Renal Failure: Surgical Considerations

The kidneys receive approximately 20 to 25% of cardiac output and regulate the composition of extracellular fluid by filtration, reabsorption, secretion, and hormone production [1]. Many important systemic parameters are influenced by the kidneys, including acid-base status, electrolyte balance, the concentration of waste products of bodily metabolism, and red blood cell mass [1-3]. The diagnosis of renal failure implies sufficient loss of renal function to cause elevated levels of metabolic waste products, possible abnormalities in fluid and electrolyte balance, and loss of renal biosynthetic function.

The loss of function is reflected in laboratory tests as an increase in nonprotein nitrogenous waste products (blood urea nitrogen (BUN) and creatinine), a condition called azotemia. The inability to excrete nonprotein nitrogenous waste products may be caused by prerenal, primary (intrinsic renal), or postrenal mechanisms. Prerenal azotemia is caused by renal hypoperfusion states such as dehydration or hypotension. Postrenal azotemia is associated with obstruction of urine flow or disruption of urinary tract structure, resulting in leakage of urine into tissues or body cavities. Azotemia caused by prerenal or postrenal mechanisms may progress to cause renal damage and thus primary renal failure. Azotemia that is caused by primary renal disease has been classified based on duration as acute or chronic; in either case, the biochemical abnormalities associated with renal failure may cause profound changes in the animal's ability to maintain a normal homeostatic state.

In surgical patients, it is important to recognize prerenal or postrenal azotemia early in the course of disease, as early correction may prevent progression to primary renal failure. Patient factors such as age, cardiac status, and the concurrent administration of nephrotoxic drugs may compound other prerenal factors and influence the progression to primary renal disease. Postrenal azotemia is readily diagnosed by a good history plus physical examination with particular attention to palpation of the bladder and urethra. Some cases however, may require urethral catheterization, abdominocentesis, or imaging techniques such as radiographic contrast studies or ultrasound to confirm azotemia as postrenal and to identify the specific anatomic defect.

Acute renal failure (ARF) is an abrupt deterioration of renal function that occurs over hours to days, resulting in azotemia and decreased ability of the kidneys to regulate water and solute balance [4]. Differentiating ARF from chronic renal failure (CRF) can be difficult; however, correct diagnosis is important as ARF is potentially reversible whereas CRF is not [5]. ARF affecting surgical patients is most likely to occur in a hospital setting. The incidence of hospital-acquired ARF in animals appears to be relatively low. However, a previous study has documented a survival rate of only 40% in such cases; thus prevention of ARF is critical [6]. ARF in small animal species usually is caused by nephrotoxins; in humans, the cause is usually hypoperfusion [6,7]. Either nephrotoxins or hypoperfusion states may cause tubulointerstitial nephritis, glomerular or vascular disease, or renal tubular necrosis. Because prerenal azotemia may progress to ARF, early recognition is imperative, so that it can be corrected and primary renal damage prevented. Primary or intrinsic renal failure has been subdivided into phases and may or may not be reversible. During the induction phase of ARF, if causative factors are removed when tubule cell dysfunction may predominate over cell necrosis, recovery of cell function is possible and more likely than when the maintenance phase of ARF is reached. Evidence of early renal damage includes low specific gravity (less than 1.030 in dogs, less than 1.035 in cats), renal tubular cells and granular casts in urine sediment, failure of BUN and creatinine to return to normal after correction of hypoperfusion, and glucosuria in the normoglycemic patient.

The maintenance phase of ARF is characterized by irreversible renal tubular cell injury, with cellular necrosis. Correction of hypoperfusion during this phase has little effect if any on BUN and creatinine concentrations, and oliguria is often present after correction of hypovolemia or hypoperfusion. Oliguria in the dog is defined as urine production of less than 0.27 ml/kg/hour [8]. Patients with ARF that are nonoliguric may have a quicker recovery. This is not always the case, however, because ARF associated with aminoglycoside toxicity may or may not be reversible but is often nonoliguric. In a recent study, 39% of animals with ARF were nonoliguric [9]. If loss of nephrons with interstitial inflammation and fibrosis occurs, recovery of adequate renal function may be impossible. Adequate healing of renal tissue, however, may occur, initiating the recovery phase of ARF. This may not occur for two to three weeks after the onset of the maintenance phase. The recovery phase is characterized by an increase in urine production, and often polyuria. If oliguria was not present, the recovery phase is characterized by resolution of azotemia [7].

