Greater level of parathyroid hormone (PTH) than healthy subject is required to maintain appropriate bone turnover in dialysis patients. The skeletal resistance to PTH is the most important genesis of this phenomenon and the mechanism has been elucidated by the recent molecular biological techniques. Insufficient level of PTH induces not only adynamic bone disease but also cardiovascular diseases by ectopic calcification in soft tissues. Cardiovascular calcification is an important risk factor for the prognosis of dialysis patients, so the development of new therapeutic tools, that can adequately control PTH levels without hypercalcemia and hyperphosphatemia, are expected.

Bone Diseases↗

PubMed2004

[Outlines of K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease].

Recently "K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease" was published. It consists of sixteen precise guidelines which cover the wide range of this field. It is expected that these guidelines contribute ESRD treatment in Japan in spite of some differences in medical practice for dialysis therapy between Japan and the United States. This article briefly summarizes the outlines of these guidelines.

Absorptiometry, Photon↗

PubMed2004

[K/DOQI clinical practice guidelines for bone metabolism and disease in CKD].

K/DOQI (Kidney Disease Outcome Quality Initiative) Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease were published last year. The Work Group screened enormous amount of articles and made up of sixteen guidelines for Bone metabolism and disease in Chronic Kidney Disease. This review provides brief an overview of guidelines with strong emphasis on vitamin D.

Aluminum↗

PubMed2003

Management of secondary hyperparathyroidism of dialysis patients.

Hyperphosphatemia, vitamin D deficiency, and resulted hypocalcemia have been regarded as classical pathogeneses of secondary hyperparathyroidism. These factors have been treated by the administration of phosphorus binder and vitamin D derivatives. However, these therapies have not brought about a successful result for the prevention and treatment of secondary hyperparathyroidism. The reason could be mainly attributed to the hypercalcemia that results from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium containing phosphorus binder (sevelamer hydrochloride) and vitamin D analogues, which suppress PTH secretion with minimum calcemic action, have been developed. These new vitamin D analogues include 19-nor-1-alpha, 25-dihydroxyvitamin D2 (paricalcitol), 1-alpha-hydroxyvitamin D2 (doxercalciferol), 22oxa-calcitriol (maxacalcitol) and F6-calcitriol (falecalcitriol). Furthermore, calcimimetics that stimulate calcium-sensing receptor of parathyroid cells as calcium and suppress PTH secretion are now under clinical trial. Percutaneous direct injection therapy of vitamin D, vitamin D analogue or calcimimetics into parathyroid gland has also been reported. The combination of these new strategies is expected to effectively and safely suppresses secondary hyperparathyroidism that has been resistant to conventional medical treatments.

Ethanol↗

PubMed2003

Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia.

BACKGROUND: A high level of parathyroid hormone (PTH) is considered to be an indicator of poor prognosis and a poor quality of life of dialysis patients; therefore, an effective and safe therapy for secondary hyperparathyroidism (SHPT) has been developed. METHODS: In 20 patients with SHPT resistant to maxacalcitol (OCT) intravenously administered, all detectably enlarged parathyroid glands were treated by percutaneous maxacalcitol injection therapy (PMIT) under ultrasonographic guidance consecutively 6 times, which was followed by OCT that was intravenously administered. The clinical effects of PMIT were evaluated based on the changes in the serum intact-PTH, adjusted Ca, phosphorus, and bone marker levels, and the parathyroid gland volume determined by ultrasonography. Morphologic examination, apoptosis analysis, and PTH mRNA expression level determination by reverse transcription-polymerase chain reaction (RT-PCR) using parathyroid tissues obtained by a biopsy technique were performed. RESULTS: PMIT and subsequent intravenous OCT administrations significantly decreased the serum intact-PTH level and parathyroid gland volume for at least 12 weeks after PMIT without major complications. Parathyroid tissues obtained after PMIT exhibited some partial defects of parathyroid cells, a marked increase in the number of the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells, the ladder formation determined by DNA electrophoresis, and the decrease in the PTH mRNA expression level. CONCLUSION: PMIT is effective and safe for the treatment of refractory SHPT, and a locally high level of OCT suppresses PTH secretion and regresses parathyroid hyperplasia, which is involved in the induction of apoptosis of parathyroid cells.

Administration, Cutaneous↗

PubMed2003

Effect of beta(2)-microglobulin adsorption column on dialysis-related amyloidosis.

