title: Differential progression of renal scarring and determinants of late renal recovery in sustained dialysis dependent acute kidney injury secondary to myeloma kidney.
abstract: BACKGROUND
  Most cases of dialysis-dependent acute kidney injury due to myeloma cast nephropathy do not recover renal function. Renal biopsy typically shows cast formation, direct tubular injury and interstitial inflammation caused by nephrotoxic monoclonal free light chains (FLC). Established scarring at presentation is rarely severe. There is little data on in situ evolution of renal injury.
  
  
  OBJECTIVE
  To conduct a detailed histological study of four patients with cast nephropathy.
  
  
  METHODS
  Cast nephropathy was confirmed by renal biopsy. Treatment consisted of chemotherapy and high cut-off dialysis to maximise extracorporeal removal of FLC and reduce renal toxicity. All four patients remained dialysis dependent at 6 weeks, at which time they underwent a further biopsy.
  
  
  RESULTS
  Three patients achieved independence from dialysis. Six-week biopsies showed differential changes in chronic damage from no progression, to accelerated progression of scarring from 10% to 42%, despite a rapid and sustained fall in FLC in all patients. In three patients there was a major reduction in intratubular cast numbers; these patients subsequently recovered renal function. In one patient who continued to have high cast formation at 6 weeks there was no subsequent renal recovery.
  
  
  CONCLUSIONS
  Some FLC clones can promote rapid renal scarring. Significant reductions in cast formation on repeat biopsy may identify the potential for late renal recovery. Early diagnosis and treatment may prove crucial in determining renal recovery. Patients who have not recovered renal function after a period of treatment may be usefully reassessed by repeat biopsy for quantitative analysis of chronic damage and cast numbers.
authors.affiliation: Department of Nephrology, Queen Elizabeth Medical Centre, Renal Institute of Birmingham, University of Birmingham, Birmingham, UK. k.basnayake@bham.ac.uk
authors.forename: Kolitha
authors.initials: K
authors.lastname: Basnayake
authors.forename: Chee Kay
authors.initials: CK
authors.lastname: Cheung
authors.forename: Michael
authors.initials: M
authors.lastname: Sheaff
authors.forename: William
authors.initials: W
authors.lastname: Fuggle
authors.forename: Dia
authors.initials: D
authors.lastname: Kamel
authors.forename: Sandra
authors.initials: S
authors.lastname: Nakoinz
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hutchison
authors.forename: Mark
authors.initials: M
authors.lastname: Cook
authors.forename: John
authors.initials: J
authors.lastname: Stoves
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Bradwell
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D001706:Biopsy; D002921:Cicatrix / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000628:therapy; D011379:Prognosis; D006435:Renal Dialysis