Renal Disease

Renal Disease Carl A. Osborne, D.V.M., Ph.D.* Donald G. Low, D.V.M., Ph.D.** Kenneth H.. Johnson, D.V.M., Ph.D.t

Although renal diseases of the cat are commonly encountered in clinical practice, comparatively little information is currently available about their incidence, etiopathogenesis, and pathophysiology. Despite the need for new information, this paper has been written with the objective of providing a practical discussion of the clinical findings, diagnosis, treatment, and prognosis of the more commonly encountered renal diseases of the cat.

APPLIED ANATOMY Familiarity with the anatomy of the kidneys is essential for meaningful palpation and radiography, and is a basic prerequisite to the understanding of the pathophysiology of various renal diseases of the cat. Gross Anatomy Although differences exist, the anatomy of the kidney of the cat is similar to that of the dog. In the cat, the normal position of the kidneys is variable, but generally they lie adjacent to the third to fifth lumbar vertebrae. The kidneys are retroperitoneal in position; only their ventral surfaces are covered with peritoneum. Neither kidney is rigidly fixed in position, and each may move a variable distance longitudinally in association with respiration. Both kidneys are loosely attached to the body wall by renal fascia, and both normally are embedded in a variable quantity of perirenal fat. The right kidney usually is more firmly attached to the body wall than the left, and is usually located I to 2 ern. *Assistant Professor, Department of Veterinary Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota **Professor and Chairman, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado tAssociate Professor, Department of Pathology and Parasitology. College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota Veterinary Clinics ofNorthAmerica- Vol. I, No.2 (May, 1971).

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cranial to the left kidney. Both kidneys usually can be palpated per abdomen with ease. The kidneys of cats are more spherical than the kidneys of dogs. Both kidneys have a "bean" shape with a smooth surface and a regular contour. The surface of cat kidneys is grooved to accommodate prominent subcapsular vessels which radiate to the hilus. Kidney size is variable with the size of the cat. Normally, both kidneys are similar in size and weight. In adult cats, kidney weight varies from 0.6 to 1.0 per cent of body weight. The kidneys are enveloped by a thin, tough, relatively inelastic fibrous capsule which normally can be peeled away easily from the cortical surface. The cut surface of the cat kidney has a well defined outer cortex and inner medulla. Like the kidneys of dogs, cat kidneys are unipyramidal without calyces. The color of cat kidneys is somewhat variable, depending on the age of the cat. In immature cats, the cut surfaces of kidneys are usually reddish-yellow. Kidneys of mature cats are typically more yellow in color than kidneys of young cats owing to an increased quantity of neutral fat in the cells of the first portion of the proximal tubules.

Histology The functional unit of the kidney is the nephron. Nephrons are comprised of a renal corpuscle (glomerulus and Bowman's capsule), proximal convoluted tubule, loop of Henle, and distal convoluted tubule. Distal tubules coalesce to form collecting tubules. The latter unite into progressively larger collecting ducts and eventually form papillary ducts which open into the renal pelvis at the common renal papilla. Each cat kidney has approximately 200,000 glomeruli, which are confined to the renal cortex. In cats there is an extensive physiologic infiltration of the proximal portion of the proximal convoluted tubules with lipid. The quantity of lipid increases with age and sometimes complicates the recognition of pathologic fatty change in proximal tubular epithelial cells. The renal vascular anatomy of the kidneys of cats is similar to that of dogs. The renal arteries are characterized by a system of end arteries which do not have a significant collateral blood supply. The renal tubules are supplied with blood which must pass through glomeruli prior to perfusing the peri tubular capillaries. As mentioned previously, cat kidneys have a well developed superficial venous system. The four large converging subcapsular venous trunks on either side of the kidney drain into the renal vein at the hilus.

APPLIED PHYSIOLOGY The principal functions of the kidney provide a constant internal environment, thereby allowing all cells within the body to function

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effectively. Homeostasis is maintained by conserving or eliminating water and electrolytes, depending on the needs of the body. The kidneys also excrete the waste products of metabolism and elaborate the hormones erythropoietin and renin. Erythropoietin is active in the regulation of erythropoiesis; renin contributes to the regulation of blood pressure and indirectly to sodium resorption. In order to accomplish its functions, the kidney must be adequately perfused with blood. Normally, about 20 to 25 per cent of the cardiac output flows through the kidneys. Because glomerular filtration depends on the energy imparted by the left ventricle, abnormalities of the cardiovascular system which result in reduced cardiac output or hypotension may seriously impair renal function. Whenever mean blood pressure falls appreciably below 100 mm. of mercury, renal function is compromised. Advanced primary heart disease, shock, severe dehydration and hypovolemia, cardiac tamponade, and aortic thrombosis are examples of diseases which may markedly affect kidney function by reducing or eliminating renal perfusion. The glomerular filtration rate also may be reduced by obstruction within the tubules, partial or complete, or by obstructive changes in the ureters or urethra. Acute swelling of the kidney may reduce the glomerular filtration rate by increasing interstitial pressure on the glomeruli and tubules.· The glomerular filtrate is an ultrafiltrate of plasma and has essentially the same composition, minus the cells and plasma proteins. The composition of the glomerular filtrate is modified as it passes through the renal tubules. Tubular Reabsorption Tubular reabsorption varies with the functional capacity of the kidney, both in health and disease, and with the need for the body to conserve the various components of the glomerular filtrate. Other organs produce hormones which also affect tubular reabsorption. The antidiuretic hormone of the posterior pituitary gland promotes reabsorption of water from the distal convoluted tubules and collecting ducts by increasing the permeability of these portions of the nephron to water. Aldosterone from the adrenal cortex stimulates the reabsorption of sodium by the renal tubules. Many substances such as glucose, amino acids, and water-soluble vitamins are "threshold substances." When present in low concentrations they are essentially completely reabsorbed from the glomerular filtrate by enzyme systems in the tubules. At higher concentrations, or in the presence of renal disease, the capacity of the enzyme systems is often exceeded, and spillage into the urine occurs. Sodium, potassium, and bicarbonate are examples of components of the glomerular filtrate which are absorbed by the tubules. Sodium is reabsorbed primarily in the proximal convoluted tubules without regard for the body's needs; in the distal tubule, aldosterone facilitates a more

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finite regulation of sodium reabsorption. Bicarbonate may be reabsorbed or excreted by the kidney, depending primarily on the animal's need for bicarbonate. Water is passively reabsorbed in the proximal convoluted tubules without regard for the body's need, by accompanying the active reabsorption of glucose, sodium, and other substances. Facultative reabsorption of water occurs in the distal tubules and collecting ducts under the influence of the antidiuretic hormone of the posterior pituitary gland and in accordance with the body's needs. In health, the reabsorption of water is so great that the final urine volume is usually less than l per cent of the volume of the glomerular filtrate.

Tubular Secretion Tubular secretion is of great importance in renal regulation of acidbase balance. An exchange mechanism in the distal convoluted tubules secretes hydrogen ions which may be bound to phosphate and excreted. The formation and secretion of ammonia facilitates excretion of hydrogen ions as a part of the ammonium ion. Tubular secretion also plays an important role in excretion of certain drugs such as penicillin, in the excretion of some iodinated radiographic contrast media, in renal function tests such as the phenolsufonphthalein test, and in measuring renal function by excretion of Diodrast or para-aminohippurate.

CLINICAL FINDINGS IN UREMIA Currently, detection of renal disease before there is serious impairment of renal function is often difficult because of the reserve capacity and adaptive capabilities of the kidney. Once the limits of renal reserve and compensation have been exhausted, signs of renal failure typically appear in rapid succession, and the condition of the patient often deteriorates rapidly, even though there has been relatively little progression in the rate of pathologic destruction of the kidneys. When the structural and functional integrity of both kidneys has been compromised to such a degree that signs of renal failure become manifest clinically, a relatively predictable symptom complex called uremia occurs, regardless of underlying cause or stage (acute or chronic). As a generality, clinical signs associated with uremia are more similar than dissimilar, because functional and morphologic abnormalities of the kidneys can be manifest clinically in only a limited number of ways. Thus clinical findings of generalized renal disease often lack specificity because they occur as a result of a variety of morphologic alterations of the kidney. Weakness, depression, anorexia, stomatitis, vomitus, central nervous system disturbances, and diarrhea or constipation may occur in association with acute or chronic, reversible or irreversible renal failure.

