Calcineurin inhibitor toxicity in renal allografts: morphologic clues from protocol biopsies.
BACKGROUND
Calcineurin inhibitors (cyclosporine and tacrolimus) are important constituents of post renal transplant immunosuppression. However, renal toxicity limits their utility. Histological features of calcineurin inhibitor toxicity (CNIT) have been the subject of few studies using protocol biopsy samples, and consensus on diagnostic criteria is still evolving.


OBJECTIVE
To analyze the spectrum of histological changes in protocol renal allograft biopsies with evidence of CNIT and identify additional features that are likely to help the pathologist in arriving at a diagnosis.


METHODS
One hundred and forty protocol allograft biopsies performed at 1, 6 and 12 months post renal transplant were studied. The defining features of CNIT included: isometric vacuolization of proximal tubular cells, arteriolar hyalinosis with medial/peripheral nodules and striped pattern of tubular atrophy/interstitial fibrosis. Other features such as global glomerulosclerosis, vacuolization of smooth muscle cells of arterioles, tubular microcalcinosis, ischemic shrinkage of glomeruli and hyperplasia of juxtaglomerular apparatus (JGA) were also analyzed and graded semiquantitatively.


RESULTS
CNIT was seen in 17/140 protocol biopsies (12.1%). In addition to the diagnostic criteria, arteriolar hyalinosis, smooth muscle cell vacuolization of arterioles and hyperplasia of JGA were found to be useful indicators of CNIT.


CONCLUSIONS
There is a relatively high incidence of CNIT in protocol allograft biopsies. A critical analysis of renal biopsy in adequate number of serial step sections to identify these features is mandatory, as many of these features are subtle and are likely to be missed if not specifically sought.
Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Alok
A
Sharma
Sumeet
S
Jain
Ruchika
R
Gupta
Sandeep
S
Guleria
Sanjay
S
Agarwal
Amit
A
Dinda
D000328:Adult; D001706:Biopsy; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006651:Histocytochemistry; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000009:adverse effects* / Q000627:therapeutic use; D014184:Transplantation, Homologous
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus