Immunohistochemical (IHC) Staining with Kappa and Lambda Confirms Monoclonality Detected by Immunofluorescence Studies (IF) and Reveals a High Percentage of “Hybrid” Proximal Tubulopathy in Light Chain Associated Monoclonal Nephropathy (LCAMN).
Wendy Wiesend, Michele Rooney, Thomas Fennell, Sharon Hicks, Ping Zhang. William Beaumont Hospital, Royal Oak, MI
Background: Basic research studies have shown that monoclonal light chains, uptaken by megalin-cubilin receptors in proximal tubules, stimulate cellular production of hydrogen peroxide and induce an inflammatory process causing tubular injury. Monoclonal proximal tubulopathy, however, is a relatively rare variant of LCAMN, based on current EM diagnostic criteria in human renal biopsies. The purpose of this study was to 1) confirm IF findings by IHC method and 2) determine whether IHC method could reveal monoclonal light chain staining in proximal tubules of LCAMN cases.
Design: The study included 18 control cases (8 FSGS and 10 immune complex mediated glomerulopathy) and 23 LCAMN cases (9 cast nephropathy, 7 light chain deposition disease, 6 AL amyloidosis and 1 “pure” proximal tubulopathy). Staining pattern for kappa and lambda by IHC method was evaluated as polyclonal (equivalent kappa and lambda stains) and monoclonal (dominant kappa or lambda staining). The monoclonal staining in proximal tubules was also recorded. PAS staining of proximal tubular brush borders was graded from 0 (intact) to 3+ (total loss of brush border) in each case.
Results: All cases in the control group showed equivalent kappa and lambda stains indicating polyclonal pattern. All cases in the LCAMN group showed either kappa or lambda dominant staining, indicating monoclonal pattern, which was 100% correspondent with the monoclonal record by IF method. Monoclonal proximal tubular staining was seen in 8/9 cases of cast nephropathy, 7/7 cases of light chain deposition disease and one “pure” proximal tubulopathy, but in only 1/6 AL amyloidosis cases. The PAS scores of all LCAMN cases ranged from 2+ to 3+, except for the 5 AL amyloidosis cases without monoclonal staining in proximal tubules, which showed 0 to 1+ PAS scores. The mean value of serum creatinine in the LCAMN group was 4.89 ± 0.73 mg/dl, which significantly correlated with the PAS scores (R value: 0.496 and p = 0.0136).
Conclusions: IHC studies confirmed the monoclonal data identified on previous IF studies. In addition, IHC revealed a high percentage of “hybrid” monoclonal proximal tubulopathy (16/22 cases, 73%, not counting the “pure” proximal tubulopathy case), defined by monoclonal staining in proximal tubules and moderate to severe loss of brush borders. We conclude that monoclonal proximal tubulopathy, “pure” or “hybrid” type, may significantly contribute to acute renal failure in patients with LCAMN.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 256, Wednesday Afternoon