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Hideki Hirakata

Publications and source records attributed to Hideki Hirakata.

At least 19 recordsLinked to original sources
PubMed2006

Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in primary focal segmental glomerulosclerosis.

The crucial involvement of podocyte failure in the development of hereditary focal segmental glomerulosclerosis (FSGS) indicates that specific podocyte proteins are closely related to podocyte function and biology. We hypothesized that podocyte failure, reflected by alteration of these proteins, leads not only to FSGS but also to resistance to steroid therapy. We investigated the association between expression of synaptopodin and glomerular epithelial protein 1 (GLEPP1) and response to corticosteroid therapy in primary FSGS. The subjects of this retrospective study were 17 adult patients with primary FSGS with nephrotic syndrome (NS) seen at Fukuoka Red Cross Hospital between 1979 and 2001. They were divided into two groups according to the response to steroid therapy at 6months: responders (n=10) and non-responders (persistence of nephrotic-range proteinuria, n=7). Expression levels of synaptopodin and GLEPP1 were examined immunohistochemically using image analysis software. Low expression levels of both proteins were associated with poor steroid responsiveness in FSGS. The average gray values for synaptopodin and GLEPP1 expression in responders vs. non-responders were 9.0+/-0.7 (mean+/-S.E.M.) vs. 6.3+/-0.9 (P=0.04) and 9.6+/-1.2 vs. 6.0+/-1.0 (P=0.04), respectively. The percentages of glomerular area staining for synaptopodin and GLEPP1 in responders vs. non-responders were 15.4+/-2.7% vs. 8.1+/-1.2% (P=0.045) and 11.9+/-1.6% vs. 6.0+/-1.3% (P=0.02), respectively. Synaptopodin expression correlated with the severity of proteinuria and with GLEPP1 expression. Reduced expression of both synaptopodin and GLEPP1 is associated with poor response to steroid therapy in primary FSGS.

Adult↗
PubMed2006

Metabolic syndrome and CKD in a general Japanese population: the Hisayama Study.

BACKGROUND: Metabolic syndrome has been linked with various atherosclerotic diseases, but has not been evaluated sufficiently as a risk factor for the development of chronic kidney disease (CKD) in the general population. METHODS: We followed up 1,440 community-dwelling individuals without CKD aged 40 years or older for 5 years and examined the effects of metabolic syndrome, defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria, on the development of CKD. RESULTS: During follow-up, 88 subjects experienced CKD. The age- and sex-adjusted 5-year cumulative incidence of CKD was significantly greater in subjects with than without metabolic syndrome (10.6% versus 4.8%; P < 0.01). In multivariate analysis, even after adjustment for other confounding factors, including insulinemia, metabolic syndrome remained an independent risk factor for the occurrence of CKD (odds ratio, 2.08; 95% confidence interval [CI], 1.23 to 3.52). Compared with subjects with 1 or fewer metabolic syndrome component, multivariate-adjusted odd ratios for CKD in subjects with 2, 3, and 4 or more metabolic syndrome components were 1.13 (95% CI, 0.60 to 2.12), 1.90 (95% CI, 0.98 to 3.69), and 2.79 (95% CI, 1.32 to 5.90), respectively. The rate of change in kidney function during 5 years decreased significantly in subjects with 4 or more metabolic syndrome components compared with those with 1 or fewer component in the age group of 40 to 59 years, whereas it also was significantly low in subjects with 3 metabolic syndrome components in the group aged 60 years or older. CONCLUSION: Our findings suggest that metabolic syndrome is a significant risk factor for the development of CKD in the general population.

Adult↗
PubMed2006

Successful treatment of six patients with neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure.

