Long-term kidney function in children with Wilms tumour and constitutional WT1 pathogenic variant.

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.