Publications by authors named "Katsusuke Yamamoto"

13 Publications

  • Page 1 of 1

Alkaline phosphatase in pediatric patients with genu varum caused by vitamin D-deficient rickets.

Endocr J 2021 Mar 24. Epub 2021 Mar 24.

Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.

An elevated serum alkaline phosphatase (ALP) level is one of the markers for the presence of rickets in children, but it is also associated with bone formation. However, its role in diagnosing genu varum in pediatric patients with vitamin D-deficient rickets is still unknown. To clarify the role of the serum ALP level in assessing the severity of genu varum, we retrospectively investigated this issue statistically using data on rickets such as serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, ALP, the level of creatinine as the percentage of the median according to age (%Cr), and the metaphyseal diaphyseal angle (MDA) in the lower extremities as an index of the severity of genu varum. A multiple regression analysis revealed that log ALP and %Cr values were negatively associated with MDA values. The former association was also confirmed by a linear mixed model, while iPTH was positively associated with MDA by path model analysis. To elucidate the association of ALP with MDA in the presence of iPTH, we investigated three-dimensional figures by neural network analysis. This indicated the presence of a biphasic association of ALP with MDA: the first phase increases while the second decreases MDA. The latter phenomenon is considered to be associated with the increase in bone formation due to the mechanical stress loaded on the lower extremities. These findings are important and informative for pediatricians to understand the significance of the serum ALP level in pediatric patients with genu varum caused by vitamin D deficiency.
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http://dx.doi.org/10.1507/endocrj.EJ20-0622DOI Listing
March 2021

Hyponatremia due to unopened septa of peritoneal dialysis fluid bags.

Pediatr Int 2020 07 23;62(7):878-879. Epub 2020 Jun 23.

Department of Pediatric Nephrology and Metabolism, Osaka Women's and Children's Hospital, Osaka, Japan.

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http://dx.doi.org/10.1111/ped.14209DOI Listing
July 2020

Clinical and genetic characterization of nephropathy in patients with nail-patella syndrome.

Eur J Hum Genet 2020 10 26;28(10):1414-1421. Epub 2020 May 26.

Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Nail-patella syndrome (NPS) is a multi-system disorder characterized by hypoplastic nails, hypoplastic patella, skeletal deformities, and iliac horns, which is caused by heterozygous variants of LMX1B. Nephropathy ranging from mild urinary abnormality to end-stage renal disease occurs in some individuals with NPS. Because of the low prevalence of NPS and the lack of longitudinal studies of its kidney involvement, the clinical, pathological, and genetic features characterizing severe nephropathy remain unclear. We conducted a Japanese survey of NPS with nephropathy, and analyzed their clinical course, pathological features, and factors associated with severe renal phenotype. LMX1B gene analysis and luciferase reporter assay were also performed. Among 13 NPS nephropathy cases with genetic validation, 5 patients who had moderate-to-massive proteinuria progressed to advanced chronic kidney disease or end-stage renal disease. Pathological findings in the early phase did not necessarily correlate with renal prognosis. Variants associated with deteriorated renal function including a novel variants were confined to the N-terminal region of the LIM domain and a short sequence in the LMX1B homeodomain, which were distinct from reported variants found in isolated nephropathy without extrarenal manifestation (LMX1B-associated nephropathy). Luciferase reporter analysis demonstrated that variants in patients with severe renal phenotype caused haploinsufficiency, but no dominant-negative effects on promoter activation. A distinct proportion of NPS nephropathy patients progressed to end-stage renal disease in adolescence or young adulthood. Patients with moderate or severe proteinuria, especially those with variants in specific regions of LMX1B, should be monitored for potential deterioration of renal function.
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http://dx.doi.org/10.1038/s41431-020-0655-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608088PMC
October 2020

Reduction in urinary angiotensinogen levels and improvement of proteinuria by renin-angiotensin system blockade in pediatric chronic kidney disease patients with very low birth weight.

Pediatr Nephrol 2020 07 11;35(7):1307-1314. Epub 2020 Mar 11.

Department of Pediatric Nephrology and Metabolism, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan.

Background: Children with low birth weight (LBW) have an increased risk of developing chronic kidney disease (CKD), and no effective strategies have been established to prevent the progression of CKD in these patients. Urinary angiotensinogen (UAGT) may represent a useful marker of intrarenal renin-angiotensin system (RAS) activation, which has been suggested to play a critical role in the development of hypertension and CKD. Herein, we conducted a prospective study to determine whether RAS blockade is beneficial for suppressing the progression of CKD in children with LBW, using UAGT as a surrogate marker of renal impairment.

