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Author(s): Katsuo Tao [sup.1] , Naoya Morisada [sup.2] , Midori Awazu [sup.3] Author Affiliations: (1) Department of Pediatrics, Fukui Aiiku Hospital, , 2-301, 910-0833, Shinbo, Fukui, Fukui, Japan (2) grid.31432.37, [...]

Author(s): Katsuo Tao [sup.1] , Naoya Morisada [sup.2] , Midori Awazu [sup.3] Author Affiliations: (1) Department of Pediatrics, Fukui Aiiku Hospital, , 2-301, Shinbo, 910-0833, Fukui, Japan (2) grid.31432.37, 0000 [...]

Introduction The fractional excretion of sodium (FE.sub.Na) has been used as an index for the differential diagnosis of acute tubular necrosis (ATN) and prerenal acute kidney injury (AKI). The reliability of this index, however, decreases with the use of the diuretic agent furosemide. The fractional excretion of urea nitrogen (FE.sub.UN) has been shown to be useful in such settings in adults. The objective of this study was to examine whether FE.sub.UN is also useful in these settings in children. Methods We assessed 102 episodes of AKI in 74 children, classifying these into three groups based on history, physical examination, urine examination and subsequent clinical course: (1) prerenal AKI without furosemide (N = 37), (2) prerenal AKI with furosemide (N = 32) and (3) ATN (N = 33). Results Of the 37 prerenal AKI episodes without furosemide, 35 showed low FE.sub.Na of Conclusions FE.sub.UN is useful in detecting prerenal AKI in children administered furosemide., Author(s): Hisayo Fujita[sup.1] , Masayoshi Shinjoh[sup.2] , Tomohiro Ishii[sup.2] , Midori Awazu[sup.2] Author Affiliations: (1) Department of Pediatrics, Hiratsuka Kyosai Hospital, KanagawaJapan (2) Department of Pediatrics, Keio University School of [...]

Background Prehypertension is defined as blood pressure (BP)≥ 90th percentile, or ≥ 120/80 mmHg, but < 95th percentile for age, sex, and height. Since the definition is made by conventional BP measurements and office BP can be quite variable, we studied whether prehypertension could be differentiated by ambulatory BP monitoring from normotension or hypertension (HTN) in children and adolescents. Methods One hundred and fifty-eight children (84 boys and 74 girls, aged 6-17 years, median 12) were studied. According to the office BP values, they were divided into normotension (80), prehypertension (20), and HTN (58). Results Systolic BP index and systolic daytime ambulatory BP (ABP) were significantly higher in prehypertensive patients than in normotensives and lower than hypertensives. When daytime ABP was used to diagnose HTN, four normotensive (5.0%), four prehypertensive (20.0%), and 27 hypertensive (46.6%) patients had HTN. Thus, in patients with prehypertension, the prevalence of masked HTN is significantly higher than in those with normotension. On the other hand, the prevalence of daytime ambulatory HTN is significantly lower, i.e., white-coat effect is more frequent, compared with hypertensive patients. Conclusion Prehypertension lies between normotension and HTN in ABP values as well and is a good candidate for identifying masked HTN. Our data emphasize the importance of identifying prehypertension in children and adolescents. Keywords Hypertension * Prehypertension * Children * Adolescents * Ambulatory blood pressure * Masked hypertension, Introduction Prehypertension is a blood pressure (BP) classification that was proposed for the adult population and has recently been used also for children. The definition is BP values > 90th [...]

