Long-term kidney function in children with Wilms tumour and constitutional WT1 pathogenic variant
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Published on: June 23, 2015
Maria Pia Falcone1,2, Kathryn Pritchard-Jones1, Jesper Brok1,3
1Department of Paediatric Oncology Great Ormond Street Hospital, UCL Institute of Child Health, NIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Insights
Wilms tumour (WT) survivors with WT1 pathogenic variants face kidney failure risks. However, nearly two-thirds maintained kidney function, supporting nephron-sparing surgery (NSS) when oncologically safe.
Area of Science:
- Pediatric Oncology
- Nephrology
- Clinical Genetics
Background:
- Wilms tumour (WT) survivors, particularly those with constitutional WT1 pathogenic variants, face an elevated risk of kidney failure.
- Associated syndromes and genitourinary anomalies in these patients further complicate long-term kidney health.
Purpose of the Study:
- To describe the long-term kidney function in children diagnosed with Wilms tumour and a WT1 pathogenic variant.
- To inform surgical strategies and oncological management for complex pediatric cases.
Main Methods:
- Retrospective analysis of patients treated between 1993 and 2016 at a single institution.
- Review of genotype, phenotype, tumour histology, laterality, treatment, patient survival, and kidney outcomes.
Main Results:
- Twenty-five patients with various WT1 pathogenic variants were analyzed; 52% had bilateral disease, and 44% had genitourinary malformations.
- Patient survival was 100%, but 28% initiated chronic dialysis, with 7 experiencing kidney failure (median 5.6 years post-diagnosis).
- Nearly two-thirds of patients maintained native kidney function, with four exhibiting normal kidney function and blood pressure at long-term follow-up.
Conclusions:
- Despite high-risk factors, a significant proportion of WT survivors with WT1 pathogenic variants retain native kidney function.
- Nephron-sparing surgery (NSS) should be considered when feasible without compromising oncological outcomes.
- Further international research is required to correlate WT1 genotype with specific kidney function phenotypes.
Background:
Wilms tumour (WT) survivors, especially patients with associated syndromes or genitourinary anomalies due to constitutional WT1 pathogenic variant, have increased risk of kidney failure. We describe the long-term kidney function in children with WT and WT1 pathogenic variant to inform the surgical strategy and oncological management of such complex children.
Methods:
Retrospective analysis of patients with WT and constitutional WT1 pathogenic variant treated at a single centre between 1993 and 2016, reviewing genotype, phenotype, tumour histology, laterality, treatment, patient survival, and kidney outcome.
Results:
We identified 25 patients (60% male, median age at diagnosis 14 months, range 4-74 months) with WT1 deletion (4), missense (2), nonsense (8), frameshift (7), or splice site (4) pathogenic variant. Thirteen (52%) had bilateral disease, 3 (12%) had WT-aniridia, 1 had incomplete Denys-Drash syndrome, 11 (44%) had genitourinary malformation, and 10 (40%) had no phenotypic anomalies. Patient survival was 100% and 3 patients were in remission after relapse at median follow-up of 9 years. Seven patients (28%) commenced chronic dialysis of which 3 were after bilateral nephrectomies. The overall kidney survival for this cohort as mean time to start of dialysis was 13.38 years (95% CI: 10.3-16.4), where 7 patients experienced kidney failure at a median of 5.6 years. All of these 7 patients were subsequently transplanted. In addition, 2 patients have stage III and stage IV chronic kidney disease and 12 patients have albuminuria and/or treatment with ACE inhibitors. Four patients (3 frameshift; 1 WT1 deletion) had normal blood pressure and kidney function without proteinuria at follow-up from 1.5 to 12 years.
Conclusions:
Despite the known high risk of kidney disease in patients with WT and constitutional WT1 pathogenic variant, nearly two-thirds of patients had sustained native kidney function, suggesting that nephron-sparing surgery (NSS) should be attempted when possible without compromising oncological risk. Larger international studies are needed for accurate assessment of WT1genotype-kidney function phenotype correlation.
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