Chronic Kidney Disease In Japan Research Articles

Physician and Patient Preferences for Treatment of Anemia Associated with Chronic Kidney Disease in Japan: A Survey Including Best-Worst Scaling.

Several treatment options are available for anemia associated with chronic kidney disease (CKD); however, there remains a lack of awareness of physician and patient preferences regarding these treatments. We aimed to explore physicians' and patients' perceptions and preferences regarding the management of anemia of CKD in Japan. A web-based survey, including best-worst scaling (BWS), was conducted with physicians who had treated ≥1 patient with anemia of CKD in the preceding year, and with patients with CKD who self-reported a clinical diagnosis of anemia of CKD or low hemoglobin levels. A three-step approach was used comprising cognitive interviews, a pilot survey, and a main survey. The BWS survey results were analyzed using multinomial logit and hierarchical Bayesian models. The survey was completed by 906 participants: 103 patients (average age 60.6 years; 77.7% male) and 803 physicians (166 nephrologists, 214 cardiologists, 137 diabetologists, and 286 general internists). Almost all (96.0%) physicians surveyed considered anemia of CKD to be an important condition to treat. Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors had the highest treatment satisfaction among physicians, whereas patients had the highest satisfaction with both erythropoietin-stimulating agent therapy and HIF-PH inhibitors. Approximately one-third (35.9%) of patients surveyed indicated that they were receiving treatment. When comparing the relative importance of attributes and levels, physicians favored efficacy (particularly improvement in hemoglobin levels), whereas patients favored safety (particularly a lower rate of severe adverse events). Although a majority of physicians consider treatment of CKD-related anemia important, differences in the perceptions and usage of medications exist between medical specialties. Preferences for the management of anemia of CKD vary between physicians and patients; therefore, patient involvement in treatment decisions may help optimize outcomes.

#1185 Cardiovascular, renal and mortality risk by the KDIGO risk classification: the first observational study in Japan

Abstract Background and Aims The prevalence of chronic kidney disease (CKD) has been increasing, affecting 850 million people worldwide and 13 million individuals in Japan. CKD is a risk factor for cardiovascular complications including heart failure, and dialysis. KDIGO risk classification is widely used for the management of people with CKD in Japan; however, risk of clinical outcomes by the KDIGO classification in Japanese population is unclear. The aim of this study is to describe the risk of major adverse cardiovascular event (MACE) and renal outcomes according to the KDIGO classification in Japanese clinical practice. Method This study was a cohort study using data collated from the RWD database which includes electronic medical records and claims data from approximately 200 medical institutions across Japan since 2000. Subjects aged ≥18 years with two or more consecutive results of eGFR <90 mL/min/1.73 m2 at least 90 days apart within a 360-day period were included, and those received renal replacement therapy (RRT; dialysis or renal transplantation) before the index date was excluded. The index date was defined as the date of the second eGFR measurement <90 mL/min/1.73 m2 between January 2004 and December 2020. Patients were categorized into KDIGO classification G2-G5 based on their eGFR values and A1-A3 based on urine protein test (quantitative test and urine dipstick) results and into `no urine protein data` if no urine protein test was available. The primary endpoint was MACE that was defined as a composite of myocardial infarction, stroke, heart failure hospitalization, and in-hospital death. The secondary endpoint was renal outcomes defined as a composite of RRT, eGFR decline >50%, eGFR <15 mL/min/1.73 m2, diagnosis of CKD stage 5, and in-hospital death, and was analyzed in the group excluding patients with eGFR <15 mL/min/1.73 m2 or with diagnosis of stage 5 CKD on or before the index date. The risk of MACE and renal outcomes were evaluated using the cox proportional hazards model with G2A1 as a reference. Sensitivity analyses were performed for the population excluding those without urine protein data and for the population with quantitative urine protein test results. Results This study included 543,606 patients who met the criteria. Mean age was 61.6 ± 15.3 years, and 50.1% was male. Of those, 222,246 (40.9%) had no urine protein data. Tables 1 and 2 show hazard ratio (HR) for MACE and renal outcomes, respectively. HR (95% confidence interval) for MACE was 1.17 (1.12-1.21) in G2A2 and 1.16 (1.12-1.20) in G3aA1, showing significantly increased risk in early stages of CKD, and continued to increase as disease advances to 2.83 (2.54-3.15) in G5A3. HR for renal outcomes was similarly significantly increased in early stages of CKD, and further increased to 19.96 (18.62-21.40) in G4A3. Results of two sensitivity analyses, excluding subjects with no urine protein data (n = 321,360, 59.1% of overall population) shown in Table 3 and 4, and excluding patients with no quantitative data (n = 36,615, 6.7% of overall population) showed similar trends, supporting the robustness of primary findings. Conclusion This study is the first to demonstrate the applicability of the KDIGO risk classification in assessing the risk of cardiovascular events, including heart failure, and renal outcomes in Japan. Risk of events was increased from early stages of CKD (G3aA1 and G2A2), suggesting the importance of early diagnosis and therapeutic intervention through appropriate testing. These findings may contribute to better management of people with CKD.