Neuroleptic malignant syndrome is a rare but potentially lethal, rare reaction to neuroleptics which is characterized by altered levels of consciousness, extrapyramidal effects, autonomic instability, hyperthermia, and elevated serum creatine phosphokinase levels. The most serious complication of neuroleptic malignant syndrome is acute renal failure. We investigated six cases of neuroleptic malignant syndrome associated with myoglobulinemic acute renal failure due to rhabdomyolysis and effect of hemodialysis or hemodiafiltration. The patients were five males and one female with a mean age of 43.5 yr. All of the patients, who developed acute renal failure induced from rhabdomyolysis, had previously received butyrophenone (haloperidol), phenothiazine, benzamide, iminomide, benzisoxazole, antidepressants, and hypnotics (benzodiazepine and barbiturate) for the treatment of schizophrenia. The clinical manifestations of neuroleptic malignant syndrome were characterized by altered consciousness, muscle rigidity and weakness, fever, and excessive perspiration. The peak laboratory data were blood urea nitrogen 102 +/- 26 (mean +/- SD) mg/dL, serum creatinine 9.1 +/- 2.1 mg/dL, serum creatine phosphokinase 229,720 +/- 289,940 IU/L, and all of them developed oliguric acute renal failure. Dantrolene sodium administration was given to five cases and hemodialysis or hemodiafiltration was performed in all of them. The serum creatinine level after hemodialysis or hemodiafiltration was 1.4 +/- 1.0 mg/dL. All patients were successfully cured of acute renal failure by hemodialysis or hemodiafiltration. As a result, myoglobulinemic acute renal failure associated with neuroleptic malignant syndrome was successfully treated by hemodialysis or hemodiafiltration.

Acute Kidney Injury↗
PubMed2006

A case of Gitelman's syndrome with decreased angiotensin II-forming activity.

Gitelman's syndrome (GS) is a variant of Bartter's syndrome (BS) characterized by hypokalemic alkalosis, hypomagnesemia, hypocalciuria and secondary aldosteronism without hypertension. A 31-year-old Japanese man who had suffered from mild hypokalemia for 10 years was admitted to our hospital. He had metabolic alkalosis, hypokalemia and hypocalciuria. Since he had two missense mutations (R261C and L623P) in the thiazide-sensitive Na-Cl cotransporter (TSC) gene (SLC12A3), he was diagnosed as having GS. He showed hyperreninism and a high angiotensin I (Ang I) level, whereas his angiotensin II (Ang II) and aldosterone levels were not elevated. His angiotensin converting enzyme (ACE) activities were normal, and administration of captopril inhibited the production of Ang II and aldosterone. We evaluated the Ang II-forming activity (AIIFA) of other enzymes in his lymphocytes. Interestingly, chymase-dependent AIIFA was not detected in the lymphocytes. Together, these results suggest that the lack of chymase activity resulted in the manifestation of GS without hyperaldosteronism.

Adult↗
PubMed2005

Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1).

MRL/lpr mice develop spontaneous glomerulonephritis that is essentially identical with diffuse proliferative glomerulonephritis (World Health Organization class IV) in human lupus nephritis. Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. Diffuse proliferative glomerulonephritis is associated with autoimmune responses dominated by Th1 cells producing high levels of IFN-gamma. The initial mounting of Th1 responses depends on the function of the WSX-1 gene, which encodes a subunit of the IL-27R with homology to IL-12R. In mice deficient for the WSX-1 gene, proper Th1 differentiation was impaired and abnormal Th2 skewing was observed during infection with some intracellular pathogens. Disruption of the WSX-1 gene dramatically changed the pathophysiology of glomerulonephritis developing in MRL/lpr mice. WSX-1-/- MRL/lpr mice developed disease resembling human membranous glomerulonephritis (World Health Organization class V) with a predominance of IgG1 in glomerular deposits, accompanied by increased IgG1 and IgE in the sera. T cells in WSX-1-/- MRL/lpr mice displayed significantly reduced IFN-gamma production along with elevated IL-4 expression. Loss of WSX-1 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of human lupus nephritis development.

Animals↗
PubMed2005

Amelioration of autoimmune nephritis by imatinib in MRL/lpr mice.

OBJECTIVE: To examine whether the platelet-derived growth factor (PDGF) receptor antagonist imatinib ameliorates glomerulonephritis in MRL/lpr mice, a condition that is similar to severe lupus nephritis in humans. METHODS: Sixteen-week-old MRL/lpr female mice having an advanced stage of glomerulonephritis were divided into 3 groups according to treatment: 1) 50 mg/kg or 2) 10 mg/kg of imatinib (administered orally 4 times a week up to 24 weeks of age) or 3) vehicle solution (untreated group). The histopathologic condition of the kidneys and salivary glands of each mouse as well as the cumulative survival rates, extent of lymphadenopathy and splenomegaly, and serum chemistry and immunologic values were assessed. RESULTS: In mice treated with 50 mg/kg imatinib, neither proliferation of glomerular cells nor crescent formation occurred. A drastic decrease in mesangial matrix was noted. Mice treated with 50 mg/kg imatinib had a prolonged life span compared with mice treated with 10 mg/kg imatinib and untreated mice. Expression of PDGF receptor and transforming growth factor beta messenger RNA in the kidneys was significantly reduced in the 50 mg/kg imatinib-treated mice compared with that in the 10 mg/kg imatinib-treated mice (P < 0.05) and the untreated mice (P < 0.01). Intriguingly, lymphadenopathy and salivary gland inflammation were also attenuated in imatinib-treated mice, in a dose-dependent manner. Serum levels of IgG and anti-double-stranded DNA antibodies were also reduced in the imatinib-treated mice. CONCLUSION: These findings indicate that imatinib has a pleiotropic therapeutic effect, namely, the inhibition of PDGF signaling and immunosuppression, on the glomerulonephritis of MRL/lpr mice, which suggests a potential application of this drug in the treatment of human lupus nephritis.