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The presence of these signs does indicate the presence of generalized renal disease, however, since approximately three quarters or more of the nephrons of both kidneys must be nonfunctional before signs characteristic of uremia become manifest clinically. Progressive weight loss, anemia, polyuria, nocturia, and polydipsia are reliable signs of chronic generalized renal disease. Palpation of generalized pitted irregularities in the surface contour of abnormally small kidneys is also a finding which indicates the presence of irreversible, generalized, chronic, inflammatory disease. (The absence of the latter does not exclude the possibility of chronic renal disease, however, since it may occur without inducing profound alterations in the gross architecture of the kidneys.) Chronicity of the disease may be inferred from the fact that all of the above signs require considerable time to develop. The generalized nature of the renal disease may be inferred from the fact that at least two thirds or three quarters or more of the functional renal parenchyma must become incapacitated before the signs become manifest clinically. Since most chronic generalized renal diseases of cats are irreversible, a guarded to poor prognosis is often justified. In summary, clinical signs of generalized renal disease are nonspecific for at least two reasons: 1. They indicate the presence of generalized renal disease but not the underlying cause; 2. Most signs do not become manifest clinically until two thirds or three quarters or more of the functional renal parenchyma of both kidneys has been incapacitated. Once the presence of generalized renal disease is suspected on the basis of clinical findings, additional laboratory, radiographic, or biopsy information should be obtained to confirm the presence of renal disease, to determine whether the underlying disease is related to extrarenal factors or primary disturbance of renal function, and to determine whether the disease is reversible or irreversible.

LABORATORY FINDINGS Laboratory tests are helpful but not infallible, and their value is directly proportional to the clinician's ability to interpret them. Socalled "normal standards" of laboratory tests should not be interpreted too rigidly. Like any other factor in renal disease, the results of laboratory tests must be evaluated in combination with available clinical, radiographic, and biopsy findings if they are to be meaningful. The purpose of renal function tests is to help determine the location and extent of impairment, and thereby to provide additional information with which to establish a meaningful diagnosis and prognosis. As was the situation with the history and physical examination, however, functional abnormalities indicated by laboratory procedures lack specificity because they are similar in a wide variety of renal diseases. At best

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they allow differentiation between a predominantly glomerular or tubular lesion, or both, irrespective of cause. Because of the limits imposed by time and economics, clinicians are forced to use qualitative and semiquantitative measurements of renal function. Unfortunately, the latter tests are relatively crude and provide only rough approximations. For this reason, and because of the functional reserve and adaptive processes characteristic of kidneys, the results may be normal in the presence of extensive histopathologic changes. Once abnormalities are severe enough to allow detection by conventional laboratory methods, there is a rough correlation between the degree of functional impairment detected by the tests, and the severity, but not the type (i.e., specific cause) of the underlying renal disease. In essence, the results of these tests are related to the amount of nonfunctional renal parenchyma. Single determinations of most tests indicate the competence of the kidneys at the time the tests are performed, but do not indicate the specific cause of the disease or the acuteness or chronicity of the underlying lesions or their degree of reversibility or irreversibility. Because single determinations are of limited diagnostic and prognostic value, renal function should be reevaluated at appropriate intervals to establish the trend of abnormal function. Urine Specific Gravity The ability of patients to excrete urine with a specific gravity above or below that of glomerular filtrate is dependent on an intact system for secretion of antidiuretic hormone (ADH), and a sufficient quantity of functional nephrons. In normal cats, evaluation of specific gravity provides information relative to the functional competence of the distal convoluted tubules and collecting ducts, since it is in these areas that water absorption or excretion is controlled by ADH. Once the specific gravity becomes fixed at that of glomerular filtrate (1.008 to 1.012), however, it is more an indication of nephron function than tubular function, since in addition to generalized tubular disease, fixation of specific gravity may occur as a result of factors not specifically related to intrinsic tubular damage. Diminution in the capacity to concentrate or dilute urine is a consistent finding in acute or chronic renal disease in which a sufficient quantity of functional nephrons have been damaged. Because the kidneys have tremendous reserve capacity, impairment of their ability to concentrate or dilute urine usually is not detectable until approximately two thirds of the functional renal parenchyma has been incapacitated. Detection of a specific gravity equal to that of glomerular filtrate in a randomly obtained sample of urine is not consistently reliable evidence of generalized renal disease. Since the ability of normal kidneys to alter

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specific gravity overlaps the specific gravity of glomerular filtrate, such an assumption can only be made if the specific gravity of urine remains at the "fixed" level after a suitable period (12 to 24 hours) of water deprivation (water concentration test), or if the patient is clinically dehydrated or uremic at the time the isosthenuric sample of urine is collected. Detection of a specific gravity greater than approximately 1.025 in association with uremia is often a favorable prognostic sign since it indicates that a sufficient quantity of functional nephrons are present to concentrate urine, and that the failure may be prerenal in origin. Detection of a specific gravity below that of glomerular filtrate (1.001 to 1.006) is reliable evidence of functional nephrons, since metabolic work is required to remove solute from glomerular filtrate. Casts

Since casts are formed in the distal convoluted tubules and collecting ducts, detection of significant numbers of casts in urine sediment is reliable evidence of renal disease. Clinical observation has revealed that the presence of a few casts in the urine sediment of otherwise normal animals is not a reliable indication of significant renal damage, however, and is of little diagnostic or prognostic significance. Any lesion in the renal tubules at the time casts are formed may be reflected in their composition; therefore, casts have been classified according to the materials they contain. The relative numbers and morphologic characteristics of casts are not of major significance, however, other than to localize the disease process to the kidneys and, depending on their type, to indicate significant damage to the distal convoluted tubules and collecting ducts. Proteinuria

Proteinuria of sufficient degree to allow detection by conventional laboratory tests should be investigated. Care must be used in interpretation of the significance of proteinuria, however, since it may be of nonrenal origin and not pathognomonic of renal disease. Persistent and severe proteinuria is the hallmark of generalized glomerular disease. Blood Urea Nitrogen and Creatinine

Determination of blood urea nitrogen (BUN) or creatinine concentration provides a crude index of glomerular filtration rate, provided that endogenous production and exogenous sources are relatively constant. Elevations in the concentration of BUN or creatinine which occur as a result of impairment of renal function are not detectable with conventional laboratory tests until approximately 70 to 75 per cent or more of the nephrons of both kidneys are nonfunctional.

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Serum Electrolytes

Evaluation of serum electrolytes per se usually is not of great diagnostic value in diseases of the kidney. Knowledge of the degree and type of electrolyte imbalance often provides information of prognostic or therapeutic significance, however, and may support or deny tentative diagnoses. In patients with generalized renal disease, the kidneys lose the ability to efficiently conserve sodium, and, as a generality, a sodium deficit exists. Serum concentration of sodium may be normal despite the deficit in total body sodium, because the loss through the kidneys is accompanied by an obligatory loss of water due to osmosis. Because of the negative sodium balance in patients with advanced renal disease, drugs containing sodium often are used as a part of the regimen in renal failure. As a generality, the body concentration of chloride tends to parallel that of sodium in patients with generalized renal disease. Significant elevations of potassium may occur in patients with acute generalized renal disease. Cats with chronic progressive renal failure typically maintain a normal serum concentration of potassium until advanced phases of renal disease have been reached. In the latter instance, maintenance of normal potassium levels is related to compensatory and adaptive changes in remaining viable nephrons. In cats with generalized renal disease, the kidneys lose the ability to efficiently conserve bicarbonate, and, as a generality, a bicarbonate deficit exists. Because bicarbonate is a significant buffer of hydrogen ions, it often is used as a part of the regimen in renal failure. Hyperphosphatemia is a consistent finding in cats with generalized renal disease, since phosphorus normally is excreted by the kidneys. Varying degrees of hypocalcemia occur in patients with chronic generalized renal disease, but usually the serum concentration of calcium tends to remain within the normal range until advanced stages of the renal disease have been reached. This fact is related to the large reserve of calcium stored in bone. The ocurrence of hypocalcemia is thought to be related to the presence of hyperphosphatemia, although the exact pathophysiologic relationship has not been established. Imbalance of the normal calcium-phosphorus ratio, excretion of abnormal quantities of phosphorus into the intestine with resultant formation of nonabsorbable calcium salts, and impaired utilization of vitamin D have all been incriminated as factors which play a causative role in the hypocalcemia of chronic generalized renal disease. Cats with renal failure typically have varying degrees of metabolic acidosis. The metabolic acidosis associated with generalized renal disease occurs as a result of the inability of the kidneys to excrete an adequate quantity of acid breakdown products of digestion and metabolism, and inability to conserve buffer ions efficiently.