Relationship between parity and the prevalence of chronic kidney disease in Japan considering hypertensive disorders of pregnancy and body mass index.

Global studies exploring the relationship between parity and chronic kidney disease (CKD) are scarce. Furthermore, no study has examined the relationship between parity and CKD in Japan. Therefore, this study aimed to examine the relationship between parity and the prevalence of CKD in a Japanese population, considering the clinical history of hypertensive disorders of pregnancy (HDP) and current body mass index (BMI) based on menopausal status. This cross-sectional study included 26,945 Japanese multiparous women (5,006 premenopausal and 21,939 postmenopausal women) and 3,247 nulliparous women (1,599 premenopausal and 1,648 postmenopausal women). Participants were divided into two groups based on their menopausal status (premenopausal and postmenopausal women). The relationship between parity and the prevalence of CKD was evaluated using a multiple logistic regression model adjusted for several covariates, including a clinical history of HDP and current BMI. The relationship between parity and the prevalence of CKD was not statistically significant in either premenopausal or postmenopausal multiparous women. A clinical history of HDP was significantly associated with an increased risk of CKD in premenopausal and postmenopausal multiparous women. However, the relationship between a clinical history of HDP and CKD in premenopausal women was weakened after adjusting for current BMI. Furthermore, the current BMI was significantly associated with an increased risk of CKD in both premenopausal and postmenopausal women. Parity is not significantly associated with the prevalence of CKD in premenopausal and postmenopausal multiparous women. A clinical history of HDP is a risk factor for CKD in both premenopausal and postmenopausal women. Current BMI is also associated with an increased risk of CKD in premenopausal and postmenopausal women. Therefore, continuous surveillance and preventive measures against CKD should be provided to women with a clinical history of HDP. In addition, maintaining an appropriate body weight is beneficial in reducing the risk of CKD.

A case series of Fabry diseases with CKD in Japan

BackgroundIt is well known that kidney injury is vital organ damage in Fabry disease (FD). Renin–angiotensin system (RAS) inhibitors are known to reduce proteinuria in patients with chronic kidney disease (CKD) by dilating the glomerular export arteries and reducing intraglomerular pressure. This improvement in intraglomerular pressure, although lowering the glomerular filtration rate, is thought to prevent renal damage and be renoprotective in the long term. RAS inhibitors may be effective in FD patients with proteinuria to prevent the progression of kidney disease, however, the degree to which they are used in clinical practice is unknown.MethodsThe J-CKD-DB-Ex is a comprehensive multicenter database that automatically extracts medical data on CKD patients. J-CKD-DB-Ex contains data on 187,398 patients in five medical centers. FD patients were identified by ICD-10. Clinical data and prescriptions of FD patients between January 1 of 2014, and December 31 of 2020 were used for the analysis.ResultsWe identified 39 patients with FD from the J-CKD-DB-Ex including those with suspected FD. We confirmed 22 patients as FD. Half of the patients received RAS inhibitors. RAS inhibitors tended to be used in CKD patients with more severe renal impairment.ConclusionsThis case series revealed the actual clinical practice of FD patients with CKD. In particular, we found cases in which patients had proteinuria, but were not treated with RAS inhibitors. The database was shown to be useful in assessing the clinical patterns of patients with rare diseases.

