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Background/Aims: The association of diastolic blood pressure (DBP) with incidence of chronic kidney disease (CKD) in the general population is not well examined. Methods: Using national health check-up database from 2008 to 2011 in the general Japanese population aged 39–74 years, we evaluated the association between DBP and incidence of CKD 2 years later in 127,954 participants without CKD. DBP was categorized by every 5 mm Hg from the lowest (<60 mm Hg) to the highest category (>100 mm Hg) and was further stratified into those with and without antihypertensive medications (BP meds). We calculated the OR for estimating adjusted risk of incident CKD using logistic regression model. Results: Participants were 62% female and 25.9% with BP meds, mean age of 76 years with estimated glomerular filtration rate of 78.2 ± 13.4 and DBP of 76 ± 11 mm Hg. Two years later, 12,379 (9.7%) developed CKD. Compared to DBP 60–64 mm Hg without BP meds as reference, multivariate analysis showed no difference in CKD risk at any DBP category among those without BP meds. However, in those with BP meds, risk increased according to lower DBP from 95 to 60 mm Hg (p for trend 0.05) with OR 1.51 (95% CI 1.14–1.99) in DBP <60 mm Hg. In subgroup analysis within those with or without BP meds, CKD risk was lower at higher DBP (p for trend 0.02) only in those without BP meds. Conclusion: Lower DBP was associated with higher risk of incident CKD only in the general population taking antihypertensive medication. [ABSTRACT FROM AUTHOR]

Background: Does the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers individually or as a combination confer a survival benefit in hemodialysis patients? The answer to this question is yet unclear.Methods: We performed a case-cohort study using data from the Mineral and Bone Disorder Outcomes Study for Japanese CKD stage 5D patients (MBD-5D), a 3-year multicenter prospective case-cohort study, including 8,229 hemodialysis patients registered from 86 facilities in Japan. All patients had secondary hyperparathyroidism, a condition defined as a parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators. We compared all-cause mortality rates between those receiving ACEI, ARB, and their combination and non-users with interaction testing. We used marginal structural Poisson regression (causal model) to estimate the causal effect and interaction adjusted for possible time-dependent confounding. Cardiovascular mortality was also evaluated.Results: Among 3,762 randomly sampled subcohort patients, those taking ACEI, ARB, and their combination at baseline accounted for 4.0, 31.6, and 3.8%, respectively. Over 3 years, 1,226 all-cause and 462 cardiovascular deaths occurred. Compared to non-users, ARB-alone users had a lower all-cause mortality rate (adjusted incident rate ratio [aIRR] 0.62, 95% CI 0.50-0.76), whereas ACEI-alone users showed a statistically similar rate (aIRR 1.01, 95% CI 0.57-1.77). On the contrary, combination users had a greater mortality rate (aIRR 2.56, 95% CI 1.22-5.37), showing significant interaction (p = 0.03). Analysis for cardiovascular mortality showed similar results.Conclusion: Among hemodialysis patients with secondary hyperparathyroidism, unlike ACEI use, ARB use was associated with greater survival than non-use. Conversely, combination use was associated with greater mortality. Controlled trials are warranted to verify the causality factors of these associations. [ABSTRACT FROM AUTHOR]

