Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 1685 Highland Ave, 4177 Medical Foundation Centennial Building, Madison, WI, 53705, USA.
Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, WI, USA.
BMC Nephrol. 2018 Nov 21;19(1):332. doi: 10.1186/s12882-018-1142-8.
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.
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.
28 (0.45%) of 6270 recipients developed PJP between 1994 and 2016. Median time since transplant was 4.6 years (interquartile range (IQR): 1.4-9.6 years). 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: 1.74-11.5 months) and median peak CMV viral load prior to diagnosis of PJP was 3684.5 IU/mL (IQR: 1034-93,300 IU/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 2 years in recipients with PJP than our control group (42.4% vs. 88.5, and 37.9% vs. 79.9%; p < 0.001).
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 6 months in the setting of CMV viremia due to the relatively low risk of therapy and potential significant impact on disease prevention.
本研究旨在确定在普遍采用一级预防的时代，肾移植和肾胰联合移植受者中发生卡氏肺孢子菌肺炎（PJP）的预测因素。
我们回顾了 1994 年 1 月 1 日至 2016 年 12 月 31 日期间在威斯康星大学接受肾移植或肾胰联合移植的成年受者。在此期间诊断为 PJP 的患者被纳入研究。通过发病率密度抽样，以 3:1 的比例随机选择未发生 PJP 的患者作为对照，与移植后时间匹配。
1994 年至 2016 年期间，6270 名受者中有 28 名（0.45%）发生 PJP。中位移植后时间为 4.6 年（四分位间距（IQR）：1.4-9.6 年）。受影响的受者年龄较大，HLA 错配更多，发生 BK 病毒血症、CMV 病毒血症和侵袭性真菌感染的可能性更高。CMV 病毒血症仍然是多变量分析中的唯一显著危险因素，也是一个强有力的预测因素（OR 6.27；p=0.002）。90%的 CMV 病毒血症既往病例在 PJP 诊断前的 1 年内被诊断；在这些病例中，从 CMV 诊断到 PJP 诊断的中位时间为 3.4 个月（IQR：1.74-11.5 个月），PJP 诊断前 CMV 病毒载量的中位峰值为 3684.5 IU/ml（IQR：1034-93300 IU/ml）。此外，在过去 1 年中患有 CMV 的患者中，88.9%在 PJP 诊断时存在活动性感染。与对照组相比，PJP 受者在 2 年内的患者和移植物存活率显著更差（42.4%对 88.5%，37.9%对 79.9%；p<0.001）。
尽管在普遍预防的时代，PJP 的总体发生率较低，但结局仍较差。我们建议在 CMV 病毒血症的情况下，至少延长或重新开始 6 个月的 PJP 预防治疗，因为治疗风险相对较低，对疾病预防可能有显著影响。
