Naoto Miura1, Hirokazu Imai2, Shogo Kikuchi3, Shogo Hayashi4, Masayuki Endoh5, Tetsuya Kawamura6, Yasuhiko Tomino7, Kumiko Moriwaki8, Hideyasu Kiyomoto8, Kentaro Kohagura9, Eiko Nakazawa10, Eiji Kusano10, Toshio Mochizuki11, Shinsuke Nomura12, Tamaki Sasaki13, Naoki Kashihara13, Jun Soma14, Tadashi Tomo15, Iwao Nakabayashi16, Masaharu Yoshida16, Tsuyoshi Watanabe17. 1. Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan. 2. Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan. imaihiro@aichi-med-u.ac.jp. 3. Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. 4. Medical Education Center, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. 5. Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan. 6. Department of Nephrology and Hypertension, School of Medicine, Jikei University, Minato-ku, Tokyo, Japan. 7. Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. 8. Department of Cardio Renal and Cerebrovascular Medicine, Kagawa University Faculty of Medicine, Miki, Kagawa, Japan. 9. Department of Cardiovascular Medicine, Nephrology and Neurology, University of the Ryukyus School of Medicine, Nishihara, Okinawa, Japan. 10. Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan. 11. Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan. 12. Departments of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan. 13. Division of Nephrology and Rheumatology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan. 14. Department of Nephrology, Iwate Prefectural Central Hospital, Morioka, Iwate, Japan. 15. Department of Internal Medicine II, Oita University Faculty of Medicine, Yufu, Oita, Japan. 16. Renal Unit, Department of Internal Medicine, Hachioji Medical Center, Tokyo Medical University, Hachioji, Tokyo, Japan. 17. Department of Internal Medicine III, School of Medicine, Fukushima Medical University, Fukushima, Fukushima, Japan.
Abstract
BACKGROUND: Tonsillectomy and steroid pulse (TSP) therapy was proposed as a curative treatment for IgA nephropathy by Hotta et al. (Am J Kidney Dis 38:736-742, 2001) based on data that about 50% of patients achieved clinical remission (CR) of urinary abnormalities. MATERIALS AND METHODS: As a primary survey, we sent a questionnaire and letter to 848 hospitals in Japan, each of which employed a Fellow of the Japanese Society of Nephrology between October and December of 2006, in order to gather information about the prevalence and efficacy of TSP therapy for patients with IgA nephropathy. As a secondary survey, we collected data from both low- and high-CR-rate groups to determine which factors predicted resistance to TSP therapy. RESULTS: A total of 2,746 patients received TSP therapy between 2000 and 2006. The CR rates, calculated by measuring urinary criteria 6 and 12 months after TSP therapy, were 32.0% (347/1,085) and 45.6% (452/991), respectively. Analysis of the 30 hospitals in which TSP therapy had been performed on at least ten patients revealed that the CR rates varied from below 10% to 100%. A secondary survey of ten hospitals revealed that, after correction of the CR rate from each hospital, patients could be categorized into three groups: those with a low CR rate (122 patients in four hospitals), a middle CR rate (78 patients in four hospitals), and a high CR rate (103 patients in two hospitals). The CR rate of all patients (N = 303) was 54.1%. A comparison of patient data between the low- and high-CR-rate groups showed a significant difference in age at onset (years; P = 0.05), amount of proteinuria (g/day; P = 0.02), total protein (g/dl; P = 0.02), pathological grade (P = 0.009), and prognostic score as described by Wakai et al. [Nephrol Dial Transplant 21:2800-2808, 2006, (P = 0.04)]. Univariate analysis revealed that there was a significant difference between non-CR and CR subgroups in duration from diagnosis until TSP therapy (6.9 +/- 6.8 versus 5.3 +/- 5.2 years; P = 0.02), amount of proteinuria (1.5 +/- 1.6 versus 0.8 +/- 0.8 g/day; P < 0.0001), serum creatinine (0.99 +/- 0.40 versus 0.87 +/- 0.34 mg/dl; P = 0.006), pathological grade (P = 0.0006), and Wakai et al.'s prognostic score (37.4 +/- 17.8 versus 28.1 +/- 15.1; P < 0.0001). A multivariate logistic analysis demonstrated that resistance to TSP therapy depends on age at onset, amount of proteinuria, hematuria grade, and pathological grade, and a score predicting resistance to TSP therapy could be derived by the formula: [(-0.0330) x (age) + (0.4772) x log (amount of proteinuria) - (0.0273) x (hematuria grade: 0, 1, 2, and 3) + (0.7604) x (pathological grade: 1, 2, 3, and 4) - 0.1894]. A receiver operating characteristic (ROC) curve showed that patients with a resistance score of greater than -0.02 easily resist TSP therapy (sensitivity 69%, specificity 75%, positive likelihood ratio 2.76). CONCLUSION: TSP therapy shows promise as a treatment that can bring about CR of urinary abnormalities, but unfortunately the average CR rate is about 50% at 1 year after treatment. Predictive factors for resistance to TSP therapy are age at onset, amount of proteinuria, hematuria grade, and pathological grade. The present study suggests that patients with either early-stage or mild to moderate IgA nephropathy easily achieve CR following TSP therapy, whereas patients with late-stage or severe disease are prone to TSP therapy resistance.