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Serum Amylase

Because amylase is dependent on renal excretion for removal from the blood, serum amylase concentration usually is elevated in uremic cats. Anemia

Progressive nonregenerative anemia associated with renal failure is reliable evidence of advanced chronic generalized irreversible disease. Depression of erythropoiesis which occurs secondary to depressed renal production of erythropoietin is the predominant cause of renal anemia. The absence of nonregenerative anemia does not necessarily exclude the presence of extensive histopathologic changes in the kidneys.

RADIOGRAPHIC EVALUATION OF THE URINARY SYSTEM Adequate radiograp_hic equipment, proper patient preparation, proper positioning, correct exposure factors, proper developing technique, and correct interpretation are essential if urologic radiography is to be consistently meaningful. Radiographic techniques are of primary value in localization of disease processes to various segments of the urinary system, and therefore should not be used as a substitute for careful clinical evaluation of the patient by history, physical examination, and pertinent laboratory procedures. Abdominal palpation is an especially important prerequisite to radiographic examination of the urinary system of the cat, as the results of palpation often allow localization of the disease p,rocess, more meaningful interpretation of radiographic findings, and determination of whether additional radiographs or special radiographic techniques are likely to be of value. Good soft tissue films and careful interpretation may reveal abnormalities without the use of special contrast techniques. The kidneys of most cats often are well visualized on scout films because of the large quantity of perirenal fat around each kidney. The different radiographic density of fat usually provides sufficient contrast to show the outline of the kidneys. Scout films also facilitate recognition of radiopaque calculi. The capacity of the kidneys to excrete circulating organic iodinated compounds in concentrations sufficiently high to cause the urine to become radiopaque is the basis of the excretory urogram. Contrast radiography of the urinary system should be considered if the organs cannot be adequately visualized on scout films. Contrast urograms also facilitate evaluation of the excretory pattern of the urinary system, and provide the only practical method of radiographic visualization of the renal pelves and ureters. As was the case with scout films, the objective usually is to localize a disease process to various segments of the urinary system. This information is especially important if surgical correction

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or biopsy is contemplated. Excretory urograms should not be used as a substitute for semiquantitative renal function tests because the degree of visualization provided by contrast material is affected by numerous variables. At best they provide a very crude qualitative evaluation of the renal function of each kidney. Tri-iodinated water soluble organic compounds usually are used for excretory urograms in cats as they provide rich contrast and are well tolerated. If an excretory urogram is indicated in a patient with marked renal insufficiency, and the standard technique does not provide adequate visualization, drip infusion urography should be considered.

RENAL BIOPSY Renal biopsy has evolved as a valuable aid to establishment of specific diagnoses because morphologic alterations constitute the principal criteria for classifying most renal diseases. Histopathologic studies of biopsy samples may also indicate the potential reversibility or irreversibility of a renal disease. Indications

Renal biopsy is not an innocuous procedure, and should not be used as a substitute for careful clinical and laboratory evaluation. Morphologic alterations detected by renal biopsy must be evaluated along with the clinical findings, when an attempt is made to evaluate the ability of the kidneys to repair disease. In general, biopsy of the kidneys is more likely to facilitate establishment of a specific diagnosis in the presence of generalized, rather than focal, renal diseases. The inability to detect focal lesions consistently is a limitation of all needle biopsy techniques. When the results of biopsy are likely to establish a specific diagnosis, to determine the type of therapy, or to indicate prognosis, the indication for biopsy is absoluteprovided the patient can tolerate the procedure without undue risk. Contraindications

Evaluation of each patient prior to needle biopsy is essential. Because excessive hemorrhage is one of the most serious potential complications, the hemostatic mechanisms of each patient should be carefully evaluated. Any abnormality in hemostasis must be corrected before biopsy. If a hemorrhagic tendency cannot be corrected, percutaneous needle biopsy of the kidney should not be performed. Besides abnormalities in hemostasis, severe circulatory dysfunction, infection in the path of needle biopsy, an uncooperative patient, an inexperienced clinician, and a damaged biopsy needle contraindicate renal biopsy.

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Although needle biopsy of patients with hydronephrosis, pyonephrosis, or renal abscesses should not be performed with conventional biopsy instruments: a 25-gauge needle and syringe may be used to aspirate a sample of fluid from the lesions for cytologic evaluation and bacterial culture. Technique The success of percutaneous biopsy jn cats depends on adequate localization and immobilization of the kidney so that a representative sample can be obtained with every biopsy attempt without serious risk. In cats, a blind percutaneous biopsy technique may be employed because both kidneys usually can be localized and immobilized by palpation. Either the right or left kidney may be biopsied. After a fast of eight to 12 hours, cats should be sedated with meperdine* (5 mg./lb. body weight) and promazine (2 mg./lb. body weight). General inhalant anesthetics may be used ih patients which are not poor risks. Use of the Franklin modified Vim-Silverman biopsy needle** (short model) allows satisfactory samples to be consistently obtained. After surgical preparation of a wide area of skin over the kidney, a local anesthetic should be injected into the body wall at the biopsy site. This area should be determined by digital displacement of the kidney against the body wall. A tiny skin incision should be made at the proposed site to facilitate entry of the needle. The needle should be positioned so that the exact route of the cutting prongs can be projected as they are thrust into the kidney. The long axis· of the needle should be directed away from the renal artery, vein, and renal pelvis to avoid inadvertent damage. Following biopsy, the tissue sample should be carefully removed from the needle and fixed. Postbiopsy Complications Self-limiting microscopic hematuria usually, but not invariably, lasts from a few hours to two to three days following biopsy. Selflimiting gross hematuria may be observed in 1 to 3 per cent of the patients. When present, severe renal hemorrhage usually is associated with faulty technique.

CONGENITAL RENAL DISEASE Congenital renal anomalies are relatively uncommon in the cat, but apparently are more common than in the dog. Unilateral renal agenesis *Demerol hydrochloride, Winthrop Laboratorie~, New York, New York. **Available from V. Mueller and Co., 6600 West Touhy Avenue, Chicago, Illinois 60648.

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or aplasia, unilateral renal hypoplasia, congenital renal dystopia (i.e., malposition), congenital renal cysts, fused kidneys (e.g., horseshoe kidneys), and variations in renal vascularization are found in cats. Bilateral renal agenesis is fatal. Bilateral renal hypoplasia may result in death prior to, or within the first year of life. Although congenital anomalies usually are not associated with clinical signs of renal disease, they often are associated with a variable decrease in the functional reserve of the kidneys. The functional reserve is of particular significance in the event of concomitant acquired renal disease. Renal cysts or polycystic kidneys may simulate acquired renal diseases such as neoplasia radiographically, or during abdominal palpation. Unilateral aplasia and unilateral or bilateral hypoplasia may be confused with acquired renal diseases which are associated with abnormally small, contracted end-stage kidneys. If congenital anomalies are associated with significant alterations in size, shape, or location of the kidneys, a tentative clinical diagnosis often can be made by palpation. Confirmation can be obtained radiographically, by laparotomy, by biopsy, or at necropsy. Most renal anomalies are discovered coincidentally with other diseases reqmnng clinical, radiographic, surgical, or pathologic evaluation. Nephrectomy should be considered if an anomalous kidney is associated with disease which is not responsive to conventional therapy. Unilateral Renal Agenesis (Aplasia) This condition is characterized by complete absence of one kidney and partial or total absence of its associated ureter. Compensatory hypertrophy of the remaining kidney is a consistent feature of this condition. Some authors designate the small fibrous remnants of kidneys which are attached to ureters as aplastic. However, even a very small residual kidney attached to its ureter should be designated hypoplastic. Renal aplasia requires complete or partial absence of the associated ureter. The portion of ureter remaining on the affected side is often abnormally small in diameter and may or may not be patent. The renal artery and vein on the affected side may be absent, but, when present, often supply the adjacent abdominal musculature. An associated uterine anomaly, especially complete absence of the ipsilateral uterine horn (i.e., uterus unicornis), is common in females with unilateral renal agenesis. The ipsilateral vas deferens or epididymis may be missing in affected males. The gonads in both sexes are not affected. The consistent association of these urogenital anomalies is explained by the fact that the ureter, uterus, vas deferens, and epididymis are embryologically derived from the same analog; whereas gonads are of separate embryologic origin. These anomalies in the cat more often involve the right side. Although it has been stated that unilateral renal agenesis affects males more frequently, there are more cases recorded in females.