Animals↗
PubMed2005

Catastrophic antiphospholipid antibody syndrome following initiation of hemodialysis.

Antiphospholipid syndrome (APS) is associated with arterial and venous thrombosis, pregnancy morbidity, and thrombocytopenia. Some APS patients develop rapid and disseminated microthrombosis and are known as having catastrophic APS or CAPS. We document here a case of CAPS in a patient who presented with various clinical symptoms and serious abnormalities of blood coagulation following initiation of hemodialysis after bilateral nephrectomy due to renal cancer. The patient developed multiple organ symptoms, including melena, visual disturbances, skin eruptions, lymph node swelling, urinary tract bleeding, backache, arteriovenous fistula occlusion, and chest pain. Based on the clinical course and serological and histological examinations, a diagnosis of CAPS was established. The patient recovered by following intensive anticoagulation and steroid therapy. Although CAPS is rare, once symptoms develop the condition deteriorates rapidly. Because of the associated high mortality, early diagnosis and prompt treatment are necessary.

Antiphospholipid Syndrome↗
PubMed2005

Increased renal resistive index in atherosclerosis and diabetic nephropathy assessed by Doppler sonography.

OBJECTIVE: The renal resistive index (RI) and pulsatility index (PI), measured using Doppler ultrasonography, reflect intrarenal vascular resistance. We evaluated the relationship between these indices and pulse wave velocity (PWV), a measure of arterial stiffness, which reflects atherosclerosis, and determined whether renal RI and PI differ depending on the underlying renal disease. METHODS: A total of 245 inpatients with or without renal impairment who underwent ultrasonographic assessment of the renal artery were enrolled in the study. Patients with renal artery stenosis or severe renal failure (serum creatinine>or=6 mg/dl) were excluded from the study. RESULTS: In univariate analysis, the RI and PI of the main renal arteries and the interlobar arteries were significantly correlated with PWV. Multivariate analyses showed that PWV was independently associated with the RI of the main renal arteries (P<0.01, R=0.256). Patients with a creatinine level less than 3 mg/dl were divided into a control group without renal diseases and three groups with different underlying renal diseases: diabetic nephropathy, chronic glomerulonephritis, and nephrosclerosis. The RI and PI of the main renal arteries and the interlobar arteries were significantly higher in patients with diabetic nephropathy than in the other three groups, even after adjusting for multiple variables, including creatinine clearance. CONCLUSION: These results suggest that the increased RI of the renal arteries is associated with the severity of systemic atherosclerosis. Furthermore, the intrarenal vascular resistance differs depending on the underlying renal disease, and appears to increase to a greater extent in diabetic nephropathy.

Adult↗
PubMed2005

Recurrent nephrotic syndrome after living-related renal transplantation resistant to plasma exchange: report of two cases.

We encountered two patients of recurrent nephrotic syndrome (NS) after renal transplantation that was resistant to plasma exchange (PEX). Case 1 was a 34-year-old man with a living-related renal transplant for type-I membranoproliferative glomerulonephritis (MPGN) related end-stage renal disease (ESRD). He developed overt proteinuria 7 months post-transplant and presented with NS 5 months later. Biopsy of the transplant kidney revealed recurrent type I MPGN, but no features of acute rejection (AR) or chronic allograft nephropathy (CAN). He was treated with cyclophosphamide (CP), oral prednisolone (40 mg/d), an anti-platelet agent, heparin sulfate, and PEX, but the nephrotic state persisted and renal function was deteriorated. He recommenced hemodialysis 3 yr and 9 months after renal transplant. Case 2 was a 47-year-old male who underwent living-related renal transplant for ESRD due to focal segmental glomerulosclerosis (FSGS). He presented with proteinuria shortly after renal transplantation. He also had frequent episodes of AR. Graft biopsy revealed recurrent FSGS. Treatment of pulse methylprednisolone and PEX was transiently effective, but NS relapsed shortly after PEX. Graft biopsy at our hospital showed features of CAN with moderate interstitial fibrosis and tubular atrophy, presence of intraglomerular foam cells but no segmental sclerosis. Treatment with 12 courses of low-density lipoprotein apheresis (LDL-A) reduced proteinuria from 9.6 to 2.0 g/d, and incomplete remission has been maintained for more than 1 yr after LDL-A with slowly progressive renal dysfunction. Despite recent therapeutic advances, including the use of immunosuppressants and PEX, treatment of recurrent disease remains difficult. The LDL-A might be useful in cases with recurrent FSGS resistant to PEX.