Background: Although dialysis is typically started in an effort to prolong survival, mortality is reportedly high in the first few months. However, it remains unclear whether this is true in Japanese patients who tend to have a better prognosis than other ethnicities, and if health conditions such as functional status (FS) at initiation of dialysis influence prognosis. Methods: We investigated the epidemiology of early death and its association with FS using Japanese national registry data in 2007, which included 35,415 patients on incident dialysis and 7,664 with FS data. The main outcome was early death, defined as death within 3 months after initiation of hemodialysis (HD). The main predictor was FS at initiation of HD. Levels of functional disability were categorized as follows: severe (bedridden), moderate (overt difficulties in exerting basic activities of daily living), or mild/none (none or some functional disabilities). Results: Early death remained relatively common, especially among elderly patients (overall: 7.1%; those aged ≥80 years: 15.8%). Severely and even only a moderately impaired FS were significantly associated with early death after starting dialysis (adjusted risk ratios: 3.93 and 2.38, respectively). The incidence of early death in those with impaired FS increased with age (36.5% in those with severely impaired FS and aged ≥80 years). Conclusions: Early death after starting dialysis was relatively common, especially among the elderly, even in Japanese patients. Further, early death was significantly associated with impaired FS at initiation of HD. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease, especially those undergoing dialysis treatment and having secondary hyperparathyroidism, have a high risk of bone fracture. The renin-angiotensin system (RAS) is associated with osteoclastic bone resorption. We aimed to examine whether the use of RAS inhibitors reduces the incidence of fracture in hemodialysis patients. Methods and Findings: This was a multicenter, 3-year, prospective, observational study. From 2008 to 2011, maintenance hemodialysis patients with secondary hyperparathyroidism (N = 3,276) treated with angiotensin converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) at baseline were followed for a mean of 2.7 years. The association between the use of ACEI/ARB and hospitalization rate owing to fracture was examined by using Cox regression models. Effect modifications by the severity of secondary hyperparathyroidism (intact parathyroid hormone [iPTH] level), sex, and systolic blood pressure were also examined. The incidence proportion of fracture-related hospitalization was 5.42% throughout the observation period. ACEI/ARB use was associated with a lower rate of fracture-related hospitalization (adjusted hazard ratio, 0.65; 95% confidence interval [CI], 0.45–0.92). This association was not significantly affected by sex (P = 0.56) or systolic blood pressure levels (P = 0.87). The hazard ratios adjusted by iPTH levels were qualitatively different, but not statistically significant (P = 0.11): 0.77 (95% CI, 0.42–1.39), 0.38 (95% CI, 0.20–0.73), 0.59 (95% CI, 0.29–1.21), and 1.29 (95% CI, 0.58–2.42) for the first, second, third and fourth quartiles of iPTH, respectively. Conclusions: Use of RAS inhibitors is associated with a lower rate of fracture-related hospitalization in hemodialysis patients with secondary hyperparathyroidism. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background/Aims: Bone fracture is often complicated in hemodialysis (HD) patients. Metabolic acidosis is related to bone disease and muscle wasting, but it is not known whether acid-base disturbance is associated with the risk of bone fractures. The aim of this study was to clarify the association of serum bicarbonate level with bone fracture in HD patients. Methods: Using a subcohort of the Mineral and Bone Disorder Outcomes Study for Japanese CKD Stage 5D Patients (MBD-5D), 890 prevalent HD patients (age: 62 years old, male: 62.8%, duration of dialysis: 8.3 years) with secondary hyperparathyroidism were studied. After measuring predialysis serum bicarbonate at a 2-day interdialytic interval, we prospectively followed them every 3 months, and examined the occurrence of any type of bone fracture or hospitalization due to fracture over a 3-year observation period. Results: Seventy-four bone fractures and 47 hospitalizations due to fracture were observed during the follow-up period. HD patients with serum bicarbonate <20 mmol/l had a 1.93 (95% CI 1.01-3.71)-fold higher risk for all-cause fractures than those with serum bicarbonate of 20.0-21.9 mmol/l. A higher bicarbonate level (≥22 mmol/l) was also related to an increased risk of bone fracture. A restricted cubic regression spline disclosed that the higher or the lower than 21.0 mmol/l of serum bicarbonate, the greater the risk for bone fracture. Conclusion: Both a lower level and a higher level of predialysis bicarbonate concentration were associated with risk of bone fracture in HD patients with secondary hyperparathyroidism. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Chronic kidney disease ( CKD) is one of the common complications after deceased donor liver transplantation. Although the worldwide pressing shortage in deceased donors has directed attention to living donor liver transplantation ( LDLT), LDLT cohort data focusing on chronic renal dysfunction is limited. A total of 280 adult LDLT recipients (median 49 yr, 156 men) at the University of Tokyo hospital between 1996 and 2006 were reviewed. A total of 224 pre-transplant liver failure patients (80.0%) showed an estimated glomerular filtration rate ( eGFR) of more than 60 mL/min/1.73 m2. However, during follow-up at a mean of 1222 d after transplantation, eGFR declined to 60 mL/min/1.73 m2 and 30 mL/min/1.73 m2 in 150 (53.2%) and 21 (7.5%), respectively, and four patients (1.4%) required maintenance renal replacement therapy. Multivariate Cox proportional hazard model regression analysis revealed that recipient age ( HR, 3.42 per 10-yr increment; p < 0.001) and pre-transplant eGFR (HR, 0.85 per 10-mL/min/1.73 m2 increment; p = 0.04) were associated independently with a post-transplant decrease in eGFR to less than 30 mL/min/1.73 m2. We conclude that higher age and lower pre-transplant eGFR of an LDLT recipient indicate a high likelihood of subsequent development of advanced CKD. Preventive or therapeutic intervention should be optimized for these high-risk patients. [ABSTRACT FROM AUTHOR]

