A case of hyperviscosity syndrome associated with Waldenström macroglobulinemia treated with membrane plasma exchange without predilution.

A 75-year-old man with blurred vision and nasal bleeding was diagnosed with hyperviscosity syndrome and central retinal vein occlusion secondary to Waldenström macroglobulinemia. Serum total protein and IgM levels were undetectable. Because of the severe symptoms, we determined that immediate plasma-exchange treatment was required to decrease the blood viscosity. The initial plasma exchange was performed using the membrane isolation method with a predilution standby. A saline predilution replacement was prepared to decrease the total membrane pressure (TMP); however, the predilution protocol was not used because the planned treatment volume could be achieved without increasing the TMP. After two consecutive days of membrane plasma exchange, all serum biochemical tests were measurable, and IgM was below 4000 mg/dL. After chemotherapy, his visual symptoms improved, and he was discharged. Since it is difficult to assess the risk of elevated TMP prior to initial plasma exchange, membrane plasma exchange with a predilution standby may be a useful strategy for initial plasma exchange for hyperviscosity syndrome in terms of safety and efficiency.

p53 and Vimentin Double Immunostaining to Differentiate between High-Grade Urothelial Carcinoma Cells and Benign Atypical Cells.

INTRODUCTION: Urine cytology is an indispensable test for detecting high-grade urothelial carcinoma (HGUC); however, the distinction between HGUC cells and morphologically similar benign atypical cells poses clinical challenges. In this study, we performed double immunostaining for p53 and vimentin to establish a diagnostic method to accurately distinguish HGUC cells from benign atypical cells. METHODS: This study included 41 cases of HGUC, 11 of urolithiasis, and 22 of glomerular disease diagnosed histopathologically or clinically. After preparing urine cytology specimens from voided urine samples, p53 immunostaining was performed, and the p53-positive intensity and p53 positivity rate were calculated. Subsequently, vimentin immunostaining was performed on the same specimens to calculate the rate of vimentin positivity. RESULTS: The HGUC cell group had a mean p53-positive intensity of 2.40, a mean p53 positivity rate of 73.2%, and a mean vimentin positivity rate of 5.1%. In contrast, the mean p53-positive intensity, p53 positivity rate, and vimentin positivity rate were 1.63, 36.7%, and 66.2%, respectively, in the benign atypical cell group. There were significant differences between the two groups for each parameter. Moreover, two multiple logistic regression models combining the results of these three parameters exhibited higher sensitivity and specificity than solely assessing the p53-positive intensity, positivity rate, and vimentin positivity rate. CONCLUSION: Since double immunostaining with p53 and vimentin distinguishes HGUC cells from benign atypical cells, it could be to improve the diagnostic accuracy of urine cytology.

Nuclear long diameter as a new criterion to distinguish high-grade urothelial carcinoma cells from benign reactive cells.

OBJECTIVE: Recently, the nuclear area has attracted attention as a morphological parameter to differentiate high-grade urothelial carcinoma (HGUC) cells from benign reactive cells. The nuclear long diameter (NLD) strongly correlates with the nuclear area and is easy to subjectively estimate. Therefore, this study examined the usefulness of the NLD-to-neutrophil diameter ratio for detecting HGUC cells in urine cytology. METHODS: This study included 29, 26 and 18 patients with HGUC, glomerular disease and urolithiasis respectively. An image analysis system was used to measure the NLD of HGUC and benign reactive cells (reactive renal tubular cells and reactive urothelial cells) and the neutrophil diameter that appeared in the voided urine in these cases. The NLD index was calculated using the NLD-to-neutrophil diameter ratio. We subsequently compared HGUC and benign reactive cells with respect to NLD and NLD indices. In addition, the HGUC cell group and benign reactive cell group were compared by selecting the five cells with the largest NLD and NLD index on each slide. RESULTS: The NLD and NLD indices of HGUC cells were significantly higher than those of benign reactive cells in all cells and in the five cells with the largest NLD and NLD indices. The cut-off value of the NLD index for detecting HGUC cells was 1.25 in all cells and 1.80 in the five cells with the largest NLD index. CONCLUSIONS: The NLD index is a useful parameter that can be introduced into routine microscopic examinations to differentiate HGUC cells from benign reactive cells.

Exercise instruction during haemodialysis treatment after changes to the insurance regime: a nationwide questionnaire survey in Japan.

