Glomerular function time trends in long-term survivors of childhood cancer: a longitudinal study.
BACKGROUND
Impaired glomerular function is one of the health problems affecting childhood cancer survivors (CCS). It is unclear whether glomerular function deteriorates or recovers. We investigated time trends and predictors of glomerular function in CCS.


METHODS
We evaluated repeated observations of estimated glomerular filtration rate (GFR) and glomerular dysfunction (GFR <90 mL/min/1.73 m(2)) among adult five-year CCS treated in the EKZ/AMC between 1966 and 2003. Ifosfamide, cisplatin, carboplatin, high-dose (HD) methotrexate, HD-cyclophosphamide, radiotherapy to the kidney region, and nephrectomy (i.e., potentially nephrotoxic therapy) were investigated as predictors of glomerular function patterns over time in multivariable longitudinal analyses.


RESULTS
At a median follow-up of 21 years after diagnosis, glomerular function was assessed in 1,122 CCS aged ≥18 years. CCS treated with potentially nephrotoxic therapy had a significantly lower GFR and higher glomerular dysfunction probability up to 35 years after cancer diagnosis compared with CCS treated without nephrotoxic therapy (P < 0.001). Especially ifosfamide, cisplatin, and nephrectomy were associated with worse glomerular function that persisted during the entire follow-up period (P < 0.001). Glomerular function deteriorated over time in all CCS (P < 0.001). CCS treated with higher doses of cisplatin seem to have a higher deterioration rate as compared with other CCS (P < 0.005).


CONCLUSIONS
The loss in glomerular function starts early, especially for CCS treated with ifosfamide, higher doses of cisplatin, and nephrectomy, and seems to be persistent. We have an indication that CCS treated with higher doses of cisplatin experience faster decline than other CCS.


CONCLUSIONS
As glomerular function continues to deteriorate, CCS are at risk for premature chronic renal failure.
Authors' Affiliations: Departments of Pediatric Oncology, Clinical Epidemiology, Biostatistics, and Bioinformatics, Medical Oncology, Radiation Oncology, and Pediatric Nephrology, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands.
Renée L
RL
Mulder
Sebastiaan L
SL
Knijnenburg
Ronald B
RB
Geskus
Elvira C
EC
van Dalen
Helena J H
HJ
van der Pal
Caro C E
CC
Koning
Antonia H
AH
Bouts
Huib N
HN
Caron
Leontien C M
LC
Kremer
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D009369:Neoplasms / Q000503:physiopathology*; D011788:Quality of Life; D012307:Risk Factors; D017741:Survivors