title: Impact of the presence and duration of donor-specific antibodies on renal function.
abstract: BACKGROUND
  Although anti-human leukocyte antigen (HLA) antibodies (DSA) is associated with graft loss, 3 things remain unclear: whether the duration and strength of DSA affect renal function; what mean fluorescence intensity (MFI) cut-off should be used; and whether the DSA effect is additive in case of multiple DSAs.
  
  
  METHODS
  A study was made of 63 patients who received living donor kidney transplants with clonal deletion protocol and were followed up for 18 months with reduced doses of immunosuppressants. DSA was tested for monthly, using Luminex Mixed and Single Antigen beads (One Lambda, Inc., Canoga Park, CA, USA). Decrease of estimated glomerular filtration rate (eGFR) was obtained at baseline and 18 months after transplantation. Association of renal damage and DSAs was compared using several DSA models with several MFI cut-offs.
  
  
  RESULTS
  Additive DSA models always showed better association with renal damage than comprehensive models. When calculating the DSA effect in additive models, "proxy-area under the curve" (AUC)-a triangular approximation of the actual AUC-showed better association with renal damage than did DSA duration (R(2) = 0.105 vs 0.087). Adjusting for other factors, 27% of the variation of GFR change was explained by proxy-AUC. No significant change of association occurred if the MFI cut-off level changed from 1000 to 3000.
  
  
  CONCLUSIONS
  Our results support the association of DSA with development of longitudinal renal damage. The clinical interpretation may be similar at MFI cut-offs of 1000, 2000, and 3000. An additive DSA effect may be expected in patients with multiple DSAs. Our study suggests the importance of frequently checking for DSA and reducing their MFI value to minimize renal damage by the antibodies.
authors: Terasaki Foundation Laboratory, Los Angeles, California, USA; Nephrology Center, Toranomon Hospital, Tokyo, Japan. Electronic address: jhoshinoind@gmail.com.
authors: J
authors: J
authors: Hoshino
authors: Terasaki Foundation Laboratory, Los Angeles, California, USA.
authors: M J
authors: MJ
authors: Everly
authors: Terasaki Foundation Laboratory, Los Angeles, California, USA.
authors: H
authors: H
authors: Kaneku
authors: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors: Y
authors: Y
authors: Ubara
authors: Nephrology Center, Toranomon Hospital, Tokyo, Japan.
authors: K
authors: K
authors: Takaichi
authors: Terasaki Foundation Laboratory, Los Angeles, California, USA.
authors: P I
authors: PI
authors: Terasaki
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D019540:Area Under Curve; D005260:Female; D005453:Fluorescence; D005919:Glomerular Filtration Rate; D006680:HLA Antigens / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D015233:Models, Statistical; D051437:Renal Insufficiency / Q000276:immunology* / Q000601:surgery*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007166:Immunosuppressive Agents