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.

Interpretations of SARS-CoV-2 IgM and IgG antibody titers in the seroepidemiological study of asymptomatic healthy volunteers.

INTRODUCTION: The usefulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in asymptomatic individuals has not been well validated, although they have satisfied sensitivity and specificity in symptomatic patients. In this study, we investigated the significance of IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects. METHODS: From June 2020, we recruited 10,039 participants to the project named the University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS), and measured iFlash-SARS-CoV-2 IgM and IgG (YHLO IgM and IgG) titers in the collected serum. For the samples with increased IgM or IgG titers, we performed additional measurements using Elecsys Anti-SARS-CoV-2 Ig (Roche total Ig) and Architect SARS-CoV-2 IgG (Abbott IgG) and investigated the reactivity to N, S1, and receptor binding domain (RBD) proteins. RESULTS: After setting the cutoff value at 5 AU/mL, 61 (0.61%) were positive for YHLO IgM and 104 (1.04%) for YHLO IgG. Few samples with elevated YHLO IgM showed reactivity to S1 or RBD proteins, and IgG titers did not increase during the follow-up in any samples. The samples with elevated YHLO IgG consisted of two groups: one reacted to S1 or RBD proteins and the other did not, which was reflected in the results of Roche total Ig. CONCLUSIONS: In SARS-CoV-2 seroepidemiological studies of asymptomatic participants, sufficient attention should be given to the interpretation of the results of YHLO IgM and IgG, and the combined use of YHLO IgG and Roche total Ig might be more reliable.

Association of erythropoietin resistance and fibroblast growth factor 23 in dialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Fibroblast growth factor 23 (FGF23) plays an important role in chronic kidney disease (CKD)-related mineral and bone disorders. High FGF23 levels are associated with increased risk of anaemia in non-haemodialysis CKD patients. FGF23 also negatively regulates erythropoiesis in mice. We hypothesized that higher FGF23 levels are associated with increased erythropoietin hyporesponsiveness among haemodialysis patients. METHODS: The study included 1044 patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) phase 5 (2012-2015). The outcome was erythropoiesis-stimulating agent hyporesponsiveness (ESA-hypo), defined as mean Hgb <10 g/dL and standardized mean ESA dose >6000 u/week over 4 months following FGF23 measurement. The association between ESA-hypo and FGF23 was estimated using multivariable-adjusted logistic generalized estimating equation regression models. RESULTS: Patients with higher levels of FGF23 were younger and had higher levels of serum albumin, creatinine, albumin-corrected calcium, phosphorus, PTH, 25(OH)-vitamin D, and had higher percentages of intravenous (IV) iron, IV vitamin D and cinacalcet use. ESA-hypo was present in 144 patients (13.8%). Compared with the third quintile of FGF23 levels, the odds ratio (95% CI) of ESA-hypo was 2.14 (0.99, 4.62) and 1.74 (0.74, 4.11) for the first and fifth quintiles, respectively. CONCLUSION: The lowest and highest levels of FGF23 were associated with higher odds of ESA-hypo in patients on maintenance haemodialysis, although the associations were not statistically significant. The relationship between FGF23 and anaemia, and particularly the increased risks of ESA-hypo at low FGF23 levels which might be the result of energy saving, must be confirmed in larger clinical studies.

Serum total iron-binding capacity and iron status in patients with non-dialysis-dependent chronic kidney disease: A cross-sectional study in Vietnam.

BACKGROUND AND OBJECTIVES: We performed this study to evaluate serum iron and ferritin concentrations, serum total iron-binding capacity (TIBC), and proportion of overall iron deficiency among patients with non-dialysisdependent chronic kidney disease (ND-CKD). METHODS AND STUDY DESIGN: A hospital-based cross-sectional observational study was conducted on 175 adult patients with stage 3-5 chronic kidney disease (CKD) by using 51 healthy age-sex-matched Vietnamese adults as the control group. We next examined the prevalence of anemia and determined the serum iron and ferritin concentrations and TIBC. Anemia in CKD was defined as hemoglobin levels <13 g/dL in men and <12 g/dL in women. Transferrin saturation (TSAT, %) was calculated as (serum iron x 100)/TIBC. Functional iron deficiency was defined as serum ferritin >100 ng/mL and TSAT <20%, and absolute iron deficiency was defined as serum ferritin <100 ng/mL and TSAT <20%. Overall iron deficiency was defined as the presence of either absolute or functional iron deficiency. RESULTS: Anemia prevalence in our study was approximately 88.6% with a mean hemoglobin concentration of 9.71±2.26 g/dL. The median serum TIBC was lower in the CKD group (50.4 µmol/L) than in the control group (66.0 µmol/L; p<0.001). The proportion of overall iron deficiency was 44.0%. TIBC had a diagnostic value for overall iron deficiency (area under the ROC curve=0.81; p<0.001). CONCLUSIONS: Anemia and iron deficiency are common in Vietnamese patients with NDCKD. TIBC had diagnostic value for overall iron deficiency.

