Acute renal failure (ARF) in cats, as distinguished from chronic renal disease, is a medical emergency due to the sensitivity of renal tissue to toxins and the irreversibility of function if perfusion and filtration are interrupted for more than 24 hours.
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Causes
There are many causes of acute renal failure:
- bacterial infections – Leptospirosis, pyelonephritis due to E. coli and other gram-negative bacteria
- nephrolithiasis due to ureteral calculi (often unilateral renal failure) and urethral calculi (often bilateral renal failure)
- end-stage chronic renal disease
- toxins (such as lily toxicity and commercial cat food-related toxins)
- renal ischaemia (haemorrhage, shock, DIC)
- antibiotic toxicity, especially aminoglycosides
Regardless of cause, the end result is oligouria (reduced urine production). There are three physiological principles that belie this concept: renal autoregulation, renal medullary hypoxia, and tubuloglomerular feedback. The first relates to the volume of material flowing along the production line of the factory, the second relates to the workers, the third a self control mechanism. We know that the kidney likes a certain rate of blood flow, and so, over a range of mean arterial pressures, renal plasma flow is kept constant by a variety of reflex mediators.
This process, autoregulation, also takes place in the brain. Similarly, the workers in the factory, the tubular cells, are fed by oxygen and nutrients derived from blood in the vasa-recta, which have the same origin as the tubular filtrate. If the renal perfusion pressure falls, the amount of oxygen and nutrients supplied to these cells also falls. They are in a precarious position in the first place – the renal medulla, due to the active countercurrent pumping of sodium and chloride, is one of the most energy hungry tissues in the body, while, the blood in the vasa recta is deoxygenated and slushy (high hematocrit). This makes tubular cells particularly vulnerable to ischemic injury. Thus, below a certain mean arterial pressure, the kidney switches off a considerable amount of its filtration activities, and the patient becomes oliguric. As this represents a self-protection reflex, the term “Acute Renal Success” has been used, and it is nicely described in scenario 2 above.
Tubuloglomerular feedback is a kind of quality control mechanism. The macula densa, which lies in the distal tubule (and this is located at the junction of afferent and efferent arterioles), monitors the concentration of sodium delivered to the distal part of the nephron.
The macula densa forms a complex with cells located in the afferent and efferent arterioles, known as the juxta-glomerular apparatus. If the concentration of sodium chloride delivered to the distal tubule falls (meaning that more is being reabsorbed proximally, and GFR has also fallen), then renin is released which stimulates production of angiotensin II, which in turn increases efferent arteriolar resistance, and reduces afferent arteriolar resistance. Aldosterone is produced which increases sodium reabsorption in the distal tubule. Likewise, and more importantly with regard to this topic, if the amount of sodium reaching the distal tubule increases, the macula densa recognizes that this represents an increase in the metabolic load for the relatively ischemic medulla, and afferent arteriolar vasoconstriction takes place, with a resultant decrease in GFR: acute renal success.
Acute renal failure is often called “acute tubular necrosis”, as, in most cases, the kidney is damaged by ischemic insult. It is believed that if medullary blood flow falls below 20% of normal, then the cells therein have inadequate supplies of oxygen for basal function, and die. Sloughing off of cells damaged by ischemia causes the collection of casts in the tubular space, obstructing urinary flow, creating a back-pressure to Bowman’s capsule, and reducing filtration by increasing hydrostatic pressure on the renal side. Acute renal success and acute renal failure can be distinguished by the capacity of the renal tubules to perform their primary function – reabsorb sodium and concentrate the urine. If the urinary sodium is high (>80mEq), and the urinary osmolality is low (equal to that of the plasma), then the patient is in acute renal failure.
Symptoms
Symptoms of acute renal failure are non-specific but relate directly to azotemia and uraemia; lethargy, vomiting, inappetance and often hypothermic (unless leptospirosis is the cause, which usually results in hyperthermia as a presenting sign).
Diagnosis
Diagnosis of ARF is often based loosely on presenting signs, and results from MBA/CBC testing, which include:
- Hyperkalaemia
- Acidosis
- Uremia
Treatment
Acute renal failure has four distinct phases including inititation, extension, maintenance and recovery. Initiation involves the period of renal injury. Therapy during the initiation phase is most likely to result in a complete return to normal or near-normal renal function.