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Unilateral Renal Hypoplasia The hypoplastic kidney is abnormally small and usually is supplied by a ureter, pelvis, and vasculature which are small. The contralateral kidney usually is significantly enlarged as a result of compensatory hypertrophy. Congenital hypoplasia sometimes is difficult to distinguish from end-stage kidneys associated with acquired renal disease, because the end stages of pyelonephritis, glomerulonephritis, interstitial nephritis, and renal amyloidosis may result in marked contraction of the affected kidneys. Histologically the hypoplastic kidney may be a miniature replica of the normal kidney (i.e., without significant fibrosis or inflammatory reaction) or may show varying degrees of fibrosis, cyst formation, and inflammation. The latter is difficult to distinguish from acquired chronic disease. Recent investigations reveal that cerebellar hypoplasia (i.e., feline ataxia) and arrested nephrogenesis causing moderately hypoplastic kidneys can be induced by the intrauterine injection into the fetus with panleukopenia virus. The relationship between this and the reportedly greater incidence of spontaneous renal aplasia and hypoplasia in the cat than in the dog requires further investigation before any generalities can be established. Dystopia Congenital renal dystopia is characterized by abnormal location of the kidney in the abdominal or pelvic cavity, and results from abnormal embryogenesis. It is reportedly uncommon in the cat. The congenitally displaced kidney may be located in the pelvic cavity, medial or lateral to its normal attachment site, or on the opposite side (i.e., crossed dystopia). Kidneys located in abnormal positions usually function normally and are not associated with clinical signs of disease. However, displacement may cause kinking or twisting of the associated ureter resulting in a predisposition to hydronephrosis and pyelonephritis. Fused Kidney (Horseshoe Kidney) This malformation results from the congenital fusion of two kidneys, usually at their caudal poles, by fibrous connective or renal tissue. Each kidney retains a separate pelvis and ureter. This anomaly is rare in cats. In other animals and in man, the condition is asymptomatic and apparently not associated with a greater frequency of acquired disease than normal kidneys. Congenital Renal Cysts Renal cysts may result from abnormal embryogenesis or from acquired renal disease. Although the pathogenesis of congenital renal cysts in animals is not completely understood, the traditional theories regarding their pathogenesis appear to have been invalidated by human

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microdissection studies. These studies reveal that congenital renal cysts develop as a result of: 1. An increase in the volume of the collecting tubules caused by hyperplasia of the epithelial cells lining the affected tubules; 2. Inhibited branching of ampullae which subsequently become cystic; 3. Cystic change anywhere along the nephron or collecting tubule; or 4. Urethral obstruction occurring as a developmental anomaly in the embryo or in early fetal life. Acquired cysts probably arise from nephrons obstructed by exudate or intertubular fibrosis. The differentiation of congenital cysts from acquired cysts is often difficult. The acquired form usually is associated with a greater degree of scarring and inflammation. Congenital cysts apparently are more common in cats than in dogs, and the condition in the cat usually is bilateral. This anomaly may be represented by a few large renal cysts, or by many small cysts (i.e., polycystic kidneys) which replace portions of the renal parenchyma. The cysts are lined by a glistening smooth epithelium and contain a serous fluid. The polycystic kidney has a honeycomb appearance. In the cat, both acquired and congenital cyst formation may result in fluid accumulation between the renal capsule and the cortex. Renal cysts may be clinically asymptomatic, or they may be associated with the onset of clinical signs at any age. The presence or absence of clinical signs depends on the severity and duration of renal parenchymal involvement, and the presence or absence of concomitant renal disease. Human bilateral polycystic disease is a hereditary condition in which the adult form is thought to be associated with an autosomal dominant characteristic, the neonatal form being associated with an .autosomal recessive characteristic. Multiple liver cysts occur in approximately one-third of human beings with polycystic kidneys. A case of feline polycystic disease associated with a polycystic liver has been reported. Anomalous Renal Vessels

The renal vascular anatomy of the cat is relatively constant, and vascular anomalies are uncommon. An anatomic study of renal arterial patterns in 1000 cats did not reveal any cases in which the vessels entered at any region except the hilus. The renal artery is almost always single in the cat, whereas two renal veins occur approximately 25 per cent of the time.

PHYSICAL INJURY

The kidneys are sometimes injured by violent external abdominal trauma. The associated lesion is usually characterized by a tear in the

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renal capsule and parenchyma, and hemorrhage. The location and extent of renal damage, and the duration of the disease process, may cause a subcapsular or retroperitoneal hematoma. If the rent opens into the peritoneal cavity, hemoperitoneum may develop. If the rent involves the pelvis, an inflammatory mass caused by the perirenal extravasation of urine may develop. In acute cases with large rents, the clinical findings may be characteristic of hemorrhagic shock. If the patient survives, a painful mass may be palpated at the site of injury. Lesions caused by trauma to other organs and body systems also may be detected. Signs associated with primary renal failure will not develop if only one kidney is damaged. A urinalysis typically reveals gross or microscopic hematuria and proteinuria. Excretory urography may be of value in determining the site and extent of renal damage, and may reveal perirenal extravasation of urine. Traumatic rupture of the kidney usually can be diagnosed on the basis of the history, physical examination, radiographic findings, and laboratory findings. If subcapsular or perirenal hemorrhage is self-limiting, cage rest may be the only treatment required. In such cases, hematomas usually undergo spontaneous resolution. If evaluation of serial hemograms reveals a rapid and progressive decline in packed cell volume, despite standard therapy for hemorrhagic shock, exploratory laparotomy is indicated. Rents in the renal parenchyma may be repaired by various suturing techniques combined with hemostatic agents (oxidized regenerated cellulose*). With uncontrollable hemorrhage or perirenal extravasation of urine, a nephrectomy should be considered, provided the opposite kidney functions adequately.

NEPHROSIS Nephrosis is a disease of the kidneys characterized by degenerative lesions of the renal tubules._ It may be caused by nephrotoxins or renal ischemia. Although renal failure caused by ischemia is clinically indistinguishable from renal failure caused by nephrotoxins, each produces a different type of renal lesion. Structural damage induced by renal ischemia is characterized by a random distribution of lesions throughout the tubules. The lesions consist of disruption, fragmentation, or dissolution of tubular basement membranes, and necrosis of tubular epithelial cells. Variable numbers of nephrons are damaged, but rarely is an entire nephron damaged. In contrast, structural damage induced by nephrotoxins is characterized by cellular degeneration and necrosis which is confined to the epithelium of the proximal portion of the *Surgicel,Johnson and Johnson, New Brunswick, N.J.

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tubules. Unlike renal ischemia, the basement membranes of the damaged portions of the renal tubules are not significantly altered. This morphologic difference in the lesions induced by ischemia and nephrotoxins is clinically significant since tubular basement membranes must be intact to allow structural and functional restoration of damaged nephrons. Because of the inherent nature of the renal lesions they produce, the potential for nephron repair usually is greater following injury by nephrotoxins than by ischemia. Nephrotoxins which may produce nephrosis in cats include ethylene glycol, diethylene glycol, arsenic, mercury, lead, carbon tetrachloride, and tetrachlorethylene. Drugs with potential nephrotoxicity include sulfonamides, neomycin, amphotericin B, kanamycin, and polymyxin. Nephrosis due to renal ischemia is usually associated with shocklike states in which reduced circulatory volume, renal vasoconstriction, intravascular hemolysis, or inadequate cardiac output occurs. Injuries, especially those in the abdomen, and major surgical procedures on poor risk patients are known causes of nephrosis and ischemic renal failure. In mild nephrosis, the injury may be self-limiting. Here, the patient usually is asymptomatic, and renal disease is suspected only following detection of transient proteinuria, hematuria, pyuria, and abnormal numbers of casts in the urine sediment. The clinical findings associated with renal failure caused by nephrosis are partially dependent on the specific underlying cause of the lesions. Uremia usually is present, regardless of etiology. Urine production may be characterized by oliguria (early disease state), or polyuria (later disease state). In addition to the signs characteristic of renal failure, the symptomatology may be complicated by signs associated with toxic or ischemic lesions in other organs and systems. Evaluation of the various renal function tests (i.e., BUN, creatinine, phenolsulfonphthalein dye excretion) will reveal findings consistent with failure. Abnormal quantities of casts, RBC, WBC, and protein may be in the urine sediment. The specific gravity of the urine obtained from patients with renal failure secondary to nephrosis is the same as that of glomerular filtrate (1.008 to 1.012) when a sufficient quantity of nephrons has been incapacitated to prevent concentration or dilution of the urine. If the urine specific gravity is above 1.025 in a patient with renal failure, it means that at least one third of the nephrons are functional. In this instance, a pre renal cause of uremia should be considered. The hemogram will not reveal a nonregenerative anemia if the disease is acute. Nephrosis may be tentatively diagnosed on the basis of the history, physical examination, and laboratory data. A history of recent shock or exposure to a potential nephrotoxic agent is helpful. Positive identification of a toxic agent in the blood or urine provides proof of exposure and

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absorption. The renal biopsy sample may reveal significant morphologic alterations, and often allows establishment of the potential reversibility or irreversibility of the disease. Response to specific therapy may provide support for the diagnosis and indicate a specific cause. · Treatment of renal failure should eliminate or correct the specific cause of nephrosis when it is known. If available, a specific antidote should be used when treating nephrotoxicity. Elimination of the source of a nephrotoxic agent may be the only treatment required for patients with mild nephrotoxic nephrosis. Conventional therapy for renal failure (osmotic diuresis, peritoneal dialysis, hemodialysis, oral sodium chloride, and sodium bicarbonate) should be considered in all cases of renal failure due to nephrosis. Osmotic diuresis is beneficial when used presurgically in poor risk patients. The prognosis of renal failure associated with nephrosis depends on the specific nature of the underlying cause, the duration of the disease, and its severity. A favorable prognosis is more often justified for patients with generalized nephrosis than for those with chronic generalized renal disease.

