Japanese Chronic Kidney Disease Patients Research Articles

The level of serum albumin is associated with renal prognosis and renal function decline in patients with chronic kidney disease

ObjectiveThe study’s purpose is to explore the link of serum albumin on renal progression in patients with chronic kidney disease (CKD).MethodsThis study was a secondary analysis of a prospective cohort study in which a total of 954 participants were non-selectively and consecutively collected from the research of CKD-ROUTE in Japan between November 2010 and December 2011. We evaluated the association between baseline ALB and renal prognosis (initiation of dialysis or 50% decline in eGFR from baseline) and renal function decline (annual eGFR decline) using the Cox proportional-hazards and linear regression models, respectively. We performed a number of sensitivity analyses to ensure the validity of the results. In addition, we performed subgroup analyses.ResultsThe included patients had a mean age of (66.86 ± 13.41) years, and 522 (69.23%) were male. The mean baseline ALB and eGFR were (3.89 ± 0.59) g/dL and (33.43 ± 17.97) ml/min/1.73 m2. The annual decline in eGFR was 2.65 mL/min/1.73 m2/year. 218 (28.9%) individuals experienced renal prognosis during a median follow-up period of 36.0 months. The baseline ALB was inversely linked with renal prognosis (HR = 0.61, 95%CI: 0.45, 0.81) and renal function decline (β = -1.41, 95%CI: -2.11, -0.72) after controlling for covariates. The renal prognosis and ALB had a non-linear connection, with ALB’s inflection point occurring at 4.3 g/dL. Effect sizes (HR) were 0.42 (0.32, 0.56) and 6.11 (0.98, 38.22) on the left and right sides of the inflection point, respectively. There was also a non-linear relationship between ALB and renal function decline, and the inflection point of ALB was 4.1 g/dL. The effect sizes(β) on the left and right sides of the inflection point were -2.79(-3.62, -1.96) and 0.02 (-1.97, 1.84), respectively.ConclusionThis study shows a negative and non-linear association between ALB and renal function decline as well as renal prognosis in Japanese CKD patients. When ALB is lower than 4.1 g/dL, ALB decline was closely related to poor renal prognosis and renal function decline. From a therapeutic point of view, reducing the decline in ALB makes sense for delaying CKD progression.

T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Association between the intake of plant and animal proteins and the serum fibroblast growth factor-23 level in patients with chronic kidney disease analyzed by the isocaloric substitution model.

Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone secreted by the bone in response to dietary phosphate intake. Since the phosphate content in the diet correlates with the protein content, both plant- and animal-based protein intake can increase the serum FGF23 level. However, a higher percentage of energy from plant protein than from animal protein is associated with a lower serum FGF23 level in patients with chronic kidney disease (CKD) in the United States. Since dietary habits differ between Asian and Western populations, we performed a cross-sectional study to determine the association between the percentages of energy from plant and animal proteins and the serum FGF23 level in Japanese CKD patients. In 107 non-dialysis CKD patients (age: 66 ± 9 years; estimated glomerular filtration rate: 56 ± 21 mL/min/1.73 m2), the percentages of energy from plant and animal proteins were assessed using a food frequency questionnaire based on food groups. Venous blood samples were used to measure the serum FGF23, phosphate, 1,25-dihydroxyvitamin D, and intact parathyroid hormone levels. The percentages of energy from plant and animal proteins showed a negative and positive association, respectively, with the serum FGF23 level. Furthermore, isocaloric substitution modeling showed that replacing animal protein with plant protein was associated with a low serum FGF23 level. Our findings suggest that encouraging diets with high plant protein level may prevent an increase in the serum FGF23 level in Japanese CKD patients.

