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ABSTRACT: The kidney chiefly maintains homeostasis of water, electrolytes, and other solutions. When kidney function is reduced, mineral metabolism is disrupted. Mineral and bone disorder in patients with chronic kidney disease associates with increased cardiovascular risk and mortality; however, management of chronic kidney disease-mineral and bone disorder in predialysis patients remains controversial. This study investigates the association between parathyroid enlargement at dialysis initiation and hyperparathyroidism management in dialysis patients. We enrolled 72 patients at dialysis initiation in this study. Using parathyroid sonography, we categorized patients based on presence (detected group; N = 18) or absence (undetected group; N = 54) of enlarged parathyroid glands and assessed the clinical characteristics and laboratory findings. A literature review of ultrasound evaluations of secondary hyperparathyroidism was conducted. Ultrasonography revealed enlarged parathyroid glands in 18 patients (25%). Serum intact parathyroid hormone levels were high in patients with enlarged parathyroid glands; however, of the 29 patients with intact parathyroid hormone levels <240 pg/mL, four had enlarged parathyroid glands. Eight of the 29 patients with serum phosphorus and calcium levels within the optimal range had enlarged parathyroid glands. Twenty of these 29 patients were followed up at 38 ± 17 months (at least 3 months): enlarged parathyroid glands were detected in 6. During follow-up, serum intact parathyroid hormone levels were significantly higher in the detected group compared with the undetected. In conclusion, enlarged parathyroid glands are frequently detected at dialysis initiation, potentially predicting the persistence of secondary hyperparathyroidism and the need for strict management.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 02/2013; 17(1):24-9. · 1.39 Impact Factor
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ABSTRACT: Background/Aims: Vascular disease is one of the critical complications of diabetes. A growing body of evidence suggests that oxidative stress plays a key role for vascular disease progression. Recent studies have demonstrated a strong link between vitamin D and cardiovascular disease. Methods: We investigated the anti-oxidative effects of a vitamin D analog, 22-oxacalcitriol (maxacalcitol), on vascular lesions in type 2 diabetic rats. We used Spontaneously Diabetic Torii (SDT) rats, a model of non-obese type 2 diabetes. At 20 weeks of age, SDT rats were randomly divided into three groups: diabetes mellitus (DM, n = 10), DM + maxacalcitol (DM + D, n = 10), and DM + insulin (DM + I, n = 10). The rats were sacrificed at 30 weeks for the evaluation of blood and urine samples as well as histopathology and mRNA expression in the aorta. Results: Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion and the number of 8-OHdG-positive cells were significantly lower in the DM + I and DM + D groups than in the DM group. Real-time polymerase chain reaction analysis demonstrated that NADPH p22 phox and NADPH p47 phox mRNA levels were markedly decreased in the DM + I and DM + D groups compared with the DM group. Furthermore, the mRNA expression of MCP-1, ICAM-1 and VCAM-1 was significantly reduced in the DM + I and DM + D groups compared with the DM group. Conclusion: Our results suggest that the vasoprotective effects of vitamin D are mediated by reducing oxidative stress.
American Journal of Nephrology 01/2013; 37(2):167-74. · 2.54 Impact Factor
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ABSTRACT: BACKGROUND: Vascular calcification is associated with mortality and cardiovascular events in patients with chronic kidney disease. AST-120, which adsorbs uremic toxins, is reported to reduce the risk of cardiovascular disease and death in chronic kidney disease patients. The aim of the current study was to investigate the association between abdominal aortic calcification and the use of AST-120 in predialysis chronic kidney disease patients. METHODS: A retrospective analysis was conducted including 199 predialysis chronic kidney disease patients (stages 4 and 5) who underwent abdominal plain computed tomography in our institution between 2005 and 2010. Abdominal aortic calcification was assessed by aortic calcification index (ACI). Patients were divided into two groups based on whether or not AST-120 was administered for at least six months, and ACI was compared between the two groups. RESULTS: The aortic calcification index was significantly lower in patients taking AST-120 [12.2 (2.5-30.3) vs. 25.7 (13.4-45.3) %, P < 0.001]. According to multivariate linear regression analysis, the use of AST-120 was independently and significantly correlated with ACI after adjusting for confounding factors. CONCLUSIONS: The use of AST-120 was independently associated with less aortic calcification in predialysis chronic kidney disease patients.