Mineral and bone disorders (MBD), including hypercalcemia and hypophosphatemia, are common complications after renal transplantation; however, the natural course of these disorders has not been well documented, and the pathogenesis of persistent post-transplant MBD still remains elusive. This study was carried out to show the natural history of mineral metabolism in recipients after living-donor kidney transplantation and also to clarify post-transplant risk factors of persistent hypercalcemia and/or hypophosphatemia at 12 months after transplantation. Living-donor kidney transplant recipients ( N = 34) at Tokyo Women's Medical University were prospectively and consecutively recruited. Parameters of MBD, including intact parathyroid hormone and full-length fibroblast growth factor 23, were followed. Serum calcium levels increased until the fourth week post-transplantation, after which it reached a plateau; and serum phosphate decreased substantially at one week post-kidney transplantation, but recovered to the reference level at two months. Fibroblast growth factor 23 gradually decreased to comparable levels for renal function, while hyperparathyroidism persisted for 12 months after transplantation. Multivariate linear regression analysis revealed that intact parathyroid hormone was the best correlating factor with both hypercalcemia and persistent hypophosphatemia at 12 months. This study suggests the need for testing of other interventions used for treatment of hyperparathyroidism which may help to offer better management of MBD after kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: Mortality and renal or cardiovascular prognosis in living kidney donors (LKDs) has been reported to be as same as the general population; however, it is known that the prevalence of hypertension, albuminuria and metabolic syndrome increases after donation. At present, data from Japanese donors are scarce and as a result the actual medical status of LKDs remains unclear. To evaluate cardiovascular disease (CVD) risk factors in Japanese LKDs, we conducted a cross-sectional study on LKDs at our tertiary care hospital and clinic. Method: Thirty-six out of 63 LKDs who underwent kidney donation at the kidney disease center of the St. Marianna University Hospital were enrolled. The kidney function, albuminuria, and CVD risk factors including hypertension, dyslipidemia, hyperuricemia, glucose intolerance (GI) and obesity were cross-sectionally investigated. Results: The kidney function by inulin clearance was 55.2 ± 10.3 ml/min/1.73 m on average, indicating that 63.9% of LKDs were categorized into chronic kidney disease (CKD) stage 3 after donation. Albuminuria developed in 16.7%. Blood pressure (BP) was not elevated after donation, but ambulatory BP monitoring revealed that 39.4% of LKDs were categorized as having non-dipper type BP. GI was shown in 25% of LKDs. Prevalence of dyslipidemia and hyperuricemia were 41.7% and 27.8%, respectively. Body mass index was not significantly changed after donation. Seven LKDs (19.4%) were diagnosed with metabolic syndrome. Conclusion: Many Japanese LKDs were experiencing decreased kidney function corresponding to CKD stage 3. They also had a significant but not lower prevalence of albuminuria and CVD risk compared to the general Japanese population. LKDs should be followed closely with special attention to the management of renal and CVD risk factors. [ABSTRACT FROM AUTHOR]

