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Background: The association between N-terminal pro brain natriuretic peptide (NT-proBNP) level and long-term mortality in Japanese hemodialysis patients has not been fully assessed., Methods: This prospective, multicenter study included 1428 hemodialysis outpatients. Baseline NT-proBNP levels were measured at the first hemodialysis session of the week and participants were followed for 5 years. The areas under the curve were calculated from receiver operating characteristic curves. Groups determined by quartiles of baseline NT-proBNP level were assessed by the Kaplan-Meier method and log-rank test. The association between NT-proBNP level and mortality was assessed using multivariate Cox proportional hazards models., Results: During the 5-year follow-up, we observed 370 deaths and 256 censored cases. The areas under the curve of pre-hemodialysis NT-proBNP for all-cause mortality and cardiovascular disease mortality after 1 year were 0.75 and 0.78, respectively, and significantly greater than the areas under the curve at the 3- and 5-year follow-up. Cut-off values for all-cause mortality and cardiovascular disease mortality after 1 year were 4550 and 5467 ng/L, respectively (sensitivity: 82% and 81%; specificity: 59% and 64%). Kaplan-Meier survival analysis showed that the group with pre-hemodialysis NT-proBNP ≥ 8805 ng/L had increased all-cause mortality (P < 0.001) and cardiovascular disease mortality (P < 0.001). Finally, multivariate Cox analysis showed that NT-proBNP level was associated with all-cause mortality (P < 0.001) and cardiovascular disease mortality (P = 0.004) independently from other clinical parameters., Conclusion: NT-proBNP is a useful marker to predict both all-cause and cardiovascular disease mortality in hemodialysis patients., (© 2021. Japanese Society of Nephrology.)

Objective A low-normal albumin level is associated with a high risk of cardiovascular disease and mortality in the general population. However, the relationship between the serum albumin level and the future decline in the kidney function is unclear. We evaluated the effect of the serum albumin level on the decline in the kidney function in the general population. Methods The data used were from 11,000 participants in a voluntary health checkup program conducted between 1998 and 2006 in Japan. The primary outcome for the kidney function was a difference in the estimated glomerular filtration rate (ΔeGFR) of≥3 mL/min/1.73 m 2 /year. The association of the risk of a decreased kidney function with the albumin level was determined using a logistic regression analysis. We fit separate multivariable logistic regressions for the serum albumin levels (g/dL) as a continuous variable and as categorical data, classified as ≤4.3 (n=2,530), 4.4-4.6 (n=5,427), and≥4.7 (n=3,043). Results Of the 11,000 participants, 346 had a ΔeGFR/year of≥3. Compared with the participants with albumin levels of≥4.7 g/dL, the risk of a decline in the kidney function was higher not only in those with albumin levels of ≤4.3 g/dL [adjusted odds ratio (OR) =2.10, 95% confidence interval (CI): 1.20-2.93] but also in those with levels of 4.4-4.6 g/dL (adjusted OR=1.53, 95% CI: 1.14-2.05). Conclusion A decreased albumin level is an independent risk factor for a rapid decline in the kidney function, even within the normal range.

Background: Chronic kidney disease (CKD) is a risk factor of cardiovascular disease (CVD) and end-stage renal disease (ESRD). Early detection and management of risk factors of incidence and progression of CKD are necessary. We have been studying these risk factors among community-based screening participants in Okinawa, Japan. Okinawa was one of the longevity areas in the world; however, the incidence and prevalence of ESRD increased. In Japan, the incidence of ESRD is 2 times higher in men compared to that in women. Such gender difference in ESRD incidence may be explained by the difference in lifestyle-related factors such as obesity and metabolic syndrome., Summary: We have shown the significance of hyperuricemia on the incidence of ESRD and progression of CKD. Hyperuricemia was associated with increased risk of developing ESRD, in particular women. Although the causal relationship between the levels of serum uric acid (SUA) and changes in estimated glomerular filtration rate (eGFR) was not clear, we observed that high SUA was associated with larger decrease in eGFR. People with hyperuricemia, >7.0 mg/dL, may have an unhealthy lifestyle. We observed to see if intensive care, involving regular monitoring of body mass index and lifestyle and intervention when appropriate by dietitians and general practitioners, led to improved renal outcomes among patients with stage 3 CKD, compared to standard care. The benefit was observed in patients with CKD stage 3b. Key Message: Hyperuricemia is closely associated with the incidence and progression of CKD. Lifestyle modification including hyperuricemia would be the basis of management of CKD patients., (© 2018 S. Karger AG, Basel.)