Clinical and Experimental Nephrology 10/2012; · 1.37 Impact Factor
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ABSTRACT: Coronary artery disease is a serious complication of chronic kidney disease (CKD); however, there is little information about coronary plaque morphology in these patients. Here we identified the characteristics of coronary culprit plaques and their clinical manifestations in 78 patients with CKD divided into four groups based on their estimated glomerular filtration rate. Patients were examined by Virtual Histology-Intravascular Ultrasound, a tomographic imaging method that can visualize atherosclerotic plaques in vivo using radiofrequency analysis of ultrasound backscatter signals. These ultrasound analyses showed an increase in the relative volumes of both dense calcium and necrotic core with decreasing renal function. The necrotic core/dense calcium ratio was significantly higher in patients with acute myocardial infarction compared to those with stable angina pectoris. Furthermore, the necrotic core/dense calcium ratio decreased in advanced CKD. Thus, the plaque composition of coronary culprit lesions changed from necrotic core-rich to extensively calcium-rich plaques as renal function decreased, suggesting that such coronary culprit composition was associated with stability, particularly in advanced CKD.
Kidney International 04/2012; 82(3):344-51. · 6.61 Impact Factor
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ABSTRACT: Cinacalcet effectively reduces elevated levels of parathyroid hormone (PTH) in patients with secondary hyperparathyroidism (SHPT), even those with severe disease for whom parathyroidectomy can be the treatment of choice. The objective of this study was to estimate the cost-effectiveness of cinacalcet treatment in hemodialysis patients with severe SHPT in Japan.
Cost-effectiveness analysis.
Patients with severe SHPT (intact PTH >500 pg/mL) who were receiving hemodialysis in Japan. MODEL, PERSPECTIVE, & TIMEFRAME: A Markov model was constructed from the health care system perspective in Japan. Patients were followed up over their lifetime. Dialysis costs were not included in the base case.
Cinacalcet as an addition to conventional treatment compared to conventional treatment alone. In both arms, patients underwent parathyroidectomy if intact PTH level was >500 pg/mL for 6 months and they were eligible for surgery.
Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).
ICERs for cinacalcet for those who were eligible for surgery and those who were not were $352,631/QALY gained and $21,613/QALY gained, respectively. Sensitivity and scenario analyses showed that results were fairly robust to variations in model parameters and assumptions. In the probabilistic sensitivity analysis, cinacalcet was cost-effective in only 0.9% of simulations for those eligible for surgery, but in more than 99.9% of simulations for those ineligible for surgery, if society would be willing to pay $50,000 per additional QALY.
Data for the long-term effect of cinacalcet on patient-level outcomes are limited. The model predicted rates for clinical events using data for the surrogate biochemical end points.
The use of cinacalcet to treat severe SHPT is likely to be cost-effective for only those who cannot undergo parathyroid surgery for medical or personal reasons.
American Journal of Kidney Diseases 03/2012; 60(2):262-71. · 5.43 Impact Factor
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Shunsuke Goto,
Hideki Fujii,
Keiji Kono,
Kentaro Nakai,
Yasuhiro Hamada,
Hideyuki Yamato,
Masami Shinohara,
Riko Kitazawa,
Sohei Kitazawa,
Shinichi Nishi,
Masafumi Fukagawa
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ABSTRACT: Diabetic bone disease is a major complication in diabetes mellitus and is characterized by low-turnover bone formation. Recent studies have demonstrated that oxidative stress could be associated with diabetic bone disease and that β-adrenergic antagonists could increase bone formation. Our study investigated the effect of carvedilol (β-blocker), possessing an antioxidant effect, on diabetic bone disease.