BACKGROUND: beta2-microglobulin (beta2-m) is considered a major pathogenic factor in dialysis-related amyloidosis (DRA), often seen in long-term dialysis patients. No effective therapy for this severely debilitating disease is currently available. Lixelle, an adsorption column, has been developed for the elimination of beta2-m; the efficacy of this column has been evaluated in this study. METHODS: Seventeen hemodialysis patients with DRA were first treated with high-flux dialysis for a minimum of 1 year. This was followed by 1-year treatment with Lixelle column connected in series to the high-flux dialyzer. Treatments were used three times a week for both phases of this study. During the study period, beta2-m, pinch strength, motor terminal latency, and activities of daily living were evaluated. RESULTS: After 1-year treatment with high-flux dialysis the beta2-m level remained unchanged; however, after 1-year treatment with the addition of the Lixelle column, beta2-m level decreased significantly from 34.5 +/- 8.4 mg/L to 28.8 +/- 7.3 mg/L (P < 0.05). After 1 year of Lixelle column use, the pinch strength increased from 6.8 +/- 4.7 pounds to 9.1 +/- 5.5 pounds (P < 0.01), and the median motor terminal latency was significantly reduced from 5.1 +/- 1.0 mseconds to 4.5 +/- 1.1 mseconds. A significant improvement was also observed in the activities of daily living score of the upper extremities. CONCLUSION: These results suggest that the addition of Lixelle to the high-flux dialyzer is associated with a significant clinical improvement in DRA patients.

Adsorption↗

PubMed2003

Health-related quality of life among dialysis patients on three continents: the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: Assessing health-related quality of life (HRQOL) can provide information on the types and degrees of burdens that afflict patients with chronic medical conditions, including end-stage renal disease (ESRD). Several studies have shown important international differences among ESRD patients treated with hemodialysis, but no studies have compared these patients' HRQOL. Our goal was to document international differences in HRQOL among dialysis patients and to identify possible explanations of those differences. METHODS: We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational, international study of hemodialysis patients. We performed a cross-sectional analysis of DOPPS data from the United States, five countries in Europe (France, Germany, Italy, Spain, and the United Kingdom), and Japan. Linear mixed models were used to analyze differences in HRQOL, using the KDQOL-SFTM. Norm-based scores were used to minimize cultural response bias. Linear regression analysis was used to adjust for confounding factors. Other variables included demographic variables, comorbidities, primary cause of ESRD, complications of ESRD and treatment, and socioeconomic status. RESULTS: In all generic HRQOL subscales, patients on all three continents had much lower scores than their respective population norm values. Patients in the United States had the highest scores on the mental health subscale and the highest mental component summary scores. Japanese patients reported better physical functioning than did patients in the United States or Europe, but they also reported the greatest burden of kidney disease. Overall, these differences remained even after adjusting for possible confounders. CONCLUSION: On all three continents, ESRD and hemodialysis profoundly affect HRQOL. In the United States, the effects on mental health are smaller than in other countries. Japanese hemodialysis patients perceived that their kidney disease imposes a greater burden, but their physical functioning was significantly higher. Different distributions of socioeconomic factors and major comorbid conditions could explain little of this difference in physical functioning. Other possible factors, such as quality of dialysis and related health care, deserve careful study.

Cost of Illness↗

PubMed2003

Creation, cannulation and survival of arteriovenous fistulae: data from the Dialysis Outcomes and Practice Patterns Study.