HYDRONEPHROSIS Hydronephrosis is characterized by dilatation of the renal pelvis and varying degrees of renal atrophy and cystic enlargement. It may be congenital or acquired, and results from partial or complete obstruction anywhere between the renal pelvis and the urethral orifice. Obstruction results in urine retention and increased pressure in the urinary system. Because the capsule is inelastic, and because tubular epithelial cells are especially sensitive to pressure, the affected kidney undergoes ischemic atrophy. This results in varying degrees of dilatation of the pelvis and atrophy of the parenchyma. Specific causes of congenital hydronephrosis include torsion or kinking of the ureter due to renal dystopia, stenosis or atresia of the urethra, and aberrant vessels that constrict the ureters. Acquired hydronephrosis results from urinary calculi, neoplasms, accidental ligation of a ureter during surgery, and inflammation and stricture of the ureter or urethra due to any cause. Cases of hydronephrosis are encountered in which no predisposing cause can be detected. Several have been reported in which a large quantity of fluid collected between the external surface of the renal cortex and the capsule. These kidneys were abnormally enlarged and could be palpated abdominally. The etiology of this form of "capsular hydronephrosis" has not been defined, although it is hypothesized that it results from lymphatic obstruction. The pathologic change in renal parenchyma and the associated clinical signs vary, depending on the location of the obstructing lesion,

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involvement of one or both kidneys, completeness of urinary obstruction, and the duration of the disease. Renal changes are more severe when there is partial rather than complete obstruction. The most severe change occurs when hydronephrosis is unilateral. Pelvic dilatation and renal atrophy are less severe in bilateral hydronephrosis, since renal failure causes death before extensive renal changes develop. The degree of pathologic change in each kidney of patients with bilateral hydronephrosis may be unequal, depending on the location and nature of the primary cause. Hydronephrotic kidneys contain clear, watery fluid in the absence of infection. Secondary bacterial infection produces pyonephrosis and the fluid becomes purulent. Hydronephrosis may be asymptomatic for a long time, especially if it is unilateral and the unaffected kidney functions adequately. Early signs are often associated with the underlying cause of urine obstruction, which may become the limiting factor in survival. Enlarged kidneys and sometimes the primary obstructing lesion can be detected by abdominal palpation. Signs of failure develop when hydronephrosis is bilateral, or when it is unilateral and the opposite kidney is diseased. Fever, leukocytosis, hematuria, pyuria, and proteinuria may be detected if partially obstructed kidneys become infected. Hydronephrosis can be tentatively diagnosed on the basis of the history, physical examination, and laboratory findings. Excretory urography may help to localize the disease. The diagnosis may be confirmed by exploratory laparotomy, or by evaluation of hydronephrotic fluid. Treatment of hydronephrosis should eliminate the underlying cause of obstruction. Nephrectomy and supportive treatment may be used with advanced unilateral hydronephrosis, when the contralateral kidney functions adequately. There is no effective treatment for advanced bilateral hydronephrosis because of irreversible damage to the parenchyma. Such patients may benefit from supportive treatment.

GENERALIZED NEPHRITIS

Generalized nephritis is a nonspecific term used to describe acute and chronic inflammatory diseases of the kidney which are associated with varying degrees of renal insufficiency. Acute Generalized Nephritis

Primary acute generalized nephritis is not common in the cat. Secondary acute generalized nephritis is also uncommon, but may develop in association with polysystemic diseases such as bacterial endocarditis, bacterial septicemias, and leptospirosis. The clinical and

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laboratory findings referable to acute generalized kidney disease are related to renal failure, and are similar to those associated with nephrotoxic or ischemic nephrosis. Also, cats with acute generalized inflammatory nephritis may be febrile and have a marked leucocytosis. Signs caused by kidney disease may be associated with signs referable to involvement of other organs and body systems. Treatment should eliminate the primary cause in addition to providing supportive therapy for renal failure. Prognosis depends on the etiology, severity, and duration of the disease.

Chronic Generalized Nephritis Chronic generalized nephritis is more common in cats than acute generalized nephritis. The chronic generalized disease includes pyelonephritis, amyloidosis, and chronic interstitial nephritis. In many cases, however, the antecedent renal disease cannot be determined by clinical or histologic evaluation. Therefore the chronic disease is popularly referred to as chronic interstitial nephritis, or end stage kidney disease. The term "chronic interstitial nephritis" is used to describe the morphologic appearance of the kidneys of cats and dogs affected with inflammatory, ischemic, chronic, progressive, and irreversible disease of unknown cause. It is related to the appearance and distribution of the lesions present, but is misinterpreted to designate a disease entity with a single cause. Chronic interstitial nephritis (end stage kidney disease) is the end stage of a variety of renal diseases of different etiologies which are characterized by a chronic, progressive, irreversible course, and a similar gross and microscopic appearance at the time of death from renal failure. Renal diseases which have progressed to an end stage are architecturally similar.· They are characterized morphologically by hyperplasia and hypertrophy of the viable nephrons superimposed on severe generalized inflammatory, regressive, and fibrous changes. It is impossible consistently to determine the underlying cause(s) of end stage kidneys on the basis of gross morphology. End stage kidneys usually are abnormally small, and have a pitted, irregular capsular surface. Retention cysts, common in the end stage kidneys of dogs, are reportedly uncommon in cats. Renal amyloidosis usually can be differentiated from other causes of end stage kidneys by histologic examiniation. Advanced chronic pyelonephritis may be morphologically indistinguishable from other causes of end stage kidneys by microscopic appearance. The clinical findings associated with chronic generalized nephritis depend on the stage of the disease. Because of the reserve capacity and functional adaptation of the kidneys, early lesions do not cause detectable clinical signs. Before the onset of uremia, clinical signs may be limited to polyuria, polydipsia, and nocturia. Progressive destruction of the parenchyma will cause signs of uremia, such as anorexia, weakness,

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weight loss, vomiting, dehydration, and diarrhea or constipation. Oral ulcers may develop, and pallor of the mucous membranes may be detected. Although chronic generalized renal disease usually is associated with polyuria, oliguria or anuria may develop as a terminal event. Although cats with chronic generalized renal disease do develop renal osteodystrophy, the bones of the skull and jaws are reportedly no more severely involved than the other bones of the skeleton. Laboratory findings in cats with chronic generalized renal disease are typical of renal failure. The history, physical examination, and pertinent laboratory data allow a tentative diagnosis of end stage kidney disease. Nonregenerative anemia, progressive weight loss, renal osteodystrophy, and the palpation of abnormally small kidneys with an irregular, pitted capsular surface, are diagnostic. This may be confirmed by histologic evaluation of a biopsy sample. Treatment is usually palliative, because the etiopathogenesis of most chronic renal diseases is unknown, and because most of the damage to the renal parenchyma is irreversible and progressive. Regeneration of damaged nephrons does not occur, and a critical point is reached at which renal compensation is no longer sufficient to sustain life. Although there is no cure, symptomatic and supportive treatment of renal failure may help the patient survive for months or years. Treatment should maintain fluid, electrolyte, and acid-base balance, by providing unlimited water, by reducing the nitrogen load, and by providing metabolites that the kidneys do not efficiently conserve. Diets containing high quality protein and readily digestible carbohydrate combined with oral sodium chloride, sodium bicarbonate, and B vitamins are beneficial. The long term prognosis for these patients is guarded to poor because of the progressive, irreversible nature of the disease.

