Clinical and experimental nephrology, Feb 25, 2024
Background Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 2... more Background Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA. Methods In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0 g/dL; and serum ferritin < 50 ng/mL [CKD]; < 12 ng/mL [non-CKD]) were randomized 1:1 to FC-low (500 mg: approximately 120 mg elemental iron/day) or FC-high (1000 mg: approximately 240 mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued. Results Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were −58.00 RU/mL in CKD and −725.00 RU/mL in non-CKD; in FC-high group, the median changes were −66.00 RU/mL in CKD and −649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 10 4 /µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD). Conclusion Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA. Clinical trial registration number jRCT2080223943. Keywords Chronic kidney disease (CKD) • Ferric citrate hydrate • Fibroblast growth factor 23 (FGF23) • Iron deficiency anemia (IDA) • Platelet count (PLT)
Background/Aims: The current treatment for anemia associated with chronic kidney disease (CKD) in... more Background/Aims: The current treatment for anemia associated with chronic kidney disease (CKD) includes the administration of erythropoiesis stimulating agents (ESAs) combined with iron supplementation. Molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, has potential to treat anemia associated with CKD through increased erythropoietin production and improved iron availability. Here, we report the effect of molidustat on iron metabolism. Method: Parameters of iron metabolism were monitored in three 16-week, randomized, controlled, phase 2 studies assessing the safety and efficacy of molidustat in the treatment of anemia associated with CKD in different populations: treatment-naïve and previously ESA-treated patients not on dialysis, and previously ESA-treated patients on hemodialysis. Iron supplementation was left at the discretion of the investigator. Results: In treatment-naïve patients not on dialysis, transferrin saturation (TSAT), hepcidin, ferritin, and iron c...
Background The impact of length of hospital stay on activities of daily living (ADLs) has not spe... more Background The impact of length of hospital stay on activities of daily living (ADLs) has not specifically been investigated among dialysis patients. Therefore, we attempt to verify the association between the length of hospital stay and decline in ADLs among hemodialysis patients. Methods This prospective cohort study used data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS). We included 2,442 hemodialysis patients aged more than or equal to 40 years from the J-DOPPS phase V (2012–2015) and then excluded those who were not independent in more than three of the five basic activities of daily living (BADLs) and for whom changes in ADLs were evaluated for less than 90 days. The main exposure was the cumulative length of hospital stay during the follow-up period. The main outcomes were a decline in at least one of the five BADLs and eight instrumental activities of daily living (IADLs). We compared risk ratios (RRs) for 30-day increments in hospital stay with ...
The article, ''The cardiothoracic ratio and all-cause and cardiovascular disease mortality in pat... more The article, ''The cardiothoracic ratio and all-cause and cardiovascular disease mortality in patients undergoing maintenance hemodialysis: results of the MBD-5D study'',
The incidence of cardiovascular disease (CVD) is higher in patients with chronic kidney disease (... more The incidence of cardiovascular disease (CVD) is higher in patients with chronic kidney disease (CKD) than in the general population, and the risk of CVD increases with reductions in renal function. However, the incidence of CVD in Japanese patients with CKD has not been sufficiently investigated. To measure this we conducted the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study over four years in 2,966 Japanese patients with CKD to examine the incidence of CVD and all-cause death. These patients had an estimated glomerular filtration rate (eGFR) of 10-59 ml/min/1.73 m 2 , were under nephrologist care, and pooled from 17 medical institutions in Japan. At the median follow-up of 3.9 years, 69 patients had died, 217 had cardiovascular events, and 514 started maintenance dialysis therapy. The incidences of cardiovascular events were 11.9, 19.1, 25.0, and 39.4 per 1,000 person-years at eGFRs of 45-59, 30-44, 15-29, and under 15 ml/min/ 1.73 m 2 , respectively. The adjusted Cox proportional hazards models showed that the risk of cardiovascular events increased as the eGFR decreased, with a significant difference only between CKD stage G5 (eGFR: under 15 ml/min/1.73 m 2 ) and CKD stage G3a (eGFR: 45-59 ml/min/1.73 m 2 ) (hazard ratio 3.16, 95% confidence interval 1.28 to 7.76). Thus, the risk of CVD and all-cause death was related to the decrease in eGFR, but not necessarily elevated in proportion to progression of the CKD stage in Japanese patients with predialysis CKD under a nephrologist's care.