We used the non-obese, type 2 diabetes model Spontaneously Diabetic Torii (SDT) rats in this study. Sprague-Dawley rats were used as controls (control, n = 6). SDT rats were divided into four groups: diabetic (DM, n = 8), DM+insulin (DM+I, n = 7), DM+carvedilol (DM+C, n = 8), and DM+N-acetylcysteine (DM+N, n = 10) at 20 weeks. The rats were sacrificed at 30 weeks, after which blood and urine samples, bone mineral density, histomorphometry, and oxidative stress were evaluated.
The number of 8-hydroxydeoxyguanosine-positive cells in bone tissue was significantly lower in the DM+C and DM+N groups than in the DM group. Mineral apposition rate and bone formation rate per bone surface in the DM+C and DM+N groups were significantly higher than those in the DM group, and these parameters were better in the DM+C group than in the DM+N group.
Our data suggest that carvedilol has stronger effects on diabetic low-turnover bone disease beyond that which can be attributed to its antioxidative stress mechanism.
American Journal of Nephrology 08/2011; 34(3):281-90. · 2.54 Impact Factor
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Shunsuke Goto,
Hirotaka Komaba,
Kensuke Moriwaki,
Akira Fujimori,
Koji Shibuya,
Masato Nishioka,
Jong-Il Kim,
Kunihiko Yoshiya,
Jeongsoo Shin,
Hirohito Hasegawa,
Masatomo Taniguchi,
Hideki Fujii,
Shinichi Nishi,
Isao Kamae,
Masafumi Fukagawa
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ABSTRACT: Lanthanum carbonate (LC) is a nonaluminum, noncalcium phosphate binder that is effective for hyperphosphatemia in dialysis patients. However, its efficacy and cost-effectiveness as second-line therapy have not been fully examined.
We first conducted a multicenter, open-label, 16-week clinical trial to examine the effect of additive LC in 116 hemodialysis patients who had uncontrolled hyperphosphatemia with conventional phosphorus-lowering therapy alone. Based on these clinical data, a state transition model was developed to evaluate the benefits and costs associated with LC as second-line therapy. Reduced risks for cardiovascular morbidity and mortality among patients treated with LC arise through more of the population achieving the target phosphorus levels. Uncertainty was explored through sensitivity analysis.
After 16 weeks of additive LC treatment, mean serum phosphorus levels decreased from 7.30 ± 0.90 to 5.71 ± 1.32 mg/dl, without significant changes in serum calcium or intact parathyroid hormone levels. A subsequent cost-effectiveness analysis showed that compared with conventional treatment, additive LC incurred an average additional lifetime cost of $22,054 per person and conferred an additional 0.632 quality-adjusted life years (QALYs). This resulted in an incremental cost-effectiveness ratio of $34,896 per QALY gained. Applying a cost-effectiveness threshold of $50,000 per QALY, a probabilistic sensitivity analysis showed that additive LC had a 97.4% probability of being cost-effective compared with conventional treatment.
Our results indicate that the use of LC as second-line therapy would be cost-effective among hemodialysis patients with uncontrolled hyperphosphatemia in Japan.
Clinical Journal of the American Society of Nephrology 06/2011; 6(6):1375-84. · 5.23 Impact Factor
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ABSTRACT: Uremic toxins are associated with various disorders in patients with end-stage renal disease and it is difficult to remove some of these toxins by dialysis. Since some uremic toxins are generated by bacterial metabolites in the colon, oral adsorbents that interfere with the absorption of uremic toxins or their precursors are believed to prevent their accumulation in the body. AST-120 adsorbs various uremic retention solutes in the gastrointestinal system and has potential for providing clinical benefit. Sevelamer hydrochloride binds some harmful compounds in addition to phosphate and seems to have pleiotropic effects that include lowering serum LDL cholesterol levels and reduction of inflammation. The effect of sevelamer hydrochloride on indoxyl sulfate and p-cresol has been shown in an in vitro study; however, in vivo studies in mice or humans did not demonstrate this effect on protein-binding uremic toxins. Oral adsorbents are thus one of the important modalities in the treatment of uremic syndrome.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 04/2011; 15(2):132-4. · 1.39 Impact Factor
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ABSTRACT: Cardiovascular disease (CVD) is a leading cause of death in chronic kidney disease (CKD) patients. One of the proposed mechanisms assumes that accumulated uremic toxins play an important role in the progression of CVD in CKD. Recently, it has been reported that AST-120 may attenuate progression of CVD through absorption of uremic toxins. In this study, we examined the association between the use of AST-120 and cardiac abnormalities in CKD patients.
