Impact of a continuous quality improvement program on contrast-induced nephropathy in outpatients with chronic kidney disease: an interrupted time-series study.

BACKGROUND: Contrast-induced nephropathy (CIN) caused by exposure to radioactive contrast media can cause acute kidney injury in patients with chronic kidney disease (CKD). We developed a multifaceted approach in a CIN-quality improvement (QI) program based on a shorter saline hydration protocol for the prevention of CIN in outpatients and assessed the effect of our CIN-QI program on decreasing both the incidence rate of CIN and overall use of contrast agents in patients undergoing contrast-enhanced computed tomography (CT). METHODS: We conducted a multi-center prospective interrupted time-series study from 2006 to 2018 investigating the efficacy of a CIN-QI program in preventing CIN among outpatients with CKD. An automatic medical record system alert was implemented to instruct physicians to consult a nephrologist and administer prophylactic hydration and follow-up when ordering contrast-enhanced imaging in patients with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2. The primary outcomes were the rates of prophylactic hydration and follow-up kidney function assessment, and the incidence of CIN for eligible patients. The usage rate of contrast-enhanced CT was also examined. RESULTS: A total of 95 594 patients who underwent contrast-enhanced CT were included in the study. The annual prophylactic hydration rate before the CIN-QI program ranged from 2.0% to 23.2% but increased to 59.2%-75.2% during the CIN-QI program (P < .001). The annual rate of follow-up kidney function testing also improved from 18.6%-25.8% to 34.1%-42.5% after implementation of the CIN-QI program (P < .001). The rate of CIN significantly declined in level by 10.0% at the start of the CIN-QI program (P = .002) and in trend by 2.9%/year (P < .001). The number of contrast-enhanced CT orders showed a positive level change in patients with advanced CKD, who were the CIN-QI program target group of patients with eGFR <45 mL/min/1.73 m2, at the start of the implementation of the CIN-QI program. After implementing the CIN-QI program, the number of contrast-enhanced CT orders showed a negative trend change across all patients, which decreased from -1.4%/year to -10.0%/year for patients with advanced CKD. CONCLUSION: The multifaceted approach in the CIN-QI program may be associated with the decreased incidence of CIN and increased rates of prophylactic hydration and follow-up kidney function testing.

Phase 3 Randomized Study Comparing Vadadustat with Darbepoetin Alfa for Anemia in Japanese Patients with Nondialysis-Dependent CKD.

BACKGROUND: Standard care for treating anemia in patients with CKD includes use of erythropoiesis-stimulating agents, which sometimes involves increased risks of cardiovascular morbidity and mortality. Previous studies in patients with anemia and nondialysis-dependent CKD (NDD-CKD) found significantly elevated hemoglobin levels with use of vadadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, compared with placebo. METHODS: In this phase 3, open-label, active-controlled noninferiority trial, we randomized 304 Japanese adults with anemia in NDD-CKD (including erythropoiesis-stimulating agent users and nonusers) to oral vadadustat or subcutaneous darbepoetin alfa for 52 weeks. The primary efficacy end point was average hemoglobin at weeks 20 and 24. Safety data included adverse events (AEs) and serious AEs. RESULTS: A total of 151 participants received vadadustat and 153 received darbepoetin alfa. Least squares mean of the average hemoglobin at weeks 20 and 24 was 11.66 (95% confidence interval [95% CI], 11.49 to 11.84) g/dl for vadadustat and 11.93 (95% CI, 11.76 to 12.10) g/dl for darbepoetin alfa. The 95% CIs for both treatments were within the target hemoglobin range (11.0-13.0 g/dl), and the lower 95% confidence limit for the difference between groups (-0.50 g/dl) was above the predefined noninferiority margin (-0.75 g/dl), demonstrating noninferiority of vadadustat to darbepoetin alfa. Similar proportions of patients in each group reported AEs and serious AEs. The most frequent AEs with vadadustat were nasopharyngitis, diarrhea, and constipation. CONCLUSIONS: In Japanese patients with NDD-CKD, vadadustat was noninferior to darbepoetin alfa, was effective up to week 52 in terms of average hemoglobin, and was generally well tolerated. These results suggest that vadadustat may be a potential treatment for anemia in this patient population.

Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. METHODS: The efficacy and safety of vadadustat, compared with darbepoetin alfa, was determined in a Phase 3 double-blind study in Japanese anemic patients on hemodialysis. Patients receiving erythropoiesis-stimulating agents (ESAs) were randomized and switched to either vadadustat or darbepoetin alfa for 52 weeks. Doses were adjusted to maintain a hemoglobin (Hb) level of 10.0-12.0 g/dL. The primary endpoint was average Hb level at Weeks 20 and 24. RESULTS: Of the 323 randomized patients, 120 and 135 completed the 52-week treatment period in the vadadustat and darbepoetin alfa groups, respectively. The average Hb levels at Weeks 20 and 24 [least square mean (LSM) and 95% confidence interval (CI)] were 10.61 (10.45-10.76) and 10.65 (10.50-10.80) g/dL in the vadadustat and darbepoetin alfa groups, respectively, demonstrating vadadustat's noninferiority to darbepoetin alfa (difference: -0.05 g/dL; 95% CI -0.26 to 0.17). In both groups, the mean Hb levels were maintained within the target range for 52 weeks. Furthermore, irrespective of patient backgrounds, the LSMs of Hb at Week 52 were within the target range. The most common adverse events were nasopharyngitis, diarrhea and shunt stenosis, which occurred at similar frequencies in both groups. No new safety concerns were identified. CONCLUSIONS: Vadadustat was as well-tolerated and effective as darbepoetin alfa in maintaining Hb levels within the target range. The findings suggest that vadadustat can be an alternative to ESA in the management of anemia in Japanese hemodialysis patients receiving ESA (ClinicalTrials.gov, NCT03439137).

Assessing urine ammonium concentration by urine osmolal gap in chronic kidney disease.

Acidemia is one of the risk factors for end-stage kidney disease and increases the mortality rate of patients with chronic kidney disease (CKD). Although urinary ammonium (U-NH4 + ) is the crucial component of renal acid excretion, U-NH4 + concentration is not routinely measured. To estimate U-NH4 + , urine osmolal gap (UOG = urine osmolality - [2(Na+ + K+ ) + urea + glucose]) is calculated and the formula (U-NH4 +  = UOG/2) has traditionally been used. However, the usefulness of this formula is controversial in CKD patients. We assessed the relationship between U-NH4 + and UOG in patients with CKD. Blood and spot urine samples were collected in 36 patients who had non-dialysis-dependent CKD. The mean ± SD age of patients was 72.0 ± 14.8 years, and the mean ± SD serum creatinine and U-NH4 + were 2.7 ± 2.3 mg/dl and 9.3 ± 9.2 mmol/L, respectively. A significant relationship was found between UOG/2 and U-NH4 + (r = .925, p < .0001). U-NH4 + estimated using the UOG was on average higher by 4.7 mmol/L than the measured one. Our results suggested that UOG could be a useful tool in clinical settings, especially in patients with moderate to severe CKD.

Serial measurement of electrolyte and citrate concentrations in blood-primed continuous hemodialysis circuits during closed-circuit dialysis.

BACKGROUND: For continuous renal replacement therapy in small infants, due to the large extracorporeal volume involved, blood priming can be necessary to prevent hypotension and hemodilution. Because packed red blood cells (RBCs) have high levels of potassium and citrate, closed-circuit dialysis is often performed. We assessed the metrics of closed-circuit dialysis and serial citrate concentration changes. METHODS: We performed dialysis of closed circuits primed with expired human packed RBC solution and 5% albumin. Blood and dialysate flow rates were 70 and 33.3 mL/min, respectively. The extracorporeal volume was 70 mL. We measured pH, electrolytes, and citrate in the closed circuit every 3 min for 15 min. We also assessed the adequacy of closed-circuit dialysis using the formula: [dialysate flow rate (mL/min) × time of dialysis (min)]/extracorporeal volume (mL) and we assessed the correlation between citrate and ionized calcium concentrations. RESULTS: To reach normal concentrations of sodium, potassium, and chloride, 2.4 times as much dialysate fluid as extracorporeal volume was needed. In contrast, for ionized calcium, bicarbonate, and citrate, 3.8 times as much dialysate fluid as extracorporeal volume was required. By simple linear regression analysis, the concentration of citrate was significantly correlated with that of ionized calcium. CONCLUSIONS: For closed-circuit dialysis using an RBC solution, the formula [dialysate flow rate (mL/min) × time of dialysis (min)]/extracorporeal volume (mL) would be a better parameter to estimate efficacy, compared with other metrics. Additionally, the citrate concentration can be readily estimated from the ionized calcium concentration during closed-circuit dialysis.

