title: Tacrolimus improves the proteinuria remission in patients with refractory IgA nephropathy.
abstract: BACKGROUND
  Tacrolimus has been reported to be effective in refractory nephrotic syndrome, such as focal segmental glomerulosclerosis and membranous nephropathy. Some IgA nephropathy (IgAN) patients with massive proteinuria showed resistance to steroids and/or cytotoxic immunosuppressants based on the supportive therapy with renin- angiotensin system blockade. The efficacy and safety of tacrolimus in such refractory IgAN patients are extremely ambiguous, and the mechanism of tacrolimus improving proteinuria remission needs to be investigated.
  
  
  METHODS
  14 refractory IgAN patients were enrolled. The patients received tacrolimus (0.05-0.1 mg/kg/day) and prednisone (0.5 mg/kg/day) for at least 6 months. Synaptopodin and calcineurin expression were detected in renal tissues of patients who received re-biopsy. A puromycin aminonucleoside (PAN)-induced human podocyte injury model was applied to investigate the possible role of tacrolimus in proteinuria remission.
  
  
  RESULTS
  Of the 14 patients enrolled, 3 were withdrawn because serum creatinine increased over 30% baseline. In 11 patients treated with tacrolimus over 6 months, 9 showed complete or partial remission and 7 achieved remission within 1 month. In renal tissues, the expression of calcineurin increased while synaptopodin decreased and recovered partially after tacrolimus therapy. In an in vitro study, F-actin disrupted in human podocytes after stimulation of PAN, while calcineurin increased and synaptopodin decreased. After co-treatment with tacrolimus the reorganization of F-actin and the expression of calcineurin and synaptopodin recovered.
  
  
  CONCLUSIONS
  Tacrolimus showed a rapid proteinuria remission in refractory IgAN patients. The possible mechanism of tacrolimus to proteinuria remission might be podocyte cytoskeleton stabilization through inhibition of calcineurin expression.
authors.affiliation: Renal Division, Department of Medicine, Peking University First Hospital, Peking University Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, PR China.
authors.forename: Qingxian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Lv
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Liu
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019703:Calcineurin / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D004351:Drug Resistance; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism; D011241:Prednisone / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology; D012074:Remission Induction; D016708:Synaptophysin / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000199:Actins; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; C504260:SYNPR protein, human; D016708:Synaptophysin; D019703:Calcineurin; D011241:Prednisone; D016559:Tacrolimus