Comparison between the clinical characteristics of patients with adrenal incidentalomas and those with hypertension-associated adrenal tumors in a single center in Japan.

In the largest retrospective study of adrenal incidentalomas (AIs) in Japan between 1999 and 2004, adrenal tumors detected during secondary hypertension (HT) screening were included. The characteristics of patients with adrenal tumors detected during HT screening may differ from those of patients with AIs. This study aimed to compare the characteristics of patients with AIs with those of patients with adrenal tumors detected during HT screening. We retrospectively analyzed patients referred to our division for detailed examination of adrenal tumors between April 2009 and April 2017. When the purposes of imaging tests included HT screening, we defined adrenal tumors as HT associated, otherwise as strictly defined AIs. We reviewed data on age, sex, purpose and modality of imaging, location of tumor, tumor diameter, and hormonal evaluation. We identified 104 patients with HT-associated adrenal tumors and 413 with AIs. Patients with HT-associated adrenal tumors were younger (54.2 years vs. 61.7 years, p < 0.001) and had smaller tumor diameters (1.3 cm vs. 1.9 cm, p < 0.001), lower prevalence of nonfunctioning tumors (24.0% vs. 67.6%, p < 0.001), and higher prevalence of primary aldosteronism (58.7% vs. 4.8%, p < 0.001) than those with AIs. There were no differences in terms of tumor location and prevalence of subclinical Cushing's syndrome, Cushing's syndrome, and pheochromocytoma (18.3% vs. 16.0%, 7.7% vs. 8.0%, and 2.9% vs. 4.6%, respectively). In conclusion, patients with HT-associated tumors were younger and had a smaller tumor with higher prevalence of primary aldosteronism than those with AIs.

Predicting 3-year mortality based on the tumor necrosis factor alpha concentration in low-flux hemodialysis patients.

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF-α and its receptors and their clinical outcomes in hemodialysis patients. However, a study assessing patients using a low-flux dialyzer reuse has not been conducted yet. The serum TNF-α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 [interquartile range, 26-79] months; 185 males and 134 females) was examined to predict their 3-year mortality. The patients were divided into tertiles according to their serum TNF-α concentrations: T1 (n = 106; serum TNF-α concentration, <41.22 pg/mL), T2 (n = 106; serum TNF-α level, from 41.22 to 67.28 pg/mL), and T3 (n = 107; serum TNF-α concentration, ≥ 67.29 pg/mL). During the 36-month follow-up period, a total of 50 (15.7%) patients died from all causes. The Kaplan-Meier analysis revealed that the all-cause mortality in T3 was significantly higher compared to that in T1 and T2 (log-rank test, P < .001). The serum TNF-α level was a significant predictor for all-cause mortality (area under the curve = 0.887, P < .001, cutoff value, 89.812 pg/mL, sensitivity = 76%, specificity = 96.3%). The serum TNF-α level was a better predictor of mortality than the duration of hemodialysis and serum albumin, serum high-sensitivity C-reactive protein, and serum beta-2 microglobulin concentrations. The serum TNF-α concentration was a good predictor of the 3-year mortality in low-flux hemodialysis patients.

Diagnostic accuracy of urine dipstick for proteinuria category in Japanese workers.

