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Byline: Kiyoshi Hamahira (1), K. Iijima (1), Ryojiro Tanaka (1), Hajime Nakamura (1), Norishige Yoshikawa (2) Keywords: KeywordsCyclosporine; Arteriolopathy; Tubulointerstitial lesions; Focal glomerular lesions; Drug discontinuation Abstract: Cyclosporine (CS) is well recognized to be effective in the treatment of children with steroid-dependent and steroid-resistant nephrotic syndrome (NS), but its use can result in chronic nephrotoxicity. The histological changes that occur after CS discontinuation are unknown. Therefore, we examined the histological changes [CS-associated arteriolopathy (CAA), tubulointerstitial lesions, and focal glomerular lesions] in renal biopsy specimens after the drug had been discontinued in eight children with idiopathic nephrotic syndrome (NS). These children had been treated with long-term moderate-dose CS and had shown mild-to-moderate chronic CS nephrotoxicity. The degree of CAA improved significantly after CS discontinuation (mean CAA grade from 1.30+-0.46 to 0.25+-0.46, P=0.028). CAA disappeared in six of these children after CS discontinuation. However, the tubulointerstitial lesions and the focal glomerular lesions did not change after CS discontinuation. In conclusion, in children with idiopathic NS, CAA is improved by discontinuation of CS, but tubulointerstitial changes and focal glomerular lesions do not regress with drug discontinuation. Author Affiliation: (1) Department of Pediatrics, Kobe University School of Medicine, 5--2 Kusunoki-cho, 7 chome, Chuo-ku, Kobe, 650--0017 Japan. kidney@kobe-u.ac.jp, JP (2) Department of Pediatrics, Wakayama Medical University, Wakayama, Japan, JP Article note: Received: 16 January 2001 / Revised: 26 April 2001 / Accepted: 27 April 2001

Byline: Kyoko Maruyama (1), Mami Yoshida (1), Hisahide Nishio (2), Taku Shirakawa (1), Takashi Kawamura (3), Ryojiro Tanaka (4), Hajime Nakamura (5), Kazumoto Iijima (5), N. Yoshikawa (6) Keywords: KeywordsaIgA nephropathy; Children; Angiotensinogen gene; Angiotensin-converting enzyme gene; Urinary protein excretion Abstract: We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32+- 1.42 versus 0.75+-0.78 g/day P=0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45+-1.50 versus 0.63+-0.56 g/day P=0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children. Author Affiliation: (1) Faculty of Health Science, Kobe University School of Medicine, Kobe, Hyogo, Japan, JP (2) Department of Public Health, Kobe University School of Medicine, Kobe, Hyogo, Japan, JP (3) Center for Student Health, Kyoto University, Kyoto, Japan, JP (4) Department of Pediatrics, Hyogo Prefectural Awaji Hospital, Sumoto, Hyogo, Japan, JP (5) Department of Pediatrics, Kobe University School of Medicine, Kobe, Hyogo, Japan, JP (6) Department of Pediatrics, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Japan 641-8510 e-mail: nori@wakayama-med.ac.jp Tel.: +81-73-4410632, Fax: +81-73-4449055, JP Article note: Received: 21 July 2000 / Revised: 8 December 2000 / Accepted: 11 December 2000

Byline: Yuji Inoue (1), Kazumoto Iijima (1), Hajime Nakamura (1), N. Yoshikawa (2) Keywords: Key wordsaChronic nephrotoxicity; Cyclosporin treatment; Minimal change nephrotic syndrome Abstract: aWe describe a prospective study of 2-year moderate-dose cyclosporin (CS) treatment in 13 children with steroid-dependent minimal change nephrotic syndrome (MCNS). CS treatment was commenced at 100--150amg/m.sup.2 per day after remission was attained with prednisolone therapy, was adjusted to a target trough level of 100ang/ml, and was administered for 2 years. The number of relapses during CS treatment significantly decreased compared with before CS treatment, all patients were able to discontinue prednisolone therapy, and steroid toxicity was reduced 54% of patients remained in remission during CS treatment. Renal biopsies performed before CS treatment all showed MCNS without tubulointerstitial lesions. Creatinine clearance and urinary [beta].sub.2-microglobulin levels during CS treatment were normal in all patients, but renal biopsies performed after CS treatment revealed chronic CS nephrotoxicity in 7 patients. Clinical data, including CS dose and CS trough blood levels, were not significantly different between patients with and without nephrotoxicity. In conclusion, 2-year moderate-dose CS treatment in children with steroid-dependent MCNS is effective in preventing relapse and decreasing steroid toxicity. This treatment can, however, result in a high incidence of chronic nephrotoxicity. Renal function is not a reliable indicator of chronic CS nephrotoxicity. Renal biopsy is therefore necessary to monitor chronic CS nephrotoxicity. Author Affiliation: (1) Department of Pediatrics, Kobe University School of Medicine, Kobe, Japan, JP (2) Faculty of Health Science, Kobe University School of Medicine, Tomogaoka 7-10-2, Suma-Ku, Kobe, Japan 654 Tel.: +81-78-796-4515, Fax: +81-78-796-4509, JP Article note: Received: 4 March 1998 / Revised: 28 April 1998 / Accepted: 25 June 1998

Byline: Kazumoto Iijima (1), Seiko Ito-Kariya (1), Hajime Nakamura (1), Norishige Yoshikawa (1) Keywords: Key words: Henoch-Schonlein nephritis; Multiple combined therapy; Histological effects; Prognosis Abstract: From 1980 through 1992, 14 children with Henoch-Schonlein nephritis (HSN) showing severe glomerular changes (grade IV or V) were given a multiple combined therapy with prednisolone, cyclophosphamide, heparin/warfarin, and dipyridamole, and were followed for 7.5+-0.9 years. The period between the onset of nephritis and the start of therapy was 0.8+-0.4 years. Ten patients underwent follow-up biopsy after therapy. The percentage of glomeruli having crescents/segmental lesions was significantly reduced after therapy (70%+-5% vs. 42%+-7%, P &lt 0.01), due mainly to the resolution of crescents (51%+-8% vs. 13%+-5%, P &lt 0.01). Thus, histological grade was significantly improved (5 grade IV and 5 grade V vs. 7 grade III and 3 grade IV, P &lt 0.01). After an average follow-up period of 7.5 years, 9 patients showed normal urine and renal function, 4 showed minor urinary abnormalities, and 1 heavy proteinuria. No patient developed chronic renal insufficiency. These findings suggest that the multiple combined therapy could be effective for histologically severe HSN, although a prospective controlled study should be performed. Author Affiliation: (1) Department of Pediatrics and Faculty of Health Science, Kobe University School of Medicine, Kobe, Japan, JP Article note: Received July 2, 1997 received in revised form September 26, 1997 accepted October 2, 1997