BACKGROUND: An arteriovenous (A-V) fistula is the optimal vascular access for hemodialysis. The National Kidney Foundation Dialysis Outcomes Quality Initiative (DOQI) recommends that fistulae should mature for at least one month before cannulation, but this recommendation is not evidence-based. If fistulae are created prior to ESRD and cannulation is possible earlier without compromising fistula survival, the need for temporary catheters would be reduced. METHODS: Prospective observational data were analyzed for a random sample (N = 3674) of incident patients at the time of initiating hemodialysis, hemofiltration or hemodiafiltration in 309 facilities in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States, taking part in the Dialysis Outcomes and Practice Patterns Study (DOPPS). RESULTS: Although the proportion of patients who had pre-dialysis care by a nephrologist differed little between countries, there were large variations in the proportion of patients who commenced hemodialysis via an A-V fistula, A-V graft or central venous catheter. The usual time interval between referral and creation of A-V fistulae also differed greatly between countries. For new hemodialysis (HD) patients initiating HD with an A-V fistula (N = 894) the following results were observed: (1). median time to first cannulation varied greatly between countries: Japan and Italy (25 and 27 days), Germany (42 days), Spain and France (80 and 86 days), UK and US (96 and 98 days). (2). No association was found between cannulation 28 days for patient characteristics of age, gender, and fifteen different classes of patient co-morbid factors. (3). Risk of A-V fistula failure was increased for incident patients who had a prior temporary access [relative risk (RR) = 1.81, P = 0.01] or who were female (RR = 1.52, P = 0.02). (4). Cannulation 14 days. (5) No significant difference in A-V fistula failure was seen for fistulae cannulated in 15 to 28 days compared with 43 to 84 days. CONCLUSION: Significant differences in clinical practice currently exist between countries regarding the creation of A-V fistulae prior to starting hemodialysis and the timing of initial cannulation. Cannulation within 14 days of creation is associated with reduced long-term fistula survival. Fistulae ideally should be left to mature for at least 14 days before first cannulation.

Adolescent↗

PubMed2003

Clinical analysis of renoprotective responding patients administrated with oral adsorbent in chronic renal failure secondary to chronic glomerulonephritis.

UNLABELLED: An oral adsorbent (AST-120) that removes uremic toxin has attenuated the progression of renal dysfunction. Although there were decreased serum creatinine (Scr) levels observed during administration, it is expected that the action of an oral adsorbent is different according to the patient. In the present study, the difference in the background was clarified. METHODS: A total of 842 patients whose Scr had increased from 3.8 to 4.8 mg/dL during the prior 5.2 months were investigated. Antihypertensive medications and dietary protein intake were unmodified during 6 months administration. The patients were divided into three efficacy groups based on the changes in Scr level: those who had a decrease in Scr were grouped as Group A (N = 290), while those with a < 1.5-fold increase were defined as Group B (N = 428) and those with a > or = 1.5-fold increase were defined as Group C (N = 124). RESULTS: Before administration, these three groups were indistinguishable by the Scr level. No Group A patient went onto dialysis, whereas 12% and 40% of Group B and C patients, respectively, required dialysis. In Group A, the slopes of 1/Scr over time, serum urea nitrogen, uric acid, phosphate, total protein, and diastolic blood pressure were all improved. Group B improved moderately and Group C showed less improvement. CONCLUSIONS: In this study, a fairly large number of patients (29% of the population) were believed to be the first case to report the reversibility of severe chronic renal failure. Except in patients with hypoproteinemia, hypercholesterolemia, anemia or hypertension, AST-120 either attenuates or arrests the progression in patients with severe chronic glomerulonephritis.

Administration, Oral↗

PubMed2003

Effect of combined treatment of oral sorbent with protein-restricted diet on change of reciprocal creatinine slope in patients with CRF.

BACKGROUND: Low-protein diet (LPD) is one therapy and AST-120, an oral carbon adsorbent, is the other therapy to reduce blood levels of indoxyl sulfate in patients with chronic renal failure (CRF). Based on the different mechanisms of reducing indoxyl sulfate levels, the addition of AST-120 to an LPD was investigated. METHODS: Seven hundred twenty-two patients with chronic glomerulonephritis (CGN) and 162 patients with diabetic nephropathy (DN) were stratified by protein intake: less than 0.50 g/kg/d (0.50-g/kg/d group), 0.51 to 0.65 g/kg/d (0.65-g/kg/d group), and 0.66 to 0.80 g/kg/d (0.80-g/kg/d group). To analyze the effect of combined AST-120 therapy (6 g/d) in patients on LPD therapy, the slope of the reciprocal of serum creatinine (1/Cr slope), which represents progression of CRF, was applied. RESULTS: (1) In patients with CGN, the addition of AST-120 with an LPD was as follows: the 1/Cr slope in the 0.50-g/kg/d (n = 152), 0.65-g/kg/d (n = 318), and 0.80-g/kg/d (n = 252) groups changed significantly from -430 x 10(-5) to -83 x 10(-5), -333 x 10(-5) to -102 x 10(-5), and -431 x 10(-5) to -116 x 10(-5) dL/mg/wk. (2) In patients with DN, the addition of AST-120 with an LPD was as follows: the 1/Cr slope in the 0.65-g/kg/d (n = 74) and 0.80-g/kg/d (n = 68) groups changed significantly from -602 x 10(-5) to -125 x 10(-5) and -646 x 10(-5) to -185 x 10(-5) dL/mg/wk. CONCLUSION: It is suggested that the addition of AST-120 to a mild LPD provides the comparable effect with a strict LPD in the point of suppressing the progress of CRF.