Particulate Matter and Incident Chronic Kidney Disease in Japan: The Ibaraki Prefectural Health Study (IPHS).

Global health hazards caused by air pollution, such as chronic kidney disease (CKD), have been gaining attention; however, air pollution-associated CKD has not been explored in Japan. We examined 77,770 men and women with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 in the Ibaraki Prefecture who participated in annual community-based health checkups from 1993 at 40-75 years old and were followed up through December 2020. The outcome was newly developed kidney dysfunction with eGFR of <60 ml/min/1.73 m2 during follow-up. To assess air pollution, a PM2.5 exposure model was employed to estimate yearly means at 1 × 1-km resolution, converted into means at the municipal level. Hazard modeling was employed to examine PM2.5 concentrations in residential areas as a risk factor for outcomes. Participants were distributed across 23 municipalities in the Ibaraki Prefecture, with PM2.5 concentrations between 16.2 and 33.4 μg/m3 (mean, 22.7 μg/m3) in 1987-1995 as the exposure period. There were 942 newly developed kidney dysfunctions during follow-up. Based on 1987-1995 PM2.5 concentrations as the baseline exposure, the multivariate-adjusted hazard ratio per 10-μg/m3 increase in PM2.5 for newly developed kidney dysfunction was 1.02 (95%CI, 0.80-1.24) in men and 1.19 (95%CI, 0.95-1.44) in women. Elevated PM2.5 did not represent a significant risk factor for incident CKD in a prefecture in Japan.

EGFR slope as a surrogate endpoint for clinical study in early stage of chronic kidney disease: from The Japan Chronic Kidney Disease Database

BackgroundIn clinical trials targeting early chronic kidney disease (CKD), eGFR slope has been proposed as a surrogate endpoint for predicting end-stage kidney disease (ESKD). However, it is unclear whether the eGFR slope serves as a surrogate endpoint for predicting long-term prognosis in Japanese early CKD populations.MethodsThe data source was the J-CKD-Database, which contains real-world data on patients with CKD in Japan. eGFR slope was calculated from the eGFR of each period, 1-year (1-year slope), 2-year (2-year slope), and 3-year (3-year slope), for participants with a baseline eGFR ≥ 30 ml/min/1.73 m2. The outcome was ESKD (defined as dialysis initiation or incidence of CKD stage G5). The relationship between eGFR slope and the sub-distribution hazard ratio (SHR) of ESKD with death as a competing event was investigated using a Fine-Gray proportional hazard regression model.ResultsThe number of participants and mean observation periods were 7768/877 ± 491 days for 1-year slope, 6778/706 ± 346 days for 2-year slope, and 5219/495 ± 215 days for 3-year slope. As the eGFR slope decreased, a tendency toward a lower risk of ESKD was observed. Compared with the 1-year slope, there was a smaller variation in the slope values for the 2-year or 3-year slope and a greater decrease in the SHR; therefore, a calculation period of 2 or 3 years for the eGFR slope was considered appropriate.ConclusionEven in Japanese patients with early stage CKD, a slower eGFR slope calculated from eGFR values over 2–3 years was associated with a decreased risk of ESKD.

Urate-lowering drugs for chronic kidney disease with asymptomatic hyperuricemia and hypertension: a randomized trial.

