Renal and Genito-Urinary
Etiology
The GU system can be damaged by a number of different mechanisms:
Bladder:
Fibrosis or direct injury:
- Surgery may remove large portion of the bladder
- Reduced bladder capacity
- Cystectomy involves removal of the entire bladder
- Increased risk of infection and back pressure leading to renal damage
- Radiation therapy (RT) can lead to:
- Scarring with loss of the elastic properties of the bladder causing:
- decreased compliance
- elevated bladder pressure
- Sustained high pressure in the bladder impedes ureteral peristalsis causing
- hydronephrosis
- reflux
- Scarring with loss of the elastic properties of the bladder causing:
- Injury to the nerve supply of the bladder (spinal cord or pelvic nerve root)
- Failure of bladder to empty leading to increased pressure in bladder and subsequent hydronephrosis and back pressure on kidneys
- Chemotherapy: Alkylating agents are associated with hemorrhagic cystitis.
Kidney
- Hypertension: Any treatment associated with high blood pressure (hypertension) in the long term leads to renal damage unless hypertension is controlled.
- Hypertension is associated with:
- Previous history of nephrotoxic treatment
- Previous nephrectomy
- Previous cranial RT (even low dose)
- Hypertension is associated with:
- Systemic therapy:
- Chemotherapy Agents:
- Cisplatin*
- Carboplatin
- Ifosfamide*
- Methotrexate
- Nitrosoureas (especially semustine)
- *Cisplatin and Ifosfamide are the commonest chemotherapy drugs to cause renal insufficiency
- Immunotherapy
- Interleukin 2 can cause reversible acute renal failure
- Rx used in supportive therapy
- antibiotics (aminoglycosides)
- anti-fungal (amphotericin B)
- Renal radiotherapy (RT)
- Bone marrow transplant (BMT) may include a combination of intensive chemotherapy and RT which is linked with subsequent increased risk of renal failure
- Renal surgery (partial or whole nephrectomy)
- Underlying disease/tumor can cause renal damage
- Directly through renal structural damage from tumor invasion or obstruction of ureter leading to hydronephrosis
- Indirectly:
- Acute tumor lysis syndrome:
- At the start of therapy
- Massive leukemia cell kill releases chemicals and proteins into blood which damage the kidney
- Severe uric acid nephropathy
- Renal damage may recover completely with intensive support
- Acute tumor lysis syndrome:
- Patient Factors:
- Many childhood survivors of Wilms tumor who develop chronic renal failure have syndromes associated with WT1 mutations or deletions that pre-dispose to renal disease.
- Incidence of end-stage renal disease in Wilms tumor survivors:
- 1% for unilateral tumor
- 12% for bilateral tumors
- 90% or so for patients with Denys–Drash syndrome, Wilms tumor aniridia syndrome or associated genitourinary anomalies.
Renal damage is almost always multifactorial
For example in BMT, renal damage secondary to:
- Conditioning therapy with carboplatin and other drugs
- Whole body low dose RT
- Early complications such as septicaemia cause hypotension
- Treatment with nephrotoxic antibiotics
- Immunosuppression after using agents like cyclosporin A