Clinical consequences of ARF include disorders of fluid balance, inadequate urine production, and electrolyte and acid-base imbalance [4]. Other body tissues such as gastrointestinal, pulmonary, and cardiac systems may also be affected by renal failure.

Multiple factors often contribute to the decreased glomerular filtration rate (GFR) seen in cases of ARF. Hemodynamic factors are probably most important during the induction phase, involving a reduction in renal perfusion pressure or vasoconstriction of afferent arterioles. Possible mechanisms include response to adrenergic stimulation, failure of intrarenal autoregulation from lack of prostaglandin production, endothelial cell swelling, activation of the renin-angiotensin system, and a decrease in glomerular permeability. Tubular factors that cause decreased GFR may be more important during the maintenance phase of ARF. Obstruction of tubules with cells, cellular debris, and precipitated protein, leads to increased back pressure, thereby reducing GFR. Damage to tubular cells may also allow leakage of glomerular filtrate into interstitial tissues, reducing urine flow and allowing reabsorption of fluid and solute [4,10].

Chronic renal failure or dysfunction is a more common clinical entity than ARF. The prevalence of CRF has been estimated to range between 0.5% and 7% in dogs and 1.6% and 20% in cats [11,12]. Causes of CRF are multifactorial and include familial, congenital, or acquired diseases. Renal lesions are most often tubulointerstitial or glomerular. In most cases, a specific initiating cause is not identified [13]. Recognition of CRF in a patient prior to anesthesia and surgery is necessary to avoid the potential for postoperative complications, prolonged hospitalization, or onset of acute renal failure. Ultimately, recognition of potential causes or risk factors for ARF in the perioperative period is important so that it may be prevented or treated early, when renal damage is least severe and potentially reversible, and metabolic complications can be avoided or minimized. Similarly, identification of patients with chronic renal disease already present is important for prognostic reasons and to prevent decompensation to a clinical diseased state or ARF after an anesthetic and/or surgical procedure. In this chapter, potential causes and risk factors for ARF in surgical patients are discussed with the goal of prevention or early treatment. The effects of uremia on the surgical patient are also discussed so that potential surgical complications may be prevented or minimized.

Etiology and Risk Factors for ARF in the Perioperative Patient

Hospital-acquired renal insufficiency is not uncommon in humans. In one study, iatrogenic factors were implicated in the majority of such episodes [14]. The most common inciting causes in 29 dogs with hospital-acquired acute renal failure were exposure to nephrotoxins and advanced age [6]. Chronic heart disease, preexisting renal disease, and anesthesia were identified as apparent contributors to ARF in these dogs. Those patients that do recover from ARF require lengthy and expensive treatment [2]. A number of risk factors and diseases have been described for the development of ARF in both the human and veterinary literature but it is unclear how many of the factors have been documented in animals (Table 64.1). Many factors have been identified in gentamicin-induced ARF in dogs, and it has been stated that those same predisposing factors likely affect the development of ARF in other cases as well [2]. Some of these factors are potentially correctable prior to an anesthetic and/or surgical treatment; thus, attention should be focused on identification and treatment of those factors. In a retrospective review of acute renal failure in dogs, pancreatitis, shock, sepsis and disseminated intravascular coagulation (DIC) were classified as ischemic disease states associated with ARF [9].