Association between hemoglobin and chronic kidney disease progression: a secondary analysis of a prospective cohort study in Japanese patients

ObjectiveAnemia has been reported as a risk factor for chronic kidney disease (CKD) progression. However, there are still few studies examining the relationship between specific hemoglobin (Hb) levels and renal prognosis and renal function decline simultaneously. Meanwhile, the possible non-linear relationship between Hb and CKD progression also deserves further exploration. On that account, our primary goal is to explore the link of Hb on renal prognosis and renal function decline in patients with CKD.MethodsThis study was a secondary analysis of a prospective cohort study, which consecutively and non-selectively collected 962 participants from the research of CKD-ROUTE in Japan from November 2010 to December 2011. We used the Cox proportional-hazards and linear regression models to evaluate the independent association between baseline Hb and renal prognosis (renal composite endpoint, initiation of dialysis during follow-up or 50% decline in eGFR from baseline) and renal function decline(annual eGFR decline), respectively. A multivariate Cox proportional hazards regression analysis with cubic spline functions model and smooth curve fitting (penalized spline method) were conducted to address Hb and CKD prognosis's non-linearity. At the same time, a generalized additive model (GAM) and smooth curve fitting (penalized spline method) was conducted to explore the exact shape of the curve between Hb and renal function decline. Additionally, we did a series of sensitivity analyses to ensure the robustness of the results. Moreover, we conducted subgroup analyses.ResultsThe mean age of the included patients was 67.35 ± 13.56 years old, and 69.65% were male. The mean baseline Hb and estimated glomerular filtration rate (eGFR) was 12.06 ± 2.21 g/dL and 33.04 ± 18.01 ml/min per 1.73 m2. The annual decline in eGFR was 2.09 mL/min/1.73 m2/year. During a median follow-up time of 33.5 months, 252(26.2%) people experienced renal composite endpoint. After adjusting covariates, the results showed that Hb was negatively associated with renal composite endpoint (HR = 0.836, 95%CI: 0.770, 0.907) and renal function decline (β = -0.436, 95%CI: -0.778, -0.093). There was also a non-linear relationship between Hb and renal composite endpoint, and the inflection point of Hb was 8.6 g/dL. The effect sizes(HR) on the left and right sides of the inflection point were 1.257 (0.841, 1.878) and 0.789 (0.715, 0.870), respectively. And the sensitive analysis demonstrated the robustness of the results. Subgroup analysis showed that Hb was more strongly associated with the renal composite endpoint in non-hypertensive, SBP < 140 mmHg, urine protein-to-creatinine ratio (UPCR) < 0.5 g/gCr, and diuretic use patients. In contrast, the weaker association was probed in hypertensive and non-diuretic use patients and the patients with SBP ≥ 140 mmHg, and UPCR ≥ 0.5 g/gCr.ConclusionThis study demonstrates a negative and non-linear relationship between Hb and renal prognosis and renal function decline in Japanese CKD patients. Hb is strongly related to renal prognosis when Hb is above 8.6 g/dL.

Non-invasive fibrosis assessments of non-alcoholic fatty liver disease associated with low estimated glomerular filtration rate among CKD patients: the Fukuoka Kidney disease Registry Study.

A growing body of evidence has shown that non-alcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). Non-invasive fibrosis assessments of NAFLD such as Fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) have been developed to substitute liver biopsy. Little is known about the association between FIB-4 index or NFS and the components of CKD. In the present cross-sectional study, we assessed of 3640 Japanese CKD patients. We examined the association between FIB-4index or NFS and the odds of having low estimated glomerular filtration rate (eGFR) defined as eGFR < 60mL/min/1.73 m2 or albuminuria defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30mg/g. Patients were divided into quartiles according to their baseline FIB-4 index and NFS levels. Linear and logistic regression analysis were conducted, with adjustment for potential confounding factors. FIB-4 index and NFS were negatively associated with eGFR, but not UACR, after adjustment for potential confounding factors. Both FIB-4 index and NFS were significantly associated with low eGFR after adjustment for potential confounding factors. Meanwhile, in the multivariable-adjusted model, no associations were found between FIB-4 index or NFS and albuminuria. The addition of FIB-4 index or NFS to the established clinical CKD risk factors improved diagnostic accuracy of prevalence of low eGFR. We also found that there was a significant trend of higher FIB-4 index and NFS with more advanced renal fibrosis using the kidney biopsy data. Higher non-invasive fibrosis assessments of NAFLD were associated with higher odds of decreased eGFR.

