TY - JOUR
T1 - Long-Term Tubular Dysfunction in Childhood Cancer Survivors; DCCSS-LATER 2 Renal Study
AU - Kooijmans, Esmee C. M.
AU - van der Pal, Helena J. H.
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 - Ronckers, C. cile
AU - Tissing, Wim J. E.
AU - de Vries, Andrica C. H.
AU - Kaspers, Gertjan J. L.
AU - on behalf of the Dutch LATER study group
AU - Bökenkamp, Arend
AU - Veening, Margreet A.
N1 - Funding Information: Funding: This research was funded by KWF Dutch Cancer Society, grant number 7889. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - childhood cancer survivor
KW - nephrotoxicity
KW - tubular dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85131693542&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers14112754
DO - https://doi.org/10.3390/cancers14112754
M3 - Article
C2 - 35681735
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 11
M1 - 2754
ER -