Methods: Nine children with CKD (stages: 1-2) who had very low birth weight (VLBW; < 1500 g) were started on RAS blockade with candesartan. We measured blood pressure and laboratory parameters, including urinary concentrations of angiotensinogen, protein, albumin, creatinine (Cr), and estimated glomerular filtration rate (eGFR), before and after candesartan treatment.

Results: Birth weight was 712 g (range, 536-800 g). Age at evaluation was 11.6 years (range, 10.3-15.6 years). After candesartan treatment for 47.6 ± 25.0 months, the UAGT to urinary Cr ratio decreased from 61.9 ± 44.7 to 16.8 ± 14.4 μg/g (p = 0.015). The urinary protein to Cr and albumin to Cr ratios also decreased (p = 0.008 and p = 0.012, respectively), whereas there was no significant change in eGFR.

Conclusions: RAS blockade reduced UAGT levels and improved proteinuria/albuminuria in children with CKD who had VLBW. Suppression of intrarenal RAS activity may slow the progression of CKD in children with LBW.
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http://dx.doi.org/10.1007/s00467-020-04520-8DOI Listing
July 2020

Complete oculocerebrorenal phenotype of Lowe syndrome in a female patient with half reduction of inositol polyphosphate 5-phosphatase.

CEN Case Rep 2020 05 9;9(2):95-100. Epub 2019 Nov 9.

Department of Pediatrics, Minoh City Hospital, 5-7-1 Kayano, Minoh City, Osaka, 562-8562, Japan.

The oculocerebrorenal disorder of Lowe syndrome is an X-linked mutation in the gene oculocerebrorenal syndrome of Lowe 1 (OCRL), characterized by the triad of congenital cataracts, severe intellectual impairment, and renal tubular dysfunction. Manifestations of phenotype in female carriers and patients are extremely rare. We present a female case with congenital cataracts, severe intellectual impairment, sensorineural hearing loss, and renal tubular dysfunction as Lowe syndrome. A 9-year-old Japanese girl visited our hospital due to prolonged proteinuria. Her renal biopsy revealed diffuse mesangium proliferation, sclerosis and dilatation of renal tubules, and mild IgA deposition in the mesangial region. Furthermore, she had congenital cataracts, severe intellectual impairment, and sensorineural hearing loss. Genetic screening did not identify mutations of the ORCL gene encoding inositol polyphosphate 5-phosphatase (IPP-5P) (46 XX, female). However, we found the reduction of enzyme activity of IPP-5P to 50% of the normal value. Furthermore, her renal function had deteriorated to renal failure within a decade. Finally, she received peritoneal dialysis and renal transplantation. We present the oculocerebrorenal phenotype of Lowe syndrome in a female patient with reduced activity of IPP-5P without OCRL gene mutation.
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http://dx.doi.org/10.1007/s13730-019-00434-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148414PMC
May 2020

Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia: Results from a Japanese clinical trial.

Clin Endocrinol (Oxf) 2017 Jul 2;87(1):10-19. Epub 2017 May 2.

Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.

Objective: Hypophosphatasia (HPP) is a rare skeletal disease characterized by hypomineralization and low alkaline phosphatase activity. Asfotase alfa (AA) has been recently developed to treat HPP complications. This study evaluated its safety and efficacy in Japan.

Design: Open-label, multicentre, prospective trial. Patients were enrolled in 11 hospitals from June 2014 to July 2015.

Patients: Thirteen patients (9 females, 4 males) ages 0 days to 34 years at baseline were enrolled and treated with AA (2 mg/kg three times weekly subcutaneously in all but one patient). All had ALPL gene mutations. HPP forms were perinatal (n=6), infantile (n=5), childhood (n=1) and adult (n=1).

Measurements: Safety determined from adverse events (AEs) and laboratory data was the primary outcome measure. Efficacy was assessed as a secondary outcome measure from overall survival, respiratory status, rickets severity and gross motor development.

Results: Injection site reactions were the most frequent AEs. Serious AEs possibly related to treatment were convulsion and hypocalcaemia observed in a patient with the perinatal form. In addition, hypercalcaemia and/or hyperphosphatemia was observed in three patients with the infantile form and a low-calcium and/or low-phosphate formula was given to these patients. With respect to efficacy, all patients survived and the radiographic findings, developmental milestones and respiratory function improved.

Conclusion: Asfotase alfa therapy improved skeletal, respiratory and physical symptoms with a few serious AEs in patients with HPP. Our results add support to the safety and efficacy of AA therapy for HPP patients.
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http://dx.doi.org/10.1111/cen.13343DOI Listing
July 2017

Risk factors associated with a decreased estimated glomerular filtration rate based on cystatin C levels in school-age children with extremely low birthweight.