Hypoperfusion States

Renal hypoperfusion may be caused by dehydration, hemorrhage, or shock. Dehydration has been cited as the most common and most important risk factor for ARF [2]. In humans, renal hypoperfusion associated with hemorrhage, surgery, or dehydration is a common cause of ARF [15]. In normal dogs, however, renal hypoperfusion by itself may not lead to persistent renal damage and ARF [16]. The canine kidney appears to be more resistant to ARF occurring secondary to shock or other hypotensive states. In contrast to animals with normal renal function, it has been shown experimentally that, after a hypotension episode, dogs with reduced renal mass had decreased GFR and mild histologic lesions compatible with ARF [17]. Similarly, it is thought that hypotension as a result of third-space disease (ascites or pleural effusion), decreased oncotic pressure (hypoalbuminemia), decreased cardiac output (cardiac failure), or an anesthetic episode may predispose the small animal surgical patient to ARF, particularly if clinical or subclinical renal disease already exists. Pancreatitis has been reported as a cause of ARF in animals, however, the pathophysiology is unclear. Possible causes include hypovolemic or septic shock, DIC, or the direct effects of trypsin or vasopressors released by the pancreas on glomerular capillaries [18,19].

Hypoperfusion may also potentiate the effects of nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAID), aminoglycoside antibiotics, anesthetic agents, and myoglobin (Table 64.2) [20]. It appears that risk factors are additive in nature, and although a specific agent may not cause clinical problems in the normal animal, dehydration will potentially initiate nephrotoxicity of an otherwise safe drug such as Cox-2 selective NSAID. In surgical patients, hypoperfusion associated with an anesthetic episode may cause renal decompensation, especially if the animal has borderline or sublcinical renal disease.

Sepsis

Sepsis is a clinically important complication in perioperative patients that may lead to acute renal failure. Sepsis leads to ARF through a variety of mechanisms, including renal hypoperfusion owing to redistribution of renal blood flow, deposition of microthrombi in renal vasculature, or from direct toxic damage to tubular cells by bacteria or endotoxin [21]. Appropriate volume expansion and antibiotic therapy in septic patients may prevent ARF.

Canine pyometra has been associated with a variety of renal lesions. Renal defects include antigen-antibody-mediated-membranoproliferative glomerulonephritis, tubulointerstitial nephritis, and nephrogenic diabetes insipidus [22,23]. Many patients, however, have decreased GFR not associated with renal lesions or hypovolemia. Decreased GFR may occur in animals with or without azotemia, suggesting that some factor associated with pyometra causes a decrease in renal perfusion. Acute renal failure in dogs with pyometra has been associated with Escherichia coli endotoxin although not all dogs with pyometra and renal failure have Escherichia coli infection [2]. Many animals with pyometra also have urinary tract infections including pyelonephritis [24]. Because of polyuria and lack of water consumption owing to malaise, prerenal azotemia may also be present. Renal hypoperfusion, glomerulonephritis, tubular damage, and pyelonephritis may all contribute to the development of ARF in patients with pyometra as may disseminated intravascular coagulation (DIC), sepsis, or septic shock. In geriatric patients with pyometra, azotemia may be present from prerenal and/or a combination of acute and chronic renal failure. The chronicity of renal disease may be difficult to determine until the pyometra is corrected [24]. Renal biopsy may assist in diagnosing the extent of renal dysfunction in such cases.

Toxins

Myoglobin is an uncommon but potential nephrotoxic cause of ARF, especially in the face of dehydration. Myoglobinuria can occur in the perioperative patient from malignant hyperthermia, exertional rhabdomyolyis, or prolonged grand mal seizures [25-28]. Early recognition and treatment will minimize potential renal damage from these diseases. Malignant hyperthermia is an acquired metabolic myopathy and has been related to exercise or general anesthesia (particularly halothane anesthesia). Greyhounds seem predisposed to the disease [26,29].