Vadadustat for anemia in chronic kidney disease patients on peritoneal dialysis: A phase 3 open‐label study in Japan

Vadadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor for the treatment of anemia in patients with chronic kidney disease (CKD). This phase 3, open‐label, 24‐week single‐arm study evaluated the efficacy and safety of vadadustat in 42 Japanese CKD patients with anemia undergoing peritoneal dialysis. Patients received oral vadadustat for 24 weeks, initiated at 300 mg/day and doses were adjusted to achieve the target hemoglobin (Hb) range of 11.0‐13.0 g/dL. Least squares mean of average Hb at weeks 20 and 24 was 11.35 g/dL, which was within the target range. The most frequent adverse events were catheter site infections (23.8%), which were not related to vadadustat treatment. Vadadustat was generally well tolerated and effective in controlling Hb levels within the target range, indicating the usefulness of vadadustat for treating anemia in Japanese CKD patients undergoing peritoneal dialysis.

Fact-finding survey on health literacy among Japanese predialysis chronic kidney disease patients: a multi-institutional cross-sectional study.

Low health literacy (HL) has been associated with poor chronic disease management and adverse outcomes. However, reports on HL in predialysis chronic kidney disease (CKD) patients are limited in Japan. From August 2019 to February 2020, the European Health Literacy Survey (Japanese version) and a patient background survey (highest level of education, income, social activities, and exercise habit) were conducted on adult predialysis CKD patients. We compared clinical parameters in two groups according to the average HL score of a healthy Japanese population. In addition, a median value of 42 items was used as a cutoff for extracting CKD patient background factors associated with HL since HLS-EU-Q47 included five items related to physical activity and exercise. Valid responses were received from 200 patients. Median general HL index was 25.2 points. The high-HL group (≥ 25.3 points) showed a low proportion of male (56.7% vs. 70.9%, p = 0.038), high social activities (69.1% vs. 48.5%, p = 0.003), and high exercise habit (36.1% vs. 13.6%, p < 0.001). In the multivariate analysis, social activity [OR (95% CI); 2.12 (1.16-3.89), p = 0.015] and exercise habit [OR (95% CI); 2.39 (1.16-4.90), p = 0.018] were extracted as the only significant variable. HL in Japanese predialysis CKD patients was associated with high social activity and exercise habit.

Lipoprotein (a) and the Risk of Chronic Kidney Disease in Hospitalized Japanese Patients.

Objective Lipoprotein(a), or Lp(a), has been shown to be associated with the development of chronic kidney disease (CKD) in populations of various ethnicities. This study aimed to investigate the association between serum Lp(a) and CKD in Japanese patients． Methods A total of 6,130 subjects who underwent a serum Lp(a) level assessment for any reason (e.g. any type of surgery requiring prolonged bed rest or risk factors for atherosclerosis, such as hypertension or diabetes) were retrospectively investigated at Kanazawa University Hospital from April 2004 to March 2014. Of these, 1,895 subjects were excluded because of the lack of clinical data. Subjects were assessed for Lp(a), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, hypertension, diabetes, smoking, body mass index (BMI), coronary artery disease (CAD), and CKD (stage ≥3)． Results When the study subjects were divided into quartiles of Lp(a) levels, significant trends were observed with regard to the presence of CKD (p = 2.7×10-13). A multiple regression analysis showed that Lp(a) was significantly associated with CKD [odds ratio (OR), 1.12; 95% confidence interval (CI), 1.08-1.17; p = 1.3×10-7, per 10 mg/dL], independent of other classical risk factors, including age, gender, BMI, hypertension, diabetes, smoking, LDL cholesterol, and triglycerides. Under these conditions, Lp(a) was significantly associated with CAD (OR = 1.11, 95% CI = 1.06-1.16; p = 1.7×10-6, per 10 mg/dL), independent of other risk factors． Conclusion Serum Lp(a) was associated with CKD, independent of other classical risk factors in a Japanese population．

Significance of revised criteria for chronic active T cell-mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation.

