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.