Association between chronic kidney disease and mortality in stage IV cancer.

BACKGROUND: Chronic kidney disease (CKD) is known to be associated with cancer mortality. However, no study has considered the well-known cancer prognostic factors, ECOG Performance Status (PS) and cancer treatment, as confounding factors. We assessed the independent relationship between CKD and cancer death in stage IV cancer patients. METHODS: In this retrospective observational study, we included stage IV cancer patients diagnosed from 2009 to 2014 in a single center. We collected baseline clinical and laboratory variables, and cancer-specific variables, and assessed the presence of CKD. Our primary outcome was all-cause mortality. The secondary outcome was cancer-specific mortality and site-specific cancer mortality. RESULTS: Among 961 eligible stage IV cancer patients (median age 69 years, 51.8% male), 150 patients had CKD. During follow-up (median 9.8 months), 638 patients died, of whom 526 patients died from cancer. After adjusting for prognostic variables, including ECOG PS and cancer treatment, all-cause mortality and cancer-specific mortality were significantly higher in CKD patients than in non-CKD patients (HR 1.41, 95% CI 1.13-1.77 and HR 1.43, 95% CI 1.12-1.83, respectively). In patients with breast and kidney and urinary tract cancers, CKD was associated with a significantly increased risk of death (HR 7.01, 95% CI 1.47-33.4 and HR 3.33, 95% CI 1.42-7.78, respectively). CONCLUSIONS: CKD at the time of stage IV cancer diagnosis was associated with all-cause mortality and cancer-specific mortality. Moreover, the association between CKD and cancer-specific death was site specific for breast cancer and kidney and urinary tract cancer.

The role and attitude of senior leaders in promoting group-based community physical activity: a qualitative study.

BACKGROUND: In the context of worldwide public health, it is very important to promote physical activity among the older people. This study explored the roles and attitudes of senior leaders in promoting group-based exercise in their local communities, specifically to determine the level and extent to which to elderly participation was encouraged. METHODS: This study conducted semi-structured face-to-face in-depth interviews and employed a subsequent thematic analysis. Participants included 10 club leaders and five sub-leaders who were working at senior clubs in Fujisawa-city, Kanagawa, Japan, from July to September 2018. RESULTS: Four themes emerged from the interview responses, including "unwavering attitude/conviction in relation to the vision," "leaders must set an example," "a search for balance in delegating responsibilities to members," and "creating and fostering culture and environment of mutual help." Further, each participant outlined several aims, including "achieving healthy longevity for the entire local community," "having older people promote healthy activities among the older people," and "creating a pro-health town." CONCLUSIONS: Findings indicate that policymakers, public health workers, and healthcare providers should recognize the pivotal roles that senior group leaders play in promoting healthy activities for the older people. These efforts should be strongly considered when developing policies and strategies designed to promote overall healthy longevity from a general community perspective.

Optimal follow-up intervals for different stages of chronic kidney disease: a prospective observational study.

BACKGROUND: Chronic kidney disease (CKD) is a public health challenge; however, evidence-based, optimal follow-up intervals for patients with CKD have not been identified. This study aimed to identify appropriate follow-up intervals for different stages of CKD. METHODS: We studied 2682 patients with CKD. The number of patients experiencing a 50% increase in creatinine and those reaching end-stage renal failure were examined on the basis of their CKD stage. The renal function testing interval was defined as the estimated time for 0.1% of the patients with CKD to have a composite renal outcome, after adjusting for clinical risk factors. Transitions from CKD stage-based subgroups were analyzed using parametric cumulative incidence models. Other sensitivity analyses involved estimation of the time to renal event occurrence for 1% of patients. RESULTS: Of the 913 patients (34%) who had a composite renal event, 29 had stage 3A (10.5%), 151 had stage 3B (16.3%), 429 had stage 4 (41.0%), and 304 had stage 5 CKD (70.9%). The estimated renal function testing intervals for patients with CKD were 6.0 months for stage 3A, 3.4 months for stage 3B, 2.0 months for stage 4, and 1.2 months for stage 5. CONCLUSIONS: The optimal follow-up intervals were longer for patients with lower CKD stages. These estimates are longer than those recommended by the current guidelines and serve as a reference for nephrologists in selecting an appropriate follow-up interval for each patient. TRIAL REGISTRATION: UMIN clinical trial registry number: UMIN000020038.

