Abstract

Childhood cancer survivors (CCS) are at risk of kidney dysfunction. Recently, the shrunken pore syndrome (SPS) has been described, which is characterized by selectively impaired filtration of larger molecules like cystatin C, while filtration of smaller molecules like creatinine is unaltered. It has been associated with increased mortality, even in the presence of a normal estimated glomerular filtration rate (eGFR). The aim of this study was to evaluate the prevalence of SPS in CCS exposed to potentially nephrotoxic therapy. In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 Renal study, a nationwide cross-sectional cohort study, 1024 CCS ≥5 years after diagnosis, aged ≥18 years at study, treated between 1963-2001 with nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide or hematopoietic stem cell transplantation participated, and 500 age- and sex-matched controls form Lifelines. SPS was defined as an eGFR_cys/eGFR_cr ratio <0.6 in the absence of non-GFR determinants of cystatin C and creatinine metabolism (i.e. hyperthyroidism, corticosteroids, underweight). Three pairs of eGFR-equations were used; CKD-EPI_cys/CKD-EPI_cr, CAPA/LMR, and FAS_cys/FAS_age. Median age was 32 years. Although an eGFR_cys/eGFR_cr ratio <0.6 was more common in CCS (1.0%) than controls (0%) based on the CKD-EPI equations, most cases were explained by non-GFR determinants. The prevalence of SPS in CCS was 0.3% (CKD-EPI equations), 0.2% (CAPA/LMR) and 0.1% (FAS equations), and not increased compared to controls. CCS treated with nephrotoxic therapy are not at increased risk for SPS compared to controls. Yet, non-GFR determinants are more common and should be taken into account when estimating GFR.

摘要

儿童癌症幸存者 (CCS) 存在肾功能障碍的风险。最近，描述了收缩毛孔综合征 (SPS)，其特征是选择性地损害较大分子（如胱抑素 C）的过滤，而较小分子（如肌酐）的过滤未改变。它与死亡率增加有关，即使在估计肾小球滤过率 (eGFR) 正常的情况下也是如此。本研究的目的是评估暴露于潜在肾毒性治疗的 CCS 中 SPS 的患病率。在荷兰儿童癌症幸存者研究 (DCCSS)-LATER 2 肾脏研究中，一项全国性的横断面队列研究，1024 例 CCS 诊断后 ≥ 5 年，研究时年龄 ≥ 18 岁，在 1963-2001 年间接受了肾切除术、腹部放疗、全身照射，顺铂，卡铂，异环磷酰胺，生命线。SPS 定义为在不存在胱抑素 C 和肌酐代谢的非 GFR 决定因素（即甲状腺功能亢进、皮质类固醇、体重不足）的情况下， eGFR _cys /eGFR _{cr比率 <0.6。}使用了三对 eGFR 方程；CKD-EPI _cys /CKD-EPI _cr、CAPA/LMR 和 FAS _cys /FAS _age。中位年龄为 32 岁。尽管 eGFR _cys /eGFR _cr根据 CKD-EPI 方程，比率 <0.6 在 CCS (1.0%) 中比在对照组 (0%) 中更常见，大多数病例由非 GFR 决定因素解释。CCS 中 SPS 的患病率为 0.3%（CKD-EPI 方程）、0.2%（CAPA/LMR）和 0.1%（FAS 方程），与对照组相比没有增加。与对照组相比，接受肾毒性治疗的 CCS 患 SPS 的风险并未增加。然而，非 GFR 决定因素更为常见，在估算 GFR 时应予以考虑。