Wu Natalie L, Hingorani Sangeeta, Cushing-Haugen Kara L, Lee Stephanie J, Chow Eric J
Department of Pediatrics, Division of Hematology/Oncology, University of Washington, Seattle Children's Hospital, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Pediatrics, Division of Nephrology, University of Washington, Seattle Children's Hospital, Seattle, Washington.
Transplant Cell Ther. 2021 May;27(5):434.e1-434.e6. doi: 10.1016/j.jtct.2021.02.013. Epub 2021 Feb 17.
Increasing numbers of patients are undergoing hematopoietic cell transplantation (HCT); however, further characterization of late kidney outcomes in HCT recipients is needed. This study investigated long-term kidney outcomes in HCT survivors and compared the risk of late kidney morbidity/mortality in these survivors with that in non-HCT cancer survivors and the general population. A cohort of long-term (≥2 years) allogeneic and autologous HCT survivors treated for cancer at our institution between 1992 and 2009 (n = 1792) was compared with a non-HCT cancer cohort selected from the state cancer registry (n = 5455) matched on diagnosis, sex, and age at year of cancer diagnosis/HCT (index date). Additional comparisons were made with a matched general population sample drawn from state driver's licensing files (DOL; n = 16,340). Statewide hospital discharge codes and death registry codes (International Classification of Diseases 9/10) were used to identify cases of acute kidney failure (AKF) and chronic kidney disease (CKD) occurring ≥2 years after the index date. Cumulative incidence rates and hazard ratios (HRs; according to multivariable proportional hazard models) estimated the absolute and relative risks of AKF and CKD. Among HCT survivors, we examined the influence of additional characteristics including estimated glomerular filtration rate (eGFR) at 1-year post-HCT. The cumulative incidence rates of late kidney complications were slightly greater in the HCT survivors versus the non-HCT cancer survivors at 10 years after the index date. Both groups were more likely to experience late AKF or CKD morbidity/mortality compared with the general population (AKF: HCT, 9.4%; non-HCT, 7.7%; DOL, 1.8%; CKD: HCT, 5.7%; non-HCT, 5.0%; DOL, 1.2%). Differences between HCT survivors and non-HCT survivors were seen primarily starting 5 years after the index date, with increased hazards for late AKF (HR, 1.4; 95% confidence interval [CI], 1.1 to 1.9) and CKD (HR, 1.9; 95% CI, 1.3 to 2.8). Among allogeneic HCT survivors, the presence of hypertension at <2 years post-HCT was significantly associated with subsequent AKF (HR, 2.9; 95% CI, 1.7 to 5.0) and CKD (HR, 5.2; 95% CI, 2.7 to 10.0) at 2 to 10 years post-HCT, with similar associations seen for autologous HCT survivors. Low eGFR (<60 mL/min/1.73 m) at 1 year post-HCT was associated with late AKF morbidity/mortality for both allogeneic (HR, 5.3; 95% CI, 2.1 to 13.2) and autologous HCT (HR, 2.7; 95% CI, 1.2 to 6.3) compared with survivors with normal eGFR (>90 mL/min/1.73 m). Overall, the risk for hospitalization or death from AKF or CKD continued to increase with time from HCT and exceeded that of non-HCT cancer survivors at >5 years after treatment. Appropriate screening and early intervention with medication adjustments or lifestyle modifications in those with hypertension or evidence of abnormal eGFR post-HCT could potentially mitigate this risk.
接受造血细胞移植(HCT)的患者数量日益增加;然而,仍需进一步明确HCT受者晚期肾脏结局的特征。本研究调查了HCT幸存者的长期肾脏结局,并比较了这些幸存者与非HCT癌症幸存者及一般人群发生晚期肾脏疾病/死亡的风险。将1992年至2009年期间在我们机构接受癌症治疗的长期(≥2年)异基因和自体HCT幸存者队列(n = 1792)与从州癌症登记处选取的非HCT癌症队列(n = 5455)进行比较,后者在癌症诊断/HCT(索引日期)的诊断、性别和年龄方面进行了匹配。还与从州驾驶执照档案中抽取的匹配一般人群样本(DOL;n = 16,340)进行了额外比较。使用全州范围的医院出院代码和死亡登记代码(国际疾病分类第9/10版)来识别索引日期后≥2年发生的急性肾衰竭(AKF)和慢性肾脏病(CKD)病例。累积发病率和风险比(HRs;根据多变量比例风险模型)估计了AKF和CKD的绝对和相对风险。在HCT幸存者中,我们研究了包括HCT后1年估计肾小球滤过率(eGFR)在内的其他特征的影响。索引日期后10年,HCT幸存者晚期肾脏并发症的累积发病率略高于非HCT癌症幸存者。与一般人群相比,两组发生晚期AKF或CKD疾病/死亡的可能性更高(AKF:HCT,9.4%;非HCT,7.7%;DOL,1.8%;CKD:HCT,5.7%;非HCT,5.0%;DOL,1.2%)。HCT幸存者与非HCT幸存者之间的差异主要在索引日期后5年开始显现,晚期AKF(HR,1.4;95%置信区间[CI],1.1至1.9)和CKD(HR,1.9;95%CI,1.3至2.8)的风险增加。在异基因HCT幸存者中,HCT后<2年出现高血压与HCT后2至10年随后发生的AKF(HR,2.9;95%CI,1.7至5.0)和CKD(HR,5.2;95%CI,2.7至10.0)显著相关,自体HCT幸存者也有类似关联。与eGFR正常(>90 mL/min/1.73 m²)的幸存者相比,HCT后1年eGFR低(<60 mL/min/1.73 m²)与异基因(HR,5.3;95%CI,2.1至13.2)和自体HCT(HR,2.7;95%CI,1.2至6.3)的晚期AKF疾病/死亡相关。总体而言,AKF或CKD导致住院或死亡的风险随着HCT后的时间持续增加,且在治疗后>5年超过了非HCT癌症幸存者。对HCT后患有高血压或有eGFR异常证据者进行适当筛查,并通过药物调整或生活方式改变进行早期干预,可能会降低这种风险。