This was a cross-sectional study of predialysis CKD patients hospitalized in our institution between April 2008 and October 2009. We divided 107 patients into two groups based on whether AST-120 had been administered for more than 6 months (AST-120 group: n = 43) or not (control group: n = 64). Echocardiography and laboratory tests were performed for all patients; we examined the relationship between clinical characteristics and cardiac abnormalities.
The number of patients with left ventricular (LV) concentric change was significantly smaller in the AST-120 group than in the control group. In multivariable analysis, the administration of AST-120, gender, and pulse pressure were significantly correlated with LV concentric change.
Our findings suggest that AST-120 prevents the development of LV concentric change in predialysis CKD patients.
American Journal of Nephrology 02/2011; 33(3):218-23. · 2.54 Impact Factor
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ABSTRACT: Fibroblast growth factor-23 (FGF23) plays a central role in the development of hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D induced by iron therapy for iron-deficiency anemia. The aim of this study was to examine the effect of intravenous saccharated ferric oxide on serum FGF23 levels and mineral metabolism in hemodialysis patients.
This prospective study enrolled 27 hemodialysis patients who had iron-deficiency anemia defined by a hemoglobin concentration < 10.5 g/dl and serum ferritin < 100 ng/ml. Intravenous saccharated ferric oxide at a dose of 40 mg was administered three times weekly over 3 weeks. The dose of active vitamin D and phosphate binders was kept unchanged. Serum FGF23, intact parathyroid hormone (PTH) and other parameters were prospectively monitored for 5 weeks.
Serum FGF23 levels were markedly elevated [3,453 (338-6,383) pg/ml] at baseline. After 3 weeks of intravenous saccharated ferric oxide treatment, serum FGF23 further increased to 4,701 (1,251-14,396) pg/ml, and returned to the baseline values after 2 weeks of observation. There was also a significant decrease in intact PTH but no changes in serum calcium and phosphorus.
Intravenous saccharated ferric oxide induces further increase in elevated FGF23 levels in hemodialysis patients. This increase does not induce hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D in the absence of functioning kidney, but may result in transient PTH suppression - possibly by directly acting on the parathyroid.
American Journal of Nephrology 01/2011; 33(5):421-6. · 2.54 Impact Factor
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Yasuhiro Hamada,
Sohei Kitazawa,
Riko Kitazawa,
Keiji Kono, Shunsuke Goto,
Hirotaka Komaba,
Hideki Fujii,
Yasuhiko Yamamoto,
Hiroshi Yamamoto,
Makoto Usami,
Masafumi Fukagawa
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ABSTRACT: It has been reported that AGEs and the receptor for AGEs (RAGEs) have been linked to the pathogenesis of diabetic microangiopathy. However, the relationship between RAGE and alteration in bone metabolism is unclear. Therefore, in order to determine the role of RAGE in bone metabolism, we investigated the effects of RAGE deletion on bone metabolism under physiological and diabetic conditions using RAGE knockout mice (RAGE-KO). Eight-week-old male RAGE-KO and wild-type littermates (WT) were intraperitoneally injected with either streptozotocin or vehicle. Mice were classified into four groups: (1) nondiabetic WT; (2) nondiabetic RAGE-KO; (3) diabetic WT; and (4) diabetic RAGE-KO. After 12 weeks of streptozotocin or vehicle treatment, the physical properties of femora and the static and dynamic parameters of bone histomorphometry of tibiae were assessed. The deletion of RAGE affected neither body weights nor hemoglobin A1c levels. RAGE deletion resulted in increased bone mineral density due to decreased osteoclast function under physiological conditions that is no accumulation of AGEs. In contrast, lacking RAGE did not affect the alteration in bone metabolism under diabetic conditions, suggesting that AGEs-RAGE interaction may not be involved in the pathogenesis of diabetic osteopenia, although RAGE plays a crucial role in bone metabolism.