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (log-rank test, P<.001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P<.001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.

Impact of lower body mass index on risk of all-cause mortality and infection-related death in Japanese chronic kidney disease patients

BackgroundSeveral studies have reported that lower body mass index (BMI) is associated with high mortality in patients with chronic kidney disease (CKD). Rate of infection-related death in CKD patients is increasing. However, the relationship between BMI and infection-related death is unclear.MethodsOverall, 2648 CKD outpatients (estimated glomerular filtration rate < 60 mL/min and/or presenting with proteinuria) under the care of nephrologists were prospectively followed for 5 years. Patients were stratified by quartile of BMI levels. Data on all-cause mortality before progression to end-stage kidney disease (ESKD) and the cause of death were collected.ResultsThe median follow-up time was 3.9 years (interquartile range, 1.7–5.0); 114 patients died and 308 started renal replacement therapy. The leading causes of death were as follows; cardiovascular (41%), infection-related (21%), and malignancy-related (18%). Advanced age and lower BMI were the significant risk factors for all-cause mortality before progression to ESKD. Advanced age was statistically associated with respective causes of death, while lower BMI was associated with infection-related death only. CKD stage had no significant impact on all-cause or individual mortality.ConclusionsLow BMI was associated with significant risk of all-cause mortality and infection-related death, which may indicate the novel clinical target to improve CKD outcomes.

P0786CLINICAL SIGNIFICANCE AND RELATED FACTORS OF GFR SLOPE IN A LARGE MULTICENTER OBSERVATIONAL STUDY IN JAPAN

Abstract Background and Aims Recently, glomerular filtration rate (GFR) slope has attracted attention as an important surrogate marker for the prognosis of chronic kidney disease (CKD), with a reduction in slope of eGFR decline by 0.75 mL/min/1.73 m2 per year reportedly having clinical significance. As few large clinical studies on Japanese CKD patients exist, this investigation addresses the clinical significance of GFR slope and its related factors. Method To evaluate the clinical impact of GFR slope, we conducted a prognostic investigation of CKD patients in Japan by means of a large, multicenter, retrospective, observational study. Patients with CKD who were seen at among 15 general hospitals between January and March 2014 were surveyed using medical records. The selection criteria were age ≥20 years, estimated GFR (eGFR) &amp;lt;60 mL/min/1.73 m2, and receiving medical treatment for CKD. Baseline patient characteristics, eGFR changes, and hard endpoints (death or end-stage kidney disease requiring renal replacement therapy) during observation were analysed. We calculated GFR slope using GFR data of 2 years following the observation start point by 2 calculation methods, the linear mixed model and least squares linear regression, and examined the relationship of GFR slope with the hazard ratio of the composite hard endpoints. The factors related to GFR slope were also assessed by multiple regression analysis. Results Among a total of 11233 collected patients, we analyzed the data of 7490 CKD G3 and G4 patients whose GFR data during 2 years could be obtained (60% male, mean age: 71 years, CKD G3a: 55%, G3b: 30%, G4: 15%, mean eGFR: 44.1 mL/min/1.73 m2, urine protein positive: 51%, diabetes mellitus: 49%, use of RAS inhibitors: 57%). The mean observation period was 1040 days. Hard endpoints after the GFR slope measurement period occurred in 301 subjects. The GFR slope of the cohort was -0.948 mL/min/1.73 m2 per year (95% confidence interval [CI] -1.016, -0.880) in the linear mixed model and -0.982 mL/min/1.73 m2 per year (95% CI -1.075, -0.889) according to least squares linear regression. Both calculated GFR slopes were significantly related to the hazard ratio of the composite hard endpoints. Hazard ratio decreased by 0.85 (linear mixed model) and 0.9 (least squares linear regression) times in case of a reduction in slope of eGFR decline by 0.75 mL/min/1.73 m2 per year. Multiple regression analysis revealed strongly significant associations for GFR slope with urine protein and CKD stage and undetectable relationships for GFR slope with diabetes and age. Conclusion This study demonstrated the clinical significance of GFR slope as a surrogate marker for renal prognosis in Japanese CKD patients. In order to reduce slope of eGFR decline, active intervention for proteinuria before the progression to an advanced CKD stage appears to be effective.

