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A Controlled Trial of Combined Therapy for Newly Diagnosed Severe Childhood IgA Nephropathy

NORISHIGE YOSHIKAWA^*, HIROSHI ITO, TADASU SAKAI^§, YASUO TAKEKOSHI^||, MASATAKA HONDA^¶, MIDORI AWAZU^#, KATSUMI ITO^**, KIKUO IITAKA^§, YASUSHI KOITABASHI, KANJI YAMAOKA, KIMIKO NAKAGAWA^§§, HAJIME NAKAMURA, SOUICHIROU MATSUYAMA^||||, YOSHIKI SEINO^¶¶, NOBUAKI TAKEDA^##, SHINZABUROU HATTORI^***, MAKOTO NINOMIYA and THE JAPANESE PEDIATRIC IGA NEPHROPATHY TREATMENT STUDY GROUP^,A

^* Faculty of Health Science, Kobe University School of Medicine, Japan.
Department of Pediatrics, Kobe University School of Medicine; Japan.
National Children's Hospital; Japan.
^§ Kidney Center, Kitasato University Hospital; Japan.
^|| Department of Pediatrics, Hokkaido University School of Medicine; Japan.
^¶ Division of Nephrology, Tokyo Metropolitan Children's Hospital; Japan.
^# Department of Pediatrics, School of Medicine, Keio University; Japan.
^** Department of Pediatric Nephrology, Tokyo Women's Medical College; Japan.
Department of Pediatrics, St. Marianna University School of Medicine; Japan.
Department of Pediatrics, Osaka University Medical School; Japan.
^§§ Department of Pediatrics, Osaka Medical Center Research Institute for Maternal and Child Health; Japan.
^|||| Kobe Children's Hospital; Japan.
^¶¶ Department of Pediatrics, Okayama University Medical School; Japan.
^## Department of Pediatrics, Kurashiki Central Hospital; Japan.
^*** Department of Pediatrics, Kumamoto University School of Medicine; Japan.
Department of Pediatrics, Kagoshima City Hospital, Japan.

Correspondence to Dr. Norishige Yoshikawa, Professor of Health Science, Kobe University School of Medicine, Tomogaoka 7-10-2, Suma-ku, Kobe 654, Japan. Phone: 81-78-7964515; Fax: 81-78-7965515; E-mail: nori{at}kobe-u.ac.jp

Abstract. The most appropriate treatment for patients with IgA nephropathy is controversial. Treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease may prevent immunologic renal injury in children with severe IgA nephropathy. To determine whether similar results can be obtained with a combination of just heparin-warfarin and dipyridamole, the effects of such treatment were compared to those of treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole in 78 children with newly diagnosed IgA nephropathy showing diffuse mesangial proliferation. The patients were randomly assigned to receive either prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr (group 1) or heparin-warfarin and dipyridamole for 2 yr (group 2). All of the 40 patients in group 1 and 34 of the 38 patients in group 2 completed the trial. The mean urinary protein excretion fell in group 1 patients (P < 0.0001), but remained unchanged in group 2 patients. The mean serum IgA concentration was reduced in group 1 patients (P = 0.0002), but was unchanged in group 2 patients. BP and creatinine clearance were normal at the end of the trial in all but one group 2 patient, who developed chronic renal insufficiency. The percentage of glomeruli showing sclerosis was unchanged in group 1 patients, but increased in group 2 patients (P = 0.006). The intensity of mesangial IgA deposits decreased in group 1 patients (P = 0.02), but remained unchanged in group 2 patients. In conclusion, the present study shows that treatment of children with severe IgA nephropathy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr early in the course of disease reduces immunologic renal injury and prevents increase of sclerosed glomeruli.

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