Lugthart Gertjan, Jordans Carlijn C E, de Pagter Anne P J, Bresters Dorine, Jol-van der Zijde Cornelia M, Bense Joell E, van Rooij-Kouwenhoven Roos W G, Sukhai Ram N, Louwerens Marloes, Dorresteijn Eiske M, Lankester Arjan C
Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands; Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands.
Willem-Alexander Children's Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, the Netherlands.
Kidney Int. 2021 Oct;100(4):906-914. doi: 10.1016/j.kint.2021.05.030. Epub 2021 Jun 5.
Chronic kidney disease (CKD) is an important sequela of hematopoietic stem cell transplantation (HSCT), but data regarding CKD after pediatric HSCT are limited. In this single center cohort study, we evaluated the estimated glomerular filtration rate (eGFR) dynamics, proteinuria and hypertension in the first decade after HSCT and assessed risk factors for CKD in 216 pediatric HSCT survivors, transplanted 2002-2012. The eGFR decreased from a median of 148 to 116 ml/min/1.73 m between pre-HSCT to ten years post-HSCT. CKD (KDIGO stages G2 or A2 or more; eGFR under 90 ml/min/1.73m and/or albuminuria) occurred in 17% of patients. In multivariate analysis, severe prolonged stage 2 or more acute kidney injury (AKI), with an eGFR under 60ml/min/1.73m and duration of 28 days or more, was the main risk factor for CKD (hazard ratio 9.5, 95% confidence interval 3.4-27). Stage 2 or more AKI with an eGFR of 60ml/min/1.73m or more and KDIGO stage 2 or more AKI with eGFR under 60ml/min/1.73m but recovery within 28 days were not associated with CKD. Furthermore, hematological malignancy as HSCT indication was an independent risk factor for CKD. One third of patients had both CKD criteria, one third had isolated eGFR reduction and one third only had albuminuria. Hypertension occurred in 27% of patients with CKD compared to 4.4% of patients without. Tubular proteinuria was present in 7% of a subgroup of 71 patients with available β2-microglobulinuria. Thus, a significant proportion of pediatric HSCT recipients developed CKD within ten years. Our data stress the importance of structural long-term monitoring of eGFR, urine and blood pressure after HSCT to identify patients with incipient CKD who can benefit from nephroprotective interventions.
慢性肾脏病(CKD)是造血干细胞移植(HSCT)的一个重要后遗症,但关于儿童HSCT后CKD的数据有限。在这项单中心队列研究中,我们评估了2002年至2012年接受移植的216名儿童HSCT幸存者HSCT后第一个十年的估计肾小球滤过率(eGFR)动态变化、蛋白尿和高血压情况,并评估了CKD的危险因素。HSCT前至HSCT后十年间,eGFR中位数从148降至116 ml/min/1.73 m²。17%的患者发生了CKD(KDIGO分期G2或A2及以上;eGFR低于90 ml/min/1.73m²和/或蛋白尿)。多因素分析显示,严重且持续时间较长的2期或更严重急性肾损伤(AKI),即eGFR低于60ml/min/1.73m²且持续28天或更长时间,是CKD的主要危险因素(风险比9.5,95%置信区间3.4 - 27)。eGFR为60ml/min/1.73m²或更高的2期或更严重AKI以及eGFR低于60ml/min/1.73m²但在28天内恢复的KDIGO 2期或更严重AKI与CKD无关。此外,以血液系统恶性肿瘤作为HSCT指征是CKD的独立危险因素。三分之一的患者符合CKD的两项标准,三分之一仅有eGFR降低,三分之一仅有蛋白尿。CKD患者中27%出现高血压,而无CKD患者中这一比例为4.4%。在71例可检测β2 - 微球蛋白尿的患者亚组中,7%存在肾小管性蛋白尿。因此,相当一部分儿童HSCT受者在十年内发生了CKD。我们的数据强调了HSCT后对eGFR、尿液和血压进行长期结构性监测的重要性,以便识别可从肾脏保护干预中获益的早期CKD患者。