In April 2022, an additional medical fee for exercise instruction during haemodialysis treatment was approved for insurance claims in Japan. We conducted a questionnaire survey to investigate the current situation regarding exercise therapy during haemodialysis treatment after this change. Questionnaires were mailed to 4257 haemodialysis facilities, almost all the haemodialysis facilities in Japan, on January 31, 2023. In total, 1657 facilities responded, of which 550 (33%) provided exercise instruction during haemodialysis treatment, and 65% of these claimed the new fee. Of the 550 facilities that had claimed the fee at the time of survey, 245 (55%) started exercise instruction in April 2022 or later. Exercise instruction focused on resistance training (81%) and aerobic exercise (62%) for 20-30 min (66%) three times a week (80%). The instructors included physicians in 45% of facilities, nurses in 74%, and physical therapists in 36%. Efficacy was evaluated in 76% of the facilities providing instruction, mainly by assessing change in muscle strength (49%). Overall, 39% of facilities had experienced some adverse events, but none were life-threatening. In conclusion, after the change in the insurance regime, exercise instruction during haemodialysis treatment has become more popular, and more patients on haemodialysis are undergoing exercise therapy.

A case of a peritoneal dialysis patient with left pleuroperitoneal communication caused by a pericardial defect after coronary artery bypass surgery.

A 74-year-old woman with reduced kidney and cardiac function and a history of coronary artery bypass surgery involving the gastroepiploic artery to the right coronary artery and posterior descending artery #4 presented with dyspnea on exertion. Shortly after the induction of peritoneal dialysis (PD), an increase in the left pleural effusion was observed, and a diagnosis of left pleuroperitoneal communication was made by puncture drainage. The pleuroperitoneal communication hole was not detected under thoracoscopic observation; however, a 10 mm-sized hole in the pericardium was found, confirming leakage of ICG-loaded peritoneal dialysate fluid (PDF). CT peritoneography using PDF mixed with iodine contrast medium revealed that the gastroepiploic artery-to-right coronary artery pathway was defective on the abdominal side. We concluded that the left pleuroperitoneal communication was caused by a two-stage fistulous pathway between the abdominal and pleural cavities through the pericardial cavity after coronary artery bypass graft surgery. Although closure of the diaphragmatic hole around the gastroepiploic artery graft should have been performed to restart PD, the patient did not wish to undergo further invasive procedures. Identification of the fistulous pathway is extremely important for prompt diagnosis and treatment of pleuroperitoneal communication.

Preference for anti-phospholipase A2 receptor antibody assay in patients with suspected membranous nephropathy: a survey study on medical practice after publication of Japanese Guidelines for Nephrotic Syndrome 2020.

BACKGROUND: International practice guidelines advocate for the use of anti-phospholipase A2 receptor (PLA2R) antibody testing to diagnose primary membranous nephropathy (pMN). This study aimed to clarify the current status of anti-PLA2R antibody testing in the diagnosis of pMN in Japan and to scrutinize the factors associated with the implementation of this antibody test. METHODS: Utilizing a web-based questionnaire for nephrologists, responses were collected from 306 facilities and 427 nephrologists between November 2021 and December 2021. Preference for anti-PLA2R antibody testing was also investigated. Factors related to the experience of quantifying anti-PLA2R antibodies were estimated by generalized estimating equations using a robust analysis of variance with clusters of facilities of affiliation. RESULTS: Of the 427 respondents, 140 (32.8%) had previous measurement experience at their current workplace and 165 (38.6%) had previous measurement experience overall. In pMN-suspected cases without contraindications to renal biopsy, 147 (34.4%) of the respondents opted to request anti-PLA2R antibody testing. The respondents' experience with anti-PLA2R antibody quantification at their current place of work was generally higher in university hospitals and increased with the annual number of kidney biopsies and the number of years since graduation. CONCLUSION: The results of this study suggest that a significant proportion of nephrologists in Japan have no experience in performing anti-PLA2R antibody assays, and that the assays may be hampered by the limited capabilities of the current workplace and the financial burden on facilities and patients.