More than 2 million people worldwide are being treated for end-stage kidney disease (ESKD). This ... more More than 2 million people worldwide are being treated for end-stage kidney disease (ESKD). This Series paper provides an overview of incidence, modality use (in-centre haemodialysis, home dialysis, or transplantation), and mortality for patients with ESKD based on national registry data. We also present data from an international cohort study to highlight differences in haemodialysis practices that affect survival and the experience of patients who rely on this therapy, which is both life-sustaining and profoundly disruptive to their quality of life. Data illustrate disparities in access to renal replacement therapy of any kind and in the use of transplantation or home dialysis, both of which are widely considered preferable to in-centre haemodialysis for many patients with ESKD in settings where infrastructure permits. For most patients with ESKD worldwide who are treated with in-centre haemodialysis, overall survival is poor, but longer in some Asian countries than elsewhere in t...
［Objective］To examine the influence of ischemic heart disease(IHD)against poor mental health(MH)i... more ［Objective］To examine the influence of ischemic heart disease(IHD)against poor mental health(MH)in dialysis patients. ［Methods］Subjects consisted of 50 patients with end-stage renal failure who underwent regular hemodialysis in a hospital affiliated with Showa University Hospital. MH was estmated by the MH score on SF-36v2.0. Moreover, depressive symptoms were assessed by the Center for Epidemiologic Studies-Depression (CES-D)Scale. All subjects underwent SF-36v2.0, CES-D Scale, clinical and laboratory tests, and were divided into two groups(IHD group or non-IHD group).［Results］Morbidity due to diabetes mellitus and serum levels of high sensitive C-reactive protein were significantly higher, and MH scores were significantly lower in patients in the IHD group. Stepwise regression analysis demonstrated that the history of IHD had a significant impact on MH score in hemodialysis patients.［Conclusion］These findings suggest that IHD may be involved in poor MH among hemodialysis patients. Ischemic heart disease may be associated with poor mental health in hemodialysis patients 【目的】透析患者を対象として，虚血性心疾患(IHD)の存在が患者のメンタルヘルスに及ぼす影響について検討 した． 【対象・方法】昭和大学病院の関連施設で治療中の維持透析患者 50 名を対象とした．メンタルヘルスの指標 は SF-36v2.0 の下位尺度 8 項目の中から Mental health(MH)score にて，うつ症状は Center for Epidemiologic Studies-Depression(CES-D)Scale にて検討した．これらの検査と同時期の週初め透析前に患者背景の調査，各 種血液検査を施行した． 【結果】IHD 群は non-IHD 群と比較して，高い糖尿病罹患率，高感度 CRP 値を認めた．さ らに，IHD 群は non-IHD 群と比較し，MH score の有意な低下を認めた．また IHD 群は，統計学的有意差はないも のの non-IHD 群と比較し高い CES-D score を認めた．ステップワイズ重回帰分析を行った結果，IHD の存在が MH score に対する有意な説明変数となった(p＜0.
The SF-36v2 (version 2 of the SF-36 health survey) is an instrument used worldwide to measure the... more The SF-36v2 (version 2 of the SF-36 health survey) is an instrument used worldwide to measure the generic health-related quality of life (HQOL). The SF-36v2 has "standard" and "acute" forms, in which respondents are asked about the previous month and the previous week, respectively. The standard form of the Japanese-language version of the SF-36v2 has already been validated, but the acute form has not. We evaluated the validity and reliability of the Japanese SF-36v2 acute form in patients with chronic kidney disease (CKD). Cross-sectional data from 210 CKD patients who enrolled a clinical trial of a long-acting erythropoiesis stimulating agent (darbepoetin alfa) were analyzed. The feasibility of question items and distributions of the response choices were examined. Cronbach's alpha was computed to assess internal-consistency reliability. Construct validity was evaluated with tests of convergent and discriminant validity, and with factor analysis. Validity w...
Treatment(JET)Study was carred out to evaluate the relationship between maintenance of Hb levels ... more Treatment(JET)Study was carred out to evaluate the relationship between maintenance of Hb levels and patient prognoses after the first application of epoetin beta formulation(Epogin)to new hemodialysis patients. Using data collected up until June 2007, we examined the baseline characteristics of patients on the first day of hemodialysis and the status of anemia treatment 3 months later. As a result, it was noted that many patients demonstrated some cardiovascular histories or complications and the mean Hb level at introduction to hemodialysis was relatively low compared to that in Europe or the US.