Hemoglobin is not nephrotoxic in well hydrated patients, however hemolysis of whole blood is known to be toxic in humans. Conditions that could lead to hemolysis and possibly acute renal failure in small animal patients include burns, rapid intravenous infusion of large volumes of hypotonic solutions, transfusion reactions or hemolysis of whole blood during improper administration, immune-mediated hemolytic disease, infection by red blood cell parasites such as Babesia or Hemobartonella, or administration of acetaminophen, particularly in cats. In addition, methylene blue, which has been used in animals during surgery to aid in identification of neoplasia of the pancreas, may cause hemolysis in dogs and cats. Acute renal failure following burns is likely multifactor and caused by both hemolytic and red blood cell membrane fragmentation as well as hemo-concentration and catecholamine response leading to redistribution of blood flow [30]. Avoidance of these conditions or early recognition of hemolysis followed by appropriate fluid therapy to maintain renal blood flow and urine output, may prevent renal damage from hemoglobinuria.

Electrolyte imbalances can increase the risk of acute renal failure. Hypercalcemia in the adult dog is often associated with neoplasms, most commonly lymphosarcoma but also anal sac apocrine gland adenocarcinoma, adenocarcinoma of the mammary gland or nasal cavity, thyroid carcinoma, and parathyroid gland tumors [31]. In a review of 29 dogs with primary hyperparathyroidism, 13 dogs had high blood urea nitrogen levels at initial presentation. Postoperatively, 7 dogs suffered from renal failure, 4 of which had elevated BUN preoperatively. Dogs that developed renal failure had significantly higher preoperative total calcium levels compared with animals that had normal renal function [32]. Hypercalcemia can contribute to prerenal azotemia because of decreased water consumption and polyuria from the direct effects of calcium on tubular concentrating ability. Chronic hypercalcemia causes tubular and interstitial damage that can lead to renal failure [33]. Acute hypercalcemia can cause defects in urine concentrating ability but does not lead to a decrease in GFR until the calcium concentration exceeds 16 mg/dl [34]. Damage caused by acute hypercalcemia may include direct tubular cell toxicity as well as ischemic injury from vasoconstriction. Early recognition of hypercalcemia in surgical patients (so that appropriate saline volume diuresis can reduce the serum calcium value) may help prevent renal damage, particularly in the face of possible renal hypoperfusion associated with anesthesia and surgery. For patients refractory to saline diuresis alone, corticosteroid and diuretic therapy may be needed to reduce serum calcium concentration to an acceptable level.

Other electrolyte abnormalities may contribute to acute renal failure concurrent with other risk factors. Hyponatremia is reported to potentiate contrast-media-induced acute renal failure in dogs [35]. Hypocalcemia, hypomagnesemia, and hypokalemia may potentiate the nephrotoxic effects of aminoglycoside antibiotics [2].

Drug-Induced ARF

Many therapeutic agents have the potential to be nephrotoxic and thus may be predisposing factors to ARF in the surgical patient (Table 64.2).

Nonsteroidal anti-inflammatory drug (NSAID) use in dogs has grown markedly in the past 10 years. This class of drugs is now commonly used in dogs for treatment of pain related to osteoarthritis and in the perioperative period to decrease pain associated with both orthopedic and soft tissue surgical procedures. Renal toxicity is the second most important NSAID toxicity, after gastrointestinal effects [36]. The primary action of NSAID is to block expression of cyclooxygenase (COX) in cell membranes. Cyclooxygenase exists as both COX 1 and COX 2 isoforms; these have roles in normal homeostasis and are induced by proinflammatory stimuli. During periods of hypotension and reduced renal perfusion, prostaglandins are important for autoregulation to maintain renal blood flow and glomerular filtration, and thus are protective in nature. NSAIDs have the potential to cause prerenal renal impairment by depleting the kidney of vasodilatory prostaglandins [37]. The introduction of selective COX-2 inhibiting NSAIDs has decreased the prevalence of gastrointestinal toxicity, but because the kidney has both COX-1 and COX-2 isoforms, there may be little difference in the incidence of renal toxicity associated with the various NSAIDs. Any NSAID may cause renal toxicity especially if in the presence of preexisting renal disease. The exact mechanisms of renal impairment are unknown, but primary effects on the renal parenchyma may include acute interstitial nephritis, which may progress to papillary necrosis [37]. It appears that the overall occurrence of ARF owing to use of the newer NSAID (carprofen, deracoxib, and meloxicam) in dogs is low. Most dogs that develop ARF as a result of these NSAIDs either ingest excessive quantities of the drug or have a concurrent disease predisposing them to ARF [38].

