PMID- 15149354
OWN - NLM
STAT- MEDLINE
DCOM- 20041215
LR  - 20051117
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 65
IP  - 6
DP  - 2004 Jun
TI  - Immunologic risk factors and glomerular C4d deposits in chronic transplant 
      glomerulopathy.
PG  - 2409-18
AB  - BACKGROUND: Chronic transplant glomerulopathy is an uncommon cause of chronic 
      transplant dysfunction of unknown pathogenesis. We evaluated the epidemiologic, 
      clinical, and histologic features of chronic transplant glomerulopathy. To 
      determine the possible contribution of humoral immune responses, we assessed 
      glomerular deposition of C4d. METHODS: From a cohort of 1111 kidney transplants 
      (1983 to 2001) with at least 6 months of graft function, we identified 18 cases 
      with chronic transplant glomerulopathy (1.6%) showing double contours of the 
      glomerular basement membrane (GBM) on light microscopy. To assess the risk 
      factors, this group was compared with 739 patients with stable function using 
      multivariate Cox regression analysis. Paraffin sections of 11/18 biopsies were 
      stained with polyclonal C4d antibodies. Sera of 13/18 patients could be tested 
      for antidonor human leukocyte antigen (HLA) antibodies by enzyme-linked 
      immunosorbent assay (ELISA). Patients with chronic allograft nephropathy without 
      chronic transplant glomerulopathy or predominant cyclosporine nephrotoxicity were 
      used as controls. RESULTS: Chronic transplant glomerulopathy was diagnosed at a 
      median of 8.3 (range 2.6-12.5) years posttransplantation. Panel reactive 
      antibodies at time of transplantation, RR 1.23 (1.05-1.45) per 10% increase, and 
      late acute rejection episodes, RR 7.6 (1.8-31.7), were independently associated 
      with chronic transplant glomerulopathy. We found glomerular C4d deposits in 10/11 
      biopsies showing chronic transplant glomerulopathy and in only 2/13 controls. 
      Peritubular capillary C4d deposits and donor-specific anti-HLA antibodies were 
      demonstrated in 4 and 3 of the 10 patients with glomerular C4d deposits, 
      respectively. CONCLUSION: Presensitization and late acute rejection episodes were 
      the risk factors identified. Glomerular C4d deposits suggest that chronic 
      transplant glomerulopathy emerges from in situ humoral rejection. Chronic 
      transplant glomerulopathy should be considered as a manifestation of 
      immune-mediated injury.
FAU - Sijpkens, Yvo W
AU  - Sijpkens YW
AD  - Department of Nephrology, Leiden University Medical Center, Leiden, The 
      Netherlands. y.w.j.sijpkens@lumc.nl
FAU - Joosten, Simone A
AU  - Joosten SA
FAU - Wong, Man-Chi
AU  - Wong MC
FAU - Dekker, Friedo W
AU  - Dekker FW
FAU - Benediktsson, Hallgrimur
AU  - Benediktsson H
FAU - Bajema, Ingeborg M
AU  - Bajema IM
FAU - Bruijn, Jan A
AU  - Bruijn JA
FAU - Paul, Leendert C
AU  - Paul LC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Peptide Fragments)
RN  - 80295-50-7 (Complement C4b)
RN  - 80295-52-9 (complement C4d)
SB  - IM
MH  - Adult
MH  - Chronic Disease
MH  - Cohort Studies
MH  - Complement C4b/*metabolism
MH  - Female
MH  - Glomerulonephritis/etiology/immunology/pathology
MH  - Graft Rejection/etiology/immunology/pathology
MH  - Humans
MH  - Kidney Diseases/etiology/immunology/pathology
MH  - Kidney Glomerulus/*immunology
MH  - Kidney Transplantation/*adverse effects/*immunology/pathology
MH  - Kidney Tubules/immunology
MH  - Male
MH  - Middle Aged
MH  - Peptide Fragments/*metabolism
MH  - Risk Factors
EDAT- 2004/05/20 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/05/20 05:00
PHST- 2004/05/20 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/05/20 05:00 [entrez]
AID - S0085-2538(15)49986-7 [pii]
AID - 10.1111/j.1523-1755.2004.00662.x [doi]
PST - ppublish
SO  - Kidney Int. 2004 Jun;65(6):2409-18. doi: 10.1111/j.1523-1755.2004.00662.x.