The kidneys have three primary functions: filtration, reabsorption, and secretion. To accomplish these functions, they receive about 25% of the cardiac output. The renal tubules and collecting ducts reabsorb up to 99% of filtered solutes, indicating that the total filtration volume is much greater than daily urine production. Neurohumoral substances and physiological factors that affect reabsorption of the filtered water and sodium include aldosterone, antidiuretic hormone (ADH), arterial blood pressure (ABP), atrial natriuretic factor, catecholamines, prostaglandins, renin-angiotensin, and stress.

Renal blood flow (RBF) is regulated by extrinsic nervous and hormonal control and by intrinsic autoregulation. Renal vasculature is highly innervated by sympathetic constrictor fibers originating in the spinal cord segments between T4 and L1. The kidneys lack sympathetic vasodilating fibers and parasympathetic innervation. Intrinsic autoregulation of RBF is demonstrated by a constant flow when mean ABP ranges from 80 to 180 mm Hg. When the mean ABP is between 80 and 180 mm Hg, the kidney can control blood flow by altering resistance in the glomerular afferent arterioles. Although the exact mechanism of renal autoregulation is not known, the significance of this phenomenon relates to protection of glomerular capillaries during hypertension and preservation of renal function during hypotension. However, even within the range of blood pressure described for function of renal autoregulation, extrinsic forces (e.g., neural, hormonal, and pharmacological) and intrinsic forces (e.g., renal insufficiency/failure) may cause alterations in RBF and glomerular filtration rate (GFR).

Catecholamines are the major hormonal regulators of RBF. Epinephrine and norepinephrine cause dose-dependent changes in RBF and the GFR. Low doses increase ABP and decrease RBF with no net change in the GFR. Higher doses cause decreased RBF and GFR. The renal vascular anatomy is unique in its distribution to cortical and medullary zones. Because of this vascular dichotomy, local tissue ischemia and hypoxia may occur even though total organ blood flow is normal. Oxygen delivery to the kidney is complex, and selective regional hypoxia is a possible source of renal injury during renal hypoperfusion. Experimental evidence indicates that the medullary thick ascending limb of Henle’s loop, because of its high metabolic rate associated with active transport of electrolytes, is selectively vulnerable to hypoxic injury.³

The pathophysiology of the kidney can be divided into acute and chronic renal failure. Acute renal failure is determined by a rapid onset of a decrease in GFR over a period of hours to days that manifests as an inability to excrete wastes (i.e., blood urea nitrogen [BUN] and creatinine) and maintain fluid and electrolyte homeostasis.⁴ Failure of the sodium–potassium ATPase pump in the renal tubules during acute tubular necrosis is the most common cause of acute renal failure with interstitial nephritis and acute glomerulonephritis comprising the other causes.⁵ Acute renal failure can be further classified into prerenal azotemia, intrinsic renal failure, and postrenal obstructive nephropathy.⁵ A thorough history, signalment, physical exam, serum chemistry panel, and urinalysis can be used to help differentiate between the three classes and direct treatments.

Chronic renal failure can be defined as the progressive loss of nephron function and decreased GFR over a prolonged period of time.⁴ Only when 60% or greater of the total number of nephrons become nonfunctional will clinical and/or laboratory signs of renal insufficiency become evident. At this point, the remaining functional renal mass is no longer able to appropriately eliminate waste, and nitrogenous compounds accumulate. The ability to concentrate filtrate and conserve free water is lost and patients may enter a state of hypovolemia. Additionally, the ability to balance electrolytes may be lost with derangements, eventually becoming severe enough to threaten physiological function of other organ systems (i.e., cardiovascular).

Patients with chronic renal failure may be anemic because of bone marrow suppression, chronic gastrointestinal tract blood loss, reduced red blood cell life span, and decreased secretion of enzymes that are responsible for the formation of erythropoietin with a resulting understimulation of bone marrow. In response to anemia, the cardiovascular system may become hyperdynamic in an attempt to maintain oxygen delivery. Chronic renal disease may therefore be associated with hypertension and increased cardiac output but reduced cardiac reserve.

Renal insufficiency/failure and azotemia in patients with renal insufficiency can alter the individual patient’s response to anesthetic medications. Azotemia can alter the blood–brain barrier, leading to increased drug penetration into the central nervous system. Azotemia can also alter the binding of drugs to carrier proteins and receptors, resulting in increased levels of circulating free drug and an increase or decrease in the expected response of the patient to drug administration. Patients with renal insufficiency/failure may be acidotic, which can lead to increased fractions of unbound injectable drugs in the plasma, thus having a similar effect as azotemia. It may be necessary to decrease the doses of highly protein-bound injectable anesthetics in azotemic and/or acidotic patients.

