Acute renal failure (ARF) is a rapid onset of azotemia over hours to days (two weeks), or pathologic oliguria which could not have been present for more than a few days, that indicates rapid deterioration or loss of renal function. While ARF may not by itself constitute an emergency, its causes (hypovolemia, shock, urinary obstruction, sepsis, etc.) often are life threatening. In addition, the potential for enhancing reversibility of renal lesions and return of renal function may be lost if therapeutic intervention is delayed. In contrast to CFR, rapid diagnosis and initiation of therapy may greatly enhance a favourable prognosis in ARF.
ARF may result from diverse renal diseases and injuries. The syndrome of acute tubular necrosis (ATN) accounts for the majority of cases. With ATN there is a rapid reduction in GFR resulting from an ischemic or toxic renal insult. Reduced GFR is thought to result from a combination of vascular and tubular effects.
The clinical course of oliguric ATN may be characterized by three sequential phases: 1) initiation and development, 2) maintenance, 3) diuresis (recovery).
The initiation phase begins with onset of renal injury and continues through onset of oliguria (reduction in urine output below 0.5-1 ml/Kg/hour). Glomerular filtration rate may begin to fall immediately following the renal insult (as in the case of shock), or it may be delayed for hours to days (as in the case with exposure to nephrotoxic drugs).
The duration is highly variable, but it usually persists about 1 or 2 weeks. The oliguric phase is characterized by predictable fluid and electrolyte imbalances including alterations in hydration, hyponatremia, hyperkaliemia, metabolic acidosis and hyperphosphatemia.
Clinical signs typically develop during the oliguric phase of ATN, including gastrointestinal, hematological and neurological manifestations. Gastrointestinal disorders are common and include anorexia, vomiting, mucosal ulceration and hemorrhage.
This hemorrhage results primarily from defective platelet function, but may also be associated with thrombocytopenia, decreases in various coagulation factors and defects in capillary function.
Progressive anemia and neurological disorders characterized by lethargy, depression, stupor and coma may occur during the oliguric phase. Transition from the oliguric to the diuretic phase heralds the onset of re-establishment of tubular continuity, dissolution and/or mobilisation of intratubular casts, and return to near normal patterns of renal perfusion.
Diagnosis of Acute Renal Failure
ARF may be recognized by an abrupt onset of azotemia or oliguria, rapidly progressive azotemia, or sudden onset of clinical signs of uremia in a previously healthy patient.
A preliminary diagnosis of ARF is based on evidence from medical history, previous data concerning renal function and lack of physical evidence of CFR (e.g., weight loss, poor haircoat condition, "rubber jaw", growth retardation in puppies). Usually, physical examination of patients with ARF typically reveals good nutritional status. Diagnostic plans should be directed toward:
1. identifying life-threatening complications
2. localizing the cause of ARF (e.g., pre-renal, post-renal or primary renal failure)
3. determining urine volume
4. differentiating ARF from CRF
5. determining the etiology of ARF
6. monitoring patient response to therapy
It is particularly important to obtain an urine sample for analysis and culture before initiating fluid therapy because fluid therapy may cause concentrated urine to become dilute, making diagnosis of prerenal azotemia difficult. In addition, fluid therapy may alter the urine sediment causing erroneous interpretation.
Medical Emergencies in ARF
Several life threatening complications may occur in patients with ARF, they are hyperkaliemia, metabolic acidosis, severe anemia, volume depletion, sepsis.
Hyperkalemia is a common complication of oliguric acute primary renal failure and urinary tract obstruction. It is less commonly associated with non-oliguric acute primary renal failure and is rarely associated with prerenal azotemia unless prerenal azotemia results from Addison's disease. Detection of bradycardia or other cardiac dysrhythmias should alert one to the possibility of hyperkalemia.
Hyperkalemia is confirmed by determination of serum potassium concentrations; however, electrocardiography provides a rapid means of detecting hyperkalemia. Typical electrocardiographic changes observed with mild to moderate hyperkalemia include tall, peaked T waves, slowing of the heart rate, flattening of P waves and prolongation of the P-R intervals and QRS complex.
Patients with azotemia, hyperkalemia, hyponatremia may have hypoadrenocorticism (Addison's disease), in this case the major disadvantage of administering hormone replacement therapy for ARF is that the catabolic effect of corticosteroid administration may increase the magnitude of azotemia.
Metabolic acidosis is a relatively common finding in ARF. The magnitude of renal dysfunction appears to be a poor predictor of metabolic acidosis. Acidosis may be more common in patients with oliguric ARF than nonoliguric ARF, but not all patients with oliguric ARF have significant metabolic acidosis. Therefore diagnosis of metabolic acidosis should be based on evaluation of blood bicarbonate (or total CO2) concentration and, if available, blood pH. Urine pH is not reliable guide to systemic acid-base status.