Xanthine oxidase (XO) inhibitors may slow down chronic kidney disease (CKD) progression. The comparative effectiveness of the different urate-lowering drugs is unknown. The aim of this study was to determine whether urate-lowering therapy with an XO inhibitor (febuxostat) and that with a uricosuric drug (benzbromarone) are comparable in slowing renal function decline in patients with CKD complicated with hypertension and hyperuricemia. This study was an open-label randomized parallel-group clinical trial of 95 patients with stage G3 CKD in Japan. The patients had hypertension and hyperuricemia without a history of gout. They were randomized to receive febuxostat ( n = 47; febuxostat group) or benzbromarone ( n = 48; benzbromarone group) and titrated to reduce their serum urate level to <6.0 mg/dl. The primary end-point was change in estimated glomerular filtration rate (eGFR) from baseline to 52 weeks. The secondary end-points included changes in uric acid level, blood pressure, urinary albumin-to-creatinine ratio, and XO activity. Of the 95 patients, 88 (92.6%) completed the trial. There were no significant differences in change in eGFR (in ml/min/1.73 m 2 ) between the febuxostat [-0.23, 95% confidence interval (CI), -2.00 to 1.55] and benzbromarone (-2.18, 95% CI, -3.84 to -0.52) groups (difference, 1.95; 95% CI, -0.48 to 4.38; P = 0.115) nor in the secondary end-points, except for XO activity. Febuxostat significantly reduced XO activity ( P = 0.010). There were no significant differences in primary and secondary outcomes between the groups. A decrease in eGFR was significantly less in the febuxostat group than that of the benzbromarone group in the CKDG3a, but not in CKDG3b, in the subgroup analysis. There were no adverse effects specific to either drug. No significant differences were found in the effects of febuxostat and benzbromarone in renal function decline in stage G3 CKD complicated with hyperuricemia and hypertension.

Effectiveness and current status of multidisciplinary care for patients with chronic kidney disease in Japan: a nationwide multicenter cohort study

BackgroundMultidisciplinary care is well established in clinical practice, but its effectiveness in patients with chronic kidney disease (CKD) remains unclear. The aim of this study was to determine whether multidisciplinary care could help to avoid worsening kidney function in patients with CKD.MethodsThis nationwide study had a multicenter retrospective observational design and included 3015 Japanese patients with CKD stage 3–5 who received multidisciplinary care. We assessed the annual decrease in estimated glomerular filtration rate (ΔeGFR) and urinary protein in the 12 months before and 24 months after the start of multidisciplinary care. All-cause mortality and initiation of renal replacement therapy were investigated according to baseline characteristics.ResultsMost of the patients had CKD stage 3b or higher and a median eGFR of 23.5 mL/min/1.73 m2. The multidisciplinary care teams consisted of health care professionals from an average of four disciplines. ΔeGFR was significantly smaller at 6, 12, and 24 months after initiation of multidisciplinary care (all P < 0.0001), regardless of the primary cause of CKD and its stage when multidisciplinary intervention was started. Urinary protein level also decreased after initiation of multidisciplinary care. After a median follow-up of 2.9 years, 149 patients had died and 727 had started renal replacement therapy.ConclusionMultidisciplinary care may significantly slow the decline in eGFR in patients with CKD and might be effective regardless of the primary disease, including in its earlier stages. Multidisciplinary care is recommended for patients with CKD stage 3–5.Trial registrationUMIN00004999.

S-28-4: ASSOCIATION BETWEEN INCOME AND PROGRESSION OF CHRONIC KIDNEY DISEASE IN JAPAN: A NATIONWIDE COHORT STUDY

Introduction: Chronic kidney disease (CKD) is one of the major public health issues, causing 1.4 million death in 2019 worldwide. While previous studies have shown the relationship between socioeconomic status and CKD, little is known about whether its relationship exists even in a country where insurance is comprehensively covered. Thus, we conducted a nationwide study to examine the association between individual income levels and the progression of CKD in Japan, a country with universal health coverage. Methods: We used the national database from the Japan Health Insurance Association (kyokai-kempo) between April 2015 and March 2021. We included 6,318,952 adults who undertook health check-ups in 2015 and had estimated Glomerular Filtration Rate (eGFR) measured at least twice during the study period. A multivariable linear regression model was used to investigate the association between income deciles and the average change in eGFR per year. A multivariable Cox proportional hazard regression model was used to estimate the hazard ratio [HR] for kidney replacement therapy (dialysis or kidney transplantation) according to deciles of individual income. We conducted the subgroup analysis by gender and prefectures. Results: The mean age was 48.8 years and 33.5 % were women. After adjusting for potential confounders, the lowest income group (bottom 10th percentile) showed a 0.08 [95%CI, 0.06–0.09] ml/min/1.73 m2/year larger decrease in eGFR than the highest income group (top 10th percentile). In our time-to-event analysis, we found an increased risk of kidney replacement therapy among the lowest income groups (HR [95%CI], 2.22 [1.99–2.48]) than among the highest income group. We found a similar pattern across gender and prefectures. Conclusion: Individual income levels were associated with the progression of CKD, particularly for the initiation of kidney replacement therapy in Japan. Our findings highlight the importance of considering socioeconomic status in CKD prevention and management even when insurance is covered.