We previously reported that p38 mitogen-activated protein kinase (p38) and phosphorylated ERK are upregulated in cyst epithelium of human renal dysplasia and obstructive uropathy in fetal lambs (Omori S, Fukuzawa R, Hida M, Awazu M. Kidney Int 61: 899-906, 2002; Omori S, Kitagawa H, Koike J, Fujita H, Hida M, Pringle KC, Awazu M. Kidney Int 73: 1031-1037, 2008). Dysplastic epithelium is characterized by proliferation, apoptosis, and upregulation of Pax2 and transforming growth factor (TGF)-[beta]1. In the present study, we investigated whether cyclic mechanical stretching of ureteric bud cells, a mimic of the hydrodynamic derangement after fetal urinary tract obstruction, reproduces events seen in vivo. Cyclic stretch activated p38 and ERK and upregulated Pax2 expression in a time-dependent manner in ureteric bud cells. Stretch-stimulated Pax2 expression was suppressed by a p38 inhibitor, SB203580, or a MEK inhibitor, PD98059.5-Deoxyuridine incorporation was increased by stretch at 24 h, which was also abolished by SB203580 or PD98059. On the other hand, apoptosis was not induced at 24 h by stretch but was significantly increased at 48 h. TGF-[beta]1 secretion was increased by stretch at 24 h, which was inhibited by SB203580 or PD98059. Inhibition of p38 or ERK as well as anti-TGF-[beta] antibody abolished the stretch-induced apoptosis. Finally, exogenous TGF-[beta]1 induced apoptosis of ureteric bud cells, which was inhibited by SB203580 and PD98059. In conclusion, cyclic stretch induces Pax2 upregulation, proliferation, and TGF-[beta]1-mediated apoptosis, features characteristic of dysplastic epithelium, via p38 and ERK in ureteric bud cells. dysplastic kidney; obstructive uropathy; kidney development; cell signaling doi: 10.1152/ajprenal.00402.2009.

Macrophage activation syndrome, a life-threatening complication of rheumatic disorders, is accompanied by the overproduction of cytokines. We describe a girl with macrophage activation syndrome complicating systemic-onset juvenile arthritis who developed hyponatremia, hypophosphatemia, and hypouricemia associated with a high level of serum tumor necrosis factor [alpha]. Renal proximal tubule dysfunction was considered to be the cause, which may be attributable to tumor necrosis factor [alpha]. Key Words: hemophagocytic lymphohistiocytosis, renal impairment, hypophosphatemia, sodium, MACROPHAGE ACTIVATION SYNDROME (MAS), a complication of rheumatic disorders (especially systemic-onset juvenile arthritis [SOJA]), is characterized by persistent fever, pancytopenia, lymphadenopathy, hepatosplenomegaly, elevated serum liver enzyme levels, and coagulation disorder. [...]

Byline: Fusako Komoda (1), Takashi Sekine (1), Jun Inatomi (1), Atsushi Enomoto (2), Hitoshi Endou (2), Toshiyuki Ota (3), Takeshi Matsuyama (4), Tsutomu Ogata (5), Masahiro Ikeda (6), Midori Awazu (7), Koji Muroya (8), Isamu Kamimaki (9), Takashi Igarashi (1) Keywords: Renal hypouricemia; Urate transporter; hURAT1; W258X mutation Abstract: Recently, a urate transporter, hURAT1 (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. hURAT1 is presumed to play the central role in reabsorption of urate from glomerular filtrate. In the present study, we analyzed SLC22A12 in seven unrelated Japanese patients with renal hypouricemia whose serum level of urate was less than 1.0 mg/dl, and their family members. We performed direct DNA sequencing of the exon and exon-intron boundaries of SLC22A12 using genomic DNA. Six of the seven patients (86%) possess mutations in SLC22A12. In five patients, a homozygous G to A transition at nucleotide 774 within exon 4 of SLC22A12, which forms a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C to T transition within exon 3, which changes threonine at codon 217 to methionine (T217 M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in six patients, 11 were the W258X mutation (92%). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. The present study demonstrates that homozygous W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese patients. Author Affiliation: (1) Department of Pediatrics, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113--8655, Japan (2) Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan (3) Department of Pediatrics, Hiroshima Prefectural Hospital, Hiroshima, Japan (4) Department of Pediatrics, Fussa General Hospital, Tokyo, Japan (5) Department of Endocrinology and Metabolism, The National Center for Child Health and Development Research Institute, Tokyo, Japan (6) Department of Nephrology, Tokyo Metropolitan Kiyose Children&apos;s Hospital, Tokyo, Japan (7) Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan (8) Department of Pediatrics, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan (9) Department of Pediatrics, National Saitama Hospital, Saitama, Japan Article History: Registration Date: 22/01/2004 Received Date: 04/08/2003 Accepted Date: 30/12/2003 Online Date: 31/03/2004

