy. These interventions may ultimately improve the long-term morbidity and mortality of SEP.

Patients with end-stage renal disease (ESRD) are at risk of prolonged radiation exposure during therapy with radioactive iodine (131I) because it is normally renally excreted. However, 131I is dialyzable and exposure can be monitored with a standard Geiger counter during dialysis. We present two cases of thyroid carcinoma in patients with ESRD who were treated successfully with 131I while continuing chronic hemodialysis (HD). In each case, single HD treatments of 3 and 4 hours performed approximately 20 hours after the administration of 131I resulted in an 80% and 70% reduction in total body radiation levels, respectively. In both cases, Geiger counter measurements after HD following 131I administration revealed levels less than 3 mR/hr, allowing safe discharge from the hospital in a timely manner. All contaminated waste was disposed of by the hospital's Department of Radiation Safety. Postdialysis monitoring revealed no residual radiation contamination of the HD machine or radiation exposure to the dialysis staff. Hemodialyzer reuse was suspended until monitoring demonstrated no appreciable evidence of radioactivity in these spent supplies. HD is a critical aspect in the treatment of patients with ESRD receiving 131I and can safely be administered with close planning between the HD staff and the staff of radiation safety.

Patients with chronic kidney disease treated by in-center conventional hemodialysis (3 times per week) have significant impairments in health-related quality of life measures, which have been associated with increased morbidity and mortality. FREEDOM is an ongoing prospective cohort study measuring the potential benefits of at-home short daily (6 times per week) hemodialysis. In this interim report we examine the long-term effect of short daily hemodialysis on health-related quality of life, as measured by the SF-36 health survey. This was administered at baseline, 4 and 12 months after initiation of short daily hemodialysis to 291 participants (total cohort), of which 154 completed the 12-month follow-up (as-treated cohort). At the time of analysis, the mean age was 53 years, 66% were men, 58% had an AV fistula, 90% transitioned from in-center hemodialysis, and 45% had diabetes mellitus. In the total cohort analysis, both the physical- and mental-component summary scores improved over the 12-month period, as did all 8 individual domains of the SF-36. The as-treated cohort analysis showed similar improvements with the exception of the role-emotional domain. Significantly, in the as-treated cohort, the percentage of patients achieving a physical-component summary score at least equivalent to the general population more than doubled. Hence, at-home short daily hemodialysis is associated with long-term improvements in various physical and mental health-related quality of life measures.