Association of Circulatory Iron Deficiency With an Enlarged Heart in Patients With End-Stage Kidney Disease.

OBJECTIVES: High prevalence of iron deficiency (ID) and cardiomyopathy have been observed in patients with end-stage kidney disease (ESKD). Our objective was to clarify associations between ID and cardiac remodeling in patients with ESKD. DESIGN AND METHODS: A cross-sectional study was conducted using 1974 Japanese patients with ESKD at the initiation of maintenance dialysis. Levels of hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the cardiothoracic ratio (CTR) were determined immediately before the first hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT) < 20%, and stored ID was defined as ferritin level <100 ng/dL. RESULTS: The mean age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored ID was found to be 38% and 34%, respectively. CTR was higher in patients with circulatory ID than in those without. Even in ESKD patients without overhydration, significant negative association was observed between TSAT and CTR. Higher odds ratios in parallel with higher CTR categories compared with the reference category of CTR <45% were found in patients with TSAT <20% on multinomial analysis, but ferritin did not show any significant associations. The odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after adjusting for confounding variables such as Hb and ferritin. However, that phenomenon was eliminated by adding usage of an iron agent. CONCLUSIONS: Circulatory ID is closely associated with an enlarged heart independent of ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney disease may prevent cardiac remodeling independent of Hb level in patients chronic kidney disease.

Possible prevention of uremic nausea by vitamin D receptor activators in non-dialysis patients with stage 5 chronic kidney disease.

BACKGROUND: Nausea is a major uremic symptom and a frequent indication for starting dialysis. However, preventive medication for uremic nausea has not yet been identified. Vitamin D receptor activators (VDRAs) may prevent uremic nausea via their pleiotropic actions. The objective of this study was to explore whether VDRA administration during the predialysis period is associated with a reduced prevalence of uremic nausea just prior to beginning dialysis. METHODS: A multicenter, retrospective, cross-sectional study was performed to identify a medication to prevent uremic nausea. Patients with stage 5 CKD who were followed-up over 3 months were included. The primary outcomes examined were the prevalence of uremic nausea, congestive heart failure (CHF), and intractable edema at dialysis commencement. The predictor variable was VDRA use during the predialysis period. RESULTS: One thousand five hundred and thirty six patients who had just begun dialysis in nine Japanese facilities between January 2006 and October 2013 were included. Two hundred and thirty (15.0%) patients had commenced dialysis because of uremic nausea, and three hundred and ninety two (25.5%) patients had been using VDRAs before initiating dialysis. Logistic regression analysis showed that, among the medications examined in this study, only VDRA use was independently associated with a lower frequency of uremic nausea (OR 0.512, 95% CI 0.347-0.738, P = 0.0003). On the other hand, CHF and intractable edema were not associated with VDRA administration. CONCLUSION: Use of VDRAs during the predialysis period was the only factor associated with a lower prevalence of uremic nausea, suggesting that VDRAs may prevent uremic nausea in patients with advanced CKD.

A low initial serum sodium level is associated with an increased risk of overcorrection in patients with chronic profound hyponatremia: a retrospective cohort analysis.

