Peritubular capillary basement membrane multilayering on electron microscopy:  a useful marker of early chronic antibody-mediated damage.
BACKGROUND
Chronic antibody-mediated rejection is an important cause of late graft failure. Developing an early marker of the disease may allow diagnosis and treatment before irreversible graft damage has occurred. The aim of this study was to assess whether, on electron microscopy examination, peritubular capillary (PTC) basement membrane multilayering precedes and predicts the development of transplant glomerulopathy (TG).


METHODS
We used a vintage matched case-control method. Sixteen case-control pairs were created among all renal transplant patients from October 2005. Cases were patients who developed TG, and controls were patients with a late (>36 months) posttransplant (indication or surveillance) biopsy without TG. Electron microscopy was carried out on a biopsy taken earlier in the posttransplantation period for both cases and controls.


RESULTS
For every additional PTC of 25 examined with three or more layers in the early biopsy, the risk of having TG in the later biopsy was increased by 1.4-fold (95% confidence interval, 1.1-1.9; P=0.015). For every PTC of 25 with five or more layers, the risk was increased by 1.6-fold (95% confidence interval, 1.0-2.7; P=0.063). Thus, the risk of future TG increased substantially with every additional PTC of 25 showing multilayering in the early biopsy.


CONCLUSIONS
Peritubular capillary basement membrane multilayering on electron microscopy is a useful marker of early chronic antibody-mediated damage, and information can be obtained by assessing PTC with three to four layers of basement membrane in addition to those with five or more layers. This finding must be validated in a prospective study.
Department of Histopathology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. Candice.Roufosse@imperial.nhs.uk
Candice A
CA
Roufosse
Ian
I
Shore
Jill
J
Moss
Linda B
LB
Moran
Michelle
M
Willicombe
Jack
J
Galliford
Ka-kit K
KK
Chan
Paul A
PA
Brookes
Hanneke
H
de Kort
Adam G
AG
McLean
David
D
Taube
H Terence
HT
Cook
D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000378:metabolism; D001706:Biopsy / Q000379:methods; D002196:Capillaries / Q000473:pathology*; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods; D008297:Male; D008854:Microscopy, Electron / Q000379:methods*; D008875:Middle Aged; D009401:Nephrosis / Q000209:etiology / Q000473:pathology*