Specific antibiotics, particularly gentamicin, have known nephrotoxic potential. Gentamicin may cause an idiosyncratic acute renal tubular cell necrosis in humans and animals [39,40]. Several factors are known to predispose to gentamicin toxicity including dehydration, concurrent administration of furosemide, and hypokalemia [41]. It is known that measurements of BUN and creatinine levels are not good early indicators of renal damage from aminoglycoside toxicity. Glycosuria, proteinuria, hematuria, cylindruria, or decreased specific gravity are better indicators of renal damage [42]. Measurement of gamma glutamyl transpeptidase (GGT) activity in the urine or use of the urine GGT-to-creatinine ratio are more sensitive indicators of early nephrotoxicity from gentamicin therapy [40,43]. Nafcillin used as prophylactic antibiotic therapy in surgical patients was suspected of causing ARF in seven dogs at one institution. None of the dogs had preexisting renal disease and none had suffered a hypotensive episode. Six dogs recovered following intensive therapy for ARF [44].

Radiographic contrast agents are often used parenterally for diagnostic purposes in surgical patients. Contrast agents used for excretory urography are hyperosmolar and cause an osmotic diuresis after administration. Possible pathogenic mechanisms for ARF caused by contrast agents include direct tubule injury, tubule precipitation of urinary proteins with contrast media causing obstruction, vasoconstriction of renal vessels leading to ischemic injury, or idiosyncratic reaction [45]. The prevalence of contrast-agent-induced renal failure in small animals appears to be very low but has been described in two case reports [46,47]. In one of the reported cases, preexisting renal disease was present prior to contrast administration. Correction of sodium or potassium imbalances is recommended prior to administration of intravenous contrast agents and the presence of preexisting renal disease should dictate caution in their administration [35]. Correction of dehydration and administration of fluids during and after the contrast study should be considered.

Vascular Disorders

Disseminated intravascular coagulation (DIC) is a clinicopathologic condition that can cause both a hemorrhagic diathesis and thrombosis of vasculature. DIC is always a secondary disease and has been associated with or caused by infectious, inflammatory, neoplastic, and toxic conditions. DIC may be seen in up to 50% of dogs with hemangiosarcoma [48]. Laboratory evidence of DIC includes thrombocytopenia, prolonged coagulation times, and decreased concentration of antithrombin III in plasma. A more recent test for the detection of elevated D-dimer protein in serum is a sensitive marker of clot lysis and strongly suggests DIC when elevated; a negative test all but excludes DIC as a diagnosis [48]. Acute renal failure from renal ischemia associated with renal vasculature thrombosis occurs in some cases of DIC. Because sluggish vascular flow, metabolic or respiratory acidosis, and shock can enhance DIC [49], it is important to recognize and correct these predisposing conditions early in perioperative patients.

Anesthesia/Surgery

Anesthesia, surgery, and renal function may interact by several mechanisms. Renal disease may cause changes in fluid homeostasis, electrolyte levels, or acid-base status. These changes along with renal disease may affect the pharmacokinetics of drugs used in anesthesia. Ketamine is eliminated almost unchanged by the kidneys in the cat; thus renal disease in cats may result in prolonged duration of effect of ketamine in that species. Azotemia causes an increased sensitivity to thiobarbiturates; a decreased dose is advised for animals with renal disease [50].

Anesthetic agents may affect renal function either by direct toxic effects or by changes produced in physiologic function. Anesthetic agents depress renal arterial pressure and the resultant hypotension causes release of renin by the juxtaglomerular apparatus. Renin, in turn, activates the angiotensin cascade, which stimulates the adrenal gland to increase aldosterone production. Aldosterone causes increased reabsorption of sodium, thereby promoting water retention, which helps maintain blood volume. Anesthetic agents such as halothane and isoflurane stimulate the renin-angiotensin system [51]. The stress of anesthesia and surgery also stimulates the renin-angiotensin system via sympathetic pathways. Hypovolemia as a result of intraoperative hemorrhage is also a potent stimulus for renin release. Glomerular afferent arteriolar vasoconstriction caused by the effects of angiotensin II and ADH in response to increased renin release is a proposed mechanism of decreased GFR in acute renal failure. Anesthesia, therefore, may contribute to the development of ARF through this mechanism.

