Biomedical subjects

Takatoshi Kakuta

Publications and source records attributed to Takatoshi Kakuta.

16 recordsLinked to original sources

PubMed2006

Efficacy of percutaneous ethanol injection therapy (PEIT) is related to the number of parathyroid glands in haemodialysis patients with secondary hyperparathyroidism.

BACKGROUND: Percutaneous ethanol injection therapy (PEIT) is used for advanced secondary hyperparathyroidism. We investigated the efficacy, remission period and risk of relapse to determine the effect of the number of hyperplastic glands and other factors on the therapeutic effect of PEIT. METHODS: We studied 321 patients divided into two groups: effective [serum corrected calcium (cCa) level < or =10.5 mg/dl and serum intact parathyroid hormone (iPTH) level < or =250 pg/ml], and ineffective (failed to achieve the target levels). Advanced hyperplasia was defined as an estimated volume > or =0.5 cm(3) on ultrasonography. RESULTS: PEIT was effective in 201 patients (62.6%), in whom serum iPTH levels dropped from 603+/-292 to 183+/-62 pg/ml (ng/l) and serum cCa levels from 10.7+/-0.8 to 10.1+/-0.5 mg/dl. Univariate analysis identified age, the number of hyperplastic glands and iPTH level as factors related to the efficacy of PEIT. The odds ratio for success vs failure by multivariate analysis was 0.55 times for the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) and 0.29 times for iPTH (> or =500 vs <500 pg/ml). Using the Kaplan-Meier method, the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) was a factor affecting the remission period, with a remission significantly longer seen in the group with one hyperplastic gland (P=0.0025). CONCLUSIONS: Superior results in efficacy rate, remission period and risk of relapse are obtained when PEIT is restricted to patients with one hyperplastic gland > or =0.5 cm(3).

Adult↗

PubMed2006

Present status and perspectives of bioartificial kidneys.

Currently, hemodialysis is not adequate as a renal replacement therapy because it provides intermittent treatment and does not provide the metabolic function of renal tubules. The next generation of artificial kidney should replace intermittent hemodialysis with continuous hemofiltration and provide the full metabolic function of renal tubules. The current decade has witnessed the development of bioartificial kidneys using artificial membranes and renal tubular epithelial cells. Active transport and metabolic functions were confirmed in the confluent monolayers of tubular cells on artificial membranes. Bioartificial kidneys have succeeded in improving the prognosis of patients with multiple organ dysfunction, presumably by lowering plasma cytokine levels in patients. For successful treatment of chronic renal failure using bioartificial kidneys, it is necessary to overcome some technical hurdles such as improving the antithrombogenic properties of the surface of artificial membranes and prolonging the function of renal tubule cells on an artificial membrane. Transfection of functional protein genes into renal tubule cells enables bioartificial tubule devices to increase their transport capacity and metabolic functions such as digoxin secretion and water transport. The development of wearable roller pumps is also essential for the clinical application of a continuous treatment system.

Biomedical Research↗

PubMed2005

Early hospital readmission was less likely for hemodialysis patients from facilities with longer median length of stay in the DOPPS study.

The length of hospital stay is considered to influence hospital readmission in general. The Dialysis Outcomes and Practice Patterns Study (DOPPS), an international prospective observational study undertaken to establish a relationship between facility practices and dialysis outcomes, started in 1996. Results suggest that the duration of hospital stay is significantly correlated with the probability of early readmission in dialysis patients. Thus, early hospital readmission was observed to be less likely for hemodialysis patients from facilities with longer median length of stay. The lengths of hospital stay for hemodialysis patients differed in the three continents studied. Although socioeconomic pressures may drive the lengths of hospital stay, the duration of hospitalization should be determined keeping in mind the safety of clinical course for each disease. In this forum, a 47-year-old female hemodialysis patient with severe secondary hyperparathyroidism, who had been treated with hemodialysis for 21 years, was hospitalized with severe clinical symptoms. Although the clinical symptoms disappeared 10 days after total parathyroidectomy with autotransplantation, severe hypocalcemia persisted despite large amounts of intravenous calcium gluconate. This patient was hospitalized for a long duration owing to the large calcium deficit in her body. Had the length of her hospital stay been shortened, either she could have needed rehospitalization or her condition could have worsened.

