What is the best treatment for chemotherapy-induced renal failure?

By | 2011-06-13

The initial goals for treating drug- and tumor-related acute renal failure in dogs and cats are to discontinue all drugs that may be nephrotoxic, to document prerenal or postrenal abnormalities, and to initiate fluid therapy. The primary objectives of fluid therapy are to correct deficits such as dehydration and excesses such as volume overload, as seen in oliguric renal failure; to supply maintenance needs; and to supplement ongoing losses, such as those due to vomiting and diarrhea. Each patient must be assessed carefully, and a treatment plan must be based on hydration status, cardiovascular performance, and biochemical data. Maintenance requirements vary from 44-110 ml/kg body weight; smaller animals require the larger amount. A simpler formula is to use 66 ml/kg/day. The amount of fluid that is needed daily for maintenance must be supplemented by an amount equal to external losses due to vomiting and diarrhea. In patients with renal failure, 1.5-3 times this amount of fluid is administered daily to achieve diuresis. The success of diuresis can be monitored by documenting adequate urine output (> 2 ml/kg/hr). Fluid therapy should meet daily needs, replace excessive losses, and correct dehydration. The percentage of dehydration should be determined; approximately 75% of the fluids needed to correct dehydration should be administered during the first 24 hours. Fluid therapy should be altered to correct electrolyte and acid-base abnormalities. In acute renal failure, potassium-containing fluids generally are not ideal because systemic hyperkalemia is often present. Until more is known about the systemic effects of sepsis, lactate-containing fluids should be avoided because sepsis and cancer are associated with hyperlactatemia, which worsens with administration of lactate-containing fluids.

Fluid Therapy for a 10-kg Dog with 5% Dehydration and Diarrhea

1. Correct dehydration. 5% (0.05) x 10 kg body weight = 0.5 kg of water needed to correct dehydration.
1000 mk/kg of water x 0.5 kg = 500 ml of water needed to correct dehydration.
75% (0.75) x 500 ml = 375 ml of fluid should be adminstered to replace 75% of dehydration.
2. Administer fluids to meet daily needs. 66 ml/kg (daily requirement) x 10 kg body weight = 660 ml needed on daily basis. Other believe that daily requirements are best estimated as [30 (kg)+ 70].
3. Replace ongoing losses. Estimated losses through diarrhea = 200 ml.
4. Fluids needed, first 24 hr. 375 ml + 660 ml + 200 ml = 1235 ml; increase fluid therapy judiciously to increase urine output to sustain mild-to-moderate diuresis.

General Approach for a Dog in Renal Failure

Stop administration of nephrotoxins. Discontinue cisplatin, methotrexate, doxorubicin, and aminoglycosides; avoid anesthesia.
Assess patient status. Complete blood count, blood chemistry profile
Specifically determine:
% dehydration
Amount of ongoing losses (e.g., vomiting, diarrhea, blood loss)
Maintenance of fluid requirements
Electrolyte and biochemical abnormalities
Cardiovascular performance
Urine output
Select and administer specific fluids. Tailor therapy to needs of each patient.
Isotonic polyionic fluid initially, preferably potassium-free (e.g., NaCl).
Correct dehydration first over 6-8 hr to prevent further renal ischemia while watching carefully for pathologic oliguria and subsequent volume overload.
Meet maintenance requirements (approximately 66 ml/kg/day).
Meet ongoing losses (vomiting, diarrhea)
Induce mild-to-moderate diuresis.
Monitor urine output, ensure adequate output. Metabolism cage or indwelling catheter.
For inadequate output (< 0.5-2 ml/kg/hr):
Mannitol or dextrose, 0.5-1.0 gm/kg in slow IV bolus
Furosemide, 2-4 mg/kg IV every 1-3 hr as needed
Dopamine, 1-3 |ig/kg/min IV (50 mg dopamine in 500 ml of 5% dextrose = 100 |ig/ml solution)
Correct acid-base and electrolyte abnormalities. Rule out hypercalcemia of malignancy; treat specifically for that if identified.
Provide mild-to-moderate diuresis. Urine output: 2-5 ml/kg/hr; monitor body weight, heart and respiratory rate, and central venous pressure for signs of overhydration.
Consider peritoneal dialysis if not responsive. Temporary or chronic ambulatory peritoneal dialysis with specific dialysate solution may be helpful.
Initiate long-term plans. Continue diuresis until blood urea nitrogen and creatinine normalize or until values stop improving despite aggressive therapy and clinically stable patient; then gradually taper fluids.
Control hyperphosphatemia if indicated (e.g., aluminum hydroxide, 500 mg at each feeding).
Treat gastric hyperacidity if indicated (cimetidine, 5-10 mg/kg every 6hr IV or orally).

If oliguric renal failure is present, a diligent and aggressive approach should be made to increase urine output, first by increasing glomerular filtration rate and renal blood flow. In addition, osmotic diuresis can be used to increase urine flow. If urine output is less than 0.5-2 ml/kg/hr despite aggressive fluid therapy, furosemide should be administered every 1-3 hours. Furosemide increases glomerular filtration rate and enhances diuresis in many patients. If furosemide is not effective, mannitol or 50% dextrose may be used as an osmotic diuretic to enhance urine production. The advantage of dextrose over mannitol is that dextrose can be detected on a urine glucose test strip. If furosemide and osmotic diuretics are not effective, dopamine may be administered as a constant-rate infusion. Dopamine enhances renal blood flow and increases urine output secondarily.

Treatment for acute renal failure should be continued until the patient is substantially improved and until abnormal biochemical parameters have been corrected or at least stabilized. Therapy then should be tapered over several days and a home treatment plan developed, including avoidance of nephrotoxic drugs, high-quality, low-quantity protein diet, maintenance of a low stress environment, and provision of fresh, clean water at will.