Nephrotoxicity in survivors of Wilms' tumours in the North of England

Abstract

One aspect of concern for survivors of Wilms' tumour has been the late outcome in terms of renal function. Previous studies have documented low glomerular filtration rate and high blood pressure in some patients. Furthermore, disorders in tubular function (especially urinary concentration defects) have been suggested but not confirmed in small studies. The aim of this study was to determine the prevalence and nature of subclinical and overt glomerular, proximal and distal renal tubular toxicity in a population based cohort of survivors of Wilms' tumour. Forty patients (24 female) with a median age of 4.3 years (3 months -11.8 years) at diagnosis were studied. Median follow-up was 8.8 (range 0.06 -27.5) years. Glomerular filtration rate was measured by 51 Cr-EDTA plasma clearance, proximal tubular function by electrolyte fractional excretions, urine excretion of low molecular weight proteins (retinol-binding protein) and renal tubular enzymes (alanine aminopeptidase; Nacetylglucosaminidase) and distal tubular function by the osmolality of the first two urines of the day on 3 consecutive days. Renal size (ultrasound) and blood pressure were also measured. Mean (range) glomerular filtration rate was 100 (61 -150) ml min 71 1.73 m 72 . Nine were below the reference range for healthy individuals with two kidneys. Most serum electrolyte concentrations (sodium, potassium, chloride, calcium, magnesium and phosphate) fell within the normal range for age, as did the fractional excretions. The values that fell outside the normal range were only marginally abnormal. Subclinical measures of tubular toxicity (retinal-binding protein, alanine aminopeptidase, N-acetylglucosaminidase) were abnormal in only four patients. Thirty-seven patients achieved maximal urine osmolalities 5800 mOsm kg 71 , but three failed to achieve this value even after DDAVP administration. Two patients had evidence of increased urinary albumin excretion. Compensatory renal hypertrophy was seen in all but two patients, but blood pressure was within normal limits in all patients. Current and past treatment for Wilms' tumour does not have any clinically important nephrotoxic effect in the majority of patients. This finding will enable paediatric oncologists to reassure patients and parents that treatment for Wilms' tumour rarely causes long-term renal impairment.

Evaluation of Renal Function in Pediatric Patients After Treatment for Wilms’ Tumor

“…Most commonly this is a type of renal-vascular hypertension caused by compression of the renal artery by a large tumor mass. The effects of treatment for Wilms' tumor on blood pressure have also been analyzed by other authors [10,12,14]. In the 2002 study conducted by Bailey et al, [10] increased blood pressure was shown in 2% of the 40 patients during follow-up examinations after treatment for nephroblastoma.…”

“…In the study by Bailey et al [10], microalbuminuria was found in 5% of the patients (n = 2), and in a study by Levitt et al [13] it was noted in 9% of the patients; in neither study did the patients show any other symptoms of renal dysfunction at the same time. In a study carried out by Di Tullio microalbuminuria was noticed in more patients: 35% of all those tested [12].…”

“…Renal toxicity risk assessment after treatment for Wilms' tumor has also been carried out by other authors [9,10]. Data reported in the literature indicate the need for special supervision of the remaining single kidney function.…”

“…Data reported in the literature indicate the need for special supervision of the remaining single kidney function. Bailey et al [10] described a reduced GFR measured by 51 Cr-EDTA clearance in 22% of 40 patients tested. GFR evaluation was performed at different times after the end of the treatment (from 21 days to 27 years, mean: 10.7 years).…”

Chronic Kidney Disease in Wilms Tumour Survivors – What Do We Know Today?

“…Some investigators consider post-nephrectomy renal dysfunction as clinically insignificant (19,20). In contrast, other investigators consider this renal dysfunction to be a harbinger of longterm consequences (21,22).…”