BACKGROUND: Urine dipstick tests are often used to evaluate proteinuria during health checkups. We examined the dipstick's accuracy in assessing the proteinuria levels among Japanese workers. METHODS: We assessed subjects aged ≥ 18 years who had a health checkup at the University of Tokyo in 2016 or 2017 (n = 5383). Proteinuria was stratified by urine protein-to-creatinine ratio (PCR): A1, < 150 mg/gCre; A2, 150-499 mg/gCre; and A3, ≥ 500 mg/gCre. The accuracy of a dipstick result of ± or higher to detect a PCR level of ≥ A2 was examined. We compared changes in dipstick results and PCR level in 136 subjects evaluated twice with a median interval of 119 days. RESULTS: The subjects' mean age was 40 years, and half were women. The dipstick results were - in 94.9%, ± in 4.1%, and ≥ 1 + in 1.0%. The PCR level was A1, A2, A3 in 98.6%, 1.2%, and 0.2% of the subjects, respectively. The sensitivity, specificity, and positive and negative predictive values of a ± or higher dipstick result to detect A2 or higher were 66.2%, 95.6%, 17.5%, and 99.5%, respectively. Among the 136 subjects examined twice, 134 (98.5%) had no change in PCR level (A1 in all cases) despite a decrease or increase in dipstick results. CONCLUSION: Urine dipstick results of ± or above had a high specificity but low sensitivity and positive predictive value to detect PCR proteinuria of A2 or higher. Confirmation by quantitative protein measurement should be recommended for individuals at high risk of chronic kidney disease.

Longitudinal change in blood pressure and risk of end-stage renal disease in a community-based cohort in Okinawa.

BACKGROUND: The appropriate blood pressure target to prevent end-stage renal disease (ESRD) is controversial. METHODS: We examined the association between systolic blood pressure (SBP) changes and ESRD incidence in 69,575 participants from the Okinawa general population aged ≥ 20 years who underwent health check-ups in 1993 and more than once in 1994-1996. ESRD incidence was identified using dialysis registry until 2011. Cox proportional hazards model was used to estimate hazard ratio (95% confidence interval) with confounding factor adjustment. RESULTS: At baseline, 29.9%, 22.1%, 20.6%, and 27.5% of subjects had SBP < 120, 120-129, 130-139, and ≥ 140 mmHg, respectively. Only 405 subjects developed ESRD. After 1 year, SBP was lowered, unchanged, and elevated in 20.8%, 54.3%, and 24.9% of subjects, respectively. Compared to the subjects with SBP < 120 mmHg both at baseline and the second measurement, there was no significant risk of ESRD in those who had SBP < 130 mmHg both at baseline and 1-3 years and or those with baseline SBP 130-139 mmHg and 1- to 3-year SBP < 140 mmHg. Subjects with baseline SBP 120-129 mmHg and 1- and 2-year SBP ≥ 130 mmHg were not significant (1.51 [0.86-2.66] and 1.73 [0.95-3.15], respectively) but 3-year SBP ≥ 130 mmHg had a significant ESRD risk (2.37 [1.23-4.56]). Subjects with baseline SBP ≥ 130 mmHg and 1- to 3-year SBP ≥ 140 mmHg had significant ESRD risk. CONCLUSION: Subjects with SBP < 130 mmHg at baseline and 1-3 years showed no significant risk of developing ESRD, in the general population.

Measuring serum beta2-microglobulin to predict long-term mortality in hemodialysis patients using low-flux dialyzer reuse.

PURPOSE: Beta2-microglobulin (ß2-M) is recognized as a surrogate marker relating to the mechanisms of dialysis-associated amyloidosis. Few studies have evaluated the association of serum ß2-M with clinical outcome in hemodialysis patients using high-flux type. However, study on patients using low-flux dialyzer reuse has not been done yet. PATIENTS AND METHODS: Using serum ß2-M level on predicting long-term mortality of hemodialysis patients was examined in 326 prevalent hemodialysis patients (45.59±14.46 years, hemodialysis duration of 47.5 (26-79) months, 186 males and 140 females). The patients were divided into 3 groups with equal number of patients, according to their serum ß2-M levels: group A (n=109, serum ß2-M concentration ≤55.7 mg/L), group B (n=109, serum ß2-M level from 55.8 mg/L to 75.4 mg/L) and group C (n=108, serum ß2-M concentration >75.4 mg/L). RESULTS: During the follow-up period of 5 years, there were 75 all-cause deaths (23.0%). Kaplan-Meier analysis revealed that all-cause mortality in the higher ß2-M group was significantly higher compared to that in the lower ß2-M groups (p<0.001). Serum ß2-M level was a significant predictor for all-cause mortality (AUC =0.898; p<0.001; Cut-off value: 74.9 mg/L, Se=93.3%, Sp=92.9%). CONCLUSION: Serum ß2-M levels were a significant predictor of long-term mortality in hemodialysis patients, who use only low-flux dialyzers and reuse 6 times.