Percutaneous ethanol injection therapy (PEIT) of the parathyroid was originally introduced as an ... more Percutaneous ethanol injection therapy (PEIT) of the parathyroid was originally introduced as an alternative to surgical parathyroidectomy. After the recent elucidation of the pathogenesis of parathyroid hyperplasia in uraemia, 'selective PEIT of the parathyroid glands' was developed, in which enlarged parathyroid glands with nodular hyperplasia are 'selectively' destroyed by ethanol injection, and other glands with diffuse hyperplasia are then managed by medical therapy. The 'Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients' proposed by the Japanese Society for Parathyroid Intervention are presented, including indications, techniques, and post-PEIT management. These guidelines also apply to direct injection therapy using drugs other than ethanol, such as calcitriol and 22-oxacalcitriol.
Background. Vascular calcification is a highly regulated process. Tumor necrosis factor-a (TNF-a)... more Background. Vascular calcification is a highly regulated process. Tumor necrosis factor-a (TNF-a) has been shown to accelerate the highly regulated osteogenic process in vascular smooth muscle cells (VSMCs). Vitamin D receptor activators (VDRAs) have been associated with beneficial cardiovascular outcomes in patients with chronic kidney disease. We examined whether maxacalcitol, a vitamin D 3 analog, exhibits a suppressive effect on VSMC mineralization induced by phosphate and TNF-a. Methods. Human VSMCs were treated with either vehicle, maxacalcitol (10 À9 to 10 À7 M), or calcitriol (10 À9 to 10 À7 M) in 2.5 mM of phosphate media with TNF-a (1 ng/mL) for 9 days. VSMC mineralization was determined and expression of genes associated with the osteogenic process was examined by real-time reverse transcription-polymerase chain reaction. Expression of 1800
Intermittent high dose administration of calcitriol or alfacalcidol is effective in suppressing s... more Intermittent high dose administration of calcitriol or alfacalcidol is effective in suppressing secondary hyperparathyroidism in chronic dialysis patients, however calcaemic action of these vitamin D derivatives is a major obstacle. 22-Oxacalcitriol (OCT) has been reported to have less calcaemic action than calcitriol, while preserving a comparable suppressive effect on parathyroid hormone (PTH) secretion. This preliminary study was conducted to examine the effects of OCT on secondary hyperparathyroidism in chronic dialysis patients. OCT was administrated intravenously immediately after every haemodialysis session three times a week for 12 weeks to three haemodialysis patients with secondary hyperparathyroidism. An initial dose of OCT of 5.5 ug/haemodialysis session was increased stepwise by 5.5 ug/haemodialysis up to 22 ug/haemodialysis according to the suppression of PTH and calcaemic action. OCT was discontinued for at least a week when serum calcium adjusted to albumin concentration measured just before haemodialysis exceeded 11.5 mg/dl. Marked reduction in plasma PTH, alkaline phosphatase and tartrate-resistant acid phosphatase was observed in all three patients. Although the dose of OCT was increased to 22 ug/haemodialysis in one patient, the final dose of OCT remained 5.5 ug/haemodialysis in the other two patients because of hypercalcaemia. It is concluded that OCT is highly effective in suppressing PTH in dialysis patients with secondary hyperparathyroidism. Hypercalcaemia may be a major factor which limits the use of OCT, though it may occur with higher doses of OCT than those of calcitriol usually given to suppress PTH hypersecretion.
PTH is a major mediator of bone and mineral metabolism. However, physiological and pathological i... more PTH is a major mediator of bone and mineral metabolism. However, physiological and pathological investigations of parathyroid cells (PTCs) have been limited because of the lack of available cell lines and because the organ is too small for detailed studies. Here, we describe a novel method for adenovirus-mediated cDNA transfer into PTCs, and we show the accuracy of the method in a rat model of uremia-induced secondary hyperparathyroidism. Rats underwent a 5/6-nephrectomy and were fed with a high-phosphate diet for 8 wk. The parathyroid glands were surgically exposed and adenoviruses containing LacZ or Ca-sensing receptor (CaSR) were directly injected into the glands under a zoom-stereo microscope. The parathyroid glands were analyzed for infection of adenovirus and immunohistochemically for expression of CaSR. The functional activity of exogenous CaSR in PTCs after this treatment was investigated based on changes of the calcium and PTH curve. A virus concentration of more than 109 p...
Uploads
Papers by Tadao Akizawa