Shrunken pore syndrome in childhood cancer survivors treated with potentially nephrotoxic therapy

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.

Keywords: Shrunken pore syndrome; cystatin C; glomerular filtration rate; kidney diseases; survivors of childhood cancer.