Calcium Gluconate↗

PubMed2005

Pyridoxamine improves functional, structural, and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats.

BACKGROUND: We previously suggested that biochemical alterations of peritoneal membrane associated with long-term peritoneal dialysis might be, at least in part, accounted for by reactive carbonyl compounds overload originating both from uremic circulation and heat sterilization of glucose peritoneal dialysis fluid. In the present study, we utilized a uremic rat model on peritoneal dialysis and evaluated the protective effects of pyridoxamine, a recently developed inhibitor of advanced glycation end product (AGE), on structural, functional, and biochemical alterations of peritoneal membrane. METHODS: Uremic rats were generated by subtotal nephrectomy, some of which were undergone peritoneal dialysis with dialysate and/or given intraperitoneal pyridoxamine. Functional [dialysate/plasma ratio (D/P)(urea, creatinine), D/D(0 glucose)], structural (density of blood vessels in peritoneal membrane tissues), and molecular biochemical [formation of pentosidine, an AGE, by high-performance liquid chromatography (HPLC) assay and expressions of vascular endothelial growth factor (VEGF), and fibroblast growth factor 2 (FGF-2), by semiquantitative polymerase chain reaction (PCR) and/or immunohistochemistry] alterations of peritoneal membrane were assessed. RESULTS: Uremic peritoneal membrane was characterized by an increased functional area of exchange for small solutes between blood and dialysate, vascular proliferation, increased AGE genesis, and up-regulated expressions of angiogenic cytokines. The peritoneal membrane alterations associated with peritoneal dialysis are similar but more severe than those in uremia without peritoneal dialysis. Pyridoxamine given in uremic rats with peritoneal dialysis significantly improved functional and structural alterations. This improvement was accompanied by reduction of AGE accumulation and of angiogenic cytokines expressions. CONCLUSION: Peritoneal carbonyl stress derived from uremia as well as peritoneal dialysis procedure might contribute to the vascular proliferation through induction of bioactive molecules and to an increased functional area, eventually leading to ultrafiltration failure. Pyridoxamine may be beneficial in protection of uremic peritoneal membrane on peritoneal dialysis.

Animals↗

PubMed2004

Evaluation of long-term transport ability of a bioartificial renal tubule device using LLC-PK1 cells.

BACKGROUND: Haemodialysis therapy does not provide renal tubule function, such as active fluid and solute transport, nor metabolic or endocrine action. Moreover, this treatment is usually associated with serious complications and high mortality. We constructed a bioartificial renal tubule device by using renal tubule epithelial cells in an artificial membrane, and evaluated transport properties of the device for 2 weeks. METHODS: A renal epithelial cell line, LLC-PK(1) (Lewis-lung cancer porcine kidney), was seeded on polysulfone hollow fibres in small and large modules. We studied perfusion and leakage of urea nitrogen (UN) and creatinine (Cr), as well as reabsorption of water, glucose and sodium for a period of 2 weeks. RESULTS: Cell-lined hollow fibre membranes significantly reduced the leakage of UN and Cr throughout the 2 week period. Reabsorption of water, glucose and sodium were adequate from days 3 to 10 and gradually decreased thereafter. LLC-PK(1) cells actively transported these substances. Scanning electron microscopy revealed that cells in the hollow fibres on day 8 became completely confluent. However, they became multi-layered and almost obstructed the hollow fibres on day 13. CONCLUSIONS: This bioartificial renal tubule device functioned to reabsorb water, glucose and sodium for approximately 10 days. This is the first report of successful long-term evaluation of a bioartificial renal tubule device. This device, in combination with continuous haemofiltration, may provide treatment to prevent complications of dialysis and raise the quality of life in chronic renal failure patients.

Animals↗

PubMed2004

Ultrapure dialysate decreases plasma pentosidine, a marker of "carbonyl stress".