Byline: Seiji Matsuoka (1), Midori Awazu (1) Keywords: Masked hypertension; Ambulatory blood pressure monitoring; Blood pressure; Reverse white coat hypertension; White coat normotension Abstract: Masked hypertension, a high ambulatory blood pressure (ABP) in the presence of normal office blood pressure (BP), is recognized as a risk factor for cardiovascular complications in the adult population. We evaluated the prevalence of masked hypertension in pediatric patients. We studied 136 patients (59 boys and 77 girls, aged 6--25 years, mean 13.1+-4.7 years). In all patients, office BP measurements with auscultatory technique were less than the 95th percentile for sex and age or &lt 140/90 mmHg for those over 18 years. Masked hypertension was diagnosed when either systolic or diastolic daytime ABP values were equal to or greater than the 95th percentile for sex and height of reference values or aY=135 mmHg systolic or 85 mmHg diastolic BP for those over 15 years. Among 136 patients, 15 (11%) had masked hypertension. The prevalence of masked hypertension was higher in boys (19%) than in girls (5%), but not different between younger (a$?15 years) and older (&gt 15 years) patients (11% vs. 12%). The diagnoses in the group with masked hypertension included 3 patients with diabetic nephropathy, 2 with obesity, and 2 with orthostatic dysregulation. In conclusion, masked hypertension is present in pediatric patients, and is more common in boys. Further study is needed to identify patients who may benefit from recognition of masked hypertension. Author Affiliation: (1) Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160--8582, Japan Article History: Registration Date: 25/02/2004 Received Date: 24/10/2003 Accepted Date: 11/02/2004 Online Date: 08/04/2004

Byline: Hisayo Fujita (1), Akira Yoshii (1), Jun Maeda (1), Kenjiro Kosaki (1), Seiichiro Shishido (2), Hideo Nakai (3), Midori Awazu (1,4) Keywords: Vesicoureteral reflux; Neurogenic bladder; Congenital varicella syndrome; Constipation; Microphthalmia Abstract: We describe a 1-year-old boy with congenital varicella syndrome who had vesicoureteral reflux (VUR) and neurogenic bladder. His mother had varicella during the 3rd month of pregnancy. At birth the patient presented with right microphthalmia, right microcornea, and persistent hyperplastic primary vitreous of the right eye. He had chronic constipation from 3 months of age. He had urinary tract infection at 1 year of age. Urological investigation revealed left grade V VUR and neurogenic bladder. His varicella zoster virus IgG titer measured by ELISA was 39.4 antibody index (normal &lt 0.1). He had repeated episodes of urinary tract infection despite antibiotic prophylaxis and clean intermittent catheterization, and underwent a uretero-vesiconeostomy at 2 years of age. Maternal infection during early pregnancy and the serological evidence of varicella zoster IgG antibodies without a history of varicella after birth led to the diagnosis of congenital varicella syndrome. Urogenital anomalies have previously been described in 14 cases of congenital varicella syndrome. Most of these patients had neurogenic bladder, the pathophysiology of which could be explained by the known neurotropic nature of the virus. Author Affiliation: (1) Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan (2) Department of Pediatric Urology and Kidney Transplantation, Tokyo Metropolitan Kiyose Children&apos;s Hospital, Tokyo, Japan (3) Department of Urology, Dokkyo University School of Medicine, Saitama, Japan (4) Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160--8582, Japan Article History: Registration Date: 22/01/2004 Received Date: 06/10/2003 Accepted Date: 31/12/2003 Online Date: 10/03/2004