The primary concern with treating acute oliguric/anuric renal failure is increasing the urine outflow. Treatment should therefore initiate with polyionic intravenous fluid administration. Monitor the animal closely by checking central venous pressure to ensure overhydration does not occur. (Merck, 2005) Once the animal’s fluid requirements have been replenished, urine outflow should be 1-2 ml/kg/day. If the animal remains oliguric, treatment with diuretics may be necessary. Diuretic administration should not be used, however in conjunction with aminoglycoside therapy due to increased risk of renal failure and death. (Ettinger, 2000; Gonzalez, 1998)
There are several diuretic options. Furosemide is the most common diuretic used in the treatment of renal failure. Furosemide is a loop diuretic that acts on the ascending loop of Henle to prevent absorption of sodium and chloride, which causes increased ultrafiltrate to form and thus increases urinary output. Additional consequences of furosemide diuresis include excretion of potassium and temporary increase in glomerular filtration rate.
If furosemide fails to restore appropriate urine output, mannitol is another diuretic that has been used with moderate success in patients with acute renal failure. Mannitol may be a preferable treatment to furosemide, because it directly affects the proximal tubule since it diureses the complete nephron. Mannitol is contraindicated, however in patients that are in danger of being over hydrated due to vascular overload.
Renal vasodilators (e.g. dopamine) are also helpful in reversing the vasoconstriction caused by the stimulation of the renin-angiotensin system. Dopamine can act in conjunction with furosemide to vasodilate renal arteries to increase renal blood flow and thus urine output.
Restoration of normokalemia is crucial in the survival of renal failure patients due to the adverse cardiovascular effects associated with hyperkalemia. To immediately counteract life threatening cardiac arrhythmias, calcium gluconate can be slowly administered while constantly monitoring cardiac function to restore the threshold potential. The effects of calcium gluconate are short lived, therefore long term management of hyperkalemia should ensue once cardiac toxicity has been resolved. Possible treatments include replacing fluids with those devoid of potassium and administering sodium bicarbonate, which will also reverse metabolic acidosis. (Ettinger, 2005)
Replacing the animal’s nutritional needs is vital to recovery from acute renal failure. A feeding tube may need to be placed for any animal experiencing azotemia. Finally, if the aforementioned treatments do not improve urine production and electrolyte imbalances, peritoneal dialysis or hemodialysis may be necessary. If neither of these treatments restores appropriate renal function, euthanasia may be the only option.
Correection of hyperkalemia
- Calcium supplementation (calcium gluconate 10%) does not lower potassium but decreases myocardial excitability, protecting against life threatening arrhythmias.
- Insulin (e.g. intravenous injection of 1-1.5IU of regular insulin {along with 5ml of 50% dextrose to prevent hypoglycemia}) will lead to a shift of potassium ions into cells, secondary to increased activity of the sodium-potassium ATPase.
- Bicarbonate therapy (e.g. 1 ampule (45mEq) infused over 5 minutes) is effective in cases of metabolic acidosis. The bicarbonate ion will stimulate an exchange of cellular H+ for Na+, thus leading to stimulation of the sodium-potassium ATPase.
- Salbutamol (albuterol, Ventolin) is a β2-selective catecholamine that is administered by nebulizer (e.g. 10–20 mg). This drug promotes movement of K into cells, lowering the blood levels.
- Refractory or severe cases may need dialysis to remove the potassium from the circulation.
IV fluids
Aggressive use of IV fluids is the mainstay of treatment of cats with oliguria due to ARF. Maintenance of urine flow via use of indwelling catheter and collection tube is necessary to monitor diuresis of IV fluids.
Diuretics
Diuretics actually have a number of potential beneficial effects:
1. Renal cortical vasodilatation (dopaminergic agents, loop diuretics).
2. Prevention of tubular obstruction (osmotic, loop diuretics).
3. Suppression of reflex vasoconstrictive responses (dopaminergic agents, atrial natiuretic peptide [ANP]
4. Decreased tubular oxygen consumption (dopaminergic agents, loop diuretics).
5. Enhanced renal tubular oxygen balance by inhibiting the active sodium pump in the medullary thick ascending loop of Henle (mTAL) thereby conferring protection against ischemic or nephrotoxic injury.
The implication is that diuretics wash out the tubules, which may be partially blocked with necrotic debris, improve blood flow when vasoconstriction is inappropriate (such as during the stress response to surgery) and reduce the metabolic activity of the tubules (remember that the medulla is relatively hypoxic and oliguria is a defense mechanism for preventing ischemia).
Diuretics however, may simply mask clinical signs and make assessment of renal recovery difficult. It is therefore not recommended in acute oliguria.