Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients.

Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion.

Changes in Fibroblast Growth Factor 23 and Soluble Klotho Levels After Hemodialysis Initiation.

Rationale & Objective: Patients with chronic kidney failure have markedly elevated fibroblast growth factor 23 (FGF-23) levels and decreased soluble Klotho levels. However, no studies have examined the effects of hemodialysis initiation on the levels of these hormones and other parameters of mineral metabolism.

Study Design: Prospective single-arm study.

Parathyroid hormone-producing cells exist in adipose tissues surrounding the parathyroid glands in hemodialysis patients with secondary hyperparathyroidism.

Possible ectopic parathyroid hormone (PTH) production in adipose tissues surrounding hyperplastic parathyroid glands was examined in patients with secondary hyperparathyroidism (SHPT). In vitro culture of adipose tissues from 31 patients excised during parathyroidectomy showed PTH secretion in 23 (74.2%) patients.

Vitamin D receptor agonist VS-105 directly modulates parathyroid hormone expression in human parathyroid cells and in 5/6 nephrectomized rats.

Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to treat secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD). Current VDRA therapy often causes hypercalcemia, which is a critical risk for vascular calcification. Previously we have shown that a novel VDRA, VS-105, effectively suppresses serum parathyroid hormone (PTH) without affecting serum calcium levels in 5/6 nephrectomized (NX) uremic rats.

Feasibility of photodynamic therapy for secondary hyperparathyroidism in chronic renal failure rats.

Background: Feasibility of photodynamic therapy (PDT) for secondary hyperparathyroidism (SHPT) was examined in a rat model of SHPT.

Methods: A photosensitizer, 5-aminolevulinic acid (5-ALA), was injected intraperitoneally, and the parathyroid glands were irradiated either after surgical exposure with 385-nm light or transdermally with 630-nm light from a light-emitting diode (LED) lamp.

Results: PDT with high 5-ALA and irradiation doses caused severe hypoparathyroidism in SHPT rats within two days.

A Case of Encapsulating Peritoneal Sclerosis Complicated by Malignant Peritoneal Mesothelioma.

We report a case of peritoneal mesothelioma discovered in a patient during peritoneal dialysis. The patient was a 55-year-old woman who had no history of asbestos exposure. Owing to end-stage kidney failure, she had been undergoing peritoneal dialysis for over 8 years, and she had been diagnosed with encapsulating peritoneal sclerosis.

Cinacalcet induces apoptosis in parathyroid cells in patients with secondary hyperparathyroidism: histological and cytological analyses.

Background/aims: Previous studies reported a reduction in parathyroid gland volume during treatment with cinacalcet in patients with secondary hyperparathyroidism (SHPT). However, it remains to be determined whether cinacalcet accelerates apoptosis of hyperplastic parathyroid cells in these patients.

Methods: The study subjects were 16 hemodialysis patients who had undergone parathyroidectomy for severe SHPT.

Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism.

Context: Klotho is a transmembrane protein that functions as a coreceptor for fibroblast growth factor 23 (FGF23). Klotho is cleaved and released into the circulation; however, the main site of production, physiological role, and regulation of soluble Klotho in humans are largely unknown.

Objective: The aim of this study was to determine the impact of parathyroidectomy (PTx) on serum FGF23 and soluble Klotho levels in patients with severe secondary hyperparathyroidism.

Evaluation of bioartificial renal tubule device prepared with human renal proximal tubular epithelial cells cultured in serum-free medium.

Bioartificial renal tubule devices (BTD) use cell therapy to improve conditions commonly observed in recipients of artificial kidneys for treatment of kidney diseases. We previously reported significant improvement of the condition of acute kidney injury (AKI) animals after treatment with BTD prepared with lifespan-extended human renal proximal tubular cells (hRPTEC). However, a major obstacle to use of BTD for patients is their biological safety, because hRPTEC are cultured in medium containing fetal calf serum.

[Bone mineral metabolism that kidney controls].

With progressive loss of kidney function, patients with chronic kidney disease develop multiple mineral metabolism abnormalities. Chronic kidney disease-mineral and bone disorder independently associated with cardiovascular disease and mortality. FGF23 which discovered in late years gave us new knowledge to elucidate these mechanisms.

Evaluation of bioartificial renal tubule device prepared with lifespan-extended human renal proximal tubular epithelial cells.

Background: Acute kidney injury (AKI), accompanied by the development of systemic inflammatory response syndrome and multiorgan dysfunction syndrome, is associated with a high risk of death. Bioartificial renal tubule device (BTD) is a cell therapy that improves the conditions common to artificial kidney recipients treated for kidney diseases. In this paper, we describe the establishment of BTD with lifespan-extended human renal proximal tubular epithelial cells.

Syndrome of inappropriate secretion of antidiuretic hormone caused by pituitary macroadenoma with hemangiomatous stroma.

A 55-year-old Japanese man was referred to our hospital because of disturbance of consciousness and hyponatremia. He had been aware of general fatigue, nausea, and headache for two weeks. Tests revealed hyponatremia, plasma hypoosmolarity with urine hyperosmolarity, an elevated level of urine sodium excretion, and normal functions of the kidney, adrenal gland, and thyroid.

Development of bioartificial renal tubule devices with lifespan-extended human renal proximal tubular epithelial cells.