Endocrine 10/2010; 38(3):369-76. · 1.42 Impact Factor
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ABSTRACT: Skeletal resistance to parathyroid hormone (PTH) in uremia is known, although the mechanism of resistance is not fully elucidated. To clarify the roles of indoxyl sulfate, which is a uremic toxin, in skeletal resistance, we examined the relationship between indoxyl sulfate and biochemical markers of bone turnover in hemodialysis patients. We obtained blood samples from 47 hemodialysis patients and measured serum indoxyl sulfate, intact PTH, oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), and various biochemical markers. The serum concentrations of alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BAP) were used as bone formation markers, and the concentration of tartrate-resistant acid phosphatase 5b (TRACP-5b) was used as a bone resorption marker. Serum indoxyl sulfate levels were much higher in hemodialysis patients than healthy subjects. Multiple regression analysis shows that indoxyl sulfate correlated negatively with ALP (beta = -1.897, P = 0.042) and BAP (beta = -0.310, P = 0.029), independent of intact PTH; however, indoxyl sulfate did not correlate with TRACP-5b or 8-OHdG. These findings suggest that indoxyl sulfate may relate skeletal resistance to PTH in uremia.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 08/2010; 14(4):417-23. · 1.39 Impact Factor
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ABSTRACT: The role of nitric oxide (NO) is controversial in diabetes nephropathy progression and the mechanisms remain unknown, especially in non-obese type 2 diabetes. To examine mechanisms of nephropathy progression in non-obese type 2 diabetes, we used spontaneously diabetic Torii (SDT) rats, a newly established model of non-obese type 2 diabetes.
Fourteen male Sprague-Dawley rats were used as a control (20 weeks, n = 6; 30 weeks, n = 8), and 20-week-old male SDT rats were divided into 2 groups: diabetic (DM, n = 8) and DM + insulin (n = 8) groups. Twenty- and 36-week-old rats were sacrificed, and blood, urine, and histomorphometric analyses, mRNA expression analysis of endothelial NO synthase (eNOS) and NADPH oxidase, and blood pressure measurement were performed.
At 36 weeks, NO metabolites, and 8-hydroxydeoxyguanosine (8-OHdG) were significantly higher in the diabetic group than in the other 2 groups. Further renal studies showed increased glomerular volume and mesangial area, and intensified eNOS, 8-OHdG, and nitrotyrosine immunostaining in the diabetic group. Oxidative and nitrosative stress were positively associated with increased glomerular volume and mesangial area, which were mostly recovered by insulin therapy.
NO and oxidative stress increased in SDT rats, suggesting that these play key roles in nephropathy progression in non-obese type 2 diabetes.