Correction to: Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome.

The original article can be found online.

Distribution and Characteristics of Hypouricemia within the Japanese General Population: A Cross-Sectional Study.

Background and objectives: There is insufficient epidemiological knowledge of hypouricemia. In this study, we aimed to describe the distribution and characteristics of Japanese subjects with hypouricemia. Materials and Methods: Data from subjects who underwent routine health checkups from January 2001 to December 2015 were analyzed in this cross-sectional study. A total of 246,923 individuals, which included 111,117 men and 135,806 women, met the study criteria. The participants were divided into quartiles according to their serum uric acid (SUA) levels. We subdivided the subjects with hypouricemia, which was defined as SUA level ≤ 2.0 mg/dL, into two groups and compared their characteristics, including their cardiovascular risks. Results: The hypouricemia rates were 0.46% overall, 0.21% for the men and 0.66% for the women (P < 0.001). The number of the subjects with hypouricemia showed two distributions at SUA levels of 0.4⁻1.1 mg/dL (lower hypouricemia group), which included a peak at 0.7⁻0.8 mg/dL, and at SUA levels of 1.4⁻2.0 mg/dL (higher hypouricemia group). The men in the higher hypouricemia group had lower body mass indexes (BMI) and triglyceride (TG) levels and had higher fasting blood glucose levels than those in the lower hypouricemia group. The women in the higher hypouricemia group were younger; had lower BMI, total protein, TG, total cholesterol and low-density lipoprotein cholesterol levels; and had higher estimated glomerular filtration rates levels compared to those in the lower hypouricemia group. Conclusions: The characteristics of the individuals in the lower and higher hypouricemia groups differed significantly, indicating different pathophysiologies within each group.

Effectiveness and safety of early enteral nutrition for patients who received targeted temperature management after out-of-hospital cardiac arrest.

AIM: Early enteral nutrition (EN) is recommended for critically ill patients; however, few reports have examined early EN for patients who received targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). We investigated the effectiveness and safety of early EN for patients who received TTM after OHCA. METHODS: We used a nationwide Japanese administrative database to identify OHCA patients who received TTM from April 2008 to March 2017. The primary outcome was 30-day mortality; secondary outcomes were incidences of all-cause infection, pneumonia, and intestinal ischemia. RESULTS: Of the 1932 OHCA patients who received TTM, 1682 met the inclusion criteria. Of these, 294 received early EN within 2 days from the initiation of TTM and 266 propensity-score matched pairs were generated. Cox regression analyses revealed no significant difference in 30-day mortality between groups (hazard ratio (HR): 0.90; 95% confidence interval (95% CI): 0.65-1.25). There was no significant difference in the incidence of all-cause infection (odds ratio (OR): 0.98; 95% CI: 0.66-1.46) or pneumonia (OR: 1.02; 95% CI: 0.68-1.55). Subgroup analyses of patients with a low body mass index (BMI; kg/m2) (< 18.5) revealed a significant decrease of 30-day mortality in the early EN group (HR: 0.30; 95% CI: 0.092-0.97) but no significant difference among patients with a BMI ≥ 18.5 (HR: 1.01; 95% CI: 0.72-1.43). CONCLUSION: Among patients who received TTM after OHCA, there was no significant association between early EN and 30-day mortality; however, early EN could be beneficial for patients with a low BMI.

Association of dialysis with in-hospital disability progression and mortality in community-onset stroke.

