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    Late Effects of Treatment for Childhood Cancer (PDQ®): Treatment - Health Professional Information [NCI] - Late Effects of the Urinary System

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    Treatment for Wilms tumor without flank or abdominal radiation therapy was not associated with significant nephrotoxicity in a study of 40 Wilms tumor survivors treated in England.[18]

    Few large-scale studies have evaluated late renal-health outcomes and risk factors for renal dysfunction among survivors treated with potentially nephrotoxic modalities. In a large cross-sectional study of 1,442 childhood cancer survivors (median attained age, 19.3 years; median time from diagnosis, 12.1 years), Dutch investigators assessed the presence of albuminuria, hypomagnesemia, hypophosphatemia, and hypertension and estimated glomerular filtration rate among survivors treated with ifosfamide, cisplatin, carboplatin, high-dose cyclophosphamide (>1 g/m2 or more per course), or high-dose methotrexate (>1 g/m2 or more per course), radiation of the kidney region, total-body irradiation, or nephrectomy. At least one abnormality of renal function or hypertension was detected in 28.1% of survivors. History of nephrectomy (OR, 8.6; 95% CI, 3.4-21.4) had the strongest association with a GFR less than 90 ml/min per 1.73 m2. The prevalence of decreased GFR was highest among those treated with multimodality therapy including nephrectomy, nephrotoxic chemotherapy, and abdominal radiation. Abdominal irradiation was the only significant treatment-related risk factor for hypertension (OR, 2.5; 95%CI, 1.4-4.5).[23]

    In the setting of hematopoietic cell transplantation, fewer than 15% of children will develop chronic renal insufficiency or hypertension; the risk is related to the nephrotoxic agents used and the cumulative total-body irradiation dose, fractionation scheme, and interfraction interval. More specifically, the radiation-associated risk rises when the total dose exceeds 12 Gy, the individual fraction size is greater than 2 Gy, or the interval-fraction is less than 4 to 6 hours.[24,25,26,27]

    Childhood cancer survivors treated with pelvic or central nervous system surgery, alkylator-containing chemotherapy including cyclophosphamide or ifosfamide, or pelvic radiation therapy may experience urinary bladder late effects including hemorrhagic cystitis, bladder fibrosis, neurogenic/dysfunctional bladder, and bladder cancer.[28]

    Table 17. Kidney and Bladder Late Effects

    Predisposing Therapy Renal/Genitourinary Effects Health Screening
    BUN = blood urea nitrogen; NSAIDs = nonsteroidal anti-inflammatory drugs; RBC/HFP = red blood cells per high-field power (microscopic exam).
    Cyclophosphamide/Ifosfamide; radiation impacting bladder/urinary tract Bladder toxicity (hemorrhagic cystitis, bladder fibrosis, dysfunctional voiding, vesicoureteral reflux, hydronephrosis) History: hematuria, urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream
    Urinalysis
    Urine culture, spot urine calcium/creatinine ratio, and ultrasound of kidneys and bladder for patients with microscopic hematuria (defined as ≥5 RBC/HFP on at least 2 occasions)
    Nephrology or urology referral for patients with culture-negative microscopic hematuria AND abnormal ultrasound and/or abnormal calcium/creatinine ratio
    Urology referral for patients with culture negative macroscopic hematuria
    Cisplatin/carboplatin; ifosfamide Renal toxicity (glomerular injury, tubular injury [renal tubular acidosis], Fanconi syndrome, hypophosphatemic rickets) Blood pressure
    BUN, Creatinine, Na, K, Cl, CO2, Ca, Mg, PO4 levels
    Urinalysis
    Electrolyte supplements for patients with persistent electrolyte wasting
    Nephrology consultation for patients with hypertension, proteinuria, or progressive renal insufficiency
    Methotrexate; radiation impacting kidneys/urinary tract Renal toxicity (renal insufficiency, hypertension) Blood pressure
    BUN, Creatinine, Na, K, Cl, CO2, Ca, Mg, PO4 levels
    Urinalysis
    Nephrology consultation for patients with hypertension, proteinuria, or progressive renal insufficiency
    Nephrectomy Renal toxicity (proteinuria, hyperfiltration, renal insufficiency) Blood pressure
    BUN, Creatinine, Na, K, Cl, CO2, Ca, Mg, PO4 levels
    Urinalysis
    Discuss contact sports, bicycle safety (e.g., avoiding handlebar injuries), and proper use of seatbelts (i.e., wearing lapbelts around hips, not waist)
    Counsel to use NSAIDs with caution
    Nephrology consultation for patients with hypertension, proteinuria, or progressive renal insufficiency
    Nephrectomy; pelvic surgery; cystectomy Hydrocele Testicular exam
    Cystectomy Cystectomy-related complications (chronic urinary tract infections, renal dysfunction, vesicoureteral reflux, hydronephrosis, reservoir calculi, spontaneous neobladder perforation, vitamin B12 /folate/carotene deficiency [patients with ileal enterocystoplasty only]) Urology evaluation
    Vitamin B12 level
    Pelvic surgery; cystectomy Urinary incontinence; urinary tract obstruction History: hematuria, urinary urgency/frequency, urinary incontinence/retention, dysuria, nocturia, abnormal urinary stream
    Counsel regarding adequate fluid intake, regular voiding, seeking medical attention for symptoms of voiding dysfunction or urinary tract infection, compliance with recommended bladder catheterization regimen
    Urologic consultation for patients with dysfunctional voiding or recurrent urinary tract infections
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