Background. Kidney transplantation (KTx) restores many of the disorders accompanying end-stage renal failure. However, hypercalcemia and hypophosphatemia are both common complications after renal transplantation. Prospective observation of these complications has not been well described and pre-transplant predictors also remain unknown. This prospective observational cohort study was carried out to clarify pre-transplant risk factors of persistent hypophosphatemia and/or hypercalcemia at 12 months after transplantation.Methods. Consecutive living donor KTx recipients (n = 39) at Tokyo Women’s Medical University were prospectively recruited. Parameters of bone and mineral metabolism including intact parathyroid hormone (iPTH) and full-length fibroblast growth factor (FGF) 23 were followed.Results. FGF23 decreased to comparable levels for renal function while hyperparathyroidism persisted at 12 months after transplantation. Multivariate linear regression analysis revealed that pre-transplant iPTH correlated with hypercalcemia at 12 months and pre-transplant FGF23 was the best pre-transplant predictor of persistent hypophosphatemia at 12 months.Conclusions. It is intriguing that although FGF23 is not a causal factor for hypophosphatemia at 12 months post-transplantation, it is a significant predictor of this common complication. [ABSTRACT FROM AUTHOR]

Renal prognosis and outcome of Japanese kidney donors, who have lower preoperative glomerular filtration rate (GFR) and are generally older than their counterparts abroad, have scarcely been investigated. Here, the longitudinal changes in renal function of Japanese kidney donors were studied to clarify the prevalence and consequences of low GFR. We reviewed charts of the living kidney donors and followed renal function by estimated GFR (eGFR, ml/min/1.73 m2) from the time of transplantation ( n = 237), until 1 ( n = 162) to 3 years after donation ( n = 77). Median eGFR at the time of transplant was 78.7. GFR declined by approximately 40% at 1 year after donation, and as a result, most (85%) Japanese kidney donors developed chronic kidney disease (CKD) stage 3, with a median eGFR of only 48.0. The result, that the mean change in eGFR at 1–3 years after donation showed a steady increment of 0.97 ml/min/1.73 m2 per year, was distinct from the generally accepted notion that GFR declines with age. This upward change was seen irrespective of the absolute values of eGFR at or 1 year after donation, even including a subgroup with the lowest postoperative eGFR of <40. Most Japanese donors developed CKD stage 3 after donation but without subsequent progression, at least for several years. Although CKD is in general regarded to confer a significant risk for progressive kidney disease, this notion might not apply to living kidney donors with low GFR but without the risk factors for progression. [ABSTRACT FROM AUTHOR]

Total and holo‐enzyme activities of tryptophan 2,3‐dioxygenase were measured in vitro in the presence and absence of the organophosphorous insecticide, dimethoate. Addition of dimethoate to the reaction mixture decreased the activities of both total and holo‐forms. Total and holo‐enzyme activities were decreased by 34% and 26%, respectively, by 1 mM dimethoate. On the other hand, 5 mM dimethoate resulted in 56% and 34% inhibition to total and holo‐enzyme activities, respectively. Lineweaver‐Burk plot of the total‐enzyme activity at different tryptophan concentration in the presence of 2 mM dimethoate gave uncompetitive type of inhibition. [ABSTRACT FROM PUBLISHER]

In order to identify the chromosomal assignment for the human indoleamine 2,3-dioxygenase (IDO) gene, we performed the polymerase chain reaction (PCR) using somatic cell hybrids and screened for the presence of amplified products. The results indicate that the human IDO gene can be assigned to chromosome 8. [ABSTRACT FROM AUTHOR]