Serum electrolyte imbalance is common in patients with renal disease. Hyperkalemia may be present in animals with renal insufficiency/failure, obstructed urethra, or rupture of the urinary bladder and can be extremely dangerous. In general, patients presenting for nonemergency anesthesia and surgery should not be anesthetized if they have a serum potassium concentration greater than 5.5mEq/L. Any patient with a serum potassium concentration greater than 6.0 mEq/L should not be anesthetized until the hyperkalemia can be addressed. Electrocardiographic (ECG) abnormalities are commonly observed with potassium concentrations exceeding 7 mEq/L and during the stress of anesthesia patients with renal disease can quickly elevate their serum potassium concentrations. The resting membrane potential of cardiac muscle depends on the permeability and extracellular concentration of potassium. During hyperkalemia, the membrane’s resting potential is raised (partially depolarized), and fewer sodium channels are available to participate in the action potential. As the serum potassium concentration increases, repolarization occurs more rapidly and automaticity, conductivity, contractility, and excitability are decreased. These changes produce the classic ECG appearance of a peaked T wave with a prolonged PR interval progressing to wide QRS complexes and loss of P waves. In cases of prolonged renal disease and chronic hyperkalemia, serum potassium should be lowered gradually to allow intracellular potassium time to reestablish physiological transmembrane concentration gradients. If hyperkalemia is acute or ECG abnormalities are noted, treatment should be initiated prior to induction of anesthesia. The most rapid treatment for the cardiac effects associated with hyperkalemia is 10% calcium chloride (0.1mg/kg IV). Calcium will increase the membrane’s threshold potential, resulting in increased myocardial conduction and contractility. Because increased serum potassium concentration causes the resting potential to be less negative (partially depolarized), the calcium ion-induced increase in threshold potential temporarily restores the normal gradient between resting and threshold potentials. It should be recognized that administration of calcium will not affect the serum potassium concentration, and its effects will therefore be short lived. Regimens to decrease the serum potassium concentration by shifting potassium intracellularly include infusion of 2.5–5% dextrose solutions and, in severe cases, addition of insulin to the dextrose. Often, acidosis is associated with the concurrent increase in serum potassium. Sodium bicarbonate can be administered to enhance hydrogen ion exchange with intracellular potassium. Additionally, during anesthesia, because acidemia favors extracellular movement of potassium and worsens hyperkalemia, intermittent positive pressure ventilation may be required to prevent anesthetic-induced hypercapnia and respiratory acidosis. Patients in renal failure with hypocalcemia are at even greater risk of the arrhythmic effects of hyperkalemia, because hypocalcemia potentiates the myocardial toxicity of hyperkalemia.

Patients with suspected or known renal disease should have a thorough workup prior to any anesthetic event. This should include a physical exam, complete blood count, serum biochemical profile, and urinalysis. Measurements of the GFR and renal tubular function, such as urine specific gravity and BUN, are not specific for renal disease. Serum creatinine is a more specific indicator of the GFR than BUN because it is influenced by fewer extrarenal variables. Patients with mild renal insufficiency may not have elevated serum creatinine, thus it is important to carefully evaluate other parameters that can be affected. In addition to azotemia, effects of renal system dysfunction can manifest as abnormalities in acid–base balance, electrolyte concentrations (especially potassium), exercise intolerance, hematocrit, hydration status, and urine production. Persistent proteinuria and/or cellular or granular cylinduria may indicate renal damage prior to the onset of renal azotemia.

Preanesthetic stabilization of patients with renal disease may be more critical to a successful outcome than the specific anesthetic drugs selected. By and large, the most important parameter for a patient with renal disease is hydration status and circulating blood volume. Maintaining RBF and GFR through adequate hydration will reduce the likelihood of further renal injury and preserve renal function.²² Hydration has been shown to be effective in the treatment of renal injury and is a good strategy to prevent the progression of renal insufficiency to frank renal failure.²² A patient can be admitted 12–24 hours prior to anesthesia and administered IV fluids to achieve hydration and diuresis. When renal function is questioned, the urinary bladder can be catheterized and urine production monitored via a closed, sterile urine collection system. Urine production is an indirect measure of renal perfusion, and normal urine output for awake dogs is 0.5–2.0mL/kg/h. Animals administered high rates of IV fluids should have urine outputs similar to the amount of fluids administered. Fluid therapy prior to anesthesia can also be used to correct electrolyte and acid–base imbalances. Anemic patients undergoing anesthesia should have a red blood cell transfusion if the hematocrit is less than 18% (cats) or 20% (dogs).