J-CKD-DB: a nationwide multicentre electronic health record-based chronic kidney disease database in Japan

The Japan Chronic Kidney Disease (CKD) Database (J-CKD-DB) is a large-scale, nation-wide registry based on electronic health record (EHR) data from participating university hospitals. Using a standardized exchangeable information storage, the J-CKD-DB succeeded to efficiently collect clinical data of CKD patients across hospitals despite their different EHR systems. CKD was defined as dipstick proteinuria ≥1+ and/or estimated glomerular filtration rate <60 mL/min/1.73 m2 base on both out- and inpatient laboratory data. As an initial analysis, we analyzed 39,121 CKD outpatients (median age was 71 years, 54.7% were men, median eGFR was 51.3 mL/min/1.73 m2) and observed that the number of patients with a CKD stage G1, G2, G3a, G3b, G4 and G5 were 1,001 (2.6%), 2,612 (6.7%), 23,333 (59.6%), 8,357 (21.4%), 2,710 (6.9%) and 1,108 (2.8%), respectively. According to the KDIGO risk classification, there were 30.1% and 25.5% of male and female patients with CKD at very high-risk, respectively. As the information from every clinical encounter from those participating hospitals will be continuously updated with an anonymized patient ID, the J-CKD-DB will be a dynamic registry of Japanese CKD patients by expanding and linking with other existing databases and a platform for a number of cross-sectional and prospective analyses to answer important clinical questions in CKD care.

Prevalence of hypothyroidism in Japanese chronic kidney disease patients

Background Major symptoms of progressive chronic kidney disease (CKD) are similar to those of hypothyroidism. Hidden symptoms of hypothyroidism underlying CKD are often observed in clinical practice. This study aimed to ascertain the frequency of hypothyroidism complicated by CKD, and to analyze factors impacting thyroid function. Methods During the period from April 2012 through October 2016, 510 CKD patients at our outpatient clinic were measured thyroid and kidney function for diagnosing hypothyroidism (overt hypothyroidism, OH; subclinical hypothyroidism, SH; non-thyroidal illness, NTI) and evaluating the stage of CKD. All patients were over 15 years of age. Results There were significant differences in age, estimated glomerular filtration rate (eGFR), urinary protein (UP), and serum albumin (Alb) among patients with OH, SH, and NTI compared to the normal group in univariate and multivariate analyses. UP showed the highest odds ratio of OH, SH, and NTI but no differences were recognized in gender in each group. Frequency distribution showed that the prevalence of thyroid dysfunction was greater among more severe stage of CKD with higher amount of UP. OH and SH did not show high positive ratio of anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb). NTI and normal subjects showed higher positive ratio as 50.0% and 42.9% of TgAb and TPOAb than OH and SH. Conclusions Hypothyroidism complicated by CKD exhibited a high prevalence. Age, eGFR, UP, and serum Alb were related to the prevalence of hypothyroidism, whereas gender was not and this was contradicted to the prevalence of hypothyroidism in general population. The prevalence of OH and SH was higher among patients with higher stage of CKD with increased UP. Hypothyroidism complicated by CKD may involve different onset mechanisms unrelated to antithyroid antibodies (ATAb). In CKD patients, assessments of OH and SH, as well as NTI, are needed for proper diagnosis.