Background: To alleviate chronic renal graft shortages in Japan, donation after circulatory death (DCD) is an increasingly used organ resource. Organs from DCD donors with progressively increased terminal creatinine (t-Cr) levels are frequently used, but the effects of this condition on kidney transplantation (KTx) remain unclear., Methods: Between 1996 and 2013, 99 KTx from DCD donors were conducted in our department. Recipients were grouped according to the t-Cr (in mg/dL) of donors: group 1, t-Cr less than < 1.5; group 2, 1.5 ≤ t-Cr < 3.0; and group 3, t-Cr ≥ 3.0. We analyzed the long-term outcomes of KTx from DCD donors retrospectively in terms of donors' terminal renal function., Results: The respective mean donor t-Cr in groups 1, 2, and 3 were 0.73 ± 0.28, 2.02 ± 0.40, and 6.69 ± 3.68. The respective death-censored graft survival rates (%) in groups 1, 2, and 3 were 90.2, 96.2, and 86.7 at 1 year and 70.3, 86.2, and 73.4 at 10 years after transplantation. Group 1 exhibited lower incidence of delayed graft function than either group 2 or group 3 (80.5% vs 100% and 93.3%). Nevertheless, no significant difference was found between groups for several measures: Cr levels 1 month after KTx and lowest Cr levels throughout the observation period, prevalence of biopsy-proven acute rejection, and graft survival. Cox proportional hazard regression showed that donor age, cerebrovascular event, terminal urine output, and history of hypertension were significantly associated with graft survival., Conclusions: Results suggest that, under certain conditions, kidneys from DCD donors with progressively increased t-Cr can be used safely with promising long-term outcomes.

Objectives: High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG., Methods: Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft-Gault equation: 1339 patients with estimated GFR of ≥ 60 ml/min/1.73 m(2) (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m(2) (ORI group)., Results: Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m(2), P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16-2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16-2.02], P < 0.01)., Conclusions: ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels.

Background: Hyperuricemia is a risk factor for end-stage renal disease. This study examined the association between serum uric acid and renal damage in a community-based population., Methods: In this study 3126 subjects without renal insufficiency were recruited at baseline and were followed for one year. The urinary albumin-creatinine ratio (UACR) and β2-microglobulin-creatinine ratio (UBCR) in morning spot urine samples were used as indices of either glomerular (UACR) or tubular (UBCR) damage., Results: The mean value of serum uric acid (mg/dL) was 5.8 ± 1.3 (SD) in men and 4.5 ± 1.1 in women. In cross-sectional analysis the increased serum uric acid levels were accompanied by higher UACR values in both men and women (P < 0.01). In contrast, UBCR values were reduced when uric acid levels increased in both men and women (P < 0.01). Multivariate analysis revealed that albuminuria (UACR ≥ 30 mg/g) was significantly associated with increased uric acid (≥7 mg/dL for men, ≥6 mg/dL for women). High UBCR (≥300 μg/g) was negatively associated with uric acid in men, but not in women, after adjustment for possible confounders. In longitudinal analysis in 1388 subjects multiple linear regression analysis showed that uric acid at baseline was an independent factor for one-year increase of UACR [coefficient 4.80 (95 % confidence interval 0.40-9.33) (mg/g) per 1 mg/dL increase in uric acid, P = 0.033]., Conclusion: This study showed that serum uric acid concentration was positively associated with UACR, suggesting that uric acid may be related to glomerular damage in a community-based population.

Objectives: This study examined whether low renal function is associated with the number of remaining teeth among community-dwelling elderly Japanese., Background Data: Many elderly individuals display both low renal function and tooth loss., Materials and Methods: Subjects comprised 405 randomly selected women (55-74 years old). Serum cystatin C level was used to assess renal dysfunction. Multiple linear regression analysis was used to evaluate the relationship between number of remaining teeth and serum cystatin C level, with number of remaining teeth as the dependent variable. Six variables were selected as independent variables in the final model: serum cystatin C; age; mean clinical attachment level; serum cross-linked N-telopeptide of type I collagen level; body mass index and smoking habits., Results: Multiple linear regression analysis revealed a significant relationship between number of remaining teeth and serum cystatin C level. The beta value for serum cystatin C level for the number of remaining teeth was -0.11 (p = 0.018)., Conclusion: This study indicates a relationship between serum cystatin C level and number of remaining teeth, suggesting that low renal function could be associated with tooth loss., (© 2011 The Gerodontology Society and John Wiley & Sons A/S.)

Although the kidneys are the major source of proinflammatory cytokines, association of tumor necrosis factor-alpha (TNF-alpha) with severity of atherosclerosis or kidney function in diabetic patients is unclear. Two hundred type 2 diabetic patients and 30 age-matched nondiabetic subjects consecutively admitted to our hospital were enrolled. The Agatston coronary artery calcium score (CACS), a quantitative marker of coronary atherosclerosis, was obtained using multidetector-row computed tomography. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). Diabetic patients had higher log(CACS+1) (p=0.0089), baPWV (p=0.0293), frequency of elevated urinary albumin excretion (UAE) (p<0.0001) and TNF-alpha (p=0.0029) and similar estimated glomerular filtration rate (eGFR) compared to nondiabetic subjects. When diabetic patients were grouped into four subgroups with or without elevated UAE and renal insufficiency (UAE of >/=30 or <30mg/24h and eGFR of <60 or >/=60ml/min per 1.73m(2)), patients with micro- and macroalbuminuric renal insufficiency showed the highest log(CACS+1) (p<0.0001), baPWV (p=0.0068) and TNF-alpha (p<0.0001) of these groups. Log(CACS+1) (p=0.0008) and baPWV (p=0.0006) positively and eGFR (p<0.0001) negatively correlated with TNF-alpha in diabetic patients. We find that coronary artery calcification, arterial stiffness, and renal insufficiency associate with circulating levels of TNF-alpha in type 2 diabetic patients.

