Pneumocystis jiroveci pneumonia in kidney and simultaneous pancreas kidney transplant recipients in the present era of routine post-transplant prophylaxis: risk factors and outcomes

Background: The goal of this study was to identify predictors for development of Pneumocystis jirovecii pneumonia (PJP) in kidney and simultaneous kidney and pancreas transplant recipients in the present era of universal primary prophylaxis. Methods: We reviewed adult recipients of kidney transplant or simultaneous pancreas and kidney transplant at the University of Wisconsin between January 1, 1994 and December 31, 2016. Patients diagnosed with PJP during this time frame were included. Controls were randomly selected from among those whose post-transplant course was not complicated by PJP, matched on time since transplant through incidence density sampling with a 3:1 ratio. Results: 28 (0.45%) of 6270 recipients developed PJP between 1994 and 2016. Median time since transplant was 4.6years (interquartile range (IQR): 1.4-9.6years). Affected recipients were older, had more HLA mismatches, and were more likely to have had BK viremia, CMV viremia and invasive fungal infections than matched controls. CMV viremia remained the only significant risk factor in multivariate analysis, and was a strong predictor (OR 6.27; p=0.002). Ninety percent of the cases with prior CMV viremia had been diagnosed in the year preceding the diagnosis of PJP; among these, median time from diagnosis of CMV to diagnosis of PJP was 3.4 months (IQR: 1.74-11.5months) and median peak CMV viral load prior to diagnosis of PJP was 3684.5IU/mL (IQR: 1034-93,300IU/mL). Additionally, 88.9% of patients with CMV in the preceding year had active infection at time of PJP diagnosis. Patient and graft survival were significantly worse at 2years in recipients with PJP than our control group (42.4% vs. 88.5, and 37.9% vs. 79.9%; p<0.001). Conclusions: Despite the low overall incidence of PJP in the era of universal prophylaxis, outcomes are poor. We suggest extending or re-initiating PJP prophylaxis for at least 6months in the setting of CMV viremia due to the relatively low risk of therapy and potential significant impact on disease prevention.