Clinical effects of acidosis are usually minimal unless blood pH is less than 7.20U. However, when blood pH drops to less than 7.10, acidosis may:
1. reduce cardiac contractility and the inotropic response to catecholamines
2. predispose to ventricular arrhythmias
3. promote neurologic signs ranging from lethargy to coma
At the time of diagnosis, most patients with ARF have some degree of volume depletion. Although volume depletion can usually be detected by physical examination, physical changes can be subtle, particularly when fluid loss has occurred quickly and recently.
Infection may be a cause or complication of ARF. Dilute urine, oliguria, anuria and urinary obstruction predispose to urinary tract infection. Furthermore uremia is characterized by reduced immunocompetence. Because of these factors, infection is an important cause of morbidity and mortality in uremic patients. Often infections are related to invasive diagnostic and therapeutic procedures such as vascular and especially urinary catheterisation. Careful attention to detail and intelligent decisions regarding application of use of catheters and invasive diagnostic and therapeutic procedures will dramatically reduce the incidence of infection-related mortality.
Examination of urinalysis, urine culture, and a complete blood cell count are indicated to rule out infection as a cause or complication of ARF. When fever, physical examination, or laboratory findings indicate the probability of infection, its location and cause should be vigorously sought so that the most appropriate and least nephrotoxic antimicrobial therapy may be initiated.
Underlying disease processes
Patients may die of the diseases process which initiated ARF (e.g., acute pancreatitis, sepsis, shock, hypercalcemia, ethylene glycol intoxication) rather than from ARF or its complications. Therefore, diagnosis and initiation of specific therapy for diseases which may have precipitated ARF should be a high priority. The history, physical examination and urinalysis are usually sufficient to rule-out prerenal and postrenal causes of azotemia.
Renal biopsy may help to differentiate acute from chronic renal failure. In addition, it may provide to have an ethologic diagnosis and may allow assessment of the potential reversibility of renal injury. However, since renal biopsy is an invasive procedure which entails several risks, it should not be performed unless necessary. Not every patient with ARF requires renal biopsy. Today, with the use of automated biopsy instruments guided by ultrasound inspection of the kidney and a correct anesthesia protocol and technique, kidney biopsy may be performed within a very acceptable margin of safety for the patient.
Prognosis of Acute Renal Failure
The prognosis for dogs and cats with acute primary renal failure has been generally considered poor. It is best determined by response to therapy. However, the outcome may not become apparent for days to weeks following diagnosis. While it is often difficult to offer an accurate prognosis early in the course of acute primary renal failure, severe, progressive hyperkaliemia, metabolic acidosis and uremic symptoms are negative prognostic indicators.
In absence of these factors, patient treatment and monitoring should be continued, even if azotemia continues to increase.
Treatment of Acute Renal Failure
Although therapy designed to eliminate the cause(s) of ARF will not directly result in repair of renal lesions, it will minimize the severity and extent of renal damage. Symptomatic and supportive therapy designed to minimize deficits and excesses in fluid, electrolyte, acid-base and nutritional balance, will often allow life to be sustained until the body can restore adequate renal structure and function. Because many of the complications of ARF are medical emergencies, it is often necessary to initiate therapy before diagnostic evaluation can be completed. Furthermore, treatment of ARF should be modified according to patient response to therapy, that is assessed by comparing pre-treatment and serial post-treatment data.
Patient with severe metabolic disturbances may require frequent laboratory and clinical evaluation, whereas patients with less severe disturbances generally require less frequent monitoring.
Most patients with ARF are volume depleted before induction of therapy. However, the decision to administer fluid therapy should be based on clinical assessment of hydration, in order to correct volume depletion, regardless of urine volume. Because hypovolemia and hypotension cause oliguria and may contribute to the genesis of ATN or predispose to further renal damage, volume depletion should be rapidly corrected. Patients should be rehydrated with replacement fluid via an aseptically placed intravenous catheter. In most cases, crystalloids, like lactated Ringer's solution are satisfactory. However, if a large amount of fluid has been lost, in order to help the increase of the blood oncotic pressure, it is advisable to administer plasma-expanders solution (colloids), up to 20ml/Kg of body weight.
Urine volume and other contemporary losses (e.g., vomiting and diarrhea) greatly influence fluid requirements during the maintenance and recovery phases of ARF. Measurement of urine volume may provide a particularly useful guide to fluid therapy during the diuretic phase of ATN. Patients are predisposed to dehydration during this phase because involuntary urine losses are often great. In order to prevent dehydration, the volume of parenteral fluids administered and oral fluids, should consider also the amount of urine volume, contemporary fluid losses and insensible fluid losses (about 20 to 25 ml/kg/day).