BACKGROUND: Tonsillectomy and steroid pulse (TSP) therapy was proposed as a curative treatment for IgA nephropathy by Hotta et al. (Am J Kidney Dis 38:736-742, 2001) based on data that about 50% of patients achieved clinical remission (CR) of urinary abnormalities. MATERIALS AND METHODS: As a primary survey, we sent a questionnaire and letter to 848 hospitals in Japan, each of which employed a Fellow of the Japanese Society of Nephrology between October and December of 2006, in order to gather information about the prevalence and efficacy of TSP therapy for patients with IgA nephropathy. As a secondary survey, we collected data from both low- and high-CR-rate groups to determine which factors predicted resistance to TSP therapy. RESULTS: A total of 2,746 patients received TSP therapy between 2000 and 2006. The CR rates, calculated by measuring urinary criteria 6 and 12 months after TSP therapy, were 32.0% (347/1,085) and 45.6% (452/991), respectively. Analysis of the 30 hospitals in which TSP therapy had been performed on at least ten patients revealed that the CR rates varied from below 10% to 100%. A secondary survey of ten hospitals revealed that, after correction of the CR rate from each hospital, patients could be categorized into three groups: those with a low CR rate (122 patients in four hospitals), a middle CR rate (78 patients in four hospitals), and a high CR rate (103 patients in two hospitals). The CR rate of all patients (N = 303) was 54.1%. A comparison of patient data between the low- and high-CR-rate groups showed a significant difference in age at onset (years; P = 0.05), amount of proteinuria (g/day; P = 0.02), total protein (g/dl; P = 0.02), pathological grade (P = 0.009), and prognostic score as described by Wakai et al. [Nephrol Dial Transplant 21:2800-2808, 2006, (P = 0.04)]. Univariate analysis revealed that there was a significant difference between non-CR and CR subgroups in duration from diagnosis until TSP therapy (6.9 +/- 6.8 versus 5.3 +/- 5.2 years; P = 0.02), amount of proteinuria (1.5 +/- 1.6 versus 0.8 +/- 0.8 g/day; P < 0.0001), serum creatinine (0.99 +/- 0.40 versus 0.87 +/- 0.34 mg/dl; P = 0.006), pathological grade (P = 0.0006), and Wakai et al.'s prognostic score (37.4 +/- 17.8 versus 28.1 +/- 15.1; P < 0.0001). A multivariate logistic analysis demonstrated that resistance to TSP therapy depends on age at onset, amount of proteinuria, hematuria grade, and pathological grade, and a score predicting resistance to TSP therapy could be derived by the formula: [(-0.0330) x (age) + (0.4772) x log (amount of proteinuria) - (0.0273) x (hematuria grade: 0, 1, 2, and 3) + (0.7604) x (pathological grade: 1, 2, 3, and 4) - 0.1894]. A receiver operating characteristic (ROC) curve showed that patients with a resistance score of greater than -0.02 easily resist TSP therapy (sensitivity 69%, specificity 75%, positive likelihood ratio 2.76). CONCLUSION:TSP therapy shows promise as a treatment that can bring about CR of urinary abnormalities, but unfortunately the average CR rate is about 50% at 1 year after treatment. Predictive factors for resistance to TSP therapy are age at onset, amount of proteinuria, hematuria grade, and pathological grade. The present study suggests that patients with either early-stage or mild to moderate IgA nephropathy easily achieve CR following TSP therapy, whereas patients with late-stage or severe disease are prone to TSP therapy resistance.
Authors: Claudio Pozzi; Simeone Andrulli; Lucia Del Vecchio; Patrizia Melis; Giovanni B Fogazzi; Paolo Altieri; Claudio Ponticelli; Francesco Locatelli Journal: J Am Soc Nephrol Date: 2004-01 Impact factor: 10.121