Diagnostic Significance of Peritubular Capillary Basement Membrane Multilaminations in Kidney Allografts: Old Concepts Revisited

Background. Injury to peritubular capillaries and capillary basement membrane multilamination (PTCL) is a hallmark of antibody-mediated chronic renal allograft rejection. However, the predictive diagnostic value of PTCL is incompletely studied. Methods. We analyzed the diagnostic significance of PTCL and propose diagnostic strategies. We evaluated 360 diagnostic native and 187 transplant kidney specimens by electron microscopy (terminology: PTCL-C, severe; PTCL subgroup C3, very severe multilamination; see Materials and Methods for definitions). Results. PTCL was not pathognomonic for any specific disease. PTCL-C/C3 was rare in native kidneys (C, 6%; C3, 1%), associated mainly with late thrombotic microangiopathy (C: 78%; C3: 11% of cases). In allografts, PTCL-C/C3 was significantly more common, especially in specimens more than 24 months after transplantation (C, 47%; C3, 31%). PTCL-C/C3 was found in acute (C, 20%; C3, 7%) and chronic T-cell rejection (C, 67%; C3, 29%), calcineurin inhibitor toxicity (C, 36%; C3, 18%), or C4d(+) specimens (C, 61%; C3, 50%) with odds ratios between 4 and 36. PTCL-C3 was more predominant in cases with antibody-mediated injury. Highest odds ratios (81Y117) for PTCL-C/C3 were noted in combined injuries, that is, mixed chronic T-cell and concurrent chronic antibody-mediated rejection. Positive predictive values of PTCL-C and C3 are the following: all rejection types, 89% and 93%; all Banff chronic rejection types, 69% and 71%; and chronic presumptive antibody rejection, 37% and 49%, respectively. Corresponding negative predictive values of C and C3 for different Banff rejection categories are between 50% and 94%. Conclusions. The presence of PTCL-C3 is a helpful adjunct finding to diagnose rejection-induced tissue injury but cannot precisely predict the Banff rejection category. Conversely, the absence of PTCL-C3 is helpful in excluding chronic, Banff category II antibody-mediated rejection.