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Kouichi Hirayama

Publications and source records attributed to Kouichi Hirayama.

At least 19 recordsLinked to original sources
PubMed2006

Tissue-specific distribution of an alternatively spliced COL4A5 isoform and non-random X chromosome inactivation reflect phenotypic variation in heterozygous X-linked Alport syndrome.

A novel type of hereditary transmission of COL4A5 in a Japanese family with X-linked Alport syndrome was detected through analysis of cDNA sequences and an X-chromosome inactivation assay. A female patient with moderately altered renal function, who was diagnosed with Alport syndrome by renal biopsy, and her mother, who was undergoing maintenance haemodialysis, showed similar tissue-specific expression of a truncated isoform of COL4A5, which was generated by alternative splicing without a splice-site mutation. Expression of the truncated isoform occurred in the renal specimen derived from the patient, but not in specimens from controls. Genomic analysis revealed two point mutations (c.4821 + 121, T>C; c.4822-151_150, ins T) in intron 49 of COL4A5 from the patient. The peripheral blood mononuclear cells of the patient and her mother showed non-random lyonization. While the females showed only renal impairment, an affected male in the same family suffered from severe renal insufficiency, visual defect and hearing disturbances. Hence, we suggest that this type of heredity COL4A5 presents with phenotypic variation in female heterozygous X-linked Alport syndrome patients.

Adult↗
PubMed2006

Tubulointerstitial nephritis and uveitis syndrome associated with hyperthyroidism.

We report a 17-year-old male patient with tubulointerstitial nephritis and uveitis (TINU) associated with hyperthyroidism. He presented with a 2-month history of fatigue, loss of appetite, low-grade fever, and a 12-kg weight loss when he was admitted to our hospital. He had iritis, which was complicated by fibrin in the anterior chamber, diagnosed by slit-lamp examination. On laboratory examinations, deteriorated renal function (blood urea nitrogen level was 25.9 mg/dl and creatinine level was 2.82 mg/dl) and elevated urinary levels of N-acetyl-beta-D-glucosaminidase (33.1 U/l) and beta2-microglobulin (78,600 microg/l) were observed. Serum thyroid-stimulating hormone (TSH) was undetectable, at less than 0.01 microIU/ml, and free triiodothyronine and free thyroxine were elevated, up to 5.23 pg/ml and 2.85 ng/dl, respectively. The titers of antithyroglobulin and antithyroid microsomal and TSH-receptor antibodies were not elevated. Abdominal and thyroidal ultrasonography showed evident bilateral enlargement of the kidneys and diffuse enlargement of the thyroid gland. Iodine-123 scintigraphy showed low uptake in the thyroid gland. The biopsied renal specimen showed mild edema and severe diffuse infiltration of mononuclear cells and few eosinophils in the interstitium, without any glomerular or vascular abnormalities. Based on the clinical features and pathological findings, a diagnosis of TINU syndrome with associated hyperthyroidism was made. Treatment was started with 30 mg/day of prednisolone. The iritis disappeared, and the patient's clinical status improved remarkably. This case suggests the possibility of thyroid dysfunction in some patients with TINU syndrome, and we believe thyroid function should be measured in all TINU patients. Moreover, histopathological diagnosis of the thyroid glands before treatment is necessary for TINU patients with thyroid dysfunction.

Adolescent↗
PubMed2005

Apheresis for MPO-ANCA-associated RPGN-indications and efficacy: lessons learned from Japan nationwide survey of RPGN.

A national survey concerning rapidly progressive glomerulonephritis (RPGN) was conducted in Japan between 1989 and 2000 and resulted in the registration of 715 patients with RPGN. Among the documented patients, the most frequent primary disease was primary pauci-immune crescentic glomerulonephritis (n = 283), and the second most frequent was microscopic polyangitis (n = 127). Overall, 370 patients had MPO-ANCA, and 23 patients had PR3-ANCA. We found that both renal and patient survivals were significantly worse in patients with MPO-ANCA-associated RPGN than patients with PR3-ANCA. Fifty-three patients received apheresis therapy with various combinations of immunosuppressive regimens. They had higher serum creatinine, higher CRP, and a higher frequency of complicated pulmonary involvements as compared to the controls without apheresis therapy. In dialysis-dependent patients, no additional benefit from apheresis therapy was observed. Only pulmonary renal syndrome patients with CRP > 6 mg/dl at presentation showed a slightly better prognosis (patient survival with apheresis; 66.7%, without apheresis; 56.7%). Furthermore, a rapid MPO-ANCA titer reduction was observed in patients treated with apheresis. Patients with MPO-ANCA-associated RPGN were older, and had more chronic and sclerotic lesions than patients with PR3-ANCA-associated RPGN. Based on these findings, we suggest that a lower dose of immunosuppressant should be considered in order to avoid opportunistic infection. In this situation, cytapheresis is the treatment of choice. Nevertheless, in patients with an aggressive form of RPGN with rapid deterioration of renal function like the PR3-ANCA-associated RPGN, or pulmonary renal syndrome complicated severe inflammation, or relapses with high MPO-ANCA titer, we conclude that apheresis therapy should be considered.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Erythropoietin-resistant anaemia in a predialysis patient with Klinefelter syndrome.

