TY - JOUR
T1 - Shrunken pore syndrome in childhood cancer survivors treated with potentially nephrotoxic therapy
AU - on behalf of the Dutch LATER study group
AU - Kooijmans, Esmee C.M.
AU - van der Pal, Helena J.H.
AU - Pilon, Maxime C.F.
AU - Pluijm, Saskia M.F.
AU - van der Heiden-van der Loo, Margriet
AU - Kremer, Leontien C.M.
AU - Bresters, Dorine
AU - van Dulmen-den Broeder, Eline
AU - van den Heuvel-Eibrink, Marry M.
AU - Loonen, Jacqueline J.
AU - Louwerens, Marloes
AU - Neggers, Sebastian J.C.
AU - van Santen, Hanneke M.
AU - Tissing, Wim J.E.
AU - de Vries, Andrica C.H.
AU - Kaspers, Gertjan J.L.
AU - Veening, Margreet A.
AU - Bökenkamp, Arend
N1 - Publisher Copyright:
© 2022 Medisinsk Fysiologisk Forenings Forlag (MFFF).
PY - 2022
Y1 - 2022
N2 - 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 eGFRcys/eGFRcr 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-EPIcys/CKD-EPIcr, CAPA/LMR, and FAScys/FASage. Median age was 32 years. Although an eGFRcys/eGFRcr 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.
AB - 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 eGFRcys/eGFRcr 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-EPIcys/CKD-EPIcr, CAPA/LMR, and FAScys/FASage. Median age was 32 years. Although an eGFRcys/eGFRcr 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.
KW - cystatin C
KW - glomerular filtration rate
KW - kidney diseases
KW - Shrunken pore syndrome
KW - survivors of childhood cancer
UR - http://www.scopus.com/inward/record.url?scp=85139720368&partnerID=8YFLogxK
U2 - 10.1080/00365513.2022.2129437
DO - 10.1080/00365513.2022.2129437
M3 - Article
C2 - 36200802
AN - SCOPUS:85139720368
JO - Scandinavian Journal of Clinical and Laboratory Investigation
JF - Scandinavian Journal of Clinical and Laboratory Investigation
SN - 0036-5513
ER -