Hypertension in long-term childhood cancer survivors after treatment with potentially nephrotoxic therapy; DCCSS-LATER 2: Renal study

Modifiable Cardiometabolic Risk Factors in Survivors of Childhood Cancer

“…Although therapy-related risk factors have not been consistently identified across studies, independent associations have been observed between hypertension and nephrectomy, moderate-dose alkylating agents, 68 abdominal radiotherapy ≥20 Gy, and TBI, suggesting a link to nephrotoxic therapy. 69 No associations were noted with steroid exposure. 68 Cardiotoxic treatments interact with an individual’s genetic risk for hypertension, together accounting for 40.2% of cases among survivors.…”

“…Frequency is risk dependent. 143 Cancer treatment – related risk factors Head/brain radiation 23 Neurosurgery involving the hypothalamic-pituitary axis, hypothalamic injury 23 Higher cranial radiation (≥18 Gy) 17 Corticosteroids 11 , 20 , 21 Alkylating agent (particularly ifosfamide) 23 Heavy metals (carboplatin, cisplatin) 23 Hematopoietic cell transplant 23 Abdominal radiotherapy ≥20 Gy and TBI 69 Nephrectomy 68 Abdomen/TBI radiation, 23 including radiation affecting pancreatic tail in dose-dependent fashion 30 Abdomen/TBI radiation 23 Chest or craniospinal field radiation 101 Platinum-based chemotherapy 104 Anthracycline doses ≥200 mg/m 2 103 Other risk factors to consider Patient factors Younger age at treatment Female sex Unfavorable health behaviors Genetic predisposition Family history and genetic predisposition Younger age at radiation exposure Family history Family history Comorbid conditions Growth hormone deficiency Hypothyroidism Hypogonadism Inability to exercise Pretreatment obesity Obesity Pre-existing renal impairment Congenital absence of kidney Obesity Growth hormone deficiency Hypogonadism Hypothyroidism Screening recommendations for survivors Modality BMI 3 skinfold Waist-to-height ratio Office blood pressure measurement Fasting blood glucose Hemoglobin A1C Fasting lipid profile Frequency Yearly <40 y: 3-5 y ≥40 y or exposed to nephrotoxic or cardiotoxic treatment: yearly 2 y 3 y in gen...…”

“… 68 In contrast, the prevalence of hypertension was similar between adult survivors (16.3%) and controls (18.2%) in the Dutch Childhood Cancer Survivor Study. 69 …”

“… 3 The risk for cardiovascular disease is further amplified by the interaction between hypertension and exposure to anthracycline chemotherapy and chest-directed radiotherapy ( Figure 2 ). 6 Additionally, hypertension has been associated with a 4- and 2-fold risk for stroke and stroke recurrence independent of cranial radiation 72 , 73 and has been linked to decreased kidney function 69 , 74 and accelerated epigenetic age. 38 …”

Prediction of kidney failure in long-term survivors of childhood cancer—an opportunity for intervention in follow-up programs

“…Since 2021, this has resulted in 23 papers addressing—among others—quality of life, fatigue and frailty, bone health, sexual function, cardiac function and oral health. The DCCSS-LATER 2 RENA study assessed late renal effects looking at glomerular ( 12 ) and tubular damage ( 11 ) and the prevalence and risk factors for hypertension after potentially nephrotoxic cancer treatment ( 14 ). For comparison with the general population the RENA study used data from 500 age- and sex-matched controls.…”