title: Misdiagnosing renal amyloidosis as minimal change disease.
abstract: BACKGROUND
  Minimal change disease (MCD) accounts for 10-15% of all adult nephrotic syndrome cases and requires normal renal histology by light microscopy and negative immunohistology. Foot process effacement on electron microscopy (EM) is typical. Renal amyloid deposits demonstrate pathognomonic green birefringence when viewed under cross-polarized light after staining tissue with Congo red (CR) and may reveal fibrils on EM. Late diagnosis and delayed treatment of renal amyloidosis negatively impact on renal and patient survival.
  
  
  METHODS
  A retrospective analysis was performed on 2116 patients referred to the National Amyloidosis Centre between 2001 and 2013, in whom renal amyloidosis was confirmed histologically. Twenty-seven of these patients had renal histology initially interpreted to be MCD.
  
  
  RESULTS
  Among 26 patients in whom biopsy specimens and/or reports were retrieved, the median age at MCD diagnosis was 62 years and presenting proteinuria averaged 7.8 g/24 h. The median time period between the two diagnoses was 241 days (range: 20-2632 days). MCD was diagnosed without CR in 17/26 (65%) biopsies, but all specimens contained amyloid on retrospective CR staining. MCD was diagnosed without EM in 17/26 (65%) cases and all of 10 such biopsies subsequently demonstrated fibrils. Sixteen patients were subjected to two or more renal biopsies when their proteinuria proved steroid refractory.
  
  
  CONCLUSIONS
  This study highlights the need to stain renal biopsies from proteinuric adults with CR, examine them under cross-polarized light and perform EM wherever possible. If the suspicion of renal amyloidosis remains high, despite apparent negative histology, specimens should be reviewed at specialist centres before undertaking a second kidney biopsy.
authors.affiliation: National Amyloidosis Centre, UCL Medical School, London, UK Centre for Nephrology, Division of Medicine, Royal Free Campus, UCL Medical School, London, UK.
authors.forename: Rabya Hussain
authors.initials: RH
authors.lastname: Sayed
authors.affiliation: National Amyloidosis Centre, UCL Medical School, London, UK.
authors.forename: Janet Anne
authors.initials: JA
authors.lastname: Gilbertson
authors.affiliation: National Amyloidosis Centre, UCL Medical School, London, UK.
authors.forename: David Frederick
authors.initials: DF
authors.lastname: Hutt
authors.affiliation: National Amyloidosis Centre, UCL Medical School, London, UK Centre for Nephrology, Division of Medicine, Royal Free Campus, UCL Medical School, London, UK.
authors.forename: Helen Jane
authors.initials: HJ
authors.lastname: Lachmann
authors.affiliation: National Amyloidosis Centre, UCL Medical School, London, UK.
authors.forename: Philip Nigel
authors.initials: PN
authors.lastname: Hawkins
authors.affiliation: Centre for Nephrology, Division of Medicine, Royal Free Campus, UCL Medical School, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Bass
authors.affiliation: National Amyloidosis Centre, UCL Medical School, London, UK Centre for Nephrology, Division of Medicine, Royal Free Campus, UCL Medical School, London, UK.
authors.forename: Julian David
authors.initials: JD
authors.lastname: Gillmore
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis*; D001706:Biopsy; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000648:ultrastructure*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000175:diagnosis*; D012189:Retrospective Studies; D013997:Time Factors
keywords: Congo red, electron microscopy; minimal change disease; renal amyloidosis