PYELONEPHRITIS Pyelonephritis is a bacterial infection of the renal parenchyma and pelvis. Escherichia coli, Proteus spp., staphylococci, and streptococci have been cultured from pyelonephritic kidneys. Pathogens may reach the kidneys hematogenously, through the ureters, or periureteral lymphatics. Bacteria seldom invade the kidneys by direct extension from an infectious process of a contiguous structure. Urinary stasis or obstruction is apparently an important predisposing cause. Once organisms invade the renal parenchyma, they cause suppuration and necrosis. Infection may remain focal, or become disseminated and destroy enough renal parenchyma to cause renal failure. Tubular lumina often serve to disseminate organisms. N ephrons destroyed by the inflammatory process are ultimately replaced with fibrous connec-

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tive tissue. Patients with advanced chronic generalized pyelonephritis have small, granular, contracted kidneys, which are similar in appearance to those of patients with advanced chronic interstitial nephritis or advanced chronic generalized renal amyloidosis. Clinical findings associated with pyelonephritis depend on the degree of renal involvement and the duration of the disease. Acute focal or healed lesions usually are not recognized ante mortem. Acute generalized pyelonephritis may be associated with varying degrees of fever, leukocytosis, hematuria, pyuria, proteinuria, WBC casts or granular casts, and bacteriuria. In nonuremic patients, it is often difficult to distinguish pyelonephritis from other inflammatory lesions of the urinary tract by urinalysis. Significant numbers of casts are indicative of kidney disease, but unfortunately, they are not a consistent finding with pyelonephritis. If generalized involvement of both kidneys occurs, the signs of renal failure usually are present. Signs referable to renal disease may be combined with, or obscured by, a predisposing lesion (i.e., an obstructive lesion or septicemia). Diagnosis of renal failure due to pyelonephritis may be tentatively established by the history, physical examination, and pertinent laboratory findings. The diagnosis may be confirmed by renal biopsy. Treatment of pyelonephritis consists of aggressive antibiotic therapy, and the elimination of predisposing causes. Antibiotics should be chosen on the basis of bacterial culture and the antibiotic sensitivity of the organism. Urine samples or a renal biopsy may be used for isolating the organisms. Treatment is continued until urinalyses reveal no signs of inflammation. A prolonged therapy may be required, and arrested but permanent renal damage may persist. Supportive therapy for renal failure should be provided. A guarded to .favorable prognosis is justified for patients with minimal involvement of the parenchyma, or acute generalized pyelonephritis which is responsive to treatment. For those with acute generalized pyelonephritis that is unresponsive to treatment, or chronic generalized pyelonephritis, a guarded to poor prognosis is justified since the parenchymal damage usually is progressive and irreversible.

PRIMARY RENAL NEOPLASMS The known incidence of primary renal neoplasms in the cat is very low but the kidneys are a common site of lymphosarcoma. Nephroblastoma (i.e., Wilm's tumor, embryonal nephroma), renal carcinomas (i.e., hypernephroma, clear-cell carcinoma), and transitional cell carcinomas of the renal pelvis are reported in the cat. Renal carcinomas are reported most frequently. Although neoplasia of mesenchymal tissue components normally present in the kidney (e.g., fibrocytes,

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adipose connective tissue cells, endothelial cells, smooth muscle cells) is possible, primary renal tumors of this derivation are not common. Cases of primary renal neoplasia usually are noticed by the client because the affected cat has an enlarged abdomen. Anorexia and emaciation often are associated with extensive neoplasia, especially if metastasis has occurred. Hematuria is usually found, and pyuria or proteinuria may also be detected. The affected kidneys and their associated masses usually are palpable. Supportive evidence for a diagnosis of primary renal neoplasia may be obtained by radiography or by laparotomy, but a definitive ante mortem diagnosis can only be established by microscopic examination of neoplastic cells in urine sediment or biopsy samples. Nephrectomy and ureterectomy are justified when the neoplastic condition is unilateral and has not metastasized, and when the opposite kidney has adequate function. Renal Carcinoma Renal carcinomas arise from renal tubular epithelial cells. Aged animals are commonly affected, but the condition is also reported in young adults. In the cit, renal carcinomas often involve both kidneys. In these cases it is difficult to determine whether the process is unilateral with contralateral renal metastasis, or whether it is multicentric. Metastasis (e.g., to lung, heart, liver, spleen, mesentery, lymph nodes etc.) is common. Renal carcinomas may be confined to one pole of the kidney, or they may replace a large portion of the parenchyma. The neoplastic tissue typically is gray-white or yellow, and may be cystic. The size of the tumors is variable, but they may be 2 to 3 times that of a normal kidney. Microscopically, more differentiated tumor cells form irregular tubular structures; more anaplastic neoplasms form solid sheets or cords. N ephroblastoma Nephroblastomas arise from undifferentiated cells contributed by the embryonic kidney (i.e., metanephros). They occur most frequently in young animals, but do occur in adults. Although this condition is rare in cats, unilateral and bilateral involvement is reported. Available information suggests that nephroblastomas are normally unilateral in other animals. Macroscopically, nephroblastomas may be characterized by a small cortical nodule, or by abnormally enlarged kidneys which are largely replaced by neoplastic tissue. The omentum may adhere to the affected kidney, and adjacent vasculature may be enveloped by the neoplasm. The neoplasm typically is gray-white to yellow, and may contain cysts filled with a gelatinous substance. Necrosis and hemorrhage are often

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seen. Metastases to other tissues (e.g., lungs, omentum, regional lymph nodes) occur, and these lesions resemble the primary neoplasm. Nephroblastomas are characterized microscopically by the formation of primitive or embryonic-appearing glomeruli and tubules. Bone, cartilage, and muscle may be present in some cases. Transitional Cell Carcinoma

Transitional cell carcinomas are uncommon in the urinary bladder, and rare in the renal pelvis. Two cases arising from the transitional epithelium of the pelvis have been reported in cats. They involved cats six and nine years old. Both neoplasms were unilateral, highly invasive, and palpable abdominally. Metastasis to the mesentery occurred in one case.

MALIGNANT LYMPHOMA Malignant lymphoma (lymphosarcoma) is a common feline neoplasm typically seen in the middle-aged and geriatric patient. Recent experiments reveal that malignant lymphoma is of viral origin. In cats, both kidneys often are extensively infiltrated by neoplastic tissue. Lymphosarcoma of the kidneys usually occurs in association with neoplasms involving other organs and tissues, especially the intestines, liver, and internal lymph nodes. Sometimes only the kidneys are affected. Involvement may be focal or diffuse, and destruction of the kidney varies independently of the involvement of other organs and tissues. Generally, the cortical parenchyma is extensively involved, although in advanced cases, the medulla also may contain extensive lesions. Occasionally the renal capsule becomes thickened due to neoplastic invasion, and adheres to the external surface of the cortex. Sometimes, hydronephrosis occurs as a result of partial or complete ureteral obstruction by the neoplasm. Clinical findings vary with malignant lymphoma, and depend on the duration and extent of the disease. Focal accumulations of malignant lymphocytes in the kidneys usually are not associated with signs of renal disease. Once extensive renal involvement occurs, palpation reveals kidneys which are enlarged, and which contain numerous large firm "bumps" which protrude from the capsular surface. Although enlarged asymmetrical kidneys may be palpated, sufficient functional capacity may remain to maintain homeostasis. Following destruction of a sufficient amount of the renal parenchyma however, signs of chronic progressive renal insufficiency develop. A specific diagnosis must be based on the microscopic detection of malignant lymphocytes in the peripheral blood, in the urine sediment, or in the biopsy sections of affected organs and tissues. Antemortem confirmation may be obtained by renal biopsy.

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There is no known cure for malignant lymphoma, therefore a guarded to grave prognosis is justified. Administration of corticosteroids or chemotherapeutic agents may result in varying degrees of temporary remission.

