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

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 51Cr-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; N-acetylglucosaminidase) 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−1 1.73 m−2. 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 ⩾800 mOsm kg−1, 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

Glomerular filtration rate and prevalence of chronic kidney disease in Wilms’ tumour survivors

Glomerular filtration rate (GFR) was evaluated in 32 Wilms’ tumour survivors (WTs) in a cross-sectional study using 99 Tc-diethylene triamine pentaacetic acid (99 Tc-DTPA) clearance, the Schwartz formula, the new Schwartz equation for chronic kidney disease (CKD), cystatin C serum concentration and the Filler formula. Kidney damage was established by beta-2-microglobulin (B-2-M) and albumin urine excretion, urine sediment and ultrasound examination. Blood pressure was measured. No differences were found between the mean GFR in 99 Tc-DTPA and the new Schwartz equation for CKD (91.8 ± 11.3 vs. 94.3 ± 10.2 ml/min/1.73 m2 [p = 0.55] respectively). No differences were observed between estimated glomerular filtration rate (eGFR) using the Schwartz formula and the Filler formula either (122.3 ± 19.9 vs. 129.8 ± 23.9 ml/min/1.73 m2 [p = 0.28] respectively). Increased urine albumin and B-2-M excretion, which are signs of kidney damage, were found in 7 (22%) and 3 (9.4%) WTs respectively. Ultrasound signs of kidney damage were found in 14 patients (43%). Five patients (15.6%) had more than one sign of kidney damage. Eighteen individuals (56.25%) had CKD stage I (10 with signs of kidney damage; 8 without). Fourteen individuals (43.75%) had CKD stage II (6 with signs of kidney damage; 8 without). The new Schwartz equation for CKD better estimated GFR in comparison to the Schwartz formula and the Filler formula. Furthermore, the WT survivors had signs of kidney damage despite the fact that GFR was not decreased below 90 ml/min/1.73 m2 with 99 Tc- DTPA