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TREATMENT

Renal failure: Mechanism of renal failure -

Precipitation of urates in the acid environment of urine

Precipitation of hypoxanthine when the urine pH exceeds 7.5

Increase in the hypoxanthine levels after starting treatment with allopurinol

Precipitation of calcium phosphate in renal microvasculature and renal tubules when the calcium x phosphate values exceed 60 (lymphoblasts contain four times the amount of phosphate present in normal lymphocytes).

Treatment

Hemodialysis or arteriovenous (A-V) hemofiltration should be used when renal failure occurs. Peritoneal dialysis should not be used. Chemotherapy such as cyclophosphamide is given immediately after dialysis and not before. Renal dialysis usually needs to be repeated every 12 hours because of continuous rapid tumor lysis.

Indications for renal dialysis are :

• An estimated glomerular filtration rate (GFR) less than 50%
  
  
                                Height (in cm) x 0.5

• Estimated GFR =     -----------------------------------
                                  Serum creatinine in (mg/dl)
  
  
• Congestive heart failure
  
  
• Anuria
  
  
• Symptomatic hypocalcemia with hyperphosphatemia
  
  
• Hyperkalemia with QRS interval widening and/or potassium greater than 6.0 mEq/l.
  
  
• High creatinine with poor urinary output
  
  
• Blood pressure (BP) higher than 150/90 and urinary output inadequate at 10 hours from the start of treatment
  

Hyperuricemia (> 8 mg/dl)

• Allopurinol: 100 mg/m2/dose tid.
  
  
• Hydration : Begin hydration at 3000 ml/m2/24 h and increase as needed to maintain urine output. The aim is to maintain urine output at 5 ml/kg/h or more before initiating chemotherapy and at 3 ml/kg/h or more once chemotherapy is begun. Strict measurement of intake and output should be carried out and verified every 2-4 hours. Insert a Foley catheter for continuous monitoring of urinary output. If urine output falls (i.e. less than 75% of input), increase hydration fluid and /or administer diuretics (furosemide / Lasix 0.5-1 mg/kg/dose or mannitol 5-15 g/m2 as 25% solution over 5-10 minutes, repeated every 6 hours as necessary). If, at 10 hours from the start of treatment, the BP is less than 130/90 and the urinary output is still inadequate, dopamine 5 mcg/kg/min should be started.
  
  
• Alkalinization of urine: To increase the solubility of the urates, alkalinize the urine with sodium hydrocarbonate (NaHCO3), which will maintain the urine pH between 6.5 and 7.5. A urine pH greater than 7.5 is associated with the precipitation of hypoxanthine and calcium phosphate in renal tubules and should be avoided. Administer NaHCO3 120 mEq/m2/24 h in IV hydration fluid.
  
  If the urine pH is less than 6.5 increase NaHCO3 and/or start Diamox 300 mg/m2 q6h.
  
  

Hyperphosphatemia (> 6.5 mg/dl)

• Prescribe a low phosphate diet
  
  
• Administer aluminum hydroxide 150 mg/kg/day PO divided q4-6h
  
  
• Maintain urine output at 3 ml/kg/h or more
  
  

Hypocalcemia (ionized calcium < 1.5 mEq/l)

When calcium x phosphate is greater than 60 due to hyperphosphatemia, a compensatory hypocalcemia occurs to maintain the calcium phosphate product at 60.

For symptomatic hypocalcemia (e.g. tetany), give 10 mg/kg of elemental calcium (i.e. 0.5-1.0 ml/kg 10% calcium gluconate). Discontinue administration when symptoms resolve. Consider dialysis if hyperphosphatemia is present. (Caution: Do not administer calcium in the same intravenous line as NaHCO3).

Hyperkalemia (> 6.0 mEq/l)

High potassium (K+) results from tumor cell lysis and/or renal failure.

• Do not administer K+ until tumor lysis is controlled.
  
  
• Use the following measures to drive K+ into the cells:
  
  
  • NaHCO3: 1-2 mEq/kg IV. For every increase in 0.1 pH unit, K+ is decreased about 1 mEq/l. The onset of action is within ½ hour and the duration of activity lasts several hours.
    
    
  • Insulin and glucose : Use dextrose 0.5 g/kg/h with insulin 0.1 unit/kg/h. Monitor serum glucose closely. In case of emergency, glucose can be used at 1 ml/kg of 50% dextrose through a central line. The onset of action is within 20-30 minutes and the duration of activity lasts several hours.
    
    
  For life threatening arrhythmias, administer calcium as calcium chloride 10 mg/kg IV. The onset of action is within minutes and the duration of action lasts about ½ hour. (Caution: Do not administer calcium in the same line as NaHCO3).
  
  
• Administer sodium polystyrene sulfonate (kayexalate) to remove 1 mEq K/1/g resin over 24 hours. Give as 1 g/kg PO q6h with sorbitol 50-150 ml. The duration of action depends on the rate of endogenous K+ release.
  
  
• Adjust antibiotic and other drug dosages appropriate for the level of renal failure as determined by blood urea nitrogen (BUN) and creatinine.