Adult↗
PubMed2005

Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study.

BACKGROUND: Chronic kidney disease has been shown to be an independent risk factor for cardiovascular disease in high-risk populations. However, this relationship is inconclusive in community-based populations. METHODS: To clarify this issue, we followed 2634 community-dwelling individuals without cardiovascular disease, aged 40 years or older, for 12 years and examined the relationship between chronic kidney disease and the incidence of cardiovascular disease. RESULTS: During the follow-up period, 99 subjects (56 men and 43 women) experienced coronary heart disease, 137 subjects (60 men and 77 women) ischemic stroke, and 60 subjects (26 men and 34 women) hemorrhagic stroke. In men, the age-adjusted incidence of coronary heart disease was significantly higher in subjects with chronic kidney disease than in those without it (6.2 vs. 2.9 per 1000 person-years) (P < 0.05), but such a relationship was not observed with ischemic stroke. In contrast, in women, the age-adjusted incidence of ischemic stroke was significantly higher in subjects with chronic kidney disease than in those without it (3.4 vs. 2.5) (P < 0.05), while that of coronary heart disease was not. Chronic kidney disease was not found to be associated with the incidence of hemorrhagic stroke. In multivariate analysis, even after adjustments for traditional and nontraditional cardiovascular disease risk factors, chronic kidney disease was found to be an independent risk factor for the occurrence of coronary heart disease in men [hazard ratio (HR), 2.26; 95% CI, 1.06-4.79], and for the occurrence of ischemic stroke in women (HR, 1.91; 95% CI, 1.15-3.15). CONCLUSION: Our findings suggest that chronic kidney disease is an independent risk factor for the occurrence of cardiovascular disease in the general Japanese population.

Adult↗
PubMed2005

Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor, calcium sensing receptor, and cell cycle regulating factors.

The parathyroid gland (PTG) is a unique endocrine organ in which the quiescent glandular cells begin to proliferate in response to the demand for maintaining calcium (Ca) homeostasis in the progressive course of renal failure, leading to secondary hypereparathyroidism (SHPT). SHPT is characterized with continuous over-secretion of parathyroid hormone (PTH) and high turn-over bone disease, osteitis fibrosa, and the major factors include a deficiency of active vitamin D, hypocalcemia, and phosphate retention. With long-term end-stage renal failure, SHPT becomes resistant to conventional medical treatment such as phosphate binders and active vitamin D supplementation, and the growth of the PTG accelerates with the pattern of hyperplasia changing from diffuse to nodular type. In this process, the sigmoid curve between extracellular Ca concentration (exCa) and the plasma level of PTH shifts to the upper-rightward, indicating both an absolute increase in PTH secretion and the resistance of PT cells to exCa. Many experimental and human studies have revealed down-regulation of vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and retinoid X receptor (RXR) in PT cells. The sustained proliferation of PT cells after obtaining autonomicity is another characteristic feature of SHPT. In this context, it has been demonstrated that the cell cycle is markedly progressed, where the expression of cyclin-dependent kinase inhibitor (CDKI), p21 and p27, is depressed in a VDR-dependent manner. These pathological features are most evident in nodular hyperplasia, in which monoclonal proliferation is obvious, indicating the phenotypic changes have occured in PT cells. It has been observed by Fukagawa and colleagues that pharmacologically high dose of active vitamin D administered orally can cause small-size PTG hyperplasia to regress in patients with advanced SHPT. Successful renal transplantation may also restore VDR and CaSR expressions in the diffuse type, in association with increasing TUNEL-positive cells. Thus, it is important to vigorously treat SHPT when the PT cell proliferation is in the reversible stage of diffuse hyperplasia.

Cell Cycle Proteins↗
PubMed2005

[Current status of pancreas transplantation in Japan].