BACKGROUND: Advanced glycation end products (AGEs) and their reactive carbonyl precursors accumulate in renal failure ("carbonyl stress"). Carbonyl stress derives from a broad derangement in the nonenzymatic biochemistry of both carbohydrates and lipids. We tested the influence of dialysate quality on plasma level of pentosidine, an AGE moiety taken as a surrogate marker of carbonyl stress, in hemodialysis patients. METHODS: Plasma pentosidine is measured by means of high-performance liquid chromatography in patients hemodialyzed successively with a conventional and an ultrapure endotoxin-free dialysate. RESULTS: Dialysate endotoxin level decreased from 0.040 +/- 0.017 EU/mL before the switch to the new water supply system to less than the detection limit (<0.001 EU/mL) after the switch. Plasma pentosidine levels decreased from 1.55 +/- 0.61 nmol/mL before the switch to 1.38 +/- 0.52 nmol/mL (P < 0.0001) and 1.31 +/- 0.50 nmol/mL (P < 0.0001) 3 and 6 months after the switch to an ultrapure dialysate, respectively. Decreases in plasma pentosidine levels were similar regardless of dialyzer membrane type; ie, high-flux polysulfone, high-flux polymethylmethacrylate, and low-flux cellulose acetate membranes. Unexpectedly, plasma triglyceride levels decreased from 150 +/- 116 mg/dL (1.69 +/- 1.31 mmol/L) before the switch to 124 +/- 79 mg/dL (1.40 +/- 0.89 mmol/L; P < 0.01) and 119 +/- 75 mg/dL (1.34 +/- 0.85 mmol/L; P < 0.01) 3 and 6 months after the switch despite unchanged total cholesterol levels, respectively. Changes in pentosidine levels were unrelated to those in triglycerides, and both were unrelated to C-reactive protein levels, which remained stable throughout the study. CONCLUSION: Ultrapure dialysate reduces plasma pentosidine levels and improves plasma triglyceride levels in hemodialysis patients through still undefined mechanisms.

Arginine↗

PubMed2004

[PEIT is the part of strategy for severe hyperparathyroidism in patients requiring hemodialysis].

Marked parathyroid hyperplasia is one of the characteristic features of severe hyperparathyroidism in patients requiring chronic hemodialysis. Most of these patients become resistant to conservative therapies such as calcitriol pulse therapy. For these patients, surgical removal of the enlarged parathyroid glands is usually necessary to control parathyroid hormone secretion. Recently, hyperparathyroidism in some of these patients have been managed by percutaneous ethanol injection therapy (PEIT) due to progress of imaging technology. In this study, we consider parathyroidectomy (PTx) and PEIT as a strategy of severe hyperparathyroidism patients. We conclude that PEIT, which is safe and effective therapy for 2HPT, makes possible to maintain long-term parathyroid function within the normal range. However 20% patients after PEIT need to convert PTx:parathyroidectomy after PEIT.

Combined Modality Therapy↗

PubMed2003

Co-expression of parathyroid hormone and chromogranin A in secondary hyperparathyroidism: a functional marker for secretory activity of hyperplastic nodules.

The relationship between secretion of parathyroid hormone (PTH) and biologic characteristics, including cell proliferation or monoclonality, is not yet fully understood. To evaluate secretory activity of glands or nodules histopathologically, we focused on the co-expression of chromogranin A (CgA) and parathyroid hormone (PTH) in each gland or nodule. A total of 55 glands from 38 patients with normal parathyroid glands, hyperplastic glands (diffuse and nodular) and primary adenomas were compared. Co-expression of PTH and CgA was decreased to 44.4% in diffuse hyperplastic glands, and to 39.6% in 91 hyperplastic nodules, in contrast to normal glands and primary adenomas that showed constant co-expression of PTH and CgA. Immunohistochemical study of PTH showed a coarse granular pattern predominantly in PTH-positive/CgA-positive nodules, and a dot-like pattern mainly in PTH-positive/CgA-negative nodules. Laser scanning microscopy and immunoelectron microscopy confirmed that a dot-like pattern is based on a positive reaction of PTH at the Golgi apparatus. MIB-1 LI was 12.6 +/- 11.6 in PTH-positive/CgA-positive, and 19.3 +/- 27.3 in PTH-positive/CgA-negative nodules. In conclusion, a combination of PTH and CgA could provide more information about the physiologic state of secretory activity of each nodule than does the simple observation of PTH immunoreactivity.