PS-C26-7: A SINGLE-CENTER, RETROSPECTIVE STUDY OF BLOOD PRESSURE EFFECTS OF DAPAGLIFLOZIN IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Backgrounds: Sodium-glucose transporter 2(SGLT2) inhibitors are reported to have blood pressure lowering effects in addition to glucose-lowering effects. Previous studies have shown SGLT2 inhibitors, including dapagliflozin, reduce systolic blood pressure among patients with type 2 diabetes. Its mechanism is still uncertain; however, previous studies suggest plasma reduction by osmotic diuresis and natriuresis may contribute to lowering blood pressure. Dapagliflozin was recently approved as the treatment for chronic kidney disease in Japan. Blood-pressure lowering effects of SGLT2 inhibitors among patients with chronic kidney disease (CKD) are still unknown; therefore, we investigated blood-pressure effects of dapagliflozin in patients with CKD. Design and method: Patients with chronic kidney disease (estimated glomerular filtration rate (eGFR) of less than 60 mL/min per 1.73 m2, or markers of kidney damage, or both, of at least 3 months duration) were given 10 mg dapagliflozin daily for at least 4 weeks. Patients who had any changes in their antihypertensive drug prescription during this observation period were excluded. Clinical data including blood pressure measurements, eGFR, urine protein/creatinine ratio, and urinary sodium excretion before and after administration were taken and compared. Results: Contrary to previous reports, there was no significant difference in blood pressure at two months after administration. However, there was a trend of blood pressure decline at four months. Since this study is retrospective, measurement procedures were not aligned among patients, and body fluid evaluation was not considered. These inconsistent conditions may have affected the results. Also, dapagliflozin was administered to most patients in this study at the end of fall or beginning of winter, as it was approved for CKD patients in Japan in August 2021. Decreasing temperature may have limited or countervailed the blood pressure lowering effect of dapagliflozin in the first two months. Conclusions: Our findings indicate that the use of Dapagliflozin may serve as adjunct blood pressure lowering therapy in patients with CKD. Prospective study is needed to further investigate the blood pressure effects of dapagliflozin in CKD patients.

Cost-Effectiveness of Dapagliflozin for Chronic Kidney Disease in Japan.

The cost-effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors for chronic kidney disease (CKD) has not been evaluated in Japan, so we analyzed the cost-effectiveness of dapagliflozin, an SGLT2 inhibitor, for CKD stages 3a and 3b. We used the Markov model for CKD to assess the costs and benefits associated with and without dapagliflozin from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as per quality-adjusted life-years (QALYs). An ICER <5 million Japanese yen (JPY)/QALY was judged to be cost-effective. The effect of dapagliflozin on renal and cardiovascular events was based on published clinical trials. In patients with CKD stage 3a, the ICER of dapagliflozin over standard treatment was 4.03 million JPY/QALY gained. With a cost-effectiveness threshold of 5 million JPY/QALY gained, the cost-effectiveness probability of dapagliflozin over standard treatment was 52.6%. In patients with CKD stage 3b, the ICER of dapagliflozin over standard treatment was 0.12 million JPY/QALY gained. The cost-effectiveness probability of dapagliflozin over standard treatment was 75.2%. The results seemed to show acceptable cost-effectiveness when dapagliflozin was used for CKD stage 3b. On the other hand, cost-effectiveness of dapagliflozin for CKD stage 3a was ambiguous, and further validation is needed.

Screening of Fabry disease in patients with chronic kidney disease in Japan.