The association between uric acid levels and renal function of CKD patients with hyperlipidemia: a sub-analysis of the ASUCA trial

BackgroundThe influence of uric acid (UA) on renal function and the significance of UA-lowering therapy are unclear. The purpose of the sub-analysis of the Assessment of Clinical Usefulness in chronic kidney disease patients with Atorvastatin (ASUCA) trial was to evaluate the influence of serum UA levels on renal function in Japanese chronic kidney disease patients with hyperlipidemia.MethodsOf 344 participants in the ASUCA trial, 279 participants whose UA levels at both baseline and 24 months were available were included. Based on UA level at baseline or mean UA level during the trial period, they were divided into four groups: < 5.0, 5.0–6.0, 6.0–7.0, or ≥ 7.0 mg/dL, irrespective of allocation. Changes in the estimated glomerular filtration rate (eGFR) after 24 months were compared among the groups in relation to baseline or mean UA levels.ResultsFor baseline UA levels (< 5.0, 5.0–6.0, 6.0–7.0, or ≥ 7.0 mg/dL), the change in eGFR after 24 months was − 1.32 ± 10.3, − 1.74 ± 8.94, − 2.53 ± 7.34, and − 3.51 ± 9.10 mL/min/1.73 m2, respectively. A negative correlation between changes in eGFR after 24 months and baseline UA level was observed with adjustment for confounding factors. The relationship between changes in eGFR and mean UA levels during trial period showed a similar trend.ConclusionIn CKD patients with dyslipidemia, hyperuricemia was an independent risk factor for CKD progression. An ongoing clinical trial (TARGET-UA, UMIN-ID 000,026,741) may reveal the significance of strict UA-lowering therapy in CKD patients.

Higher estimated net endogenous acid production with lower intake of fruits and vegetables based on a dietary survey is associated with the progression of chronic kidney disease

BackgroundDietary acid load has been suggested to mediate the progression of chronic kidney disease (CKD). However, it is unclear what kinds of foods are actually associated with dietary acid load in patients with CKD. The self-administered diet history questionnaire (DHQ), which semi-quantitatively assesses the dietary habits of Japanese individuals through 150 question items, can estimate average daily intake of various foods and nutrients during the previous month. Using the DHQ, we investigated the association of dietary acid load with CKD progression. We also analyzed the kinds of food that significantly affect dietary acid load.MethodsSubjects were 96 outpatients with CKD (average estimated glomerular filtration rate [eGFR], 53.0 ± 18.1 ml/min/1.73 m2) at Niigata University Hospital, who had completed the DHQ in 2011. We calculated net endogenous acid production (NEAP) from potassium and protein intake evaluated by the DHQ in order to assess dietary acid load. CKD progression was assessed by comparing eGFR between 2008 and 2014.ResultsNEAP was not correlated with protein intake (r = 0.088, p = 0.398), but was negatively correlated with potassium intake (r = − 0.748, p < 0.001). Reduction in eGFR from 2008 to 2014 was estimated to be significantly greater in patients with higher NEAP (NEAP > 50.1 mEq/day, n = 45) than in those with lower NEAP (NEAP ≤50.1 mEq/day, n = 50) by 5.9 (95% confidence interval [95%CI], 0.1 to 11.6) ml/min/1.73 m2. According to multiple logistic regression analysis, higher NEAP was significantly associated with lower intake of fruits (odds ratio [OR], 6.454; 95%CI, 2.19 to 19.00), green and yellow vegetables (OR, 5.18; 95%CI, 1.83 to14.66), and other vegetables (OR, 3.87; 95%CI, 1.29 to 11.62).ConclusionsElevated NEAP could be a risk factor for CKD progression. Low intake of fruits and vegetables would increase dietary acid load and might affect the progression of renal dysfunction in Japanese CKD patients.