American Journal of Nephrology 03/2010; 31(4):342-52. · 2.54 Impact Factor
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Hirotaka Komaba, Shunsuke Goto,
Hideki Fujii,
Yasuhiro Hamada,
Akira Kobayashi,
Koji Shibuya,
Yoshihiro Tominaga,
Naoki Otsuki,
Ken-Ichi Nibu,
Kimie Nakagawa,
Naoko Tsugawa,
Toshio Okano,
Riko Kitazawa,
Masafumi Fukagawa,
Tomoyuki Kita
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ABSTRACT: Fibroblast growth factor 23 (FGF23) exerts its effect by binding to its cognate FGF receptor 1 (FGFR1) in the presence of its co-receptor Klotho. Parathyroid glands express both FGFR1 and Klotho, and FGF23 decreases parathyroid hormone gene expression and hormone secretion directly. In uremic patients with secondary hyperparathyroidism (SHPT), however, parathyroid hormone secretion remains elevated despite extremely high FGF23 levels. To determine the mechanism of this resistance, we measured the expression of Klotho, FGFR1, and the proliferative marker Ki67 in 7 normal and 80 hyperplastic parathyroid glands from uremic patients by immunohistochemistry. All uremic patients had severe SHPT along with markedly high FGF23 levels. Quantitative real-time reverse transcription PCR showed that the mRNA levels for Klotho and FGFR1correlated significantly with their semi-quantitative immunohistochemical intensity. Compared with normal tissue, the immunohistochemical expression of Klotho and FGFR1 decreased, but Ki67 expression increased significantly in hyperplastic parathyroid glands, particularly in glands with nodular hyperplasia. These results suggest that the depressed expression of the Klotho-FGFR1 complex in hyperplastic glands underlies the pathogenesis of SHPT and its resistance to extremely high FGF23 levels in uremic patients.
Kidney International 11/2009; 77(3):232-8. · 6.61 Impact Factor
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ABSTRACT: Fabry disease (FD) is a rare disease and one of the causes of progressive renal dysfunction. It results from an X-linked deficiency of alpha-galactosidase A activity. It has been reported that its prevalence is much higher in hemodialysis patients than in the general population. However, its prevalence in Japanese hemodialysis patients and cardiovascular manifestations remain unclear.
We screened the alpha-galactosidase A activity of 1,024 Japanese hemodialysis patients using a dried blood spot test. Patients with a low alpha-galactosidase A activity were assessed clinically, and a genetic study of the alpha-galactosidase A gene was performed for these patients. Furthermore, patients with FD underwent detailed cardiovascular examination.
Forty-six patients had low alpha-galactosidase A activity, and 1 man and 2 women had alpha-galactosidase A mutations (0.29%). All of these patients had a previously identified mutation (E66Q). The result of detailed cardiovascular examination showed that 2 patients had significantly impaired coronary flow reserve, reduced myocardial contraction and relaxation tissue Doppler velocities, and left ventricular hypertrophy.
Measurement of the alpha-galactosidase A activity and the results of a genetic analysis indicated that the prevalence of FD in our hemodialysis patients was 0.29% (0.16% in men and 0.5% in women). Furthermore, comprehensive examination detected cardiovascular abnormalities in Japanese hemodialysis patients with FD.
American Journal of Nephrology 10/2009; 30(6):527-35. · 2.54 Impact Factor
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ABSTRACT: Secondary hyperparathyroidism is one of the most popular complications in patients with chronic kidney disease. Phosphate retention, decreasing 1,25-dihydroxyvitamin D3, and hypocalcemia with kidney dysfunction stimulate the secretion of parathyroid hormone. Persistent hyperparathyroidism leads to the development of parathyroid hyperplasia, thereby resisting to medical therapy. Fibroblast growth factor (FGF) 23, which is the novel phosphaturic hormone, increases in patients with chronic kidney disease. In the early stage of chronic kidney disease, high serum FGF23 levels increase the excretion of phosphate, thereby improving hyperphosphatemia due to chronic kidney disease. However, it is not fully elucidated how high serum FGF23 levels effect secondary hyperparathyroidism in end-stage renal failure. Further studies will be necessary to clarify the pathophysiology of secondary hyperparathyroidism in chronic kidney disease.
Clinical calcium 07/2009; 19(6):809-14.
