Long-Term Tubular Dysfunction in Childhood Cancer Survivors; DCCSS-LATER 2 Renal Study

Esmee C M Kooijmans, Helena J H van der Pal, Saskia M F Pluijm, Margriet van der Heiden-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, Cécile Ronckers, Wim J E Tissing, Andrica C H de Vries, Gertjan J L Kaspers, Arend Bökenkamp, Margreet A Veening, On Behalf Of The Dutch Later Study Group

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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.
Original languageEnglish
Issue number11
Publication statusPublished - 1 Jun 2022


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