Therapy of Potassium and Acid-Base imbalance
Hyperkaliemia is commonly associated with oliguric ARF and may cause skeletal muscle weakness, reduce cardiac contractility and cause a variety of cardiac conduction disturbances.
If serum potassium concentration exceed 8.0 mEq/l, or if serious cardiotoxicity occurs, therapy with sodium bicarbonate, glucose, with insulin, or calcium gluconate should be considered. Of these drugs, sodium bicarbonate (0.5 to 1.0 mEq/Kg body weight over 15 minutes) is commonly used first because many hyperkalemic patients also require this drug for treatment of concurrent metabolic acidosis. Administration of glucose (20% at the dose of 0.5 to 1.0 gm/kg body weight) and insulin (1 unit each 3 grams of glucose administered) or calcium gluconate (10% solution, not exceed 0.5 to 1.0 gm/kg body weight) are indicated primarily for rapid correction of severe hyperkalemic cardiotoxicity.
Oliguria versus non oliguria
Therapy specifically designed to convert oliguria to non-oliguria should be considered only for oliguric patients unresponsive to fluid volume replacement. In this case use of diuretics alone or associated with vasodilators should be considered.
Furosemide has been the most commonly used diuretic in canine and feline patients. Initially it should be administered intravenously at the dose of 1-2mg/kg body weight. If no substantial diuresis develops within one hour after administration, the dose may be doubled (4mg/kg). If this dose also fails to induce diuresis, the dose may be further increased to 6 mg/kg body weight. If diuresis still does not occur, the combination of furosemide and dopamine may be considered.
Mannitol is an osmotic diuretic commonly used to treat oliguric ARF. Mannitol has at least three theoretical advantages over furosemide: 1) it may enhance renal function by minimizing renal tubular cell swelling via its osmotic properties, 2) mannitol exerts its diuretic effects along the entire nephron and therefore may directly affect the proximal tubule, 3) mannitol may expand the extracellular fluid volume.
The major disadvantage of mannitol is the potential for vascular overload if oliguria persists. Therefore it should be avoided in overhydrated oliguric patients. Mannitol (20%-25% solution) is administered intravenously over 20 minutes at a dose of 0.5 to 1g/kg body weight. If substantial diuresis ensues, administration of mannitol can be repeated every 4 to 6 hours, or administered as maintenance infusion ( 8 to 10% solution ) during the initial 12 to 24 hours of treatment.
Because reduced renal flow may contribute to the pathogenesis of ARF, vasodilators are the logical therapy for patients with ARF. Dopamine, a precursor of norepinephrine, has been suggested for patients that are unresponsive to osmotic and/or loop diuretics. Infusion of low doses of dopamine reduces renal vascular resistance and increases renal flow, particularly to the inner renal cortex. Dopamine should be administered by intravenous infusion at the rate of 1 to 3 µg/kg body weight/min, using an intravenous fluid administration pump or under close supervision to assure accurate fluid delivery rate.
Clinical manifestations of uremia are improved by combination of a correct dietary protein amount and pharmacologic control of uremic gastritis and vomiting. It limits the catabolic effects of starvation and may be performed also using enteral or parenteral feeding.
Control of uremic vomiting
Uremic gastritis is a major cause of vomiting in patients with renal failure. Vomit is usually controlled by administration of Metoclopramide, that is an antiemetic drug acting directly on the CRTZ as a D2 dopaminergic antagonist. Cimetidine and ranitidine and famotidine have been recommended for control of uremic hemorrhagic gastritis because they block gastrin-stimulated gastric hyperacidity. For dogs in uremic crises, cimetidine is given intravenously at an initial dose of 10 mg/kg body weight every 12 hours (5mg/Kg for cats) and ranitidine is administered at 2mg/Kg. Famotidine is also very practical since it may be administered once a day, at the dosage of 0.5 mg/kg PO.
Once uremic gastritis has been controlled and oral medication may be tolerated, cimetidine can be administered orally at a dose of 5 mg/Kg every 12 hours for 2 to 3 weeks. The dosage is reduced to 5 mg/kg given once daily for 2 to 3 weeks before being withdrawn. Dosage recommendations for cats are approximately one-half of the canine dose. Because uremic vomiting may also result from stimulation of the chemoreceptor trigger, intravenously administered centrally-acting antiemetics may be useful in controlling vomiting. However, hypotension and sedation are potential pitfalls associated with antiemetic therapy. Chlorpromazine (0.5 mg/kg), prochlorperazine (0.13 mg/kg q 6 hrs), trimethobenzamide (3 mg/kg q 8 hrs) are centrally-acting antiemetics which may help to control nausea and vomiting in uremic patients.