A diabetic predialysis patient who had significantly reduced sensitivity to erythropoietin therapy was admitted to Tsukuba University Hospital. Many factors that might have been the cause of the erythropoietin resistance were examined, and a diagnosis of refractory anaemia was made based on a bone marrow aspiration biopsy. A cytogenetic abnormality (47, XXY) was also detected in the bone marrow biopsy specimen, and hence the patient was also diagnosed with Klinefelter syndrome. It was suspected that the sex chromosome abnormality influenced glucose intolerance, renal insufficiency, and erythropoietin resistance due to myelodysplastic changes in the bone marrow.

Anemia↗
PubMed2005

Acute multifocal bacterial nephritis complicated with acute renal failure and thrombocytopenia.

A 50-year-old woman was transferred to our hospital because of acute renal failure and thrombocytopenia. Due to rapid enlargement of the kidney, we first suspected that she had diffuse renal invasion of anaplastic carcinoma or lymphoma of the kidney. Anti-bacterial treatment for complicated urinary tract infection and hemodialysis treatment resulted in recovery of both renal function and thrombocytopenia. Serial CT study demonstrated disappearance of kidney swelling and multiple masses within the kidney. We finally made a diagnosis of acute multifocal bacterial nephritis. Timely initiation of dialysis therapy and appropriate anti-bacterial treatment was essential to rescue this case.

Acute Disease↗
PubMed2004

In vivo imaging of oxidative stress in ischemia-reperfusion renal injury using electron paramagnetic resonance.

Oxidative stress during ischemia-reperfusion acute renal failure (IR-ARF) was noninvasively evaluated with in vivo electron paramagnetic resonance (EPR) imaging. Female ICR mice underwent left nephrectomy and 30-min ischemia-reperfusion of the right kidney. Oxidative stress was evaluated as organ reducing activity with the half-lives of the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) using 1) conventional L-band EPR, which showed organ-reducing activity in the whole abdominal area; and 2) EPR imaging, which showed semiquantitative but organ-specific reducing activity. The results were compared with the reducing activity of organ homogenate and phosphatidylcholine hydroperoxide (PC-OOH) concentrations. Half-lives of carbamoyl-PROXYL in the whole upper abdominal area, measured by L-band EPR, were prolonged on day 3 after ischemia-reperfusion and recovered to the level of nontreated mice on day 7. This trend resembled closely that of serum creatinine and blood urea nitrogen concentration. The EPR imaging-measured carbamoyl-PROXYL half-life was also prolonged on day 3 in both the kidney and the liver. However, in the kidney this showed only partial recovery on day 7. In the liver, this convalescence was more remarkable. The ex vivo studies of organ reducing activity and PC-OOH agreed with the results from EPRI, but not with those from L-band EPR. These results indicate that renal reducing activity shows only partial recovery on day 7 after ischemia-reperfusion, when serum creatinine and blood urea nitrogen have recovered. EPR imaging is an appropriate and useful method for the noninvasive evaluation of oxidative stress in the presence of renal injury.

Acute Kidney Injury↗
PubMed2004

Age distribution and yearly changes in the incidence of ESRD in Japan.

BACKGROUND: Although several treatment and screening methods have been tried, the incidence of patients with end-stage renal disease (ESRD) on renal replacement therapy (RRT) continues to increase worldwide. By making a detailed analysis of the major primary renal diseases, we found there have been some favorable effects in the incidence rate of ESRD recently in Japan. METHODS: A total of 339,478 patients in Japan and 909,591 patients in the United States started RRT between 1983 and 1999. We compared trends of average age and incidence rate in each age group with major primary renal diseases and in racial groups after adjusting for general population aging by using a linear regression analysis. RESULTS: All trends in ESRD incidence rates among Japanese, US total, US white, and US black patients showed significant increases (P < 0.001). A significant positive linear relationship between year and mean age at start of RRT also was observed (P < 0.001). After adjustment for general population aging, the mean age increment in Japanese patients with glomerulonephritis was increased significantly, and the proportion of Japanese patients who had glomerulonephritis and were younger than 45 years was decreased, but this decrement was not observed in US patients with glomerulonephritis. CONCLUSION: The reduced number of new patients with ESRD with glomerulonephritis might be caused by early detection and early referral to nephrologists as a result of the Japanese urinalysis-screening program. To reduce the ESRD population, it will be necessary to establish more effective treatment methods to delay exacerbation of progressive renal diseases.