Administration, Oral↗

PubMed2003

New strategies for the treatment of secondary hyperparathyroidism.

Classic pathogeneses of secondary hyperparathyroidism (2HPT), hyperphosphatemia, vitamin D deficiency, and hypocalcemia, have been treated by the administration of phosphorus binders and vitamin D derivatives. However, these therapies have not brought about a successful result. The main reason could be attributed to hypercalcemia resulting from the administration of calcium salts as a phosphorus binder and the calcemic action of vitamin D. To prevent hypercalcemia, non-calcium-containing phosphorus binders and vitamin D analogues, which suppress parathyroid hormone (PTH) secretion with minimum calcemic action, have been developed. Furthermore, calcimimetics that stimulate the calcium-sensing receptor of parathyroid cells and suppress PTH secretion are now under clinical trial. Direct injection therapy of vitamin D analogues or calcimimetics into the parathyroid gland also has been reported. These new strategies are expected to effectively and safely suppress 2HPT, which has been resistant to conventional medical treatments.

Animals↗

PubMed2003

Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients.

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.

Ethanol↗

PubMed2003

Effect of percutaneous calcitriol injection therapy on secondary hyperparathyroidism in uraemic patients.

BACKGROUND: The impetus to develop percutaneous calcitriol injection therapy (PCIT) was the lack of therapeutic tools to treat secondary hyperparathyroidism (2HPT) resistant to medical therapy. METHODS: Nine dialysis patients resistant to intravenous calcitriol or calcitriol analogues underwent daily PCIT 5-10 times consecutively. The PCIT involved the injection of a volume of calcitriol equal to that of the enlarged parathyroid glands (PTGs) under ultrasonographic guidance. All patients had follow-up intravenous calcitriol after PCIT. RESULTS: The serum intact PTH concentration was markedly reduced following PCIT and was maintained for 12 weeks with intravenous calcitriol without significant changes in serum adjusted calcium and phosphorus concentrations. All patients tolerated PCIT without serious adverse events. Serum bone alkaline phosphatase concentrations and the volume of the enlarged PTGs were also significantly reduced. CONCLUSION: PCIT is a safe and effective treatment, which may also suppress parathyroid hyperplasia and improve bone turnover for refractory 2HPT.

Aged↗

PubMed2003

Effects of argatroban as an anticoagulant for haemodialysis in patients with antithrombin III deficiency.

BACKGROUND: In congenital or acquired antithrombin III-deficient patients undergoing haemodialysis, coagulation or residual blood in the blood circuit and dialyser is commonly observed under anticoagulation with heparin. Argatroban, a synthetic thrombin antagonist, directly inhibits thrombin activity in a manner that is different from that of heparin, thereby displaying an anticoagulating effect without the activation of antithrombin III. For this reason, the anticoagulating effect of argatroban in haemodialysis patients with antithrombin III deficiency was investigated. METHODS: A retrospective nationwide survey was conducted among patients with congenital or acquired antithrombin III deficiency who had undergone haemodialysis with argatroban as an anticoagulant from April 1996 to April 2000. Inclusion criteria were patients with antithrombin III activity <70% of normal, and patients in whom blood coagulation or residual blood in the extracorporeal circuit could not be prevented by the use of heparin during haemodialysis. RESULTS: Of 80 patients who underwent haemodialysis with argatroban, 59 met the inclusion criteria. Compared with the data before the administration of argatroban, significant improvements of residual blood in the dialyser and arterial and venous drip chambers were observed at the last administration of argatroban. A significant rise in antithrombin III activity was also observed. Among 80 safety analysis cases, no adverse events were reported in 66 patients (82.5%). As severe adverse events, one showed bleeding tendency and one had prolongation of prothrombin time. CONCLUSION: Argatroban was an effective and safe anticoagulant for haemodialysis in patients with congenital or acquired antithrombin III deficiency.

Aged↗