Dapagliflozin Utilization in Chronic Kidney Disease and Its Real-World Effectiveness Among Patients with Lower Levels of Albuminuria in the USA and Japan.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors such as dapagliflozin have been proven effective for slowing chronic kidney disease (CKD) progression in large outcomes trials that mainly included patients with higher levels of albuminuria. Understanding the real-world utilization and effectiveness of these drugs among patients with CKD with lower levels of albuminuria can inform clinical decision-making in this population. METHODS: Claims data from the USA and Japan were used to describe patients with CKD and urinary albumin-to-creatinine ratio (UACR) < 200 mg/g who were eligible for dapagliflozin 10 mg treatment (initiators and untreated) following its approval for CKD. A quantile regression analysis was performed to evaluate the effect of dapagliflozin 10 mg initiation versus no initiation on estimated glomerular filtration rate (eGFR) slope in a propensity score-matched cohort, using a prevalent new-user design. RESULTS: Dapagliflozin initiators (n = 20,407) mostly had stage 3-4 CKD (69-81% across databases). The most common comorbidities were type 2 diabetes, hypertension and cardiovascular disease. At baseline, a renin-angiotensin system inhibitor was prescribed in 53-81% of patients. Eligible but untreated patients were older and had a higher eGFR and lower comorbidity burden than initiators. Following dapagliflozin initiation, the differences in median eGFR slope between initiators and matched non-initiators were 1.07 mL/min/1.73 m2/year (95% confidence interval [CI] 0.40-1.74) in all patients with UACR < 200 mg/g and 1.28 mL/min/1.73 m2/year (95% CI - 1.56 to 4.12) in patients with UACR < 200 mg/g without type 2 diabetes. CONCLUSIONS: Dapagliflozin 10 mg was prescribed to a broad range of patients with CKD. In patients with UACR < 200 mg/g, dapagliflozin initiation was associated with a clinically meaningful attenuation of eGFR slope compared with non-initiation. These findings supplement available clinical efficacy evidence and suggest that dapagliflozin effectiveness may extend to patients with CKD and UACR < 200 mg/g. Graphical Abstract and Video Abstract available for this article. (Video Abstract 245964 kb).

Partial replacement of d-glucose with d-allose ameliorates peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid in rats.

BACKGROUND: Peritoneal dialysis (PD) is a crucial dialysis method for treating end-stage kidney disease. However, its use is restricted due to high glucose-induced peritoneal injury and hyperglycaemia, particularly in patients with diabetes mellitus. In this study, we investigated whether partially replacing d-glucose with the rare sugar d-allose could ameliorate peritoneal injury and hyperglycaemia induced by peritoneal dialysis fluid (PDF). METHODS: Rat peritoneal mesothelial cells (RPMCs) were exposed to a medium containing d-glucose or d-glucose partially replaced with different concentrations of d-allose. Cell viability, oxidative stress and cytokine production were evaluated. Sprague-Dawley (SD) rats were administrated saline, a PDF containing 4% d-glucose (PDF-G4.0%) or a PDF containing 3.6% d-glucose and 0.4% d-allose (PDF-G3.6%/A0.4%) once a day for 4 weeks. Peritoneal injury and PD efficiency were assessed using immuno-histological staining and peritoneal equilibration test, respectively. Blood glucose levels were measured over 120 min following a single injection of saline or PDFs to 24-h fasted SD rats. RESULTS: In RPMCs, the partial replacement of d-glucose with d-allose increased cell viability and decreased oxidative stress and cytokine production compared to d-glucose alone. Despite the PDF-G3.6%/A0.4% having a lower d-glucose concentration compared to PDF-G4.0%, there were no significant changes in osmolality. When administered to SD rats, the PDF-G3.6%/A0.4% suppressed the elevation of peritoneal thickness and blood d-glucose levels induced by PDF-G4.0%, without impacting PD efficiency. CONCLUSIONS: Partial replacement of d-glucose with d-allose ameliorated peritoneal injury and hyperglycaemia induced by high concentration of d-glucose in PDF, indicating that d-allose could be a potential treatment option in PD.

Practice patterns of rituximab for primary membranous nephropathy 2021 in Japan: a web-based survey of board-certified nephrologists.

BACKGROUND: Although rituximab (RTX) is recommended by kidney disease improving global outcomes as one of the standard therapies for primary membranous nephropathy (pMN), given the constraint of insurance coverage, it is not clear how the drug is used in Japan. METHODS: This cross-sectional study was conducted via a web-based survey between November and December 2021. The participants were certified nephrologists and recruited through convenience sampling. Experience with RTX for pMN was compared to experience with RTX for minimal change nephrotic syndrome (MCNS). Reasons for withholding RTX for pMN, even when it is indicated, were also investigated. Furthermore, the proportion difference in RTX experience was analyzed. RESULTS: Responses from 380 nephrologists across 278 facilities were analyzed. RTX was used for pMN by 83 (21.8%), which was less than the 181 (47.6%) who had used RTX for MCNS (ratio of proportions: 0.46). RTX use for pMN was more frequent in facilities performing 41-80 and 81 or more kidney biopsies annually (vs. none) and by physicians with experience in anti-PLA2R antibody measurement. RTX administration for pMN was covered by insurance for 56 (67.5%), was facility-paid for 10 (12.0%), and was copaid by patients for 6 (7.2%). The most common reason for withholding RTX for pMN was difficulty in ensuring financing (146, 79.3%). CONCLUSIONS: RTX use for pMN is less common than for MCNS but not infrequent. Treatment with RTX was more frequent in biopsy-intensive facilities, and it was fully paid by the facility or patient in one-fifth of cases.

