title: Outcomes of primary nephrotic syndrome in elderly Japanese: retrospective analysis of the Japan Renal Biopsy Registry (J-RBR).
abstract: OBJECTIVE
  There are very little data available regarding nephrotic syndrome (NS) in elderly (aged ≥65 years) Japanese. The aim of this study was to examine the causes and outcomes of NS in elderly patients who underwent renal biopsies between 2007 and 2010.
  
  
  METHODS
  From July 2007 to June 2010, all of the elderly (aged ≥65 years) Japanese primary NS patients who underwent native renal biopsies and were registered in the Japan renal biopsy registry (J-RBR; 438 patients including 226 males and 212 females) were identified. From this cohort, 61 patients [28 males and 33 females including 29, 19, 6, 4, and 3 patients with membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), and other conditions, respectively] were registered from the representative multi-centers over all districts of Japan, and analyzed retrospectively. The treatment outcome was assessed using proteinuria-based criteria; i.e., complete remission (CR) was defined as urinary protein level of <0.3 g/day or g/g Cr, and incomplete remission type I (ICR-I) was defined as urinary protein level of <1.0-0.3 g/day or g/g Cr, and renal dysfunction was defined as a serum creatinine (Cr) level of 1.5 times the baseline level.
  
  
  RESULTS
  In this elderly primary NS cohort, MN was the most common histological type of NS (54.8 %), followed by MCNS (19.4 %), FSGS (17.4 %), and MPGN (8.4 %). Of the patients with MN, MCNS, or FSGS, immunosuppressive therapy involving oral prednisolone was performed in 25 MN patients (86.2 %), 18 MCNS patients (94.7 %), and all 6 FSGS patients (100 %). CR was achieved in all 19 (100 %) MCNS patients. In addition, CR and ICR-I were achieved in 16 (55.2 %) and 18 (62.1 %) MN patients and 4 (66.7 %) and 5 (83.3 %) FSGS patients, respectively. There were significant differences in the median time to CR among the MCNS, FSGS, and MN patients (median: 26 vs. 271 vs. 461 days, respectively, p < 0.001), and between the elderly (65-74 years, n = 7) and very elderly (aged ≥75 years, n = 12) MCNS patients (7 vs. 22 days, p = 0.037). Relapse occurred in two (6.9 %) of the MN and nine (47.4 %) of the MCNS patients. Renal dysfunction was observed in five (7.2 %) of the MN patients. Serious complications developed in eight (14.8 %) patients, i.e., two (3.7 %) patients died, four (7.4 %, including three MCNS patients) were hospitalized due to infectious disease, and two (3.7 %) developed malignancies. The initiation of diabetic therapy was necessary in 14 of the 61 patients (23.0 %) with much higher initial steroid dosage.
  
  
  CONCLUSIONS
  Renal biopsy is a valuable diagnostic tool for elderly Japanese NS patients. In this study, most of elderly primary NS patients respond to immunosuppressive therapy with favorable clinical outcomes. On the other hand, infectious disease is a harmful complication among elderly NS patients, especially those with MCNS. In future, modified clinical guidelines for elderly NS patients should be developed.
authors.affiliation: Division of Nephrology, Kanazawa Medical University School of Medicine, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan. hyokoyama-npr@umin.ac.ip.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. hitoshis@md.okayama-u.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. naritai@med.niigata-u.ac.jp.
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.affiliation: General Medical Research Center, Fukuoka University School of Medicine, Fukuoka, Japan. tsaito@fukuoka-u.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Nephrology, Faculty of Medicine, University of Tsukuba, Ibaragi, Japan. k-yamaga@md.tsukuba.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan. saorin@med.hokudai.ac.jp.
authors.forename: Saori
authors.initials: S
authors.lastname: Nishio
authors.affiliation: Department of Hemovascular Medicine and Artificial Organs, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. fujimos@med.miyazaki-u.ac.jp.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Fujimoto
authors.affiliation: Department of Nephrology, Shizuoka General Hospital, Shizuoka, Japan. noriko-mori@i.shizuoka-pho.jp.
authors.forename: Noriko
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Nephrology, Fujita Health University School of Medicine, Nagoya, Japan. yukio.kidney@gmail.com.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
authors.affiliation: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan. seokuda-circ@umin.ac.jp.
authors.forename: Seiya
authors.initials: S
authors.lastname: Okuda
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. marus@med.nagoya-u.ac.jp.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan. hsymhs2i@m.tohoku.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Pathology, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan. yoshi@dokkyomed.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. makino@md.okayama-u.ac.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.affiliation: Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan. smatsuo@med.nagoya-u.ac.jp.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsuo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000188:drug therapy / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007564:Japan; D007668:Kidney / Q000473:pathology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D009402:Nephrosis, Lipoid / Q000188:drug therapy / Q000473:pathology; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D011239:Prednisolone / Q000008:administration & dosage; D011507:Proteinuria / Q000652:urine; D012008:Recurrence; D012042:Registries; D012189:Retrospective Studies; D012263:Ribonucleosides / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine; D016572:Cyclosporine; D003520:Cyclophosphamide; D011239:Prednisolone; D003404:Creatinine; D009173:Mycophenolic Acid; D008775:Methylprednisolone
keywords: Complication; Elderly; Immunosuppressive therapy; Japanese; Nephrotic syndrome; Outcome