PMID- 11532096
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20071114
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 60
IP  - 3
DP  - 2001 Sep
TI  - Intravenous immunoglobulin protects against experimental thrombotic 
      microangiopathy.
PG  - 1018-25
AB  - BACKGROUND: Intravenous immunoglobulin (IVIG) has been utilized in several forms 
      of vasculitis and has many potential mechanisms of action, including the 
      inhibition of C3 activation. We have previously demonstrated that IVIG can reduce 
      glomerular injury in a model of membranous nephropathy mediated by C5b-9 [1]. 
      C5b-9 has also been shown to mediate the thrombotic microangiopathy (TMA) induced 
      by antibody to glomerular endothelial cells leading to a hemolytic uremic 
      syndrome-type lesion [2]. METHODS: To test the hypothesis that IVIG might be 
      effective in treating antibody-induced TMA, male uninephrectomized rats underwent 
      right renal artery perfusion with goat anti-rat glomerular endothelial cell (GEN) 
      antibody (20 mg/kg). Sheep IgG (200 mg/kg) was administered either 30 minutes 
      before the renal artery perfusion (group I, N = 6) or 30 minutes postperfusion 
      (group II, N = 9). A third control group received phosphate-buffered saline (PBS; 
      group III, N = 12). A survival biopsy was performed at 15 minutes, and the 
      animals were sacrificed on day 2. RESULTS: There were no significant differences 
      in proteinuria or hematocrit between the groups. Animals pretreated with IVIG had 
      significantly improved survival and renal function, which was associated with a 
      decrease in glomerular C3 deposition. The protective effect of IVIG was abolished 
      if the administration was delayed 30 minutes after perfusion. CONCLUSIONS: IVIG 
      is effective in reducing injury in experimental TMA only if given 
      prophylactically. The effect is mediated by inhibition of local intraglomerular 
      complement activation.
FAU - Jefferson, J A
AU  - Jefferson JA
AD  - Division of Nephrology, University of Washington, Seattle, Washington, USA. 
      ashley.jefferson@bch.n-i.nhs.uk
FAU - Suga, S I
AU  - Suga SI
FAU - Kim, Y G
AU  - Kim YG
FAU - Pippin, J
AU  - Pippin J
FAU - Gordon, K L
AU  - Gordon KL
FAU - Johnson, R J
AU  - Johnson RJ
FAU - Couser, W G
AU  - Couser WG
LA  - eng
GR  - DK-43422/DK/NIDDK NIH HHS/United States
GR  - DK-47695/DK/NIDDK NIH HHS/United States
GR  - DK-52121/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Complement C3)
RN  - 0 (Immunoglobulins, Intravenous)
SB  - IM
MH  - Animals
MH  - Antigen-Antibody Complex
MH  - Complement Activation/drug effects
MH  - Complement C3/analysis
MH  - Immune Complex Diseases/etiology/pathology/*prevention & control
MH  - Immunoglobulins, Intravenous/*pharmacology
MH  - Kidney Glomerulus/immunology/pathology
MH  - Kidney Tubules/pathology
MH  - Male
MH  - Perfusion
MH  - Proteinuria/etiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Renal Artery
EDAT- 2001/09/05 10:00
MHDA- 2001/10/05 10:01
CRDT- 2001/09/05 10:00
PHST- 2001/09/05 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/09/05 10:00 [entrez]
AID - S0085-2538(15)47956-6 [pii]
AID - 10.1046/j.1523-1755.2001.0600031018.x [doi]
PST - ppublish
SO  - Kidney Int. 2001 Sep;60(3):1018-25. doi: 10.1046/j.1523-1755.2001.0600031018.x.