Long-Term Kidney and Cardiovascular Complications in Pediatric Cancer Survivors.

OBJECTIVE: The objective of this study was to describe the burden of adverse kidney and hypertension outcomes in patients evaluated by pediatric nephrology in a multidisciplinary survivorship clinic. STUDY DESIGN: Retrospective chart review of all patients followed up by nephrology in our multidisciplinary survivorship clinic from August 2013 to June 2021. Data included clinic blood pressure, longitudinal ambulatory blood pressure monitoring (ABPM), echocardiography, serum creatinine, and first-morning urine protein/creatinine ratios. For patients with multiple ABPMs, results of initial and most recent ABPMs were compared. RESULTS: Of 422 patients followed in the multidisciplinary cancer survivorship clinic, 130 were seen by nephrology. The median time after therapy completion to first nephrology visit was 8 years. The most common diagnoses were leukemia/myelodysplastic syndrome (27%), neuroblastoma (24%), and Wilms tumor (15%). At the last follow-up, 68% had impaired kidney function, 38% had a clinical diagnosis of hypertension, and 12% had proteinuria. There were 91 ABPMs performed in 55 (42%) patients. Patients with multiple ABPMs (n = 21) had statistically significant reductions in overall median blood pressure loads: systolic initial load 37% vs most recent 10% (P = .005) and diastolic load 36% vs 14% (P = .017). Patients with impaired kidney function were more likely to have received ifosfamide. Patients with hypertension were more likely to have received total body irradiation or allogeneic stem cell transplant. CONCLUSIONS: History of leukemia/myelodysplastic syndrome, neuroblastoma, and Wilms tumor was frequent among survivors seen by nephrology. There was significant improvement in cardiovascular measures with increased recognition of hypertension and subsequent treatment.

Kidney Outcomes and Hypertension in Survivors of Wilms Tumor: A Prospective Cohort Study.

OBJECTIVE: To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT). STUDY DESIGN: This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing therapy, excluding those with preexisting hypertension, prior dialysis, or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90th percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for kidney injury molecule-1, interleukin-18, epidermal growth factor, albumin, and creatinine. The estimated glomerular filtration rate (eGFR) was calculated using the bedside chronic kidney disease in children equation. Recent kidney ultrasound examinations and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy, respectively. Clinical follow-up data were collected for approximately 2 years after study enrollment. RESULTS: Thirty-two participants (median age, 13.6 years [IQR, 10.5-16.3 years]; 75% stage 3 or higher WT) were evaluated at a median of 8.7 years (IQR, 6.5-10.8 years) after therapy; 29 participants underwent unilateral radical nephrectomy, 2 bilateral partial nephrectomy, and 1 radical and contralateral partial nephrectomy. In this cohort, 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 mL/min/1.73 m2 (IQR, 84.6-114.0; 11 [34%] had an eGFR of <90 mL/min/1.73 m2). Abnormal ABPM results were found in 22 of 29 participants (76%), masked hypertension in 10 of 29 (34%), and microalbuminuria in 2 of 32 (6%). Of the 32 participants, 22 (69%) had abnormal epidermal growth factor; few had abnormal kidney injury molecule-1 or interleukin-18. Seven participants with previous unilateral nephrectomy lacked compensatory contralateral kidney hypertrophy. None had left ventricular hypertrophy. CONCLUSIONS: In survivors of WT, adverse kidney outcomes were common and should be closely monitored.

Fertility Preservation in Children and Adolescents With Cancer.

OBJECTIVE: Advancements in oncologic therapy have increased long-term survival rates for children with childhood cancers. As survival has increased, the secondary effects of treatment have come into focus for patients and family. Infertility preservation in prepubertal children is a particularly difficult task as options are limited compared to adult counterparts with mature gametes. METHODS: A systematic review of the published literature was conducted using keywords relevant to fertility preservation in the pediatric population undergoing oncologic treatment. RESULTS: We review the impact of cancer therapy upon gonadal function and identify the risk factors for future infertility in the prepubertal population. Treatment modifications that could modify the degree of potential damage to reproductive organs yet maintain oncologic principles were highlighted. Pubertal males and females have the opportunity to donate mature sperm or oocytes as do their adult counterparts; however, for the prepubertal child this is not the case. The options for these patients are considered investigational at this point and center on testicular tissue cryopreservation in males and oophorectomy vs ovarian cortical tissue cryopreservation in females. CONCLUSION: Infertility is an unfortunate side effect of oncologic treatment. Options are limited in the prepubertal population but tissue preservation and potential fertility should be discussed with all at-risk patients and their parents.

Body composition abnormalities in long-term survivors of pediatric hematopoietic stem cell transplantation.

OBJECTIVE: To quantify lean mass (LM) and fat mass (FM) in survivors of childhood allogeneic hematopoietic stem-cell transplantation (alloHSCT) compared with healthy reference participants and identify risk factors for body composition abnormalities. STUDY DESIGN: Whole body LM and FM were measured with dual energy x-ray absorptiometry in 54 survivors (ages 5-25 years) and 894 healthy reference participants in a cross-sectional study. Multivariate regression models were used to compare sex- and race-specific Z-scores for LM for height (LM-Ht) and FM for height (FM-Ht) in survivors and reference participants and to identify correlates of LM-Ht and FM-Ht Z-scores in alloHSCT. RESULTS: Height Z-scores were significantly lower in alloHSCT survivors (P < .001) compared with reference participants; body mass index Z-scores did not differ (P = .13). Survivors had significantly lower mean LM-Ht Z-scores (-0.72; 95% CI, -1.02--0.42; P < .001) and greater FM-Ht Z-scores (1.10; 95% CI, 0.84-1.39; P < .001) compared with reference participants. LM-Ht Z-score deficits in alloHSCT survivors were larger (-1.26; 95% CI, -1.53--0.99; P < .001) after adjustment for FM-Ht Z-scores. Endocrinopathies and alloHSCT characteristics were not associated with LM-Ht or FM-Ht Z-scores. CONCLUSION: Survivors of childhood alloHSCT have significant LM deficits and FM excess. Future studies should identify the mechanism and consequences of these abnormalities.