Adult↗
PubMed2004

Treatment with the purine synthesis inhibitor mizoribine for ANCA-associated renal vasculitis.

BACKGROUND: The common treatment for antineutrophil cytoplasmic autoantibody (ANCA)-associated renal vasculitis is oral cyclophosphamide (CYC)-corticosteroid combination therapy. However, there are serious complications associated with long-term use of CYC. In this study, we investigate the efficacy of a purine synthesis inhibitor, mizoribine, for patients at high risk for relapse. METHODS: Our study included 5 patients, 4 patients with myeloperoxidase (MPO)-ANCA-associated renal vasculitis and 1 patient with proteinase 3 (PR3)-ANCA-associated renal vasculitis, who had achieved remission through treatment with methylprednisolone pulse therapy, corticosteroids, and CYC. When their ANCA titers were found to be greater than normal range after remission status, mizoribine treatment was initiated. RESULTS: Median time from initial treatment to first administration of mizoribine was 40.0 months (range, 24 to 51 months). Median follow-up was 13.0 months (range, 6 to 16 months). Before initiation of mizoribine treatment, no patient had experienced relapse and ANCA titers were less than the detectable range in all patients at 3 months before mizoribine administration. When mizoribine administration was started, ANCA titers were elevated in all patients (median MPO-ANCA, 101 ELISA units [EU]; range, 65 to 154 EU; PR3-ANCA, 55 EU), but no new symptoms or signs of relapse were noted. After 2 months of mizoribine treatment, only 1 patient had experienced a relapse; however, ANCA titers had decreased in all other patients and normalized in 3 patients. No adverse effects appeared in any patient. CONCLUSION: Considering the balance between suppression of disease activity and adverse effects of treatment, mizoribine may be useful for preemptive treatment for patients with ANCA-associated renal vasculitis at high risk for relapse.

Aged↗
PubMed2004

Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.

BACKGROUND: IgA nephropathy is the most common form of glomerulonephritis worldwide. We previously reported a novel form of glomerulonephritis with glomerular IgA deposits following methicillin-resistant Staphylococcus aureus (S. aureus) infection. We investigated the role of S. aureus related antigens in the immunopathogenesis of IgA nephropathy by producing several monoclonal antibodies against S. aureus surface antigens and determining the epitopes of deposited antigens in patients with IgA nephropathy. METHODS: Cell membrane proteins were isolated from cultured S. aureus. Mouse monoclonal antibodies against these proteins were generated, and their target epitopes were determined by antibody affinity chromatography and amino acid sequence analysis, and by monoclonal antibody screening of Escherichia coli clones transfected with plasmids from the Lambda S. aureus Genomic Library. Renal biopsy specimens from 116 patients with IgA nephropathy and 122 patients with other forms of renal disease were examined for glomerular antigen depositions by immunofluorescence microscopy. RESULTS: . The major antigen recognized by monoclonal antibodies against S. aureus cell membrane was identified as the S. aureus cell envelope antigen designated 'probable adhesin' (ACCESSION AP003131-77, Protein ID; BAB41819.1). In 68.1% (79/116) of renal biopsy specimens from patients with IgA nephropathy, S. aureus cell envelope antigen was localized in the glomeruli, and the data confirmed that S. aureus cell envelope antigen was co-localized with IgA antibody in the glomeruli. No deposition of this antigen was detected in the glomeruli of patients with non-immune complex deposit forms of glomerulonephritis. CONCLUSION: S. aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.

Amino Acid Sequence↗
PubMed2004

[Epidemiology of nephrotic syndrome].

Causes of nephrotic syndrome are varied with age, the times, geographical location and race. In children, minimal change nephrotic syndrome (MCNS) is common; however, membranous nephropathy (MN) is most frequent in adult. Incidence of membranoproliferative glomerulonephritis (MPGN) is decreased in advanced nations, although it remains a common in developing countries. In advanced nations, incidence of focal and segmental glomerular sclerosis (FGS) is increased, particularly in black populations. In Japan, MCNS was most frequent (37.7%), and then, MN was 23.3%, FGS was 7.2% and MPGN was 8.3% by a former research (in 1985). The recent research (in 1994) showed that MCNS was 41.5%, and next MN was 24.7%. FGS was increased to 11.8% and MPGN was decreased to 4.9%.

