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

Esmee C. M. Kooijmans; Helena J. H. van der Pal; the Dutch LATER Study group; Maxime C. F. Pilon; Saskia M. F. Pluijm; Margriet van der van der Loo; Leontien C. M. Kremer; Dorine Bresters; Eline van Dulmen-den Broeder; Marry M. van den Heuvel-eibrink; Jacqueline J. Loonen; Marloes Louwerens; Sebastian J. C. Neggers; Hanneke M. van Santen; Wim J. E. Tissing; Andrica C. H. de Vries; Gertjan J. L. Kaspers; Margreet A. Veening; Arend Bokenkamp

doi:10.1080/00365513.2022.2129437

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

Esmee C. M. Kooijmans^*, Helena J. H. van der Pal, the Dutch LATER Study group, Maxime C. F. Pilon, Saskia M. F. Pluijm, Margriet van der van der Loo, Leontien C. M. Kremer, Dorine Bresters, Eline van Dulmen-den Broeder, Marry M. van den Heuvel-eibrink, Jacqueline J. Loonen, Marloes Louwerens, Sebastian J. C. Neggers, Hanneke M. van Santen, Wim J. E. Tissing, Andrica C. H. de Vries, Gertjan J. L. Kaspers, Margreet A. Veening, Arend Bokenkamp

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	541-548
Number of pages	8
Journal	Scandinavian Journal of Clinical & Laboratory Investigation
Volume	82
Issue number	7-8
Early online date	6 Oct 2022
DOIs	https://doi.org/10.1080/00365513.2022.2129437
Publication status	Published - 2022

Bibliographical note

Funding
This research was funded by KWF Dutch Cancer Society, grant number 7889.

© 2022 Medisinsk Fysiologisk Forenings Forlag (MFFF)

Funding Information:
This research was funded by KWF Dutch Cancer Society, grant number 7889. The authors thank the other members of the Dutch LATER consortium (Cécile Ronckers, Birgitta Versluys, Martha Grootenhuis, Flora van Leeuwen, Lideke van der Steeg, Geert Janssens, Jaap den Hartogh, Lilian Batenburg, Hanneke de Ridder, Nynke Hollema, Lennart Teunissen, Anke Schellekens), all physicians, research nurses, data managers and participating patients, parents and siblings for their contribution. In addition, the authors wish to acknowledge services of the Lifelines Cohort Study, the contributing research centers delivering data to Lifelines, and all the study participants. The Lifelines initiative has been made possible by a subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University and the Provinces in the North of the Netherlands (Drenthe, Friesland, Groningen).

Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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Kooijmans, E. C. M., van der Pal, H. J. H., the Dutch LATER Study group, Pilon, M. C. F., Pluijm, S. M. F., van der van der Loo, M., Kremer, L. C. M., Bresters, D., van Dulmen-den Broeder, E., van den Heuvel-eibrink, M. M., Loonen, J. J., Louwerens, M., Neggers, S. J. C., van Santen, H. M., Tissing, W. J. E., de Vries, A. C. H., Kaspers, G. J. L., Veening, M. A., & Bokenkamp, A. (2022). Shrunken pore syndrome in childhood cancer survivors treated with potentially nephrotoxic therapy. Scandinavian Journal of Clinical & Laboratory Investigation, 82(7-8), 541-548. https://doi.org/10.1080/00365513.2022.2129437

@article{fa4f1ca9232046ec90f8430bb076e5d7,

title = "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.",

author = "Kooijmans, {Esmee C. M.} and {van der Pal}, {Helena J. H.} and {the Dutch LATER Study group} and Pilon, {Maxime C. F.} and Pluijm, {Saskia M. F.} and {van der van der Loo}, Margriet and Kremer, {Leontien C. M.} and Dorine Bresters and {van Dulmen-den Broeder}, Eline and {van den Heuvel-eibrink}, {Marry M.} and Loonen, {Jacqueline J.} and Marloes Louwerens and Neggers, {Sebastian J. C.} and {van Santen}, {Hanneke M.} and Tissing, {Wim J. E.} and {de Vries}, {Andrica C. H.} and Kaspers, {Gertjan J. L.} and Veening, {Margreet A.} and Arend Bokenkamp",