Adenoma↗

PubMed2003

Adenovirus-mediated functional gene transfer into parathyroid cells in vivo and in vitro.

Chronic renal failure patients usually develop secondary hyperparathyroidism and, as the disease progresses, there is a decrease in the number of vitamin D and calcium-sensing receptors (CaRs) in the parathyroid glands. Parathyroid cell function can be controlled if a functional gene is transferred into these cells using an adenovirus vector. Vitamin D or CaR genes transferred by the infected adenovirus vector induced a reduction in parathyroid hormone secretion. These results suggest that adenovirus-mediated gene transfer is a useful technique for control of parathyroid cell function.

Adenoviridae↗

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

Long-term (3 years) prognosis of parathyroid function in chronic dialysis patients after percutaneous ethanol injection therapy guided by colour Doppler ultrasonography.

BACKGROUND: Secondary hyperparathyroidism (2HPT) is one of the most important complications in chronic dialysis (CD) patients. Percutaneous ethanol injection therapy (PEIT) of the parathyroid glands was introduced initially as an alternative treatment to parathyroidectomy and, with the technical progress of parathyroid imaging, it has now become a useful adjunct to medical therapy. The present study examined the possibility of maintaining parathyroid function in the long term (3 years) after PEIT. METHOD: PEIT, guided by power-Doppler flow mapping, was performed in 33 CD patients with severe 2HPT, and all glands >5.0 mm in diameter were destroyed. RESULTS: All patients showed a decline in the serum intact parathyroid hormone (i-PTH) concentration, on average from 695.5 to 248.0 pg/ml, after 1 year. After 3 years, the i-PTH concentration was controlled at <300 pg/ml in 85% of patients. The mean serum alkaline phosphatase (ALP) concentration also decreased from 322.7 to 154.4 IU/l after 1 year. In 76% of patients, ALP was maintained within the normal range (between 76 and 260 IU/l) at 3 years. Patients were classified into four groups according to the number of parathyroid glands detected by ultrasonography: one gland in group 1, two in group 2, three in group 3, and four in group 4. At 3 years after PEIT, i-PTH was controlled at <300 pg/ml in 100, 79, 83 and 82% of the patients in groups 1-4, respectively. CONCLUSIONS: It was possible to maintain long-term parathyroid function after PEIT in patients with 2HPT by using medical therapy, such as oral calcitriol pulse therapy and additional PEIT.

Adult↗

PubMed2003

Long-term prognosis of parathyroid function for chronic dialysis patients after minimally invasive radioguided parathyroidectomy (MIRP).

BACKGROUND: Minimally invasive radioguided parathyroidectomy (MIRP) for primary hyperparathyroidism for one gland, located by scanning with technetium 99m-labelled sestamibi (MIBI), has been performed. Total parathyroidectomy with autotransplantation or percutaneous ethanol injection therapy (PEIT) for severe secondary hyperparathyroidism (2HPT) has also been performed. METHODS: The present study examined the possibility of maintaining parathyroid function within a target range [intact parathyroid hormone (i-PTH) <or=300 pg/ml] in the long term after MIRP for 2HPT. Three patients resistant to calcitriol therapy gave their informed consent for MIRP. The principle of MIRP for chronic dialysis patients is to extract a hyper-functioning parathyroid gland resistant to medical therapy, including calcitriol pulse therapy, and then control the remaining glands with medical therapy. The follow-up period for this study was 2 years. RESULT: Two of the cases were controlled by MIRP followed by calcitriol pulse therapy. In all three cases, MIBI scintigraphy showed a solitary radioactive nodule; however, ultrasonography showed that in the two cases that were controlled by MIRP and calcitriol pulse therapy, there was one radioactive gland, but in the other case there were three, and this case required additional PEIT for control of hyperparathyroidism.