AIM: End-stage renal disease is associated with increased risk of cerebrovascular disease, but the effect on post-stroke clinical outcomes has not been thoroughly investigated. METHODS: Using the Japanese Diagnosis Procedure Combination database, which includes administrative claims and discharge abstract data, we examined the association between risk factors including dialysis therapy and in-hospital disability progression or mortality in patients with community-onset stroke. We extracted data of patients aged ≥ 20 years old who were admitted to the hospital within 3 days after onset of stroke between July 2010 and March 2013. The disability level was divided into modified Rankin Scale (mRS) 0-1, 2-3, 4-5, and 6 (death). Disability progression was defined as an increase in disability level. Odds ratios for in-hospital disability progression and mortality were calculated using logistic regression models. RESULTS: Of 435 403 patients, 7562 (1.7%) received dialysis therapy. The median length of stay was 21 and 20 days for patients with and without dialysis, respectively. During the hospital stay, disability progressed in 100 402 (23.1%) patients and 45 919 (10.5%) died. Patients on dialysis had a higher prevalence of disability progression (26.8%) and mortality (13.1%) compared to those without dialysis (23.0% and 10.5%, respectively). Dialysis was associated with an increased risk of in-hospital disability progression (odds ratio, 1.56; 95% confidence interval, 1.47-1.66) and mortality (odds ratio 1.70; 95% confidence interval, 1.57-1.84). These risks were comparable among subtypes of stroke. CONCLUSIONS: Dialysis was associated with an increased risk of in-hospital disability progression and mortality among patients with community-onset stroke, regardless of stroke subtype.

Association of Serum Triglycerides With Arterial Stiffness in Subjects With Low Levels of Low-Density Lipoprotein Cholesterol.

BACKGROUND: The independent role of serum triglyceride (TG) levels as a cardiovascular risk factor is still not elucidated. We aimed to investigate if the effect of TG on arterial stiffness is influenced by the serum level of low-density lipoprotein cholesterol (LDL-C). Methods and Results: We studied 11,640 subjects who underwent health checkups. They were stratified into 4 groups according to LDL-C level (≤79, 80-119, 120-159, and ≥160 mg/dL). Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). In each group, univariate and multivariete logistic regression analyses were performed to investigate the association between high TG (≥150 mg/dL) and high baPWV (>1,400 cm/s). In the univarite analysis, high TG was significantly associated with high baPWV in LDL-C <79 mg/dL (OR, 3.611, 95% CI, 2.475-5.337; P<0.0001) and 80-119 mg/dL (OR, 1.881; 95% CI, 1.602-2.210; P<0.0001), but not in LDL-C 120-159 mg/dL and ≥160 mg/dL. In the multivariate analysis, high TG was significantly associated with high baPWV in LDL-C ≤79 mg/dL (OR, 2.558; 95% CI, 1.348-4.914; P=0.0040) and LDL-C 80-119 mg/dL (OR, 1.677; 95% CI, 1.315-2.140; P<0.0001), but not in LDL-C 120-159 mg/dL and ≥160 mg/dL. CONCLUSIONS: High TG and increased arterial stiffness showed an independent relationship in a Japanese general population with LDL-C ≤119 mg/dL. TG-lowering therapy might be an additional therapeutic consideration in these subjects.

Correlation between dental conditions and comorbidities in an elderly Japanese population: A cross-sectional study.

The purpose of this study was to investigate the correlation between dental conditions and comorbidities in an elderly population in Japan.A database constructed using data obtained from 12 nursing homes in Japan was used in this study. The study period ranged from January 2014 to December 2015, and elderly individuals with dental and other medical records were included in the analysis. Linear regression models were used to analyze univariate and multivariate correlation between dental conditions, comorbidities, and other sociodemographic/clinical backgrounds.After excluding individuals with missing data, 289 elderly individuals (107 men and 182 women; mean age, 85 years) were included in the analysis. These individuals had an average of 11.6 teeth, and the number decreased with older age (P < .001). The average number of decayed teeth was 1.4. A total of 116 subjects (40.1%) had dementia. In terms of comorbidities, dementia was not significantly associated with the number of present teeth (P = .56), but it was associated with the number of decayed teeth (P = .018). This association was also observed after adjusting for confounding variables in the multivariate regression analysis (P = .030).The number of decayed teeth was associated with dementia. While causality cannot be inferred from these observational results, the findings indicate that dental health could represent a marker of impending dementia, and probably represent a marker of general health status in the elderly population. Additional longitudinal studies are highly desirable to understand the causal relationships between dental conditions and comorbidities.

Persistence of and switches from teriparatide treatment among women and men with osteoporosis in the real world: a claims database analysis.