Age Factors↗
PubMed2003

EPR imaging of reducing activity in Nrf2 transcriptional factor-deficient mice.

Mice that lack the Nrf2 (NF-E2-related factor 2) transcription factor develop a lupus-like autoimmune nephritis. The tissue-reducing activity of Nrf2-deficient mice was evaluated using a combination of real-time EPR imaging and spin probe kinetic analysis. Substantial delay in the spin probe 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL) disappearance in the liver and kidneys of Nrf2-deficient mice was observed by EPR imaging. The half-life of the spin probe in the upper abdominal area was prolonged in both the Nrf2-deficient mice and in aged mice. The combination of Nrf2 deficiency and aging in female mice resulted in the most prolonged half-life of disappearance, which was four times longer than that of juvenile female mice with a wild-type genotype. These results indicate that the low reducing activity in these organs is brought about by both Nrf2 deficiency and the aging process, and it may play a key role in the onset of autoimmune nephritis. This combination of the EPR imaging and half-life analysis appears to be a very powerful tool in the real-time analysis of reducing activity.

Animals↗
PubMed2003

Oxidative stress during leukocyte absorption apheresis.

Leukocyte absorption apheresis absorbs leukocytes to the apheresis columns involving leukocyte activation. This process is regarded as bioincompatible and avoided in hemodialysis or other extracorporeal circulation processes. Thus, leukocyte apheresis has a potential risk to exacerbate in vivo oxidative stress. We evaluated the changes in plasma oxidative stress during leukocyte apheresis. Patients diagnosed as ulcerative colitis (UC) and treated with leukocyte apheresis were studied. Adacolumn (celluloseacetate beads) or Cellsorba EX (polyethylenephtarate fiber) was used for the leukocyte absorption device. Oxidative stress was measured by thiobarbituric acid reactive substances (TBARS) and hydroxyl radical ((*)OH) scavenging activity. Plasma samples were collected from the pre- and post-column sampling port at the start, and from the pre-column sampling port at the end of the treatment. The (*)OH signal intensities (OHRI) significantly increased during a column passage, indicating a loss of plasma (*)OH scavenging activity. However, OHRI was reduced at the end, suggesting a recovery of radical scavenging activity during leukocyte apheresis. Significant decreases of OHRI and TBARS were only observed in the early phase of the therapeutic course. No differences of OHRI and TBARS levels were observed between the two columns. These results indicate that though the plasma antioxidant activity was diminished by a column passage, plasma antioxidant activity recovers during the procedure. This efficient antioxidative effect is limited to the early phase of the therapeutic course.

Biocompatible Materials↗
PubMed2002

Mitochondrial DNA mutations in focal segmental glomerulosclerosis lesions.

Glomerular epithelial cells are primary pathogenic sites in focal segmental glomerulosclerosis (FGS) lesions. Glomerular epithelial cells are regarded as terminally differentiated cells that do not proliferate. These characteristics are also noted for neurons and muscular cells, which are major sites of mitochondrial DNA (mtDNA) mutation accumulation. Screening for mtDNA mutations was performed with renal biopsy specimens from patients with primary FGS and patients with IgA nephropathy (as subjects with secondary FGS and as control subjects). mtDNA extracted from kidney biopsy specimens was amplified with appropriate primer pairs for study of the mtDNA point mutations 3243A-->G, 3271T-->C, 8344A-->G, and 8993T-->G/C, as well as the common deletion (a 4977-bp deletion spanning mtDNA nucleotide pairs 8469 to 13447). In situ amplification of both total mtDNA and the common deletion was also performed. Two patients with FGS demonstrated the 3243A-->G point mutation; 12 patients with FGS and seven patients with IgA nephropathy accompanied by glomerulosclerotic lesions exhibited the common deletion in their kidney tissue. No patient demonstrated the mtDNA mutations 3271T-->C, 8344A-->G, or 8993T-->G/C. The degree of heteroplasmy for the 3243A-->G point mutation was >85%; however, the heteroplasmy for the common deletion was <1%. As determined with in situ PCR, normal mtDNA was mainly distributed in the tubular epithelium and mtDNA with the common deletion was mainly distributed among glomerular epithelial cells. In conclusion, it is suggested that mtDNA mutations are distributed in glomerular epithelial cells among some patients with primary FGS or secondary FGS with IgA nephropathy. These mutations may be related to glomerular epithelial cell damage.

Adolescent↗