Anesthesia and surgery may adversely affect normal renal function by causing increased release of ADH from the posterior pituitary. ADH causes vasoconstriction in the splanchnic and renal circulation while increasing the tubular reabsorption of water. Restricting the oral intake of water prior to anesthesia and/or administration of halothane or thiopental causes a mild elevation in ADH concentration. ADH secretion is a protective mechanism in most instances, but it may compound ischemia caused by hypovolemic shock.

The only anesthetic agent with direct nephrotoxicity that is commonly used in veterinary practice is the inhalant methoxyflurane [50]. This agent is now essentially obsolete because of lack of availability and because agents exist with safer and more desirable characteristics. The liver metabolizes methoxyflurane to free fluoride and oxalate. The fluoride ion is a potent nephrotoxic agent but by itself uncommonly caused renal disease in dogs [52,53]. A combination of methoxyflurane anesthesia, preexisting renal disease, and/or concurrent use of another nephrotoxic drug such as an NSAID makes methoxyflurane potentially dangerous [54]. Sevoflurane metabolism also produces fluoride ion; however, it has been determined that the potential for nephrotoxicity in dogs is low [55]. Sevoflurane also decomposes to the nephrotoxic agent Compound A in the carbon dioxide absorbent of a circle system. Low oxygen flow rates may raise the concentration of Compound A; thus it is recommended to avoid oxygen flow rates of less than 20 ml/kg/minute with this agent, especially in animals with renal disease [50].

Chronic Renal Failure

Chronic renal disease/dysfunction (CKD) is the most common kidney disease in dogs and cats [13]. CKD is characterized by renal damage that has existed for 3 months or more or by a decrease in GFR of more than 50% from normal persisting for 3 months [13]. Many disease processes including neoplastic, infectious, and immune-related have been identified as causes of chronic renal failure in dogs and cats. When considering dogs with primary renal azotemia, tubulointerstitial nephritis, glomerulonephropathy, and amyloidosis are the most common lesions. The clinical magnitude of renal disease in animals with CKD varies considerably as the disease may or may not affect renal function. In early chronic renal disease, the animal is not azotemic and may have few clinical or laboratory abnormalities associated with disease. As the condition progresses, animals with chronic renal failure may have anemia, systemic hypertension and electrolyte and mineral imbalances. Hyperphosphatemia, hypercalcemia, or hypocalcemia are also seen in animals, depending on the stage of renal failure. Azotemia causes metabolic acidosis and may progress to uremia and anorexia and vomiting.

Identification of patients with chronic renal disease is important during the preoperative workup. The animal may be presented for a surgical problem unrelated to the urinary tract; however, the outcome of treatment for the primary surgical problem may depend on accurate assessment and awareness of problems related to renal disease.

Effects of Renal Failure on Surgical Patients

Wound Healing

Uremia has a detrimental effect on wound healing. Experimentally, azotemic and uremic rats show delayed gain of tensile strength in healing wounds [56]. The decreased wound strength may be a result of synthesis of poor quality collagen or increased collagen degradation [57,58]. Depressed formation of granulation tissue and division of epithelial cells have also been reported in uremic mice [59].

The effects of uremia on wound healing may be theoretically clinical as wounds in azotemic and uremic patients proceed to heal normally, although more slowly. Selection of appropriate suture materials in view of potential slower wound healing is advised.

Hemostasis

Platelet function may be abnormal in animals with renal failure [3,13]. It is thought that uremia and one or more uremic toxins cause impairment of platelet adhesiveness and aggregation [13,61]. Diminished thromboxane-A2 production, abnormal intracellular calcium mobilization, and increased intracellular cAMP have been described in uremic platelets [61]. Coagulation factors are normal, so the most practical test of hemostasis in the uremic patient is a buccal mucosal bleeding time.