Adult↗

PubMed2003

[Vitamin D and its analogs in the treatment of hypoparathyroidism].

Hypoparathyroidism patients devided two groups. One group is low PTH group and the other is pseudo hypoparathyroidism group. Hypoparathyroidism in these patients has been managed by 1,25- (OH)(2)D(3) or 1alpha-OHD(3). However inappropriately high doses active vitamin D usually lead to marked hypercalciuria. It is important to control serum Ca level (absolute hypo within normal values) without hypercalciuria.

English Abstract↗

PubMed2002

Prognosis of parathyroid function after minimally invasive radioguided parathyroidectomy (MIRP) and percutaneous ethanol injection therapy (PEIT) for primary hyperparathyroidism.

During parathyroidectomy (PTx) for primary hyperparathyroidism (PHP), we surgically explored the contralateral parathyroid glands as well as those whose localization was clarified by ultrasonography and parathyroid scintigraphy. Although it is important to explore the contralateral side and other glands, we frequently treat only the gland whose localization is confirmed. Recently, we have performed minimally invasive radioguided parathyroidectomy (MIRP) that resects only one gland observed on the imaging under technetium 99m-labeled sestamibi (MIBI) scanning guidance after obtaining prior informed consent. In this surgery, even if recurrence is observed contralaterally, it is possible to apply a similar procedure to the contralateral side again. We examined six PHP patients who underwent MIRP and two PHP patients treated with percutaneous ethanol injection therapy (PEIT). The follow-up period was 2 years. PEIT was selected as a treatment method for two patients based on the patients' characteristics. When only one gland is treated, the efficacy of PEIT was considered to be similar to that of MIRP.

Administration, Cutaneous↗

PubMed2002

[Intervention therapy for secondary hyperparathyroidism].

We reported that selective PEIT in parathyroid glands guided by color doppler flow mapping is effective for severe secondary hyperparathyroidism (2HPT) in chronic dialysis patients. According to the recent Survey by the Japanese Working Group on PEIT of Parathyroid, more than 600 patients have been treated by PEIT in Japan by September, 1998. Based on the results of this survey and based on pathophysiological consideration, Working Group proposed a guideline of selective PEIT of parathyroid. I give a brief summary here. But PEIT has a risk of side effects such as recurrent nerve palsy. Recently another way of percutaneous injection therapy (PIT) using Calcitriol, maxacalcitol and acetic acid has been developed and used. These data suggest that parathyroid intervention (IVR) is an effective adjunct to medical therapy for the management of hyperparathyroidism in uremia.

English Abstract↗

PubMedDate not supplied

Evaluation of proliferation and functional differentiation of LLC-PK1 cells on porous polymer membranes for the development of a bioartificial renal tubule device.

To develop a bioartificial renal tubule system using renal tubular cells and porous polymer membrane hollow fibers, long-term maintenance of a confluent monolayer and the functionally differentiated condition of cells is essential. We examined the proliferation and functional differentiation of LLC-PK1 (Lewis-lung cancer porcine kidney 1) cells on two types of membranes: polysulfone and cellulose acetate. Cell proliferation was significantly higher on the polysulfone membrane than on the cellulose acetate membrane, and was enhanced by coating the membranes with various extracellular matrices. Confluent monolayer formation of cells was observed on matrix-coated polysulfone membrane but not on matrix-coated cellulose acetate membrane within 1 week. Cell proliferation continued for 3 weeks after confluent monolayer formation. Messenger RNA (mRNA) expression of glucose transporters, indicators of the functional differentiation of the LLC-PK1 cells, was observed in the polysulfone and cellulose acetate membrane groups, but was not observed in the nonporous polystyrene plate group under subconfluent conditions. Expression of glucose transporters mRNA was maintained for 3 weeks after confluent monolayer formation. Polysulfone membrane is more suitable than cellulose acetate membrane for a bioartificial renal tubule system with regard to LLC-PK1 cell proliferation. Extracellular matrix coating of the membrane further improves cell proliferation.

Animals↗