A multi-institutional, observational study of outcomes after catheter placement for peritoneal dialysis in Japan.

BACKGROUND: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications. METHODS: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest. RESULTS: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines. CONCLUSION: PD catheter placement in Japan was proven to be safe and appropriate.

Japanese clinical practice patterns of primary nephrotic syndrome 2021: a web-based questionnaire survey of certified nephrologists.

BACKGROUND: With the publication of the "Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020," we examined nephrologists' adherence to the recommendations of four of its clinical questions (CQs). METHODS: This was a cross-sectional web-based survey conducted between November and December 2021. The target population comprised nephrologists certified by the Japanese Society of Nephrology who were recruited using convenience sampling. The participants answered six items regarding the four CQs about adult patients with nephrotic syndrome and their characteristics. RESULTS: In total, 434 respondents worked in at least 306 facilities, of whom 386 (88.9%) provided outpatient care for primary nephrotic syndrome. Of these patients, 179 (41.2%) answered that they would not measure anti- phospholipase A2 receptor antibody levels in cases of suspected primary membranous nephropathy (MN) in which kidney biopsy was not possible (CQ1). Regarding immunosuppressants as maintenance therapy after relapse of minimal change nephrotic syndrome (CQ2), cyclosporine was the most common choice (290 [72.5%] and 300 [75.0%] of 400 respondents after the first and second relapses, respectively). The most common treatment for steroid-resistant cases of primary focal segmental glomerulosclerosis (CQ3) was cyclosporine (323 of 387, 83.5%). For the initial treatment of primary MN with nephrotic-range proteinuria (CQ4), corticosteroid monotherapy was the most common choice (240 of 403, 59.6%), followed by corticosteroid and cyclosporine (114, 28.3%). CONCLUSION: Gaps in recommendations and practices regarding serodiagnosis and treatment of MN (i.e., CQ1 and 4) are observed, suggesting the need to address the barriers to their insurance reimbursement and the lack of evidence behind them.

The usefulness of nuclear area in the diagnosis of high-grade urothelial carcinoma cells in voided urine cytology.

OBJECTIVE: The Paris System for Reporting Urinary Cytology considered the nuclear-to-cytoplasmic (N:C) ratio as the most important cytomorphological feature for detecting high-grade urothelial carcinoma (HGUC) cells. Few quantitative studies have been conducted on other features although quantitative studies on the N:C ratio have been reported. Therefore, this study quantitatively analysed important cytomorphological features in distinguishing benign reactive cells from HGUC cells. METHODS: We analysed 2866 cells from the urine of 52 patients. A digital image analyser was used to quantitatively measure the nuclear area, cell area, N:C ratio, and nuclear roundness for HGUC cells and benign reactive cells. Additionally, the diagnostic value of quantitative cytomorphological criteria in HGUC cells was evaluated by the receiver operating characteristic curve. RESULTS: The area under the curve for the prediction of HGUC cells for all cells and the top five cells was in the following order: nuclear area (0.920 and 0.992, respectively), N:C ratio (0.849 and 0.977), cell area (0.781 and 0.920), and nuclear roundness (0.624 and 0.605). The best cutoff value of the N:C ratio to differentiate HGUC cells from benign reactive cells was 0.438, and using the N:C ratio of 0.702, the positive predictive value obtained was 100%. CONCLUSIONS: Our study indicated that nuclear area is a more important cytomorphological criterion than the N:C ratio for HGUC cell detection. Moreover, extracted data of the top five cells were more valuable than the data of all cells, which can be helpful in the routine practice and future criteria definition in urine cytology.

Serological and histopathological assessment of galactose-deficient immunoglobulin A1 deposition in kidney allografts: A multicenter prospective observational study.