Background: Renal insufficiency is common in patients with chronic heart failure (CHF), so to improve the prognosis of patients with cardiovascular risks clinical guidelines recommend estimating the glomerular filtration rate (GFR), which detects chronic kidney disease more accurately than does the serum creatinine level alone. However, the clinical usefulness of the estimated GFR (eGFR) in Japanese CHF patients is still unclear., Methods and Results: Of 1,278 patients registered in a Japanese CHF registry, termed the Chronic Heart Failure Analysis and Registry in the Tohoku District study, the study population included 920 symptomatic patients with sufficient data. Baseline eGFR (ml .min(-1) . 1.73 m(-2)) was calculated using the Cockcroft-Gault equation. Patients were divided into three groups based on eGFR: > or =60, 30-59, and <30 ml . min(-1) .1.73 m(-2). Kaplan-Meier analysis revealed that the incidence of the combined event of all-cause death and admission because of CHF was significantly higher in patients with reduced eGFR and such patients were older and more frequently had an ischemic etiology of CHF, a higher prevalence of diabetes, lower hemoglobin level, and higher B-type natriuretic peptide level. Multivariate Cox regression analysis showed that reduced eGFR was significantly associated with the combined endpoint., Conclusions: GFR should be evaluated in all Japanese patients with CHF to improve risk stratification and treatment.

Objective: Patients with impaired renal function or diabetes are considered to be prone to hyperkalemia. Furthermore, hyperkalemia is an adverse drug reaction of inhibitors of the renin-angiotensin system (RAS) that are established to be efficacious in these patients. However, the current status of hyperkalemia in the clinical setting remains obscure., Methods: A total of 9,117 patients treated at Toranomon Hospital between January and October 2005, who had serum creatinine levels below 5 mg/dL were studied. Patients on dialysis and patients using cation exchange resin or diuretics that lower serum potassium were excluded., Results: Serum potassium increased significantly accompanying the increase in serum creatinine, and was significantly elevated in diabetic patients compared to non-diabetic patients. Serum potassium also increased significantly with the administration of angiotensin-II receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEI) or beta-blockers. A combination of diabetes and RAS inhibitor administration significantly increased serum potassium compared to each factor alone in patients with a serum creatinine level below 1.5 mg/dL but not in those with a higher serum creatinine level. According to step-wise multiple regression analyses, an elevated serum creatinine level had the strongest positive correlation with the serum potassium level, followed by diabetes, ACEI use, ARB use, and age., Conclusion: Lowered renal function, diabetes, use of RAS inhibitors and old age are independent factors that increase the serum potassium level. Caution should be exercised when using RAS inhibitors in diabetic patients even if their renal function is relatively preserved. In selected patients with diabetes or impaired renal function, however, RAS inhibitors can be used without hyperkalemia.

Serum soluble transferrin receptor (sTfR) has been reported to be higher in patients with iron deficiency or with elevated erythropoiesis. In the present study, serum sTfR was measured in various anemic diseases and their clinical significance was examined in a multi-institutional joint study. Serum sTfRs in patients with the following anemic diseases were markedly higher than those in normal healthy adults: non-treated iron deficiency anemia (IDA) (9.13 +/- 7.04 mg/l, n = 52, p < 0.0001), anemia of chronic disorders (ACD) (3.45 +/- 1.38 mg/l, n = 20, p < 0.0001), hemolytic anemia (HA) (5.57 +/- 3.26 mg/l, n = 17, p < 0.0001), and myelodysplastic syndrome (MDS) (4.03 +/- 2.83 mg/l, n = 20, p < 0.0001). There were significant differences between IDA and ACD (p < 0.0001), between aplastic anemia (AA) (1.58 +/- 1.26 mg/l, n = 16) and MDS (p < 0.001), and between AA and MDS with refractory anemia (MDS-RA) (4.16 +/- 3.40 mg/l, n = 9) (p < 0.02). In patients with chronic renal failure (CRF), serum sTfR levels and serum sTfR/log serum ferritin ratios (sTfR/F index) were compared in the two classified groups according to Muirhead's criteria, as IDA and non-IDA groups with or without recombinant human erythropoietin (rHuEPO) treatment. Significantly high levels of both serum sTfR (p < 0.0001) and the sTfR/F index (p < 0.0001) were observed in IDA without rHuEPO treatment. Especially in CRF with rHuEPO treatment, the sTfR/F index showed marked elevation in the IDA group (p < 0.0001) compared with serum sTfR (p < 0.001), indicating more diagnostic efficacy of the sTfR/F index for CRF with IDA. In conclusion, the serum sTfR concentration is a useful diagnostic tool for discrimination between IDA and ACD, and between AA and MDS-RA, and for the detection of iron deficiency in CRF patients in the Japanese population.