Nephrology (Carlton) 2017 Jun;22(6):463-469

Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.

Aim: A single centre retrospective cohort study was designed to investigate the estimated glomerular filtration rate (eGFR) in school-age children born with extremely low birthweight (ELBW) and to determine risk factors predictive of decreased eGFR.

Methods: We compared eGFR based on cystatin C (CysC-eGFR) between school-age children born with ELBW (ELBW group, n = 48; median gestational age: 26.9 weeks; median birthweight: 792 g) and children born at term (control group, n = 48). The ELBW group was then further divided into a decreased CysC-eGFR subgroup (eGFR <90 mL/min per 1.73 m , n = 20) and a normal CysC-eGFR subgroup (n = 28), and perinatal background factors were compared.

Results: The ELBW group showed a significantly lower CysC-eGFR compared with the control group (P < 0.001). Comparison between the decreased and normal CysC-eGFR subgroups in the ELBW group showed that children with lower birthweight, shorter gestational age, lower 5-min Apgar score, longer length of mechanical ventilation, lower weight gain in the first 11 weeks, chronic lung disease, and postnatal corticosteroid administration had significantly decreased CysC-eGFR. Multivariate logistic regression showed that a lower 5-min Apgar score was the only independent risk factor for decreased CysC-eGFR.

Conclusions: CysC-eGFR might already be decreased at school age in children born with ELBW. Renal assessment in regular follow-up examinations is recommended.
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http://dx.doi.org/10.1111/nep.12807DOI Listing
June 2017

Early therapy with neuraminidase inhibitors for influenza A (H1N1) pdm 2009 infection.

Pediatr Int 2013 Dec 12;55(6):714-21. Epub 2013 Aug 12.

Department of Pediatrics, Minoh City Hospital, Osaka, Japan.

Background: Neuraminidase inhibitors have been reported to decrease mortality in patients infected with influenza A (H1N1) pdm 2009 (H1N1 pdm09), but it is not clear whether they are effective against H1N1pdm09 in apparently healthy children.

Methods: The effect of early treatment with neuraminidase inhibitors on 70 otherwise healthy children with possible H1N1 pdm09 (pH1N1pdm09) infection was investigated. The children were simultaneously treated with a neuraminidase inhibitor (oseltamivir or zanamivir) and maoto, a Japanese traditional herbal medicine, which had been reported to be effective against seasonal influenza. Clinical severity was assessed using patient history, namely the worst values for clinical vital signs and laboratory data on admission. After refining these parameters with univariate, decision tree and multiple regression analysis, mean covariance structure equation analysis was used to investigate the association of estimated clinical severity to the selected parameters.

Results: Total path analysis using a Bayesian method indicated that the estimated clinical severity of pH1N1pdm09 was positively associated with maximum body temperature, pulse rate, respiration rate, duration necessary for defervescence, admission duration and log urinary β2-microglobulin/creatinine level, and negatively associated with age and the presence and duration of treatment with the neuraminidase inhibitor in the outpatient clinic.

Conclusions: This study provides the first clinical evidence that early treatment with neuraminidase inhibitors in outpatient clinic decreased the estimated clinical severity of pH1N1pdm09 in apparently otherwise healthy pediatric inpatients.
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http://dx.doi.org/10.1111/ped.12154DOI Listing
December 2013

Serum immunoglobulin G subclass levels and estimated clinical severity caused by possible influenza A (H1N1) pdm 2009 infection.

J Infect Chemother 2013 Oct 7;19(5):833-42. Epub 2013 Mar 7.

Department of Pediatrics, Minoh City Hospital, 5-7-1 Kayano, Minoh, Osaka, 562-8562, Japan,

The clinical severity of the 2009 pandemic H1N1 influenza (H1N1 pdm09) was thought to be related to the difference between the amount of viral load and condition of the host immune response. We investigated the role of serum levels of IgG and its subclasses in clinical severity using the data from 45 child inpatients suffering from bronchitis or mild pneumonia caused by possible H1N1 pdm09 (pH1N1 pdm09) infection. After selecting parameters for serum IgG subclasses and logarithmically transformed urinary beta-2 microglobulin/creatinine (b2MG/Cr) values and admission duration, we performed path analysis using a mean covariance structure equation analysis to investigate the relationship between the clinical severity and the foregoing selected parameters. Total path analyses using a Bayesian method revealed that the estimated clinical severity caused by pH1N1 pdm09 was positively associated with maximal respiration rates, admission duration, and log urinary b2MG/Cr levels, whereas negatively associated with serum IgG, IgG1, IgG2, and IgG3 levels, duration of neuraminidase inhibitor therapy in outpatient clinics, and age. Serum IgG and its subclasses (IgG1-IgG3) reduced estimated clinical severity in children with pH1N1 pdm09 infection.
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http://dx.doi.org/10.1007/s10156-013-0570-4DOI Listing
October 2013

IgG3 deficiency and severity of 2009 pandemic H1N1 influenza.