We investigated the expression of ERK, p38 mitogen-activated protein kinase (p38), and JNK in renal tubules of diabetic rats following 3 wk after streptozotocin injection (DM). Although the expression of ERK was not different between controls and DM, phosphorylated ERK was expressed more intensely in DM. p38 And phosphorylated p38 were detected only in the diabetic kidney and were localized in all tubular segments. JNK and phosphorylated JNK were expressed similarly in controls and DM. Transforming growth factor (TGF)-[beta] was expressed in all tubular segments of DM, coinciding with the localization of p38. In LLC-P[K.sub.1] cells, phosphorylation of ERK and p38 increased after 24- to 72-h exposure to high glucose (HG). Coincubation with a p38 inhibitor SB-203580 or a MEK inhibitor, PD-98059, suppressed the HG-induced increases in protein content, [[sup.3]H]leucine incorporation, and the protein-to-DNA ratio. SB-203580 or PD-98059 also abolished the HG-stimulated expression of TGF-[beta] protein. These results demonstrate that ERK and p38 are activated in renal tubular cells of DM and may mediate HG-induced cellular hypertrophy and TGF-[beta] expression. mitogen-activated protein kinase; diabetes; kidney

The effect of arachidonate cyclooxygenase (COX) on renal vasoconstriction induced by endothelin (ET) was studied in microperfused rat kidney afferent (AA) and efferent (EA) arterioles. Indomethacin reduced the duration of vasoconstrictive effect of ET, but demonstrated no significant effect on maximal contraction of AA and EA. COX inhibition preserved glomerular filtration rate, but had no effect during tromboxane A2 antagonism. Results suggest that COX products, such as prostaglandin F2alpha, sustain AA and EA constriction induced by ET.

Byline: Y. Tanaka (1), Kiyoko Sugita (1), Takako Saito (2), Koji Muroya (3), San-e Ishikawa (2), Midori Awazu (3), Tsutomu Ogata (3) Keywords: Keywords Active water resorption; Dominant disorder; AVP; AQP2; SIADH Abstract: We report on a three-generation family (daughter, mother, and maternal grandmother) with a syndrome of inappropriate secretion of antidiuretic hormone (SIADH)-like condition in the absence of inappropriate ADH secretion. In the three females, a water load test showed severely reduced urinary water excretion, with the ratio of urine volume to the loaded water being 10--33% (normal value: 70.2+-7.8%). Urinary AQP2 excretion was normal, as was the DNA sequence of AVPR2 and AQP2. The results suggest the presence of a new dominantly inherited disorder for tubular water resorption. Author Affiliation: (1) Department of Pediatrics, Ichikawa General Hospital, Tokyo Dental College, 5-11-13 Sugano Ichikawa-shi, Chiba 272-8513, Japan. ytanaka7@aol.com, JP (2) Department of Endocrinology and Metabolism, Jichi Medical School, Tochigi, Japan, JP (3) Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan, JP Article note: Received: 5 January 2001 / Revised: 16 May 2001 / Accepted: 21 May 2001

The pathogenesis of tubulointerstitial nephritis and uveitis (TINU) syndrome remains unknown, but T cell-mediated immune response has been postulated to play a role. On the other hand, TINU syndrome is characterized by hypergammaglobulinemia and high serum immunoglobulin G (IgG) levels, suggesting an involvement of humoral immunity. We describe a case of TINU syndrome in a 13-year-old girl with multiple tubular dysfunctions including renal glucosuria, tubular proteinuria, phosphaturia, uricosuria, and concentrating and acidifying defect. IgG antibody from her serum was reactive against 125-kDa human kidney protein. Immunofluorescence study using mouse kidney revealed that the antibody was against cortical renal tubular cells. The antibody disappeared as the renal symptoms resolved. We suggest that IgG antibody may contribute to tubular dysfunction in some patients with TINU syndrome. Pediatrics 2001;107:1443-1446; tubulointerstitial nephritis, uveitis, antibody, kidney, renal tubule, hypergammaglobulinemia., ABBREVIATIONS. TINU, tubulointerstitial nephritis and uveitis; IgG, immunoglobulin G; PBS, phosphate-buffered saline; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis. Tubulointerstitial nephritis and uveitis (TINU) syndrome was originally described by Dobrin [...]