The pancreas transplantation is widely performed for the patients with type 1 diabetes. To date in Japan we had 20 SPK or PAK transplants under the new brain death law launched in 1997. Despite severe shortage of organ donors and marginal donors such as old age, unstable homodynamic situation at agonal phase and atherosclerosis, all patients enjoy a post-operative life except two patients who had grafts removed due because of thrombosis and perforation. There are some reports recently presented at the meeting with respect to simultaneous pancreas kidney transplantations from living donors. It will be expected to have more donors and transplantation with satisfactory results in Japan as well.

Adult↗
PubMed2004

Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune diseases.

Suppressor of cytokine signaling (SOCS)-1 is a cytokine-inducible, negative regulatory molecule of Janus kinases (JAK) and its deficiency causes hyper-response to various cytokines. SOCS-1(-/-) mice spontaneously develop a fatal disease depending on aberrantly activated lymphocytes. Here, we show that partial restoration of SOCS-1 in lymphoid cells rescues SOCS-1(-/-) mice from the early-onset fatal disease, indicating that SOCS-1 expression in vivo is especially required in lymphocytes. However, SOCS-1 expression in these SOCS-1-restored mutant mice (E( micro )-SOCS-1(-/-) mice) was insufficient for proper down-regulation of its target signaling, and these mice spontaneously exhibit hyperactivation of lymphocytes, an increase in the levels of serum Ig and anti-DNA autoantibodies, and glomerulonephritis with glomerular IgG deposition. These phenotypes resemble those of murine systemic autoimmune diseases, models for systemic lupus erythematosus (SLE). Interestingly, similar phenotypes were also observed in adult female SOCS-1(+/-) mice, indicating that the autoimmune phenotypes of these mice can be ascribed primarily to the inadequate expression of SOCS-1. In addition, autoimmune phenotypes were not observed in SOCS-1(+/-)CD4(-/-) mice, suggesting that autoimmunity is dependent on hyper-activated CD4(+) T cells. Our findings also suggest that insufficient expression of SOCS-1 results in impaired function of CD25(+)CD4(+) regulatory T cells, which may contribute to aberrant activation of CD4(+) T cells. These findings suggest that dysfunction of SOCS-1 can be a pathogenic factor of systemic autoimmune diseases such as SLE.

Animals↗
PubMed2004

Up-regulated interleukin-4 production by peripheral T-helper cells in idiopathic membranous nephropathy.

BACKGROUND: Helper T (Th) cells are classified into Th1 and Th2 subsets based on cytokine production and the Th1/Th2 paradigm explains differences in inflammatory effector pathways in various human diseases. Membranous nephropathy (MN) is an immune complex disease associated with Th2 nephritogenic immune response. However, overproduction of interleukin (IL)-4, a principal Th2 cytokine, has not been demonstrated. We investigated Th1/Th2 cytokine production by peripheral Th cells and its association with the degree of proteinuria in MN. METHODS: We analysed production of Th1/Th2 cytokines, interferon (IFN)-gamma and IL-4 by peripheral Th cells, using an intracellular cytokine detection method with flow cytometry in patients with MN (n = 24). The data were compared with data from healthy subjects (n = 51), subjects with minimal change nephrotic syndrome (MCNS; n = 13) and subjects with focal segmental glomerulosclerosis (FSGS; n = 12). We compared the percentages of IFN-gamma+ and IL-4+ Th cells and the peripheral Th1/Th2 ratio (IFN-gamma/IL-4 ratio) among the four groups. We also examined the association of IFN-gamma and IL-4 production with clinical parameters of MN. RESULTS: The mean percentage of IL-4+ cells in MN (3.9+/-1.2%) was significantly higher than in the control (2.4+/-1.0%), MCNS (2.3+/-1.4%) and FSGS (2.3+/-1.2%) groups (P<0.001, respectively). The Th1/Th2 ratio was significantly lower in MN (5.3+/-2.0) than in the control (8.2+/-4.2, P<0.05), MCNS (10.0+/-5.3, P<0.01) and FSGS (10.2+/-5.3, P<0.01) groups. Moreover, the percentage of IL-4+ cells correlated significantly with the amount of proteinuria in MN (r = 0.57, P<0.01). CONCLUSIONS: IL-4 production by peripheral Th cells is up-regulated in patients with MN and correlated with the severity of proteinuria. Intracellular cytokine analysis could be a useful index in idiopathic MN.

Adult↗