Risk of opportunistic infection in kidney transplant recipients with cytomegalovirus infection and associated outcomes.

BACKGROUND: Cytomegalovirus (CMV) infection in kidney transplant recipients has been anecdotally observed with concomitant or subsequent opportunistic infections (OI), but this association has yet to be defined or quantified.

METHODS: Patients who received a renal transplant between 1/1/2005 and 6/30/2014 and developed CMV infection were matched to controls in a ratio of 1:2 and the rates of opportunistic co-infection were calculated within pre-specified time frames (-30 days to +90 days and -30 days to +180 days). The primary outcome was composite OI rate, and secondary outcomes included time to OI and patient and graft outcomes. CMV-OI association rates were estimated via conditional logistic regression.

RESULTS: There were 2405 patients who received a renal transplant during the study period; 394 cases of CMV infection were identified. These cases were matched to 783 controls for a total of 805 participants. OI occurred in 14 patients in the CMV case group (CMV+) and in 5 patients in the control group (CMV-) in the -30 to +90 day time period (3.55% vs 0.64%, OR = 5.60, 95% CI: 2.02-12.55). When considering 180-day follow-up, OI occurred in 17 CMV+ patients and 8 CMV- patients (4.3% vs 1%, OR = 4.25, 95% CI: 1.83-9.85). Mean time from CMV diagnosis to OI was 33 ± 64 days (median 7 days). Mortality was 3 times more likely in the group with concomitant OI (CMV+/OI+) as compared to a matched cohort of patients with CMV infection without OI (CMV+/OI-) (unadjusted HR 3.02, 1.64-5.55, Tables 6 and 7). Cumulative survival for CMV+/OI+ patients was significantly worse than CMV+/OI- patients (P < 0.01).

CONCLUSIONS: CMV is associated with a significantly increased risk of co-infection with OI, particularly fungal infections. Clinical suspicion for concomitant OI should drive further workup after a CMV diagnosis. Future studies are needed to better define those patients at highest risk to elucidate subpopulations where the benefits of prophylaxis outweigh the potential risks associated with these therapies.