ESPN 53rd Annual Meeting

ESPN 2021


 
TUBULAR DYSFUNCTION AND TREATMENT-RELATED RISK FACTORS IN LONG-TERM CHILDHOOD CANCER SURVIVORS; DCCSS-LATER 2: RENA.
ESMEE C.M. KOOIJMANS 1 HELENA J.H. VAN DER PAL 2 SASKIA PLUIJM 2 DORINE BRESTERS 2 ELINE VAN DULMEN-DEN BROEDER 1 MARGRIET VAN DER HEIDEN-VAN DER LOO 2 MARRY M. VAN DEN HEUVEL-EIBRINK 2 LEONTIEN C.M. KREMER 2 JACQUELINE LOONEN 3 MARLOES LOUWERENS 4 CECILE M. RONCKERS 2 WIM J.E. TISSING 2 ANDRICA C.H. DE VRIES 5 GERTJAN J.L. KASPERS 2 AREND BOKENKAMP 6 MARGREET A. VEENING 2 ON BEHALF OF THE DUTCH LATER STUDY GROUP 2

1- EMMA CHILDREN’S HOSPITAL, AMSTERDAM UMC, VRIJE UNIVERSITEIT AMSTERDAM, PEDIATRIC ONCOLOGY, AMSTERDAM, THE NETHERLANDS
2- PRINCESS MAXIMA CENTER FOR PEDIATRIC ONCOLOGY, UTRECHT, THE NETHERLANDS
3- DEPARTMENT OF HEMATOLOGY, RADBOUD UNIVERSITY MEDICAL CENTER, NIJMEGEN, THE NETHERLANDS
4- DEPARTMENT OF INTERNAL MEDICINE, LEIDEN UNIVERSITY MEDICAL CENTER, LEIDEN, THE NETHERLANDS
5- DEPARTMENT OF PEDIATRIC ONCOLOGY, SOPHIA CHILDREN’S HOSPITAL/ERASMUS MEDICAL CENTER, ROTTERDAM, THE NETHERLANDS
6- EMMA CHILDREN’S HOSPITAL, AMSTERDAM UMC, VRIJE UNIVERSITEIT AMSTERDAM, PEDIATRIC NEPHROLOGY, AMSTERDAM, THE NETHERLANDS
 
Introduction:

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).

Material and methods:

For the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort (1963-2001) part 2; clinical visit & questionnaire study; RENA project, 1,024 CCS (≥5 years after diagnosis), aged ≥18 years at time of study, treated between 1963 and 2001 with potentially nephrotoxic therapy (i.e. nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide(≥1g/m2 per course or ≥10 g/m2 in total), or bone marrow transplantation participated. Five-hundred age- and sex matched controls were used from the Lifelines cohort study. Renal electrolyte loss was defined as low serum levels in combination with increased renal excretion, or receiving electrolyte supplementation. α1-microglobulin:creatinine ratio >1.7 mg/mmol was considered as low-molecular weight proteinuria (LMWP). Chi-Square analysis was used to compare the prevalence in both groups. Multivariable logistic regression analyses were performed to assess risk factors and expressed as odds ratio (OR) with 95% confidence interval (95%CI).

Results:

Median age at diagnosis was 4.7 years (interquartile range [IQR] 2.4-9.2), at study 32.5 years (IQR 27.7-38.0), and follow-up time 25.5 years (IQR 21.4-30.3). Risk factor for magnesium loss was cisplatin (OR 10.1, 95%CI 3.9-26.0), for potassium loss these were ifosfamide (OR 2.4 [1.2-4.7]) and cisplatin (OR 3.5 [1.6-7.5]) and for phosphate loss ifosfamide (OR 2.3 [1.2-4.3]). LMWP was associated with ifosfamide (OR 2.8 [2.0-4.1]). Overall prevalence of renal losses in CCS (magnesium 5.6%, potassium 4.5%, phosphate 5.5%) was not higher compared to controls, while LMWP was significantly more prevalent (CCS 20.1% versus controls 0.4%, p<0.001).

Conclusions:

After a median follow-up of 25.5 years CCS had an increased prevalence of LMWP compared to controls, but not of renal electrolyte losses. Ifosfamide and cisplatin were associated with tubular toxicity over time.