Kooijmans Esmee C M, van der Pal Helena J H, Pluijm Saskia M F, van der Heiden-van der Loo Margriet, Kremer Leontien C M, Bresters Dorine, van Dulmen-den Broeder Eline, van den Heuvel-Eibrink Marry M, Loonen Jacqueline J, Louwerens Marloes, Neggers Sebastian J C, Ronckers Cécile, Tissing Wim J E, de Vries Andrica C H, Kaspers Gertjan J L, Bökenkamp Arend, Veening Margreet A
Department of Pediatric Oncology, Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.
Cancers (Basel). 2022 Jun 1;14(11):2754. doi: 10.3390/cancers14112754.
The aim of this nationwide cross-sectional cohort study was to determine the prevalence of and risk factors for tubular dysfunction in childhood cancer survivors (CCS). In the DCCSS-LATER 2 Renal study, 1024 CCS (≥5 years after diagnosis), aged ≥ 18 years at study, treated between 1963 and 2001 with potentially nephrotoxic therapy (i.e., nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide, or hematopoietic stem cell transplantation) participated, and 500 age- and sex-matched participants from Lifelines acted as controls. Tubular electrolyte loss was defined as low serum levels (magnesium < 0.7 mmol/L, phosphate < 0.7 mmol/L and potassium < 3.6 mmol/L) with increased renal excretion or supplementation. A α1-microglobulin:creatinine ratio > 1.7 mg/mmol was considered as low-molecular weight proteinuria (LMWP). Multivariable risk analyses were performed. After median 25.5 years follow-up, overall prevalence of electrolyte losses in CCS (magnesium 5.6%, potassium 4.5%, phosphate 5.5%) was not higher compared to controls. LMWP was more prevalent (CCS 20.1% versus controls 0.4%). LMWP and magnesium loss were associated with glomerular dysfunction. Ifosfamide was associated with potassium loss, phosphate loss (with cumulative dose > 42 g/m2) and LMWP. Cisplatin was associated with magnesium loss and a cumulative dose > 500 mg/m2 with potassium and phosphate loss. Carboplatin cumulative dose > 2800 mg/m2 was associated with potassium loss. In conclusion, long-term tubular dysfunction is infrequent. Yet, ifosfamide, cisplatin and carboplatin are risk factors.
这项全国性横断面队列研究的目的是确定儿童癌症幸存者（CCS）肾小管功能障碍的患病率及其危险因素。在DCCSS-LATER 2肾脏研究中，1024例CCS（诊断后≥5年）参与了研究，这些患者在研究时年龄≥18岁，于1963年至2001年间接受了可能具有肾毒性的治疗（即肾切除术、腹部放疗、全身照射、顺铂、卡铂、异环磷酰胺、大剂量环磷酰胺或造血干细胞移植），并选取了来自生命线研究的500名年龄和性别匹配的参与者作为对照。肾小管电解质丢失定义为血清水平降低（镁<0.7 mmol/L、磷酸盐<0.7 mmol/L和钾<3.6 mmol/L）且肾脏排泄增加或需要补充。α1-微球蛋白与肌酐比值>1.7 mg/mmol被视为低分子量蛋白尿（LMWP）。进行了多变量风险分析。经过中位25.5年的随访，CCS中电解质丢失的总体患病率（镁5.6%、钾4.5%、磷酸盐5.5%）与对照组相比并不更高。LMWP更为普遍（CCS为20.1%，而对照组为0.4%）。LMWP和镁丢失与肾小球功能障碍相关。异环磷酰胺与钾丢失、磷酸盐丢失（累积剂量>42 g/m2）和LMWP相关。顺铂与镁丢失相关，累积剂量>500 mg/m2与钾和磷酸盐丢失相关。卡铂累积剂量>2800 mg/m2与钾丢失相关。总之，长期肾小管功能障碍并不常见。然而，异环磷酰胺、顺铂和卡铂是危险因素。