This study investigated the real-world persistence rate and switches of teriparatide-treated patients using a claims database in Japan. The persistence rate of teriparatide at 12 months was 34.9%, and approximately one-third of the patients were not treated with any osteoporosis drugs after teriparatide. Improvement in persistence and switches are desired. PURPOSE: We aimed to elucidate the persistence rates and switches before and after teriparatide treatment in real-world osteoporosis patients based on data from a medical claims database in Japan. METHODS: We reviewed the records of patients with diagnoses of osteoporosis who were prescribed teriparatide at least once from January 2005 to June 2017. Patients with a follow-up ≤ 90 days before the first and ≤ 90 days after the last prescription of teriparatide were excluded. Discontinuation was defined as no treatment for > 90 days. We investigated treatment duration, compared characteristics of patients with persistence ≤ 12 and > 12 months, and osteoporotic medications before and after teriparatide by weekly or daily teriparatide. RESULTS: Among the 553 patients extracted for the study, 81.9% were women, 45.6% were aged ≥ 65 years, and 67.3% had a fracture. The most common fracture site was the spine (39.2%). The overall persistence rate of teriparatide > 12 months was 34.9% (weekly, 23.5%; daily, 43.1%). The subjects with persistence > 12 months comprised a higher proportion of women and they had a higher prevalence of rib and sternum fractures than those with ≤ 12 months. After teriparatide, 38.2% were switched to active vitamin D3, 35.1% to bisphosphonates, and 13.7% to denosumab allowing duplication. However, 34.0% of the patients were not switched to any subsequent medication for osteoporosis. CONCLUSIONS: Persistence rate over 12 months of teriparatide treatment was 34.9% in Japan. Approximately one-third of patients had no subsequent treatment immediately after teriparatide. Monitoring persistence and considering subsequent drugs for osteoporosis are necessary for teriparatide treatment.

Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is caused by complement overactivation, and its presentation and prognosis differ according to the underlying molecular defects. The aim of this study was to characterize the genetic backgrounds of aHUS patients in Japan and to elucidate the associations between their genetic backgrounds, clinical findings, and outcomes. METHODS: We conducted a nationwide epidemiological survey of clinically diagnosed aHUS patients and examined 118 patients enrolled from 1998 to 2016 in Japan. We screened variants of seven genes related to complement and coagulation, as well as positivity for anti-CFH antibodies, and assessed clinical manifestations, laboratory findings, and clinical course. RESULTS: The most frequent genetic abnormalities were in C3 (31%) and the frequency of CFH variants was relatively low (10%) compared to Western countries. The predominant variant in this cohort was C3 p.I1157T (23%), which was related to favorable outcomes despite frequent relapses. A total of 72% of patients received plasma therapy, while 42% were treated with eculizumab. The prognosis of Japanese aHUS patients was relatively favorable, with a total mortality rate of 5.4% and a renal mortality rate of 15%. CONCLUSIONS: The common occurrence of genotype C3, especially the p.I1157T variant was the characteristic of the genetic backgrounds of Japanese aHUS patients that differed from those of Caucasian patients. In addition, the favorable prognosis of patients with the unique C3 p.I1157T variant indicates that understanding the clinical characteristics of individual gene alterations is important for predicting prognosis and determining therapeutic strategies in aHUS.

Importance of glomerular filtration rate change as surrogate endpoint for the future incidence of end-stage renal disease in general Japanese population: community-based cohort study.

BACKGROUND: Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients' prognosis. METHODS: Subjects with serum creatinine level for a baseline period over 1-3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. RESULTS: Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m2. Among the subjects recruited, 15.81% had a low eGFR (<60 ml/min/1.73 m2) and 36.1/100,000 person years developed ESRD. Cox proportional hazards models adjusted for baseline characteristics showed that the risk of ESRD tended to be high with high rates of decrease in %eGFR changes over 2 or 3 years in the high- and low-eGFR groups. The specificities and positive predictive values for ESRD based on a cutoff value of %eGFR change of less than -30% over 2 or 3 years were high in the high- and low-eGFR groups. CONCLUSIONS: %eGFR change tends to be associated with the risk of ESRD. %eGFR change of less than -30% over 2 or 3 years can be a candidate surrogate endpoint for ESRD in the general Japanese population.