During the perianesthetic period, pharmacological manipulation of cardiovascular and renal physiology may be beneficial in renal disease patients. Dopamine infusions (1–10 mcg/kg/min) have long been considered useful in improving myocardial function and cardiac output. In human patients with renal disease, renal doses of dopamine (2mcg/kg/min) have been shown to increase urinary output but does not improve overall outcome when compared to IV fluid therapy.²³ In dogs, low doses (1–3 mcg/kg/min) are used to promote RBF and GFR, but studies showing benefit are lacking. Controversy exists as to the use of dopamine to improve renal function in cats. Questions remain as to whether or not cats have appropriate dopamine receptors in their kidneys and low-dose dopamine has not been shown to have a diuretic effect in cats.²⁴ Doses of dopamine above approximately 10 mcg/kg/min may cause α-adrenergic renal vasoconstriction and decreased RBF and should be avoided.

Furosemide has also been investigated as to its use during anesthesia in patients with renal dysfunction. As a loop diuretic, furosemide decreases the metabolic activity of the renal tubules; however, furosemide infusion has been shown to result in elevated creatinine levels in anesthetized human patients and its use is not recommended.^23,25

The osmotic diuretic mannitol has many potentially beneficial effects on the kidney. Mannitol is freely filtered and non-reabsorbed by the kidney and therefore acts as an osmotic agent in the renal tubules as well as in the systemic circulation. Administration of mannitol can induce renal arteriole dilation, decrease vascular resistance and blood viscosity, and scavenge oxygen free radicals.²⁶ RBF in cats may be improved by administering an IV loading dose of mannitol (500 mg/kg) and continuing a constant rate infusion (1 mg/kg/min) during the anesthetic period.²⁷ The author uses mannitol infusions in both cats and dogs with known or suspected renal impairment during anesthesia.

Fenoldopam is a dopamine receptor agonist at the DA₁ receptor that has renal vasodilating properties. Fenoldopam has no effect on DA₂ or alpha receptors that can cause vasoconstriction and result in decreased RBF and GFR. In fact, fenoldopam increases RBF and may assist in preserving renal function. Fenoldopam has been shown to decrease creatinine and improve renal function at a dose of 0.1 mcg/kg/min when compared to dopamine infusion and may be effective in decreasing renal hypoperfusion.²⁸

Postanesthetic care of any patient that has had a procedure associated with a painful condition should be treated with analgesic medications. In renal patients, analgesic drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), that are potentially nephrotoxic should be avoided. Pain can usually be managed with opioid analgesics.

Patients with urethral obstruction often present with metabolic derangements. These include hyperkalemia, azotemia, acidosis, and hyperphosphatemia. Cats may also develop hyperglycemia, hypocalcemia, and hyponatremia. If the disease condition included rupture of the urinary bladder, the animal may develop more severe electrolyte abnormalities and acidosis. In these cases, potassium enters the abdominal cavity from the ruptured bladder and is reabsorbed into the circulation, causing an increased serum potassium concentration. It is important to recognize that acute urethral obstruction and ruptured bladder are medical emergencies and that any metabolic abnormalities should be evaluated and addressed prior to anesthesia and surgical correction. Hyperkalemia is the primary concern in most cases of urethral obstruction, and an electrocardiogram assessment is warranted. Treatment of hyperkalemia has been discussed earlier.

In animals with urethral obstruction, fine-needle centesis of the urinary bladder may be performed prior to anesthesia, although bladder injury is a potential concern. In animals with uroperitoneum, abdominocentesis can be performed. Removal of urine can help reduce the potassium load and relieve patient discomfort. Once the patient is stabilized, anesthesia can be induced by the previously described techniques. IV ketamine with a benzodiazepine has been used in obstructed cats even though active metabolites of the drug are excreted by the kidney. The rationale is that, once the obstruction is relieved, excretion of the anesthetic will proceed normally. However, cats with a long-term urethral obstruction may develop metabolic disturbances and renal insufficiency such that elimination of drugs is slowed even after the obstruction has been removed. As with other patients with renal disease, IV fluid therapy should be continued throughout the anesthetic period and into the postanesthetic period until ongoing acid-base and electrolyte disturbances are corrected.

Revised from “Renal Disease” by Stephen A. Greene and Gregory F. Grauer in Lumb and Jones’ Veterinary Anesthesia and Analgesia, Fourth Edition.

1. Boyd L.M., Langston C., Thompson K., et al. Survival in cats with naturally occurring chronic kidney disease (2000–2002). J Vetlntern Med 22: 1111–1117, 2008.

2. Polzin D.J., Osborne C.A., Jacob F., et al. Chronic renal failure. In: Textbook of Veterinary Internal Medicine, 5th ed. S.J. Ettinger and E.C. Feldman, eds. Philadelphia, PA: W.B. Saunders Company, 2000, pp 1634–1662.

3. Brezis M., Rosen S. Hypoxia of the renal medulla: its implications for disease. N Engl J Med 332(10): 647–655, 1995.

4. Stoelting R.K., Hillier S.C. Kidneys. In: Pharmacology & Physiology in Anesthetic Practice, 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2006, pp 817–830.

5. Thadhani R., Pascual M., Bonventre J.V. Acute renal failure. N Engl J Med 334: 1448–1460, 1996.