This investigation aimed to evaluate glomerular dysfunction among childhood cancer survivors in comparison with matched controls from the general population. In the Dutch Childhood Cancer Survivor... Show moreThis investigation aimed to evaluate glomerular dysfunction among childhood cancer survivors in comparison with matched controls from the general population. In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis, a nationwide cross-sectional cohort study, 1024 survivors five or more years after diagnosis, aged 18 or more 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. In addition, 500 age and sex-matched controls from Lifelines, a prospective population-based cohort study in the Netherlands, participated. At a median age of 32.0 years (interquartile range 26.6-37.4), the glomerular filtration rate was under 60 ml/min/1.73m(2) in 3.7% of survivors and in none of the controls. Ten survivors had kidney failure. Chronic kidney disease according to age-thresholds (glomerular filtration rate respectively under 75 for age under 40, under 60 for ages 40-65, and under 40 for age over 65) was 6.6% in survivors vs. 0.2% in controls. Albuminuria (albumin-to-creatinine ratio over3 mg/mmol) was found in 16.2% of survivors and 1.2% of controls. Risk factors for chronic kidney disease, based on multivariable analyses, were nephrectomy (odds ratio 3.7 (95% Confidence interval 2.1-6.4)), abdominal radiotherapy (1.8 (1.1-2.9)), ifosfamide (2.9 (1.9-4.4)) and cisplatin over 500 mg/m(2) (7.2 (3.4-15.2)). For albuminuria, risk factors were total body irradiation (2.3 (1.2-4.4)), abdominal radiotherapy over 30 Gy (2.6 (1.4-5.0)) and ifosfamide (1.6 (1.0-2.4)). Hypertension and follow-up 30 or more years increased the risk for glomerular dysfunction. Thus, lifetime monitoring of glomerular function in survivors exposed to these identified high risk factors is warranted. Show less
Kooijmans, E.C.M.; Pal, H.J.H. van der; Pilon, M.C.F.; Pluijm, S.M.F.; Loo, M.V.V. van der van der; Kremer, L.C.M.; ... ; Dutch LATER Study Grp 2022
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... Show moreChildhood 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-EPIcys/CKD-EPIcr, 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. Show less
Kooijmans, E.C.M.; Pal, H.J.H. van der; Pluijm, S.M.F.; Bresters, D.; Dulmen-den Broeder, E. van; Heiden-van der Loo, M. van der; ... ; Dutch LATER Study Grp 2022
Purpose: To evaluate the prevalence of and risk factors for hypertension in child-hood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. Methods: In the Dutch... Show morePurpose: To evaluate the prevalence of and risk factors for hypertension in child-hood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. Methods: In the Dutch Childhood Cancer Survivor Study LATER cohort part 2 renal study, 1024 CCS >= 5 years after diagnosis, aged >= 18 years at study participation, treated between 1963 and 2001 with nephrectomy, abdominal radiotherapy, total body irradiation (TBI), cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide (>= 1 g/m(2) per single dose or >= 10 g/m(2) total) or haematopoietic stem cell transplantation participated and 500 controls from Lifelines. Hypertension was defined as blood pressure (BP) (mmHg) systolic >= 140 and/or diastolic >= 90 or receiving medication for diagnosed hypertension. At the study visit, the CKD-EPI 2012 equation including creatinine and cystatin C was used to estimate the glomerular filtration rate (GFR). Multivariable regression analyses were used. For ambulatory BP monitoring (ABPM), hypertension was defined as BP daytime: systolic >= 135 and/or diastolic >= 85, night time: systolic >= 120 and/or diastolic >= 70, 24-h: systolic >= 130 and/or diastolic >= 80. Outcomes were masked hypertension (MH), white coat hypertension and abnormal nocturnal dipping (aND). Results: Median age at cancer 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 25.5 years (IQR 21.4-30.3). The prevalence of hypertension was comparable in CCS (16.3%) and controls (18.2%). In 12% of CCS and 17.8% of controls, hypertension was undiagnosed. A decreased GFR (< 60 ml/min/1.73 m(2)) was associated with hypertension in CCS (OR 3.4, 95% CI 1.4-8.5). Risk factors were abdominal radiotherapy >= 20 Gy and TBI. The ABPM-pilot study (n Z 77) showed 7.8% MH, 2.6% white coat hypertension and 20.8% aND. Conclusion: The prevalence of hypertension was comparable among CCS who were treated with potentially nephrotoxic therapies compared to controls, some of which were undiagnosed. Risk factors were abdominal radiotherapy >= 20 Gy and TBI. Hypertension and decreased GFR were associated with CCS. ABPM identified MH and a ND. (C) 2022 The Author(s). Published by Elsevier Ltd. Show less
Kooijmans, E.C.M.; Pal, H.J.H. van der; Pluijm, S.M.F.; Heiden-van der Loo, M. van der; Kremer, L.C.M.; Bresters, D.; ... ; Dutch LATER Study Group 2022
Simple Summary: We studied survivors of childhood cancer who received cancer treatment that might affect the kidneys and compared them to controls from the general population. We investigated if... Show moreSimple Summary: We studied survivors of childhood cancer who received cancer treatment that might affect the kidneys and compared them to controls from the general population. We investigated if there was a difference in the occurrence of tubular dysfunction. The tubules are the part of the kidney responsible for reabsorption of needed substances to the blood and the removal of wastes. After around 25 years since their cancer diagnosis, we found that in general there were no differences between survivors and controls, but survivors more often had losses of small proteins in the urine. Yet, some survivors of childhood cancer were found to have an increased risk of tubular dysfunction. Namely, survivors treated with the chemotherapeutic agents ifosfamide, cisplatin or carboplatin. Therefore, these patients should be monitored during their follow-up. 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 alpha 1-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/m(2)) and LMWP. Cisplatin was associated with magnesium loss and a cumulative dose > 500 mg/m(2) with potassium and phosphate loss. Carboplatin cumulative dose > 2800 mg/m(2) was associated with potassium loss. In conclusion, long-term tubular dysfunction is infrequent. Yet, ifosfamide, cisplatin and carboplatin are risk factors. Show less
Sol, J.J.; Loo, M. van de; Boerma, M.; Bergman, K.A.; Donker, A.E.; Hoeven, M.A.H.B.M. van der; ... ; Ommen, C.H. van 2018