Background: The bioartificial renal tubule device is a cell therapy system for renal failure. The major obstacle in the development of the bioartificial renal tubule device is the obtainment of a large number of viable renal tubule cells to seed on the inner surface of hollow fibers. Although our previous studies had used a transformed cell line, they may be dangerous for clinical uses.

Atypical thymic carcinoid associated with Cushing's syndrome.

A 56-year-old Japanese woman with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) was admitted to hospital, where she was diagnosed as having a mediastinal tumor with ectopic ACTH production. The tumor and associated lymph node metastases were resected endoscopically, and the pathological diagnosis was atypical thymic carcinoid. Radiation therapy and administration of metyrapone, an inhibitor of 11b-hydroxylase to decrease the cortisol level, were attempted, but the levels of ACTH and cortisol were unresponsive.

Black adrenal adenoma causing preclinical Cushing's syndrome.

Functioning black adrenal adenoma (BAA) rarely causes preclinical Cushing's syndrome (CS). In the present case, a 46-year-old Japanese Peruvian woman presented with left flank pain and hypertension. Abdominal computed tomography showed that she had a 15-mm in diameter, round, left adrenal adenoma.

Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients.

Background: Some trials have indicated that coronary artery calcification progresses more slowly in sevelamer-treated dialysis patients than in those using calcium-based binders. Effects of phosphate binders on circulating advanced glycation end products (AGEs) are unknown.

Study Design: Randomized trial with parallel-group design.

L157X nonsense mutation of the succinate dehydrogenase subunit B gene in a Japanese patient with right paraaortic paraganglioma.

Nuclear genes succinate dehydrogenase B subunit and succinate dehydrogenase D subunit, which encode two mitochondrial complex II subunits, are associated with the development of familial paraganglioma (PGL). Succinate dehydrogenase B subunit gene mutation is highly associated with extraadrenal PGL and subsequent distant metastasis. We describe the case of a 29-year-old Japanese man with a 3-year history of hypertension, headache, and palpitation.

[CKD-MBD (Chronic Kidney Disease-Mineral and Bone Disorder). Gene therapy for secondary hyperparathyroidism].

Secondary hyperparathyroidism (SHPT) is one of the most important complications of chronic kidney disease. Although 1,25-D pulse therapy is effective for SHPT, hyperplastic parathyroid (PT) cells gradually develop resistance to 1,25-D. Vitamin D(3) receptor (VDR) levels are decreased in the PT glands of dialysis patients and animal models of renal failure.

Small-cell carcinoma of the endometrium presenting as Cushing's syndrome.

Small-cell carcinoma (SCC) of neuroendocrine type is an uncommon tumor of the endometrium. No previous report has documented Cushing's syndrome due to ectopic ACTH production by SCC of the endometrium. We describe a 56-year-old Japanese woman with SCC of the endometrium and multiple lung metastases presenting as Cushing's syndrome.

Can cinacalcet replace parathyroid intervention in severe secondary hyperparathyroidism?

A 6-month observational study was conducted in 61 patients (33 men and 28 women, mean age 54.8 +/- 12.4 years) treated with cinacalcet in whom parathyroid intervention was indicated.

Suppression of parathyroid hormone production in vitro and in vivo by RNA interference.

We used RNA interference, which causes sequence-specific degradation of target mRNAs to suppress the production of parathyroid hormone by cells of patients with secondary hyperparathyroidism in vitro and in vivo. Transfection of small interfering RNA (siRNA) against human parathyroid hormone into monolayers of parathyroid cells cultured from these patients caused a dose-dependent decrease of secretion and mRNA levels with 80% or more suppression using 40 nM siRNA. Parathyroid cells cultured on non-adherent plastic produced spheroid cell aggregates which secreted parathyroid hormone for more than 150 days.

Relationship between the weight of parathyroid glands and their secretion of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism.

Secondary hyperparathyroidism is one of the common and important abnormalities of mineral metabolism in hemodialysis patients. In this study we investigated the relationship between the weight of individual parathyroid glands (PTG) and their secretion of parathyroid hormone (PTH). Sixty-four PTGs in 16 patients undergoing parathyroidectomy (PTx) at our hospital were included in this study.

Atrial fibrillation induced by post-parathyroidectomy transient thyrotoxicosis.

We describe a 59-year-old Japanese woman with post-parathyroidectomy transient thyrotoxicosis and atrial fibrillation. She underwent parathyroidectomy for secondary hyperparathyroidism due to chronic renal failure. Three days after surgery, she complained of palpitation and chest pain due to atrial fibrillation.

Enhancement of permeability in endothelial cells for the development of an antithrombogenic bioartificial hemofilter.

For the development of an antithrombogenic bioartificial hemofilter, in which the inner surface of hollow fibers is lined by endothelial cells, it is essential to increase the permeability of the cells in order to achieve a sufficient ultrafiltrate. We tried to increase it by using an actin microfilament polymerization inhibitor, cytochalasin B (CyB). Fifty microg/mL CyB was added for 2 h to the culture medium of confluent rat glomerular endothelial cells (RGEC) and human umbilical vein endothelial cells (HUVEC).

Prevention of LLC-PK(1) cell overgrowth in a bioartificial renal tubule device using a MEK inhibitor, U0126.

A common approach to construct a bioartificial renal tubule system is to utilize renal tubular cells seeded in porous polymer membrane hollow fibers. We have reported that overgrowth of renal tubular cells was not beneficial for the transport and reabsorption functions of bioartificial tubules. Therefore, long-term maintenance of a confluent monolayer of cells in hollow fibers is essential and technically challenging.