BACKGROUND: Recurrent immunoglobulin A (IgA) nephropathy is an important risk factor for kidney allograft loss. However, there is no classification system for IgA deposition in kidney allografts based on serological and histopathological evaluation of galactose-deficient IgA1 (Gd-IgA1). This study aimed to establish a classification system for IgA deposition in kidney allografts based on serological and histological evaluation of Gd-IgA1. METHODS: This multicenter prospective study included 106 adult kidney transplant recipients in whom an allograft biopsy was performed. Serum and urinary Gd-IgA1 levels were investigated in 46 transplant recipients who were IgA-positive and classified into four subgroups according to the presence or absence of mesangial Gd-IgA1 (KM55 antibody) deposits and C3. RESULTS: Minor histological changes without an acute lesion were observed in recipients with IgA deposition. Fourteen (30%) of the 46 IgA-positive recipients were KM55-positive and 18 (39%) were C3-positive. The C3 positivity rate was higher in the KM55-positive group. Serum and urinary Gd-IgA1 levels were significantly higher in KM55-positive/C3-positive recipients than in the other three groups with IgA deposition. Disappearance of IgA deposits was confirmed in 10 of 15 IgA-positive recipients in whom a further allograft biopsy was performed. The serum Gd-IgA1 level at the time of enrollment was significantly higher in recipients in whom IgA deposition continued than in those in whom it disappeared (p = 0.02). CONCLUSIONS: The population with IgA deposition after kidney transplantation is serologically and pathologically heterogeneous. Serological and histological assessment of Gd-IgA1 is useful for identifying cases that should be carefully observed.

Efficacy of pre-emptive kidney transplantation for adults with end-stage kidney disease: a systematic review and meta-analysis.

BACKGROUND: Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively. METHODS: This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I. RESULTS: Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification. CONCLUSIONS: The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia.

INTRODUCTION: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients' quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. METHODS: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6-12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. RESULTS: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (ß coefficient -6.935, 95% confidence interval, 13.313 to-0.556, p = 0.034). CONCLUSION: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

Hyporesponsiveness to erythropoiesis-stimulating agent in non-dialysis-dependent CKD patients: The BRIGHTEN study.

Among non-dialysis-dependent chronic kidney disease (ND-CKD) patients, a low hematopoietic response to erythropoiesis-stimulating agents (ESAs) is a predictor for poor renal and cardiovascular outcome. To assess the method for evaluating hyporesponsiveness to ESA in patients with ND-CKD, a multicenter, prospective, observational study of 1,980 adult patients with ND-CKD with renal anemia was conducted. Darbepoetin alfa (DA) and iron supplement administrations were provided according to the recommendation of the attached document and the guidelines of JSDT (Japanese Society of Dialysis and Transplantation). The primary outcomes were progression of renal dysfunction and major adverse cardiovascular events. ESA responsiveness was assessed using pre-defined candidate formulae. During the mean follow-up period of 96 weeks, renal and cardiovascular disease (CVD) events occurred in 683 (39.6%) and 174 (10.1%) of 1,724 patients, respectively. Among pre-set candidate formulae, the one expressed by dividing the dose of DA by Hb level at the 12-week DA treatment was statistically significant in predicting renal (hazard ratio [HR], 1.449; 95% confidence interval [CI], 1.231-1.705; P<0.0001) and CVD events (HR, 1.719; 95% CI, 1.239-2.386; P = 0.0010). The optimum cut-off values for both events were close to 5.2. In conclusion, hyporesponsiveness to ESA in ND-CKD cases, which is associated with a risk for renal and CVD events, may be evaluated practicably as the dose of DA divided by the Hb level at the 12-week DA treatment, and the cut-off value of this index is 5.2. A search for the causes of poor response and measures for them should be recommended in such patients. Trial registration: ClinicalTrials. gov Identifier: NCT02136563; UMIN Clinical Trial Registry Identifier: UMIN000013464.

Prevalence and factors related to hypouricemia and hyperuricemia in schoolchildren: results of a large-scale cross-sectional population-based study conducted in Japan.

Hypouricemia in children including renal hypouricemia, which is a major cause of exercise-induced acute renal injury (EIAKI), is an important clinical problem, in addition to hyperuricemia. However, no large-scale studies of serum uric acid (UA) concentrations in the general pre-adolescent population have been carried out. We conducted a population-based cross-sectional study to measure the prevalences of hypouricemia and hyperuricemia and identify the associated factors. We analyzed 31,822 (16,205 boys and 15,617 girls) 9-10-year-old children who underwent pediatric health check-ups in Kagawa prefecture between 2014 and 2018. Hypouricemia and hyperuricemia were defined using serum UA concentrations of ≤ 2.0 mg/dL and ≥ 6.0 mg/dL, respectively. The prevalence of hypouricemia was 0.38% in both 9- and 10-year-old boys and girls, and was not significantly associated with age, sex, or environmental factors, including overweight. The prevalence of hyperuricemia was significantly higher in boys (2.7%) than in girls (1.9%), and was significantly associated with age, overweight, future diabetes risk, hypertriglyceridemia, low high-density lipoprotein-cholesterol, and liver damage, but not with high low-density lipoprotein cholesterol. Therefore, some pre-adolescent children in the general population in Japan showed hypouricemia. A means of identifying children with hypouricemia and lifestyle guidance measures for the prevention of EIAKI should be established.