Renal failure results when approximately three fourths of the nephrons of both kidneys cease to function. Acute renal failure (ARF) results from an abrupt decline in renal function, and is usually caused by an ischemic or toxic insult to the kidneys. Ischemic or toxicant-induced injury most frequently results in damage to the metabolically active proximal tubular and thick ascending loop of Henle's epithelial cells, causing impaired regulation of water and solute balance. Nephrotoxicants interfere with essential tubular cell functions and cause cellular injury, swelling, and death. Renal ischemia causes cellular hypoxia and substrate insufficiency, which leads to ATP depletion and cellular swelling and death. Vasoconstriction secondary to toxic or ischemic tubular epithelial injury further decreases glomerular filtration. It is important to note that tubular lesions and dysfunction caused by toxic and ischemic insults may be reversible.

In contrast, nephron damage associated with chronic renal failure (CRF) is usually irreversible. Whether the underlying disease process primarily affects glomeruli, tubules, interstitial tissue, or renal vasculature, irreversible damage to any portion of the nephron renders the entire nephron nonfunctional. Healing of irreversibly damaged nephrons occurs by replacement fibrosis, and therefore a specific etiology is rarely determined once end-stage kidney damage is present. Chronic renal failure occurs over a period of months or years and is a leading cause of death in dogs and cats. Improvement of renal function is usually not possible in cats and dogs with CRF; therefore treatment is aimed at reducing renal workload and the clinical signs associated with the decreased renal function, as well as preventing progression of the renal lesions.

Many different and sometimes confusing terms are used to describe renal function and its deterioration. Renal disease implies that renal lesions are present; it does not qualify the etiology, severity, or distribution of the lesions nor the degree of renal function. Renal reserve may be thought of as the percentage of nephrons not necessary to maintain normal renal function. Although it probably varies from animal to animal, it is greater than 50% in normal cats and dogs. Renal insufficiency begins when renal reserve is lost. Animals with renal insufficiency appear outwardly normal but have reduced capacity to compensate for stresses such as infection or dehydration. Azotemia is increased concentrations of urea nitrogen, creatinine, and other nonproteinaceous nitrogenous waste products in the blood. Renal azotemia denotes azotemia caused by renal parenchymal lesions. Renal failure is a state of decreased renal function that allows persistent abnormalities (azotemia and inability to concentrate urine) to exist; it is a term used to indicate a level of organ function rather than a specific disease entity. Uremia is the presence of urine in the blood. Uremia may occur secondary to renal failure or postrenal disorders, including urethral obstruction and urinary bladder rupture. The uremic syndrome is a constellation of clinical signs, including anemia, gastroenteritis, acidosis, pneumonitis, osteodystrophy, and encephalopathy, which occur secondary to uremia. Recently, a staging system for chronic kidney disease in dogs and cats has been adapted that helps alleviate some of the above confusion.

Clinical signs of renal failure are often nonspecific and include lethargy, depression, anorexia, vomiting, diarrhea, and dehydration; occasionally uremic breath and/or oral ulcers may be present. A diagnosis of renal failure is confirmed when azotemia with concurrent isosthenuria or minimally concentrated urine is persistent. Prerenal dehydration and azotemia superimposed on an inability to concentrate urine (e.g., Addison's disease or overzealous use of furosemide) initially mimics renal failure; however in this case, volume replacement results in resolution of the azotemia.

Acute renal failure occurs within hours or days of exposure to the insult. Unique clinical signs and clinicopathologic findings associated with ARF include enlarged or swollen kidneys, high hematocrit, good body condition, normoglycemic glucosuria, an active urine sediment (e.g., granular casts and renal epithelial cells), and relatively severe hyperkalemia and metabolic acidosis (especially in the face of oliguria). Clinical signs associated with ARF tend to be severe when compared with those of a patient with CRF and the same magnitude of azotemia. Renal ultrasonography findings in dogs and cats with ARF are usually nonspecific with diffuse normal to slightly hyperechoic renal cortical echotexture. In patients with calcium oxalate nephrosis associated with ethylene glycol ingestion, the renal cortices can be very echodense. Histopathologic examination of renal cortical biopsies from patients with ARF will reveal varying degrees of tubular necrosis. Evidence of tubular epithelial regeneration can be observed as early as three days after the acute insult and is a positive prognostic indicator.

In contrast to ARF, CRF occurs over a period of months or years, and its clinical signs are often relatively mild for the magnitude of the azotemia. Unique signs of CRF include a long-standing history of weight loss and polydipsia-polyuria, poor body condition, nonregenerative anemia and small and irregular kidneys. A diagnosis of CRF is usually based on a combination of compatible historical, physical examination, clinicopathologic and imaging findings. Plain film radiographs can confirm the presence of small kidneys. Renal ultrasonography will usually reveal diffusely echo dense renal cortices with loss of the normal cortico-medullary boundary. The increased cortical echogenicity is caused by fibrous scar tissue replacement of irreversibly damaged nephrons. Radiology and ultrasonography can also help rule out potentially treatable causes of CRF like pyelonephritis and renal urolithiasis. Renal biopsy is not routinely performed on CRF patients unless the diagnosis is in question. Renal histopathology will show some combination of loss of tubules with replacement fibrosis and mineralization, glomerulosclerosis and glomerular atrophy, and foci of mononuclear cells (small lymphocytes, plasma cells, and macrophages) within the interstitium associated with fibrous scar tissue replacement.