BackgroundFabry disease (FD), an X-linked lysosomal storage disorder caused by a deficiency in alfa-galactosidase A (α-Gal A) activity due to mutations in the GLA gene, has a prevalence of 0–1.69% in patients undergoing haemodialysis; however, its prevalence in patients with chronic kidney disease (CKD) Stages 1–5 is unknown.MethodsSerum α-Gal A activity analysis and direct sequencing of GLA were used to screen for FD in 2122 male patients with CKD, including 1703 patients with CKD Stage 5D and 419 with CKD Stages 1–5. The correlation between serum α-Gal A activity and confounding factors in patients with CKD Stages 1–5 was evaluated.ResultsFD prevalence rates in patients with CKD Stage 5D and CKD Stages 1–5 were 0.06% (1/1703) and 0.48% (2/419), respectively. A patient with CKD Stage 5D exhibited a novel GLA mutation, p.Met208Arg, whereas two patients with CKD Stages 1–5 had c.370delG and p.Met296Ile. p. Met208Arg caused moderate structural changes in the molecular surface region near the substituted amino acid residue but did not affect the catalytic residues Asp170 and Asp231 in α-Gal A. Serum α-Gal A activity in patients with CKD Stages 1–5 was inversely correlated with age (P < 0.0001) but directly correlated with estimated glomerular filtration rate (P < 0.0001).ConclusionsFD prevalence was much higher in male patients with CKD Stages 1–5 than in those with CKD Stage 5D. FD screening in patients with CKD Stages 1–5 may improve patient survival, decreasing the number of patients with CKD Stage 5D.

Prevalence, recognition and management of chronic kidney disease in Japan: population-based estimate using a healthcare database with routine health checkup data.

BackgroundWe aimed to update information on the prevalence of chronic kidney disease (CKD) in Japan. We also explored whether CKD was properly recognized and managed.MethodsWe used data from annual health checkups in 2017, compiling records for 5 million persons. These included laboratory results and were linked to healthcare utilization records via personal identifiers. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. The prevalence was compared with that in 2005. Healthcare utilization, including laboratory tests, disease coding and medication for comorbid diabetes mellitus (DM) and hypertension (HT), was used as an indicator for the recognition and management of CKD.ResultsOf the 761 565 records [median age 46 years (interquartile range 50–62)], CKD was found in 50 091 persons; the crude and age-adjusted prevalences were 63.1 and 71.8 per 1000 persons, respectively. CKD prevalence was significantly higher in 2017 than in 2005, with an increase of 14.1 per 1000 persons. Among persons with CKD, >95% sought medical services and 64.6% received laboratory tests within 180 days of the checkup. However, the diagnostic code suggestive of CKD was recorded in only 23.2% of patients and prescriptions for DM and HT were found in 31.2% (1590/5096) and 36.7% (8081/22 019) of comorbid persons, respectively.ConclusionsThe prevalence of CKD in Japan has increased over the past decade. However, recognition of CKD is likely suboptimal and there is room to improve the management of comorbid DM and HT.

Dysbiosis in the Salivary Microbiome Associated with IgA Nephropathy-‍A‍ ‍Japanese Cohort Study.

IgA nephropathy is one of the leading causes of chronic kidney disease in Japan. Since the origin and mechanisms by which IgA nephropathy develops currently remain unclear, a confirmed disease diagnosis is currently only possible by highly invasive renal biopsy. With the background of the salivary microbiome as a rich source of biomarkers for systemic diseases, we herein primarily aimed to investigate the salivary microbiome as a tool for the non-invasive diagnosis of IgA nephropathy. In a comparison of salivary microbiome profiles using 16S rRNA amplicon sequencing, significant differences were observed in microbial diversity and richness between IgA nephropathy patients and healthy controls. Furthermore, recent studies reported that patients with IgA nephropathy are more likely to develop inflammatory bowel diseases and that chronic inflammation of the tonsils triggered the recurrence of IgA nephropathy. Therefore, we compared the salivary microbiome of IgA nephropathy patients with chronic tonsillitis and ulcerative colitis patients. By combining the genera selected by the random forest algorithm, we were able to distinguish IgA nephropathy from healthy controls with an area under the curve (AUC) of 0.90, from the ulcerative colitis group with AUC of 0.88, and from the chronic tonsillitis group with AUC of 0.70. Additionally, the genus Neisseria was common among the selected genera that facilitated the separation of the IgA nephropathy group from healthy controls and the chronic tonsillitis group. The present results indicate the potential of the salivary microbiome as a biomarker for the non-invasive diagnosis of IgA nephropathy.