BACKGROUND: Even with abundant evidence for osmotic demyelination in patients with hyponatremia, the risk factors for overcorrection have not been fully investigated. Therefore the purpose of this study is to clarify the risks for overcorrection during the treatment of chronic profound hyponatremia. METHODS: This is a single-center retrospective observational study. We enrolled 56 adult patients with a serum sodium (SNa) concentration of ≤125 mEq/L who were treated in an intensive care unit by nephrologists using a locally developed, fixed treatment algorithm between February 2012 and April 2014. The impact of patient parameters on the incidence of overcorrection was estimated using univariable and multivariable logistic regression models. Overcorrection was defined as an increase of SNa by >10 mEq/L and >18 mEq/L during the first 24 and 48 h, respectively. RESULTS: The median age was 78 years, 48.2% were male, and 94.6% of the patients presented with symptoms associated with hyponatremia. The initial median SNa was 115 mEq/L (quartile, 111-119 mEq/L). A total of 11 (19.6%) patients met the criteria for overcorrection with 9 (16.0%) occurring at 24 h, 6 (10.7%) at 48 h, and 4 (7.1%) at both 24 and 48 h. However, none of these patients developed osmotic demyelination. Primary polydipsia, initial SNa, and early urine output were the significant risk factors for overcorrection on univariable analysis. Multivariable analysis revealed that the initial SNa had a statistically significant impact on the incidence of overcorrection with an adjusted odds ratio of 0.84 (95% confidence interval, 0.70-0.98; p = 0.037) for every 1 mEq/L increase. Additionaly, the increase in SNa during the first 4 h and early urine output were significantly higher in patients with overcorrection than in those without (p = 0.001 and 0.005, respectively). CONCLUSIONS: An initial low level of SNa was associated with an increased risk of overcorrection in patients with profound hyponatremia. In this regard, the rapid increase in SNa during the first 4 h may play an important role.

Effect of ninjin'yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer's disease: 2 years of observation.

BACKGROUND: Only a few approved drugs are capable of alleviating the cognitive and behavioural symptoms of people living with Alzheimer's disease (AD). In recent years, however, the number of studies examining the clinical effects of herbal medicines on cognitive function in patients with AD has increased considerably. This study evaluated the long-term effects of a traditional Japanese medicine (Kampo medicine) known as ninjin'yoeito (NYT) on cognitive impairment and mood status in patients with AD over a 2-year period. METHODS: Twenty-three patients with mild-to-moderate probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria were included. Each participant had exhibited an insufficient response to treatment with donepezil alone before the start of the trial. Eleven patients received treatment with donepezil alone, and the remaining patients received a combined treatment of donepezil and NYT for 2 years. Patients were assessed by the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version for cognitive function, and the Neuropsychiatric Inventory was used to evaluate the patients' mood status at baseline and every 6 months for 2 years. RESULTS: The Mini-Mental State Examination results showed no significant differences between the two groups. Significant improvements were observed on the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version and the Neuropsychiatric Inventory depression scores of patients who received the combined therapy with donepezil and NYT (Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, 12 months: P < 0.01, 18 months: P = 0.04, 24 months: P < 0.01; Neuropsychiatric Inventory depression, 6 months: P < 0.05, 24 months: P < 0.05). CONCLUSIONS: A 2-year follow-up of patients receiving donepezil and NYT treatment showed an improved cognitive outcome and alleviation of AD-related depression.

[Two Cases of Locally Recurrent Rectal Cancer after Intersphincteric Resection That Were Controlled with a Combination of Chemoradiotherapy and Abdominoperineal Resection].

We report 2 cases of locally recurrent rectal cancer after intersphincteric resection(ISR)that were controlled with a combination of chemoradiotherapy and abdominoperineal resection(APR). In Case 1, we performed preoperative chemoradiotherapy( TS-1 plus RT 45 Gy)and APR for the local recurrence of ISR. On pathology, viable neoplastic cells were noted. In Case 2, we performed preoperative chemotherapy(Bmab plus mFOLFOX6)and APR for the local recurrence of ISR. On pathology, no viable neoplastic cells were noted. However, a local recurrence developed again 3 months later. Therefore, we performed chemoradiotherapy(TS-1 plus RT 53 Gy). The 2 patients survived without recurrence until now. Their pathology tissues and clinical courses showed that control of local recurrence with only chemoradiotherapy or surgical resection was likely to be difficult. We might be able to improve the prognosis of patients with a combination of chemoradiotherapy and surgical resection.

[Report of a Case of Long-Term Survival with Mulitidisciplinary Therapy for a Patient with Multiple Liver Metastases from Rectal Cancer].

