title: Contribution of polyclonal free light chain deposition to tubular injury.
abstract: BACKGROUND
  Excretion of monoclonal free light chains (MFLC) beyond the renal threshold can cause kidney injury, but evidence for polyclonal free light chains (PFLC)-mediated injury is limited. We aimed to study the degree of PFLC deposition in the proximal tubules of chronic kidney disease (CKD) and hypothesized that excess deposition may contribute to tubular injury.
  
  
  METHODS
  In this retrospective study, immunohistochemical staining to assess the degree of FLC deposition, periodic acid-Schiff staining for the degree of tubular brush border injury and trichrome staining for interstitial fibrosis were evaluated. Normal renal parenchyma from tumor nephrectomy specimens (control group I, n = 39), minimal change disease controls (group II, n = 13), renal biopsies from CKD and proteinuria (polyclonal study group III, n = 33) and monoclonal light chain nephropathy (group IV, n = 37) were studied. The results of the study including serum creatinine were compared between groups.
  
  
  RESULTS
  Both polyclonal and monoclonal groups (groups III and IV) had significantly higher light chain deposition and brush border injury by periodic acid-Schiff scores compared to control groups (groups I and II). When the first three polyclonal groups (groups I-III) were analyzed together, polyclonal light chain deposition was significantly correlated with serum creatinine levels, brush border injury and interstitial fibrosis.
  
  
  CONCLUSIONS
  The results of our study suggest that in CKD patients with proteinuria, excess PFLC deposition in the proximal tubules may cause acute tubular injury akin to monoclonal gammopathy and lead to renal chronicity.
authors.affiliation: Department of Transplant Surgery, William Beaumont Hospital, Royal Oak, Mich., USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Parasuraman
authors.forename: Stacy C
authors.initials: SC
authors.lastname: Wolforth
authors.forename: Wendy N
authors.initials: WN
authors.lastname: Wiesend
authors.forename: Francis
authors.initials: F
authors.lastname: Dumler
authors.forename: Michele T
authors.initials: MT
authors.lastname: Rooney
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ping L
authors.initials: PL
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry; D003404:Creatinine / Q000097:blood; D005260:Female; D005355:Fibrosis; D006801:Humans; D007147:Immunoglobulin Light Chains; D007150:Immunohistochemistry; D007668:Kidney / Q000293:injuries; D007674:Kidney Diseases / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000276:immunology / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D007147:Immunoglobulin Light Chains; D003404:Creatinine