Administration of desmopressin acetate (DDAVP) has been reported to shorten bleeding times in uremic humans. Hemorrhagic diathesis of chronic renal failure is likely clinically insignificant in animals unless other coagulation disorders are present [3].

Anemia

Patients with chronic renal failure frequently have mild to severe nonregenerative anemia. The anemia is characterized by normochromic, normocytic red blood cells. Although the anemia of chronic renal failure is often multifactorial, the most important cause of the anemia is a relative erythropoietin deficiency [63]. The lack of sufficient erythropoietin results in hypoplasia of erythroid precursors in the bone marrow; leukocyte and platelet production are not affected.

Other factors suggested to contribute to anemia in animals with renal failure are shortened red blood cell survival, platelet dysfunction, nutritional abnormalities, and gastrointestinal hemorrhage from mucosal ulceration [13,62]. Serum iron concentrations are also frequently below normal.

Cardiopulmonary Function

Pulmonary function can be impaired in animals with renal failure, thus potentially compromising their ability to tolerate anesthesia and surgery. Interstitial pneumonitis has been reported in a group of 10 dogs with chronic renal failure [63]. Of these dogs, 4 had respiratory signs and 3 had alveolar infiltrates within the lungs. Pulmonary arterial thromboembolism leading to dyspnea has occurred in canine patients with the nephrotic syndrome associated with glomerular disease [66]. This appears to be caused by a hypercoagulable state associated with excessive urinary loss of antithrombin III or with abnormal platelet function associated with hypoalbuminemia [64,65]. The clinical significance of pulmonary disease secondary to uremia for the anesthetized veterinary patient is unknown and seems questionable.

Cardiovascular abnormalities may occur as co-morbidities in animals with renal failure. Clinically, the most important potential abnormality is systemic hypertension. Systemic hypertension may be a cause or a consequence of chronic kidney disease [13]. The incidence of hypertension in dogs with chronic disease is reported to be from 30% to 90% [66,67]. Apparently, the condition is much more common in the cat, occurring in up to 66% of animals affected with renal disease [68]. The presence of a high initial systolic blood pressure (164 to 217 mm Hg) in dogs with renal disease increases the risk of having a uremic crisis and also seems to be a predictor of a faster decline in renal function in affected animals [66]. Hypertension also impairs the ability of the kidney to autoregulate renal perfusion, thus potentially complicating an anesthetic episode [69]. Pericardial effusion has been described in two clinically affected dogs secondary to renal disease [70,71]. In a further review of necropsy records from another 150 dogs with renal disease, 11 dogs had varying amounts of clear or hemorrhagic pericardial fluid [70]. The clinical significance of pericardial effusion as a result of renal failure in dogs is unknown but its occurrence seems uncommon.

Nutrition or Malnutrition

Anorexia and weight loss are nonspecific but common clinical signs associated with advanced kidney disease. Nausea and vomiting leading to malnutrition are also common, especially as uremia becomes advanced. Uremic gastropathy and gastrointestinal mucosal ulceration associated with gastric hyperacidity and histamine release from mast cells within mucosa contribute to nausea and vomiting. Oral lesions such as ulcers or stomatitis may be associated with anorexia especially in cats.

The importance of proper nutrition for prevention or treatment of disease in animals is well recognized. Protein-energy malnutrition can further intensify the catabolic state associated with general anesthesia and surgery. Deleterious effects of protein-energy malnutrition that are of particular importance to the surgical patient include impaired immune function, increased susceptibility to infection, and delayed wound healing [72]. Inadequate energy intake leads to use of body protein for energy, which worsens azotemia (and perhaps uremia) in animals with renal failure and reduces the protein available for renal repair in ARF [73]. Animals that have remained anorectic for more than 3 days or that have lost more than 10% of their body weight should receive nutritional supportive therapy [73].