Prevalences of hyperuricemia and electrolyte abnormalities in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD.MethodsIn total, 35,508 adult outpatients with estimated glomerular filtration rates of 5–60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsLogistic regression analysis showed that prevalence of hyperuricemia was associated with CKD stages G3b (adjusted odds ratio [95% confidence interval]: 2.12 [1.90–2.37]), G4 (4.57 [3.92–5.32]), and G5 (2.25 [1.80–2.80]). The respective prevalences of hyponatremia, hypercalcemia, hyperphosphatemia, and narrower difference between serum sodium and chloride concentrations were elevated in patients with CKD stages G3b, G4, and G5, compared with those prevalences in patients with CKD stage G3a. The prevalences of hyperkalemia were 8.3% and 11.6% in patients with CKD stages G4 and G5, respectively. In patients with CKD stage G5, the proportions of patients with optimal ranges of serum uric acid, potassium, corrected calcium, and phosphate were 49.6%, 73.5%, 81.9%, and 56.1%, respectively.ConclusionsWe determined the prevalences of hyperuricemia and electrolyte abnormalities in Japanese patients with CKD using data from a nationwide cohort study.

Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB).

BackgroundThe Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD.MethodsIn total, 31,082 adult outpatients with estimated glomerular filtration rates of 5–60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively.ResultsThe mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09–2.58]), G4 (5.50 [4.80–6.31]), and G5 (9.75 [8.13–11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5.ConclusionsWe determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study.

A Phase 3, Multicenter, Randomized, Two-Arm, Open-Label Study of Intermittent Oral Dosing of Roxadustat for the Treatment of Anemia in Japanese Erythropoiesis-Stimulating Agent-Naïve Chronic Kidney Disease Patients Not on Dialysis

Introduction: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved for the treatment of anemia in Japan for patients with dialysis-dependent (DD) chronic kidney disease (CKD). Objective: Multicenter, randomized, open-label, noncomparative, phase 3 study to evaluate roxadustat for anemia of non-dialysis-dependent (NDD) CKD in Japan. Methods: Erythropoiesis stimulating agent (ESA)-naïve NDD-CKD patients were randomized to roxadustat (initial dose, 50 or 70 mg 3 times weekly), titrated to maintain hemoglobin (Hb) within 10.0–12.0 g/dL, for ≤24 weeks. Patients with either transferrin saturation of ≥5% or serum ferritin of ≥30 ng/mL during the screening period were eligible. Endpoints included response rate (proportion of patients achieving Hb ≥10.0 or ≥10.5 g/dL and Hb increase ≥1.0 g/dL from baseline) at end of treatment; average Hb (weeks 18–24); change of average Hb from baseline to weeks 18–24; maintenance rate (proportion of patients achieving Hb 10.0–12.0 g/dL at weeks 18–24); rate of rise (RoR) of Hb from weeks 0–4, discontinuation, or dose adjustment. Adverse events were monitored throughout the study. Results: Of 135 patients who provided informed consent, 100 were randomized and 99 received roxadustat (50 mg, n = 49; 70 mg, n = 50). The mean (SD) dose of roxadustat per intake at week 22 was 36.3 (22.7) mg in the roxadustat 50 mg group and 36.8 (16.0) mg in the roxadustat 70 mg group. Prior medications included oral iron therapy (20.2%) and intravenous iron therapy (1.0%). Overall response rate (95% CI) was 97.0% (91.4, 99.4; Hb ≥10.0 g/dL) and 94.9% (88.6, 98.3; Hb ≥10.5 g/dL). Mean (SD) Hb (weeks 18–24) was 11.17 (0.62) g/dL. Mean (SD) change of Hb from baseline (weeks 18–24) was 1.34 (0.86) g/dL. Maintenance rate (95% CI) was 88.8% (80.3, 94.5) among patients with ≥1 Hb measurement during weeks 18–24. Mean (SD) RoR of Hb was 0.291 (0.197) g/dL/week (50 mg) and 0.373 (0.235) g/dL/week (70 mg). Nasopharyngitis and hypertension were the most common adverse events. Conclusion: Roxadustat increased and maintained Hb in ESA-naïve, partially iron-depleted NDD-CKD patients with anemia.