Multidisciplinary therapy is necessary to prevent recurrence of advanced rectal cancer and advanced cancer with metastases. Here we report a case of long-term survival of a patient with advanced rectal cancer with multiple liver metastases. An 80's woman had previously undergone both Hartmann's operation and a partial hepatectomy for advanced rectal cancer with multiple liver metastases. A year after chemotherapy, a CT scan revealed multiple liver metastases. Thus, we performed partial liver resection. After another round of chemotherapy, a CT scan revealed lung metastases and local recurrence of the rectal cancer; therefore, we performed partial lung resection and a Miles operation. These procedures were conducted 4 years after her first operation. The following year, PET-CT revealed a mediastinum lymph node metastasis; consequently, we performed radiation therapy. New lung metastases and local recurrences of rectal cancer were identified after the radiation therapy; thus, we resumed the therapy, including a molecular targeting drug. Although the patient is in a tumor-bearing state, she is still alive 10 years after her first operation.

Modified Cut-Off Value of the Urine Protein-To-Creatinine Ratio Is Helpful for Identifying Patients at High Risk for Chronic Kidney Disease: Validation of the Revised Japanese Guideline.

Chronic kidney disease (CKD) is a global public health issue, and strategies for its early detection and intervention are imperative. The latest Japanese CKD guideline recommends that patients without diabetes should be classified using the urine protein-to-creatinine ratio (PCR) instead of the urine albumin-to-creatinine ratio (ACR); however, no validation studies are available. This study aimed to validate the PCR-based CKD risk classification compared with the ACR-based classification and to explore more accurate classification methods. We analyzed two previously reported datasets that included diabetic and/or cardiovascular patients who were classified into early CKD stages. In total, 860 patients (131 diabetic patients and 729 cardiovascular patients, including 193 diabetic patients) were enrolled. We assessed the CKD risk classification of each patient according to the estimated glomerular filtration rate and the ACR-based or PCR-based classification. The use of the cut-off value recommended in the current guideline (PCR 0.15 g/g creatinine) resulted in risk misclassification rates of 26.0% and 16.6% for the two datasets. The misclassification was primarily caused by underestimation. Moderate to substantial agreement between each classification was achieved: Cohen's kappa, 0.56 (95% confidence interval, 0.45-0.69) and 0.72 (0.67-0.76) in each dataset, respectively. To improve the accuracy, we tested various candidate PCR cut-off values, showing that a PCR cut-off value of 0.08-0.10 g/g creatinine resulted in improvement in the misclassification rates and kappa values. Modification of the PCR cut-off value would improve its efficacy to identify high-risk populations who will benefit from early intervention.

Darbepoetin alfa for the treatment of anemia in children undergoing peritoneal dialysis: a multicenter prospective study in Japan.

BACKGROUND: Darbepoetin alfa (DA) is an attractive alternative to recombinant human erythropoietin (rHuEPO) in managing renal anemia. Since DA has not been approved by the appropriate Japanese drug regulatory agencies for the indication of renal anemia in children in Japan, we have conducted a multicenter prospective study to determine the efficacy and safety of DA in Japanese children undergoing peritoneal dialysis (PD). METHODS: Pediatric patients subcutaneously receiving rHuEPO were switched to DA treatment for a period of 28 weeks. The conversion to the initial dose of DA was calculated as 1 µg DA for 200 IU rHuEPO, and DA was administered intravenously once every 2 weeks. The target hemoglobin (Hb) concentration was defined as 11.0 to ≤13.0 g/dL. In some patients, the dose of DA was adjusted appropriately to achieve this target level, and/or the dosing frequency changed to once every 4 weeks. RESULTS: In the 25 patients switched from rHuEPO to DA the mean Hb concentration increased from 9.9 ± 1.0 to 11.1 ± 1.0 g/dL at 8 weeks following commencement of the DA treatment. The target Hb concentration was achieved in 88 % of these patients, and 60 % maintained this target value on completion of the study. The dosing frequency was extended to once every 4 weeks in 60 % of patients. Twenty-four adverse events were noted in 11 of 25 patients (44 %); however, there was no causality between DA and adverse events. CONCLUSIONS: The results of this study suggest that intravenous administration of DA once every 2 or 4 weeks is an effective and safe treatment for renal anemia in Japanese children undergoing PD.