note = "Funding This research was funded by KWF Dutch Cancer Society, grant number 7889. {\textcopyright} 2022 Medisinsk Fysiologisk Forenings Forlag (MFFF) Funding Information: This research was funded by KWF Dutch Cancer Society, grant number 7889. The authors thank the other members of the Dutch LATER consortium (C{\'e}cile Ronckers, Birgitta Versluys, Martha Grootenhuis, Flora van Leeuwen, Lideke van der Steeg, Geert Janssens, Jaap den Hartogh, Lilian Batenburg, Hanneke de Ridder, Nynke Hollema, Lennart Teunissen, Anke Schellekens), all physicians, research nurses, data managers and participating patients, parents and siblings for their contribution. In addition, the authors wish to acknowledge services of the Lifelines Cohort Study, the contributing research centers delivering data to Lifelines, and all the study participants. The Lifelines initiative has been made possible by a subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University and the Provinces in the North of the Netherlands (Drenthe, Friesland, Groningen). Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2022",

doi = "10.1080/00365513.2022.2129437",

language = "English",

volume = "82",

pages = "541--548",

journal = "Scandinavian Journal of Clinical & Laboratory Investigation",

issn = "0036-5513",

publisher = "Informa Healthcare",

number = "7-8",

}

Kooijmans, ECM, van der Pal, HJH, the Dutch LATER Study group, Pilon, MCF, Pluijm, SMF, van der van der Loo, M, Kremer, LCM, Bresters, D, van Dulmen-den Broeder, E, van den Heuvel-eibrink, MM, Loonen, JJ, Louwerens, M, Neggers, SJC, van Santen, HM, Tissing, WJE, de Vries, ACH, Kaspers, GJL, Veening, MA & Bokenkamp, A 2022, 'Shrunken pore syndrome in childhood cancer survivors treated with potentially nephrotoxic therapy', Scandinavian Journal of Clinical & Laboratory Investigation, vol. 82, no. 7-8, pp. 541-548. https://doi.org/10.1080/00365513.2022.2129437

TY - JOUR

T1 - Shrunken pore syndrome in childhood cancer survivors treated with potentially nephrotoxic therapy

AU - Kooijmans, Esmee C. M.

AU - van der Pal, Helena J. H.

AU - the Dutch LATER Study group

AU - Pilon, Maxime C. F.

AU - Pluijm, Saskia M. F.

AU - van der 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 - Bokenkamp, Arend

N1 - Funding This research was funded by KWF Dutch Cancer Society, grant number 7889. © 2022 Medisinsk Fysiologisk Forenings Forlag (MFFF) Funding Information: This research was funded by KWF Dutch Cancer Society, grant number 7889. The authors thank the other members of the Dutch LATER consortium (Cécile Ronckers, Birgitta Versluys, Martha Grootenhuis, Flora van Leeuwen, Lideke van der Steeg, Geert Janssens, Jaap den Hartogh, Lilian Batenburg, Hanneke de Ridder, Nynke Hollema, Lennart Teunissen, Anke Schellekens), all physicians, research nurses, data managers and participating patients, parents and siblings for their contribution. In addition, the authors wish to acknowledge services of the Lifelines Cohort Study, the contributing research centers delivering data to Lifelines, and all the study participants. The Lifelines initiative has been made possible by a subsidy from the Dutch Ministry of Health, Welfare and Sport, the Dutch Ministry of Economic Affairs, the University Medical Center Groningen (UMCG), Groningen University and the Provinces in the North of the Netherlands (Drenthe, Friesland, Groningen). Publisher Copyright: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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 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.

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 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.

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DO - 10.1080/00365513.2022.2129437

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C2 - 36200802

SN - 0036-5513

VL - 82

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EP - 548

JO - Scandinavian Journal of Clinical & Laboratory Investigation

JF - Scandinavian Journal of Clinical & Laboratory Investigation

IS - 7-8

ER -

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

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