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ABSTRACT: Measurement of bioactive parathyroid hormone (PTH) is essential for the optimal management of secondary hyperparathyroidism and its associated bone disorders in chronic kidney disease (CKD) patients. For this purpose, three generations of increasingly specific PTH assays have been developed over the last 4 decades. To date, however, only second-generation PTH assays are most widely used, although these have been shown to cross-react with large PTH fragments having a partially preserved N-structure, mostly PTH(7-84). The newly developed third-generation PTH assays are believed to be the most specific means of measuring PTH(1-84), but their clinical utility remains debatable. More recently, these latter assays have also been shown to react with a new N-form of PTH, which has been identified in patients with severe hyperparathyroidism and parathyroid carcinoma. Progressive research in this area has advanced our understanding considerably regarding the circulating molecular forms of PTH and their pathophysiological roles in bone abnormalities associated with CKD. However, developing an ideal PTH assay continues to be difficult because of key issues such as the reliability of PTH as a surrogate marker for bone turnover, practicality of employing third-generation PTH assays, and unknown biological implications of N-PTH and other PTH fragments. Further research exploring these issues is mandatory to understand and optimally manage parathyroid disorders and bone abnormalities in CKD patients.
Bone 01/2009; 44(4):666-70. · 4.02 Impact Factor
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NDT Plus 08/2008; 1(suppl 3):iii2-iii8.
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Hirotaka Komaba,
Naoya Igaki,
Mototsugu Takashima, Shunsuke Goto,
Kazuki Yokota,
Hisako Komada,
Toshiyuki Takemoto,
Maki Kohno,
Hiraku Kadoguchi,
Yoshiaki Hirosue,
Takeo Goto
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ABSTRACT: Mineral and bone disorders frequently cause cardiovascular complications and mortality in hemodialysis patients, but few observational studies of Japanese patients have investigated this matter. A retrospective cohort study of 99 patients (53 males, 46 females; mean age: 65 +/- 12 year; 38% with diabetes mellitus) on maintenance hemodialysis in our dialysis center was conducted. Mean serum Ca, P and intact parathyroid hormone (iPTH) levels were 9.2 +/- 0.9 mg/dL, 6.1 +/- 1.7 mg/dL, and 233 +/- 333 pg/mL, respectively. The cutoff values for each of these three parameter were defined according to the target ranges recommended by the Japanese Society for Dialysis Therapy (JSDT) guidelines (Ca: 8.4-10.0 mg/dL; P: 3.5-6.0 mg/dL; iPTH: 60-180 pg/mL). During a 45-month follow up, patients with all parameters outside the target ranges showed the highest incidence of cardiovascular events and all-cause deaths (16.6 and 29.2 per 1000 person-years, respectively). The relative risks of cardiovascular events and all-cause deaths were analyzed by multivariate Cox regression models. The hazard ratio (HR) for cardiovascular events was significantly lower for patients who achieved serum Ca and P objectives compared with others (HR: 2.12; 95% CI: 1.04-4.34; P < 0.05), and similar differences were observed for all-cause deaths (HR: 3.10; 95% CI: 1.13-8.53; P < 0.05). However, the relationship between iPTH levels and each of the endpoints was less pronounced. The results of this study provide support for the JSDT guidelines, which give priority to the control of serum Ca and P levels over the control of parathyroid function.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 02/2008; 12(1):42-8. · 1.39 Impact Factor
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ABSTRACT: Disturbances in mineral and bone metabolism due to loss of kidney function greatly influence morbidity and quality of life, so Kidney Disease: Improving Global Outcomes (KDIGO) proposed the concept of chronic kidney disease-mineral and bone disorder (CKD-MBD). Japanese Society for Dialysis Therapy has created guidelines for the management of secondary hyperparathyroidism associated prognosis in hemodialysis patients, and we are managing parathyroid function of hemodialysis patients under this guideline. Bone biopsy is not recommended as part of routine evaluation for CKD-MBD because bone biopsy is the invasive examination. KDIGO proposed new histological classification of renal osteodystrophy, TMV classification, for standardizing a result of bone histomorphometry. We expect that new guideline improve the prognosis of hemodialysis patients.
Clinical calcium 01/2008; 17(12):1830-4.