RENAL AMYLOIDOSIS Pathogenesis

Amyloid is generally recognized with the light microscope as an extracellular acidophilic protein deposit that is stained preferentially, if not specifically, by Congo red, methyl and crystal violet, and thioflavine T stains. When amyloid deposits are examined with an electron microscope they appear as characteristic unbranching fibrils. Recent evidence supports the hypothesis that amyloid represents a locally formed substance produced by a variety of cell types. Pyroninophilic lymphoreticular cells are commonly incriminated in the local production of amyloid, but several other cell types have also been incriminated. It is suggested that prolonged antigenic stimulation of pyroninophilic cells results in exhaustion, and dysfunctional synthesis of an abnormal insoluble glycoprotein (i.e., amyloid). This does not support earlier hypotheses which incriminated certain serum proteins as the major constituents of amyloid. Investigations based on the electron microscopic demonstration of intracellular amyloid fibrils support the concept that amyloid is synthesized intracellularly by a variety of cell types. Occurrence of Amyloidosis in the Cat

Reports of amyloidosis in cats are rare. However, this may not be an accurate reflection of its incidence. A high incidence of generalized amyloidosis in cats is reported in Australia. The Australian incidence is probably related to chronic hypervitaminosis A associated with the practice of feeding cats raw beef liver exclusively. The generalized development of amyloid is thought to be associated with prolonged storage of vitamin A-containing lipid within reticuloendothelial cells. Amyloid was demonstrable in the kidneys, liver, spleen, adrenals, thyroid, gastrointestinal tract, and lungs of affected cats. In the kidney, most amyloid was found in the interstitial tissue of the medulla, but glomerular deposits also were present in most animals. Concurrent renal fibrosis, papillary necrosis, and amyloidosis occur in cats with no clinical or histopathologic evidence of diabetes mellitus. Again, the amyloid was primarily located interstitially at the corticomedullary junction, but was also present in the glomeruli and tubular basement membranes. Generalized amyloidosis and concurrent steatitis have also been observed.

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A localized form of amyloidosis characterized by deposits restricted to the pancreatic islets, is occasionally observed.

Clinicopathologic Findings The hallmark of renal amyloidosis clinically is persistent and severe proteinuria. However, the owner's initial complaint may be related to a predisposing infectious or neoplastic disease. Signs may occur without the clinical manifestations of a predisposing disease. Acidosis, retention of phosphorus, and retention of nonprotein nitrogen (BUN, creatinine) signify a generalized replacement of glomeruli by amyloid and a resultant decrease in glomerular perfusion. Hyaline, granular, or waxy casts may be present in the urine sediment, but they are not a consistent finding. Hypoproteinemia, related to a loss of albumin in the urine, is sometimes observed. Renal amyloidosis is a progressive and jrreversible disease. Advanced (i.e., chronic) amyloidosis, characterized histologically by progressive replacement of glomeruli with amyloid, secondary atrophy and destruction of tubules, and interstitial fibrosis, produces additional clinical signs. These include decreased excretion of PSP dye, urine of low specific gravity, and nonregenerative anemia. A conclusive antemortem diagnosis of renal amyloidosis depends on microscopic demonstration of amyloid in a renal biopsy sample. Depending on the duration of the disease, the kidneys may be of normal size and contour (very early in the course of the disease), enlarged with normal contour (acute form), or small and irregularly contracted (chronic form). Amyloid is demonstrable histologically as a smoothly homogeneous and, .lightly eosinophilic extracellular deposit in the glomeruli, tubular basement membranes, interstitial tissue, and renal vessels. Renal amyloidosis usually is associated with similar deposits in other organs (e.g., liver, spleen, adrenal, and gastrointestinal tract). Although a cure for amyloidosis is not available, symptomatic and supportive treatment of progressive renal failure often is beneficial and may prolong the patient's life.

BACTERIAL ENDOCARDITIS Bacterial endocarditis is an acute or subacute febrile systemic disease characterized by bacterial infection of the heart valves and endocardium, with subsequent formation of vegetative thrombi. The thrombi are composed of fibrin, platelets, cellular debris, and bacteria. Because of their composition, the thrombi are friable and often break to form emboli which escape into the general circulation. Patients with congenital or acquired lesions of the heart are predisposed to bacterial endocarditis.

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Clinically bacterial endocarditis is characterized by signs of systemic infection (depression, intermittent fever), cardiac abnormalities (murmurs, decreased cardiac output), and signs related to systemic embolism (paraplegia, cardiac conduction disturbances, CNS disturbances). The kidneys are predisposed to embolism and infarction because they contain a system of end arteries which do not have a significant collateral circulation. They also receive approximately 25 per cent of the cardiac output. Aseptic embolism of the renal artery or one of its major branches may result in total or subtotal necrosis of the affected kidney. Small aseptic emboli typically produce small conical renal infarcts. Septic emboli may produce areas of suppuration in addition to infarction. Recurrent episodes are indicated by infarcts or abscesses in varying stages of progression. The degree of renal dysfunction varies, and depends on the size and number of emboli, whether the emboli are septic or aseptic, and on the presence or absence of concomitant renal disease. Urinalysis may reveal findings consistent with an inflammatory lesion of the kidneys (i.e., casts, hematuria, pyuria, proteinuria). When renal infarction or suppuration is massive, signs of renal insufficiency may develop. A hemogram may reveal a marked neutrophilia with immature WBC. A nonregenerative anemia may be detected in chronic cases. Antemortem diagnosis of bacterial endocarditis is sometimes difficult because of the polysystemic nature of the disease. A typical history, physical findings, and laboratory findings provide supportive evidence. Culture of bacteria from the blood provides strong supportive evidence, but the inability to isolate bacteria from the blood does not eliminate bacterial endocarditis as a diagnostic possibility. Blood to be cultured is obtained aseptically prior to the onset of antimicrobial therapy. Treatment should eliminate the causative organism(s). Antibiotics are selected on the basis of antibiotic sensitivity tests when possible, and should be given in high doses for prolonged periods. Bacteria trapped in vegetative lesions are difficult to eradicate. When an embolus occludes a major blood supply, surgical correction may be considered. Surgery is often unsuccessful however, since it does not eliminate the primary disease.

TREATMENT OF UREMIA Treatment of chronic progressive renal diseases in veterinary medicine is generally limited to conservative medical management. The objectives of conservative treatment are to increase urine volume, to replace those substances which may be lost in excessive amounts in the urine, and to reduce the excretory load of the kidneys.

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Conservative Medical Management

Differentiation between prerenal, renal and postrenal uremia is essential to effective treatment and prognosis of renal failure. (See section on laboratory tests.) Since the most common causes of prerenal uremia are dehydration, hypotension (including shock), and reduced cardiac output, special consideration should be given to diagnosis of diseases associated with these changes. Efforts should serve to correct the underlying diseases in addition to symptomatic treatment of uremia. Treatment of prerenal uremia caused by hypotension, congestive heart failure, hypoadrenalcorticism, etc., should consist of efforts to eliminate or relieve the underlying cause in addition to reestablishment of effective renal perfusion. When severe dehydration is associated with prerenal uremia, its severity should be estimated and an appropriate amount of a balanced electrolyte solution administered parenterally. When dehydration is detectable clinically, the patient may be assumed to have lost 5 per cent of its body weight (5 per cent dehydration). Twenty-five ml. of fluid per pound of body weight is required for adequate rehydration. At 8 to 10 per cent dehydration, the skin becomes less pliable, and the eyes become slightly soft and sunken. Forty to 50 ml. of fluid per pound of body weight are required to repair a deficit of this magnitude. At 12 per cent dehydration, the loss of elasticity in the skin, softening of the eyes, and drying of the mucous membranes are more severe. Sixty ml. or more of fluid per pound of body weight are required. Ringer's or lactated Ringer's solutions are effective rehydrating agents. Dextrose solutions, in any concentration, are poor for rehydration. Since dehydrated animals are deficient in both water and electrolytes, both should be replaced. An advantage of using balanced electrolyte solutions is that they are usually absorbed rapidly from the subcutaneous tissues. In contrast, the absorption of subcutaneously administered dextrose solutions is slower and may result in "fluid rebound." Osmotic diuresis may benefit some patients with prerenal uremia, and will be discussed later.

