TREATMENT OF POLYOMAVIRUS (BK) NEPHRITIS AND VIREMIA WITH CIDOFIVIR AND REDUCTION OF IMMUNOSUPPRESSION: HIGH RATE OF REJECTION BUT GOOD GRAFT OUTCOME

COMPLICATIONS - INFECTIONS

M. Damasiewicz, F. Ierino
Nephrology, Austin Health, Heidelberg/AUSTRALIA

Body: Aim: To analyse clinical outcomes of renal transplant recipients with BK nephritis or high BK viral load who were treated with reducing immunosuppression and cidofovir. Methods: Patients with biopsy-proven BK nephritis (n= 9) and a subgroup of patients with significant BK viraemia (n=4) were treated with reducing immunosuppression and low-dose cidofovir. We examined changes in immunosuppression level, serum BK viral load (BKVL) using polymerase chain reaction (PCR), rejection rates and graft function. Cidofovir (0.25-0.3mg/kg intravenously) was administered fortnightly and continued until the serum BKVL was negative. Results: Median time to diagnosis of BK (nephritis and/or viraemia) following transplantation was 2.9 (range, 0.9-28.6) months. Median time from BK diagnosis to commencement of cidofovir treatment (average 16 doses) was 28 (range, 14-119) days; the median time to achieving negative BKVL was 6.9 (range, 1.9-25.8) months. Median follow-up time was 17.1 months (range, 6.6-46.5); overall graft survival at end of follow was 85% (2 graft losses due to recurrent IgA disease and rejection). The median creatinine at diagnosis, 6 and 12 months was 144, 154 and 134 mmol/L respectively. During the follow-up period, 9/13 (69%) patients were diagnosed with rejection (6 cell mediated rejection, 2 antibody mediated rejection, 1 combined rejection). As a result of the high rejection rate only modest reduction in maintenance immunosuppression was possible (see table).

	1 month (m)before BK detection	1 m after BK detection	1-3 m after BK detection	3-6 m after BK detection	Mean decrease (%)3m after BK detection
CyA level (mean)	1107 range (430 -1519)	902 range (602 - 1151)	813 range (631 - 974)	485 range (309 – 710)	26.5
FK level (mean)	9.2 range (6.8-11.8)	9.7 range (7.2-9.8)	8.6 range (6.7-9.8)	6.7 range (4.1-9.1)	6.5
MMF daily dose (mean)	1654 range (1000-2000)	1208 range (0-2000)	1062 range (500-2000)	1022 range (500-2000)	35.8
	At BK detection	0-3 m after BK detection	3-6 m after BK detection	6-9 m after BK detection	9-12 m after BK detection
BKVL (median, copies/ml)	432,250 range (3,425 - 13,743,909)	992,135 range (34,681 - 19,833,947)	74,124 range (0- 18,479,038	2608 range (0- 9,040,101)	19148 range (0- 190,200)

Conclusions: The high rejection rates in our patient cohort and the subsequent treatment may explain the longer than expected duration of BK viraemia and modest reduction in overall immunosuppression. Rejection that occurs concurrently with BK infection presents a difficult diagnostic and management problem. The maintenance (and escalation) of immunosuppression for rejection needs to be balanced with control of BK viraemia and prevention of nephropathy. In our study one graft was lost to rejection, and there was no graft loss from BK nephropathy. The administration of cidofovir may enable maintenance of effective doses of immunosuppression to treat rejection whilst controlling the extent of BK viraemia. Randomized studies are necessary to further assess the efficacy of cidofovir in addition to reducing immunosuppression alone, determine the optimal duration of anti-viral treatment, and determine the optimal BKVL at which therapy is initiated and ceased.

Disclosure: All authors have declared no conflicts of interest.