Peritubular Capillary Basement Membrane Multilayering:  A Marker of Allograft Nephropathy or Not?

 

Patricia Campbell, Debra Bergstrom, Sita Gourishankar, Sandra Cockfield, Philip Halloran and Kim Solez, Division of Nephrology, Depts of Medicine and Laboratory Medicine, University of Alberta. Edmonton

 

Peritubular capillary basement membrane multilayering (PTCBMML) has been reported to be a marker of chronic rejection. Whether this is a specific finding and whether alone it can be used to diagnose chronic rejection is controversial. The purpose of this study was to determine the prevalence and variability of PTCBMML in renal allograft biopsies and its relationship to clinical characteristics and chronic allograft changes.

 

Inclusion criteria were; a biopsy for graft deterioration >3 months post transplant and tissue available for staining by C4d and EM.  Clinical data was obtained from the renal transplant database. To determine PTCBMML the circumference of the PTC was measured. Significant PTC layering was defined as >4 layers for >10% of the PTC circumference. We compared these finding to > 3 layers in 50% of the circumference which was previously reported as a definition of multilayering3.

90 biopsies, representing 84 grafts, were available for evaluation. PTCBMML is not related to previous graft injury from delayed graft function, acute rejection at the time of biopsy or previous to the biopsy. Markers of chronic allograft nephropathy correlated with some of the categories for multilayering but not others.  Chronic glomerulopathy (CG) is associated with multilayering whereas CI, CT and CV are not. A C score > 6 (CG+CI+CV+CT) was associated with > 4 or >6 layers in 10% of the basement membrane but not with > 50%. C4d scores which were generally not significant with the >4 or 6 layers, but were significant with > 3 layers in 50%. This may explain the conflicting observations previously reported.

 

Graft loss and proteinuria do not appear to be related to the number of layers. As a marker for chronic allograft injury PTCBMML is poorly linked to outcome and proteinuria, which are quoted as clinical criteria for chronic "rejection”.