Antihypertensive treatment and risk of cardiovascular mortality in patients with chronic kidney disease diagnosed based on the presence of proteinuria and renal function: A large longitudinal study in Japan.

Several recent clinical trials and meta-analyses have shown that lowering blood pressure reduces the risk of cardiovascular disease. However, current evidence that describes general demographics in blood pressure and mortality with chronic kidney disease is sparse in Japan. Using a population-based longitudinal cohort that received annual health checkups in Japan in 2008, hypertensive status, self-reported use of antihypertensive drugs, and prognosis were examined through 2012. Chronic kidney disease was defined as positive proteinuria or estimated glomerular filtration rate <60 ml/min/1.73 m2. Subjects were 40 to 74 years old (n = 227,204) with median 3.6 years follow-up period, and patients with and without chronic kidney disease were analyzed separately (n = 183,586 and n = 43,618, respectively). Cardiovascular disease mortality, comprising coronary heart diseases and stroke as entered in the national death registry using ICD-10 coding, was examined. Among all subjects, 346 deaths (96 in chronic kidney disease and 250 in non-chronic kidney disease) due to cardiovascular disease occurred. Compared with cardiovascular disease mortality in chronic kidney disease patients with untreated normal blood pressure, the multivariable adjusted hazard ratio was 3.08 (95% confidence interval: 1.75-5.41) for those with untreated hypertension, 2.30 (1.31-4.03) for those who became normotensive after treatment, and 3.28 (1.91-5.64) for those who remained hypertensive despite treatment. In non-chronic kidney disease subjects, the ratios were 1.90 (1.33-5.41), 1.95 (1.35-2.80), and 1.77 (1.18-2.66), respectively. These results from a nationwide cohort could be one of representative demographics of controlling blood pressure and cardiovascular disease deaths when treating patients with chronic kidney disease in Japan in recent years. Even after development and spread of anti-hypertensive drugs, preventing development of hypertension is preferable, because any hypertension treatment status comparing untreated normal blood pressure was a risk of cardiovascular mortality at baseline year.

Association of the combination of weight gain after 20 years of age and current obesity with chronic kidney disease in Japan: a cross-sectional study

ObjectivesWeight gain after 20 years of age is associated with chronic kidney disease (CKD). However, the impact of weight gain on CKD might differ by current obesity status. We investigated...

Knowledge and awareness of nonpharmacist salespersons regarding over-the-counter drug use in patients with chronic kidney disease in Japan.

IntroductionPatients with chronic kidney disease (CKD) depend on advice from healthcare professionals to avoid using unsuitable over-the-counter (OTC) drugs. Recently, qualified, registered nonpharmacist salespersons became licensed to sell OTC drugs in Japan. However, registered salespersons’ knowledge and awareness of precautions regarding unsuitable OTC drugs for use in patients with CKD are unclear.ObjectivesThis study aimed to clarify the awareness, knowledge, and implementation of precautions by registered salespersons regarding OTC drugs used by patients with CKD. Additionally, we evaluated the change of registered salespersons’ knowledge and awareness of this topic generated by a pharmacist intervention.MethodsA questionnaire survey and pharmacist intervention were applied to 175 registered salespersons. The intervention comprised a 50-minute lecture imparted by a pharmacist who was trained in nephrology. The knowledge, awareness, and implementation of precautions by participants with respect to nonsteroidal anti-inflammatory drugs (NSAIDs) and antacids were evaluated before and after the intervention.ResultsApproximately half of the registered salespersons reported previous experience with selling OTC drugs that were inappropriate for patients with CKD (NSAIDs, 48.0%; antacids, 39.7%). Few participants recognized the need to check renal function when selling those drugs to such patients (NSAIDs, 25.7%; antacids, 47.5%). The registered salespersons’ awareness and knowledge were significantly higher after the intervention than before it.ConclusionThe results indicate that before the intervention, the registered salespersons had low levels of awareness and knowledge regarding OTC drug use in patients with CKD despite having prior experience selling unsuitable OTC drugs. However, the pharmacist intervention improved the registered salespersons’ awareness and knowledge. The educational program for registered salespersons might be necessary to prevent inappropriate OTC drug use by patients with CKD.