Childhood cancer survivors treated with nephrectomy and potentially nephrotoxic therapy are at increased risk for chronic kidney disease (CKD) and albuminuria, especially after age 40 years, investigators reported in Kidney International.
In the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis, investigators compared long-term outcomes between 1024 survivors and 500 age- and sex-matched control participants. Selected childhood cancer survivors were treated during 1963-2001 with nephrectomy, abdominal radiation therapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide, or hematopoietic stem cell transplantation. The more common cancers included leukemia (30.7%) and Wilms tumor (25.4%). Kidney cancers affected 9.7%.
At a median age of 32 years, 3.7% of childhood cancer survivors had stage 3-5 CKD (including 1.1% with end-stage kidney disease) compared with none of the controls, using the CKD-EPI 2012 creatinine and cystatin C equation for estimating glomerular filtration rate (eGFR), Esmee C.M. Kooijmans, MD, of Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam in the Netherlands, and colleagues reported. CKD defined by age-thresholds (GFR less than 75, 60, and 40 mL/min/1.73 m2 for patients aged younger than 40, 40-65, and older than 65 years, respectively) was 6.6% among survivors compared with 0.2% among the control group. Albuminuria (albumin-to-creatinine ratio exceeding 3 mg/mmoL) occurred in 16.2% of survivors vs 1.2% of the control group.
Significant risk factors for CKD included nephrectomy, abdominal radiation therapy, ifosfamide (especially more than 12 g/ m2), and cisplatin exceeding 500 mg/m2, and the risks increased per year of age and after 30 or more years of follow-up, the investigators reported. Significant albuminuria risk factors included total body irradiation, abdominal radiation therapy exceeding 30 Gy, ifosfamide, and hypertension.
Survivors of solid tumor cancers, including neuroblastoma, renal tumors, bone tumors, and soft tissue sarcomas, had significantly increased odds for kidney function decline.
“The results of this study emphasize the need for lifelong monitoring of glomerular function among [childhood cancer survivors] with identified high-risk factors and minimizing nephrotoxic exposures,” Dr Kooijmans’ team concluded. They noted that hypertension remains a key modifiable risk factor.
Treatment of childhood cancers evolved over the study period, 1963-2001, and likely influenced results. It has also changed remarkably over the last 20 years.
Among the study’s other limitations, the investigators could not assess the effects of nephrotoxic supportive care drugs and acute kidney injury episodes on kidney dysfunction. They also did not adjust for predisposing syndromes.
Kooijmans ECM, van der Pal HJH, Pluijm SMF, et al. The Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 kidney analysis examined long-term glomerular dysfunction in childhood cancer survivors. Kidney Int. Published online June 27, 2022. doi:10.1016/j.kint.2022.05.029