Evaluation of changes in ferritin levels during sucroferric oxyhydroxide treatment.

BackgroundA sub-analysis of a Phase III study was conducted to identify factors that might predict increased ferritin levels during long-term sucroferric oxyhydroxide (SO) treatment in hemodialysis patients.MethodsThe open-label, multicenter, Phase III study assessed the efficacy and safety of SO 750–3000 mg/day for 52 weeks in Japanese patients with chronic renal failure and hyperphosphatemia. A total of 125 of 161 patients from the Phase III trial, and who had data for ferritin levels after 28 weeks of SO treatment, were evaluated.ResultsBaseline ferritin was the strongest contributor (P < 0.0001) to ferritin increases during SO treatment. By Week 28, there were significant differences (P < 0.05/3) in ferritin increases between patients with higher [quartile 4 (Q4)] versus lower (Q1, Q2 and Q3) baseline ferritin. An erythropoiesis-stimulating agent dosage reduction was observed in patients with the lowest baseline ferritin level (Q1), and only slight reductions were noted in the other patient subsets. SO dosages administered to patients in baseline ferritin quartiles Q2, Q3 and Q4 were comparable throughout the study with slight fluctuations. SO dosages in Q1 were considerably lower than those in the other quartiles.ConclusionsIn summary, of the baseline variables found to predict increased ferritin, and changes in iron-related parameters, during SO treatment in Japanese chronic kidney disease patients undergoing hemodialysis, baseline ferritin was the most relevant variable.

An equation to estimate the renal cortex volume in chronic kidney disease patients.

The renal cortex volume is associated with the kidney function and chronic kidney disease (CKD) risk factors, and it may also be a prognostic factor. We aimed to create an equation to estimate the renal cortex volume of CKD patients in day-to-day clinical practice. The subjects included 116 ethnic Japanese CKD patients who were ≥18years of age. The renal size (length, width and thickness) was measured by ultrasound. The body height, weight, year of age, sex, birth weight, gestational age, diabetes status, hypertension status, family history of CKD and dialysis and estimated glomerular filtration rate (eGFR) were collected as expected dependent variables. We made models for the equation regarding the renal cortex volume measured by non-contrast magnetic resonance imaging as a true renal cortex volume. Stepwise multiple linear regression analyses were performed with the log-transformation of dependent and independent variables. The accuracy of the models was compared using the leave one out cross-validation method. The estimated volume of the renal cortex (cm3)=0.012×renal length (cm)0.92×width (cm)0.53×body weight (kg)0.40×body height (cm)0.67×eGFR (ml/min/1.73m2)0.22×1.12 if diabetes. The adjusted R 2 value and the accuracy within 30 and 50% were 0.73, 0.94 and 0.99, respectively. This study provided a new method for estimating the renal cortex volume in day-to-day clinical practice.

A nationwide prospective cohort study of patients with advanced chronic kidney disease in Japan: The Reach-J CKD cohort study.

Epidemiology and outcomes of Japanese patients with advanced chronic kidney disease (CKD)-an estimated glomerular filtration rate (eGFR)<45ml/min/1.73m2-has remained largely unexamined. We conducted a nationwide survey to determine the distribution of Japanese CKD patients, and are conducting a cohort study of these patients. A questionnaire eliciting details about facilities and their CKD practices was sent to all clinics/hospitals with nephrologists. Based on the survey results, we recruited 2400 advanced CKD patients receiving nephrologist care from at least 30 representative facilities throughout Japan, selected randomly with stratification by region and facility size. Through patient questionnaires and nephrologist-practice surveys aligned with the international CKD Outcomes and Practice Patterns Study (CKDopps), we shall annually or semi-annually collect patient, physician and clinic data prospectively, detailing CKD practices for 5years, with a primary outcome of death or renal replacement therapy initiation, and secondary outcomes being decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular event. Of 790 eligible, responding facilities, 330 (41.8%) treat ≥80 advanced CKD patients in the average 3-month period. Regional distribution of these facilities is similar to that of persons in the general population. Hence, the 30 facilities selected for data collection appear to be geographically representative in Japan. Our study will enhance understanding of various CKD practices and biological data associated with CKD progression, and allow international comparisons using the CKDopps platform. This will provide evidences to improve the health and quality of life for patients with advanced CKD.