Pediatr Int 2012 Dec 9;54(6):758-61. Epub 2012 Oct 9.

Department of Pediatrics Minoh City Hospital, Osaka, Japan.

Background: The severity of the 2009 pandemic H1N1 influenza (H1N1 pdm 09) in immune deficient children is unknown. The aim of the present study was to investigate this in a case of complete IgG3 deficiency complicated by pneumonia and asthma attack.

Methods: The clinical parameters of the IgG3 deficiency patient were compared with those of four control patients using 95% confidence intervals. These control patients were selected from 71 patients admitted due to pneumonia or bronchitis caused by H1N1 pdm 09, and were chosen according to age, absence of pretreatment with oseltamivir before admission, presence of a past history of asthma, use of antibiotics, and combination of inhalation of a beta2 agonist and treatment with i.v. methylprednisolone for asthma attack.

Results: The IgG3 deficiency patient had significantly longer duration of admission and period of oseltamivir, with a significantly decreased pulse oxygen saturation and increased maximum serum C-reactive protein, creatine kinase and urinary excretion of β2-microglobulin/creatinine, compared with the controls (P < 0.05).

Conclusions: Complete IgG3 deficiency is possibly associated with severity of the clinical course of pneumonia and asthma attack in children suffering from H1N1 pdm 09.
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http://dx.doi.org/10.1111/j.1442-200X.2012.03691.xDOI Listing
December 2012

[A case of Denys-Drash syndrome with prophylactic bilateral nephrectomy].

Nihon Jinzo Gakkai Shi 2003 ;45(1):42-6

Division of Nephrology and Bone Metabolism, Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka.

Denys-Drash syndrome is a rare disorder consisting of pseudohermaphrodism, Wilms' tumor and nephropathy. We describe here a boy with severe hypospadias and undescended testes, who presented with end-stage renal failure at the age of 1 year and 8 months when he was referred to our hospital. Emergency hemodialysis was performed because of oliguria, edema and severe hypertension, and then peritoneal dialysis was started. The findings of the renal biopsy showed diffuse mesangial sclerosis, consistent with the characteristic change in Denys-Drash syndrome. The analysis of WT1 gene revealed a G-to-A point mutation at 1,186 resulting in a change from Asp to Asn at 396 in exon 9. Since he had no urine output and his kidneys were not functional and in addition, patients with this mutation have been reported to have a high risk of Wilms' tumor, bilateral nephrectomy was performed. The removed kidneys showed no malignancies. Since Denys-Drash syndrome is frequently associated with Wilms' tumor, renal biopsy and gene analysis should be performed on male patients with gonadal anomaly, such as hypospadias and/or undescended testes, and proteinuria.
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May 2003

Characterization of renal chloride channel (CLCN5) mutations in Dent's disease.

J Am Soc Nephrol 2000 Aug;11(8):1460-1468

MRC Molecular Endocrinology Group, Hammersmith Hospital, London, United Kingdom.

Dent's disease is an X-linked renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and renal failure. The disease is caused by mutations in a renal chloride channel gene, CLCN5, which encodes a 746 amino acid protein (CLC-5), with 12 to 13 transmembrane domains. In this study, an additional six unrelated patients with Dent's disease were identified and investigated for CLCN5 mutations by DNA sequence analysis of the 11 coding exons of CLCN5. This revealed six mutations: four frameshift deletions involving codons 392, 394, 658, and 728, one nonsense mutation (Tyr617Stop), and an A to T transversion at codon 601 that would result in either a missense mutation (Asp601Val) or creation of a novel donor splice site. These mutations were confirmed by restriction endonuclease or sequence-specific oligonucleotide hybridization analysis and were not common polymorphisms. The frameshift deletions and nonsense mutation predict truncated and inactivated CLC-5. The effects of the putative missense Asp601Val mutant CLC-5 were assessed by heterologous expression in Xenopus oocytes, and this revealed a chloride conductance that was similar to that observed for wild-type CLC-5. However, an analysis of the mutant CLCN5 transcripts revealed utilization of the novel donor splice site, resulting in a truncated CLC-5. Thus, all of the six mutations are likely to result in truncated CLC-5 and a loss of function, and these findings expand the spectrum of CLCN5 mutations associated with Dent's disease.
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http://dx.doi.org/10.1681/ASN.V1181460DOI Listing
August 2000