Peritubular capillaries in chronic renal allograft rejection: a quantitative ultrastructural study

Area of Science:

• Nephrology
• Transplantation Immunology
• Pathology

Background:

• Peritubular capillaries (PCs) with multilayered basement membranes have been proposed as an indicator of chronic renal allograft rejection (CR).
• Quantitative analysis of this ultrastructural lesion is crucial for validation as a diagnostic marker.

Purpose of the Study:

• To validate the circumferentially multilayered basement membrane lesion in peritubular capillaries (PCs) as a specific and sensitive marker for chronic renal allograft rejection (CR).
• To investigate the quantitative features, specificity, and sensitivity of this lesion in various kidney conditions.

Main Methods:

• Analysis of 169 renal biopsy specimens, including those with CR, acute rejection, normal kidneys, and native kidney diseases.
• Quantitative assessment of circumferential PC layers (PCcirc) and grading of lesions (mild, moderate, severe).
• Comparison of PC lesion incidence between CR and other kidney conditions using statistical analysis.

Main Results:

• A significantly higher number of circumferentially multilayered PCs (PCcirc) was observed in CR biopsy specimens compared to other groups (P < .001).
• Severe lesions were exclusive to CR, while moderate lesions were significantly more prevalent in CR (16-21%) than in native kidney diseases (0.6%).
• The presence of three or more PCs with a moderate lesion (cpc) demonstrated a sensitivity of 59% for CR and was specific for CR, even in the absence of transplant glomerulopathy.

Conclusions:

• Circumferentially multilayered PCs (cpc) are a specific marker for chronic renal allograft rejection (CR).
• The incidence of cpc increases with CR progression, suggesting it arises from low-grade rejection injury to PCs.
• Ultrastructural evaluation of cpc and transplant glomerulopathy offers a more precise diagnosis of CR than light microscopy alone.