B-type natriuretic peptide and renal function in Japanese patients with type 2 diabetes mellitus: The Dogo Study.

Among patients with type 2 diabetes mellitus, the association between B-type natriuretic peptide (BNP) and renal function remains controversial. We therefore investigated this issue among Japanese patients with type 2 diabetes mellitus. This study included 687 Japanese patients with type 2 diabetes mellitus. BNP levels were divided at quartile points on the basis of the distribution. We used four outcomes regarding the renal function: 1) chronic kidney disease (CKD): estimated glomerular filtration rate (eGFR) < 60ml/min/1.72m2, 2) advanced CKD: eGFR < 30ml/min/1.72m2, 3) microalbuminuria: urinary albumin creatinine ratio (UACR) ≥ 30 mg/g creatinine, and 4) macroalbuminuria: UACR ≥ 300 mg/g creatinine. The prevalence values of CKD, advanced CKD, microalbuminuria, and macroalbuminuria were 27.4％, 2.5%, 31.4%, and 9.3%, respectively. Highest BNP (≥ 39.2 ng/ml) was independently positively associated with microalbuminuria and macroalbuminuria (adjusted ORs, 2.61 [95% CI: 1.53-4.49] and 3.45 [95% CI: 1.46-8.72], respectively). High BNP was not associated with advanced CKD or CKD. There was a statistically significant positive exposure-response relationships between the BNP level and advanced CKD, microalbuminuria, and macroalbuminuria (p for trend = 0.047, 0.001, and 0.003, respectively). BNP level may be independently positively associated with advanced CKD, microalbuminuria, and macroalbuminuria but not CKD in Japanese patients with type 2 diabetes mellitus.

Effects of Daprodustat, a Novel Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor on Anemia Management in Japanese Hemodialysis Subjects

Background: Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treatment of anemia associated with chronic kidney disease (CKD). The effect of daprodustat in Japanese CKD patients with anemia has not been previously investigated. Methods: We evaluated the relationship between daprodustat dose and hemoglobin response in Japanese patients on hemodialysis (HD) with anemia in a 4-week, phase II, double-blind, placebo-controlled study. After interrupting their erythropoiesis-stimulating agent for between 2 and 8 weeks, subjects with hemoglobin 8.5-10.5 g/dL were randomized to placebo or daprodustat 4, 6, 8, or 10 mg orally once daily. Hemoglobin, erythropoietin (EPO), and vascular endothelial growth factor (VEGF) levels during therapy were evaluated. Results: Eighty-six of 97 randomized subjects completed the study. Mean baseline hemoglobin ranged from 9.68 to 9.92 g/dL across groups. After 4-week administration, mean hemoglobin changes were -0.28, -0.01, 0.54, and 0.97 g/dL in the 4, 6, 8, and 10 mg groups, respectively, as compared to -1.41 g/dL for placebo. Dose-dependent increase in plasma EPO concentration were observed up to 8 mg, with the 10 mg dose responses being similar to 8 mg. Plasma VEGF concentrations were minimally changed, even though 5 subjects treated with 6-10 mg reached EPO >500 mIU/mL. Conclusion: Daprodustat 4-10 mg once-daily produced dose-dependent increase in hemoglobin relative to placebo in Japanese HD subjects. The doses evaluated in the study have moderately increased endogenous EPO without changes in circulating VEGF levels.