TREATMENT OF RENAL UREMIA Animals in early renal failure usually do not require extensive fluid therapy. Vomiting is rarely a problem and most medication can be given orally. Because sodium and chloride are usually lost in excessive amounts during renal failure, a body deficit of sodium develops even though serum concentrations are normal. Sodium chloride should be administered orally at the rate of one to two grams daily to repair any existing deficit, to compensate for the excessive loss of sodium in the urine, to

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encourage greater water consumption, and to increase the glomerular filtration rate. Salt may be added to the food, at least in part, or gelatin capsules filled with sodium chloride may be administered. A number 4 (human) capsule holds approximately .25 gram of sodium chloride. The dosage may be increased or decreased depending on the response of the patient. When edema or ascites is present, sodium should be administered with great caution, if at all. In acute renal failure, the use of salt may be discontinued when the blood urea nitrogen concentration is normal and recovery seems to be complete. In chronic, progressive renal failure, the use of sodium chloride should be continued for the remainder of the patient's life. An increased dosage may be required as the disease advances. Additional sodium should be provided as sodium bicarbonate at a dose of 10 to 20 grains per day, using 5 grain tablets. Sodium bicarbonate is very well tolerated orally. Since the failing kidney has a reduced ability to excrete a large acid load, the use of sodium bicarbonate is beneficial. A low quantity-high quality protein diet is useful because it reduces the nitrogen load that the kidneys must excrete. Such diets are not associated with any known curative effect, and are not associated with any known effect which reduces or halts the rate of progression of generalized renal disease. Reduction of the quantity of nonprotein nitrogen to be excreted is associated with a reduction in the obligatory urine volume that the patient must form each day in order to maintain normal nitrogen balance. Ideally, low quantity-high quality protein diets should contain just enough protein of high biologic value to meet the eat's protein requirement. Because water soluble vitamins are handled as threshold substances by the kidneys, B complex vitamins and vitamin C should be administered· at therapeutic levels. It is assumed, but not proved, that surviving nephrons are unable to efficiently reabsorb water soluble vitamins because of the intense diuresis which must exist for the animal to survive. Anabolic steroids appear to be beneficial in uremia. They promote the incorporation of protein into body tissues, may aid in reducing the severity of uremia, promote better utilization of dietary protein, may stimulate the patient's appetite, and may enhance the compensatory hypertrophy and hyperplasia of viable nephrons. Treating the Uremic Crisis

If emesis is a problem and oral medication cannot be used administration of large quantities of lactated Ringer's solution subcutaneously may result in sufficient rehydration and diuresis to reduce the severity of the uremic crisis. After vomition ceases, oral therapy should be followed as discussed above. When the subcutaneous administration of

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lactated Ringer's solution does not result in remission of the uremic crisis, the intravenous route should be considered. Glucose or mannitol may then be administered intravenously, as outlined below, to induce an osmotic diuresis. Treatment by osmotic diuresis should consist of the following: 1. Weigh the cat. 2. Rehydrate the cat using lactated Ringer's solution. The quantity of fluid administered should be calculated on the basis of the dehydration present. 3. Weigh the cat again following rehydration. This weight should be used as the reference point for comparing future gains or losses when estimating the adequacy of fluid therapy. Further weight gains imply overhydration and fluid retention, while excessive weight loss suggests inadequate fluid replacement and dehydration. 4. Administer 10 per cent dextrose or 10 per cent mannitol intravenously. Use about 10 mi. of 10 per cent dextrose per pound of body weight, varying the amount on the basis of rate of urine formation. Administer the dextrose at a rate of 3 to 4 mi. per minute for 10 to 15 minutes to elevate the blood sugar concentration. Then reduce the rate of infusion to 1 or 2 mi. per minute to maintain the blood concentration of glucose. 5. It is important to establish the rate of urine formation. Palpate the bladder to establish the degree of distention. After administering dextrose for 10 to 15 minutes, empty the bladder either by palpation or catheterization. Test the urine for glucose. If glucose was not present prior to the use of osmotic diuresis, the presence of glucosuria following intravenous administration of glucose establishes that the renal threshold of glucose has been exceeded and that osmotic diuresis should occur. Note the rate of urine formation by the rapidity with which the bladder fills, or preferably, by the rate at which urine drips from a catheter. If a rate of urine formation of about l mi. per minute or more can be established, the procedure will usually be effective in reducing the severity of uremia. The rate of urine formation must be carefully evaluated because some patients may be oliguric or anuric. lf an adequate rate of urine formation cannot be established, infusion of dextrose mus't be stopped or serious hydremia, associated with pulmonary edema and death may result. Cats appear to be more susceptible to the development of pulmonary edema than dogs, and fluid administration should be discontinued if moist rales are detected. 6. Repeat the above steps as needed, examining the patient frequently and evaluating the clinical response carefully. Blood urea nitrogen or creatinine concentrations should be determined frequently as they provide a useful index with which to evaluate the effectiveness of therapy. The cat should be weighed frequently and accurately to monitor changes in weight. B complex vitamins should be added to the infusions. Low doses of promazine may be used if the patient is restless.

When severe acidosis occurs, three parts lactated Ringer's solution should be mixed with one part .17 Molar sodium lactate for rehydration. The evaluation of blood pH and plasma bicarbonate concentrations is desirable if testing facilities are available. If extensive osmotic diuresis is required, potassium depletion may become a problem, and is usually characterized by the sudden onset of

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marked muscular weakness. Monitoring an electrocardiogram or measuring serum potassium concentration is valuable. When the uremic crisis subsides, oral therapy should be substituted.

Peritoneal Dialysis If osmotic diuresis is ineffective in reestablishing the unne flow, peritoneal dialysis should be considered. The procedure is as follows: l. Prepare an area over the midabdomen as for surgery. 2. Anesthetize a small area just posterior to the umbilicus with a local anesthetic. 3. Make a small incision into the peritoneal cavity and introduce a sterile plastic <;atheter with multiple openings. Suture the catheter in place. 4. Administer enough peritoneal dialysis solution (Inpersol* 1.5 per cent) through the catheter to cause mild distention of the abdomen. 5. After 30 minutes to one hour, remove the fluid from the peritoneal cavity by siphoning the fluid back into the original container which is placed below the body of the patient. 6. Repeat the procedure as often as is indicated by the response of the patient and by repeated BUN determinations. 7. Though other alternatives are rarely available the procedure should be used with caution following recent abdominal surgery or in the presence of peritonitis. Limited clinical experience with the latter circumstance reveals that the risk of complications is not great. 8. When the uremic crisis subsides, the oral therapeutic regimen should be instituted. Cats with acute renal failure can frequently be supported by conservative medical management until renal repair occurs. Because repair is often complete, a normal life expectancy is reestablished. In chronic progressive renal disease, conservative medical management does not affect the progression of renal disease per se, but does extend the period of time t.hat the patient can survive in comfort.

When available, specific treatments for various diseases of the kidneys are described with each disease.

GENERAL REFERENCES Clark, L., and Seawright, A. A.: Generalized amyloidosis in seven cats. Path. Vet., 6:117, 1969. Hull, Y. E., and MacGregor, W. W.: Relation of kidney weight to body weight in the cat. Anat. Rec., 69:319, 1937. Harrison,]. B., Sussman, H. H., and Pickering, D. E.: Fluid and electrolyte therapy in small animals. J.A.V.M.A., 137:637, 1960. Jonsson, L., and Rubarth, S.: Ethylene glycol poisoning in dogs and cats. Nord. Vet. Med., 19:265, 1967. Kilham, L., Margolis, G., and Colby, E. D.: Congenital infections of cats and ferrets by feline panleukopenia virus manifested by cerebellar hypoplasia. Lab. Invest., 17: 465, 1967. Kunkel, P. A.: The number and size of the glomeruli in the kidney of several mammals. Bull. Johns Hopkins Hosp., 47:285, l 930. Latimer, H. B.: Prenatal growth of the cat. VIII. The weights of the kidneys, bladder, gonads, and uterus with weights of adult organs. Growth, 3:89, l 939. *Abbott Laboratories, North Chicago, Illinois

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Lucke, V. M.: Renal disease in the domestic cat.]. Path. & Bact., 95:67, 1968. Lucke, V. M.: Diseases of the urinary system of the cat. Vet. Rec., 84:325, 1969. Oliver, J., MacDowell, M., and Tracy, A.: The pathogenesis of acute renal failure associated with traumatic and toxic injury. Renal ischemia, nephrotoxic damage, and the ischemuric episode.]. Clin. Invest., 30:1307, 1951. Osborne, C. A., et a!., Percutaneous renal biopsy in the dog and cal. J.A.V.M.A., !51: 1474, 1967. Osathanondh, V., and Potter, E. L.: Pathogenesis of polycystic kidneys. Arch. Path., 77:459, 1964. Potkay, S., and Garman, R.: Nephroblastoma in a cat. The effects of nephrectomy and occlusion of the caudal vena cava . .J. Sm. Anim. Pract., 10:345, 1969. Smith, C., and Freeman, B. L.: Distribution of lipids, lipase and alkaline phosphatase in the renal tubule of the cat. Proc. Soc. Exp. Bioi. Med., 86:475, 1954. Story, H. E.: A case of horseshoe kidney and associated vascular anomalies in the domestic cat. Anat. Rec., 86:307,1943. Ticer,]. W.: Capsulogenic renal cyst in a cat. J.A.V.M.A., 143:613, 1963. Worden, A. N., Waterhouse, C. E., and Shellwood, E. H. B.: Studies on the composition of normal cat urine. J. Sm. Anim. Pract., 1:11, 1960.