Calcineurin inhibitor nephrotoxicity: reduction in dose results in marked improvement in renal function in patients with coexisting chronic allograft nephropathy.
BACKGROUND
Calcineurin inhibitors (CNI) have significantly reduced the incidence of acute rejection. Nephrotoxicity however, may contribute to long-term allograft dysfunction.


METHODS
Forty-six biopsies from patients who had been transplanted for more than 6 months were examined. Sixteen biopsies had evidence of chronic allograft nephropathy (CAN) alone, 21 biopsies had evidence of coexisting CAN in addition to histological evidence of calcineurin inhibitor nephrotoxicity (CNIN) while nine had neither evidence of nephrotoxicity nor CAN. Patients with evidence of nephrotoxicity underwent a reduction in dose of CNI while those with CAN alone had no change in therapy. Renal function was followed for a mean of 17.4 months after biopsy.


RESULTS
The serum creatinine at the time of diagnostic renal biopsy was comparable between those with CAN alone (mean 0.25 +/- 0.18 mmol/L) and those with coexisting CNIN (mean 0.23 +/- 0.05 mmol/L, p=0.33). The patients with CNIN however, had a rapid improvement in renal function within 1 month after dose reduction. This was sustained for the duration of follow-up (mean serum creatinine 0.162 +/- 0.038 mmol/L at 1 yr after dose reduction; p=0.001). In comparison, those with CAN alone had a gradual decline in renal function with a serum creatinine at 1 yr after biopsy of 0.31 +/- 0.187, p=0.01.


CONCLUSIONS
Reduction in the dose of CNI in those with histological evidence of nephrotoxicity resulted in a sustained improvement in renal function.
Pilmore
Helen L
HL
Auckland Renal Transplant Group, Department of Renal Medicine, Auckland Hospital, Grafton, Auckland, New Zealand. hpitmore@adhb.govt.nz
Dittmer
Ian D
ID
D065095:Calcineurin Inhibitors; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology; D008297:Male; D014184:Transplantation, Homologous
D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine