OVERVIEW OF THE
URINARY SYSTEM
Primary functions of the urinary system
1) Excretion of waste products of metabolism
2) maintenance of a constant extracellular environment through conservation and excretion of water and electrolytes
3) production of the hormone erythropoietin, which regulates hematopoiesis
4) production of the enzyme renin, which regulates blood pressure and sodium reabsorption
5) metabolism of vitamin D to its active form (1,25-dihydroxycholecalciferol).
Method of
Collection Advantages Disadvantages
Spontaneous micturition
No risk (eg, trauma, bacterial infection) to animal. Avoids iatrogenic hematuria.
May contain debris (eg, bacteria, exudate) from lower urinary and genital tract. If bacterial growth appears on urine culture, must differentiate between urethral contamination and urinary tract infection. Quantitative urine culture required.
Manual
compression of urinary bladder
Provides method to obtain urine sample when voluntary micturition has not occurred.
May induce trauma to urinary tract, resulting in hematuria. May be stressful for animal, especially if bladder is painful. If bacterial growth appears on urine culture, must differentiate between urethral contamination and urinary tract infection.
Quantitative urine culture required.
Catheterization Provides method to obtain urine sample when other methods of collection have failed.
Potential for trauma to urinary tract, especially urethra. More invasive than other methods; sedation may be required. Risk of introducing bladder infection. If bacterial growth appears on urine culture, must differentiate between urethral contamination and urinary tract infection. Quantitative urine culture required. Least desirable method of urine collection.
Cystocentesis Preferred method of collection for urine culture. Avoids
contamination of sample from lower urinary tract.
Potential risk of trauma if performed incorrectly or animal moves during procedure. Potential for iatrogenic hematuria. More invasive than spontaneous micturition. Potential for bacterial contamination of sample if needle penetrates colon during procedure.
Advantages and Disadvantages of Urine Collection Methods
COMPLETE
URINALYSIS PANEL
URINE CLARITY
In most animals, normal urine is clear to slightly cloudy Values Below Reference Range
In an animal that typically shows cloudy urine, a clear urine would suggest absence of crystalluria.
Values Above Reference Range
Excessively cloudy urine can be the result of high numbers of crystals, leukocytes, erythrocytes, bacteria, mucus, casts, lipids, or possibly sperm.
Other Laboratory Tests
Microscopic examination of the urine sediment is advised.
URINE SPECIFIC GRAVITY
• Specific gravity is a reflection of solute concentration.
• It should be determined by refractometry as dipsticks are inaccurate.
• Assuming normal hydration status and no treatments that alter water resorption by the kidneys, expected specific gravity results are:
Dogs: 1.015–1.045 Cats: 1.035–1.060
• The amount of other substances in urine should be interpreted in
consideration of the specific gravity
Values Below Reference Range
• Hyposthenuria indicates that the kidney can dilute the glomerular filtrate, but cannot concentrate it.
• Hyposthenuria can be indicated by:
• Lack of ADH (primary diabetes insipidus)
• Resistance to ADH (renal diabetes insipidus)
• Increased water consumption (primary polydipsia)
• Lack of medullary concentrating ability
• Isosthenuria indicates that the kidney can neither dilute nor concentrate the glomerular filtrate.
• Specific gravity above isosthenuria but below normal specific gravity reflects inadequate renal tubular function.
Related Findings
Low specific gravity can be caused by diuretics, glucocorticoids and fluid therapy.
It is important to check specific gravity before administration of any of these treatments.
Values Below Reference Range
Values Above Reference Range
• Elevated specific gravity must be interpreted in light of BUN, creatinine concentrations and hydration status.
• High specific gravity does not rule out the presence of diseases associated with PU/PD, such as:
Hepatic insufficiency
Hyperadrenocorticism
Hyperthyroidism
Related Findings
Very concentrated urine is often associated with dehydration
URINE PH
• Urine pH is a measure of the hydrogen ion concentration in urine.
• Urine pH is determined by the kidney's ability to regulate hydrogen ion and bicarbonate concentrations within the blood.
• In fresh urine samples from healthy dogs and cats, the pH range is 5.5–
8.5. This parameter is specific for the detection of hydronium ions, with the pH being the negative common logarithm of the hydronium ion concentration.
• The test pad contains the indicators methyl red, phenolphthalein and
bromthymol blue.
Values Below Reference Range
Respiratory acidosis
Metabolic acidosis
High protein diet
Vomiting with chloride depletion
Severe diarrhea
Fever
Starvation
Prolonged exercise
Urinary acidifiers
Recent meal
Metabolic alkalosis
Respiratory alkalosis
Bacterial infection
Renal tubular acidosis
Purely vegetable diet
Values Above Reference
Range
URINE LEUKOCYTES
• The reaction detects the presence of esterases that occur in granulocytes.
• The reaction is not affected by bacteria, trichomonads or erythrocytes present in the urine.
Formaldehyde (stabilizer) and medication with antibiotics containing imipenem, meropenem or clavulanic acid may cause false-positive reactions.
• If the urine specimen is strongly, the reaction color may be masked.
• Normal values are dependent on method of urine collection.
• Normal values are 0–8/hpf for voided sample, 0–5/hpf for catheterized sample and 0–3/hpf
for cystocentesis sample.
Values Below Reference Range
Normal: The normal range includes zero.
Artifact due to lysis: Alkaline urine, dilute urine or prolonged exposure to room temperature will cause WBC lysis.
Values Above Reference Range
• Urinary tract infection (kidney or urinary bladder)
• Patients with diabetes mellitus or hyperadrenocorticism may have urinary tract infections but not show pyuria.
• Genital tract contamination (voided or catheterized samples)
• Calculi
• Neoplasia
Related Findings
• Signs of urinary tract infection: Dysuria, pollakiuria, foul-smelling urine, hematuria
• Signs of pyelonephritis: Fever, depression, anorexia, polydipsia, polyuria
• Casts: WBC casts are almost pathognomonic for pyelonephritis.
Other Laboratory Tests
• Urine culture and sensitivity
• Radiographs, contrast studies and ultrasound
URINE PROTEIN
• Trace amounts of protein (50 mg/dL or less) can normally be found in urine.
• This test is based on the principle that proteins bind to an acid-base indicator dye. The test is particularly sensitive to albumin, but may react with hemoglobin and globulins.
Values Below Reference Range
Values below reference range are not clinically significant.
Inflammation
• Involvement of upper or lower urinary tract
• Reflected in an active urinary sediment (leukocytes, possibly bacteria)
Hemorrhage
• Positive for urine occult blood and possibility of sediment with
erythrocytes
Renal glomerular disease
• Glomerulonephritis
• Amyloidosis
Prerenal
• Occasional mild proteinuria may be secondary to increased glomerular permeability (shock, heart disease, fever, CNS disease, increased physical exercise).
• Overflow proteinuria [high concentrations of low molecular weight proteins (myoglobin, Bence Jones protein)] in the peripheral blood that can be filtered and fail to be resorbed totally by the tubules.
Values Above Reference Range
Related Findings
Urine specific gravity must be taken into account when interpreting proteinuria.
Other Laboratory Tests
• Urine protein:urine creatinine ratio is used to determine if proteinuria is significant.
• Urine protein:urine creatinine ratio can replace the 24 hour urine
collection.
URINE GLUCOSE
• Glucose is not normally found in the urine of dogs and cats.
• The glucose present in the glomerular filtrate is almost completely reabsorbed in the proximal tubules.
• The determination of glucose is based on the specific glucose-oxidase/peroxidase reaction. This test is independent of pH and specific gravity of the urine and is not affected by the presence of ketone bodies. The effect of ascorbic acid has been largely eliminated, such that false negatives are unlikely to occur at glucose concentrations of 100 mg/dL (5.5 mmol/L) and above.
Values Below Reference Range
Not applicable. Glucose is not present normally in urine.
Values Above Reference Range
• Glucosuria occurs when blood glucose exceeds the renal threshold.
• Stress or excitement (cats)
• Diabetes mellitus
• Infusion of fluid rich in dextrose
• Occasionally in hyperadrenocorticism, pheochromocytoma
• Renal threshold is reached in dogs when blood glucose is >180 mg/dL and in cats when blood glucose is >300 mg/dL.
• Glucosuria also occurs when there is abnormal proximal tubular function.
• Fanconi’s syndrome
• Acute renal failure
• Primary glucosuria
• Secondary to aminoglycoside toxicity
• Rarely in familial renal disease
URINE KETONES
• Ketones, such as beta-hydroxybutyrate, acetoacetate and acetone, are produced by lipolysis and are filtered by the glomerulus.
• Normally, ketones are completely resorbed by the proximal tubules.
• This test is based on the reaction of nitroprusside with acetoacetic acid and acetone. This test does not detect beta- hydroxybutyric acid. Captopril, mesna (2-mercaptoethanesulfonic acid sodium salt) and other substances containing sulfhydryl groups may produce false-positive results.
Values Below Reference Range
Urine should be negative for ketones
Values Above Reference Range
Diabetic ketoacidosis
Prolonged fasting
Starvation
Low carbohydrate diet
Glycogen storage disease
Persistent fever
Persistent hypoglycemia
URINE UROBILINOGEN
• Intestinal bacteria convert conjugated bilirubin to urobilinogen.
• Most is excreted in the feces. A small amount is delivered back to the liver via the portal system where the urobilinogen is then removed by the liver or excreted into the urine.
• A fresh sample is necessary as urobilinogen can be catabolized into urobilin while standing within the bladder. Nomal values are 0.1–1.0 Ehrlich units. The correlation between elevated urine urobilinogen and liver disease in animals is poor.
• Expected results range between 0.2–1.0 mg/dL or normal to 1.0 mg/dL on
urine strips.
Values Below Reference Range
Reagent strips are semiquantitative but cannot detect the absence of urobilinogen.
Urobilinogen is unstable while in the bladder; many normal animals have no detectable urobilinogen.
True absence of urobilinogen would indicate an obstructed bile duct.
Values Above Reference Range
Hemolytic disease
Liver disease
There is a poor correlation between high urine urobilinogen and liver disease
in animals.
URINE BILIRUBIN
•Conjugated bilirubin will readily travel through the glomerulus into the filtrate. It is not absorbed by the tubules, and therefore it passes into the urine.
•Unconjugated bilirubin is bound to albumin and will not pass through the glomerulus.
•Dogs have a low renal threshold for bilirubin; trace amounts may be found in very concentrated urine, especially in male dogs.
•Bilirubin in urine is ultraviolet-light sensitive and delay in performing urinalysis may cause false-negative results.
Standing at room temperature exposed to air can also cause a false-negative result.
•The test for bilirubin is based on the coupling of bilirubin with a diazonium salt to produce a color change. Even the slightest pink coloration constitutes a positive result. Large quantities of ascorbic acid can lead to low or false-
negative results for bilirubin.
•Urine discoloration may interfere with an accurate reading of the test strip.
•Expected bilirubin results in dogs can be negative to 1+, with trace and 1+ reactions found in more concentrated samples.
Values Below Reference Range
Not applicable. Zero bilirubin in urine is clinically not significant.
Values Above Reference Range
In dogs (especially male dogs), trace amounts of bilirubin may be seen in very concentrated urine.
Any bilirubinuria in cats is significant.
Bilirubinuria usually precedes bilirubinemia.
o May be present when serum bilirubin concentration is within normal limits.
Intrahepatic or extrahepatic biliary obstruction with subsequent regurgitation of conjugated bilirubin into the blood.
Intravascular hemolysis and hemoglobinuria
o Conjugated bilirubin is increased and readily passes into glomerular filtrate.
o Renal tubular cells can form conjugated bilirubin from absorbed hemoglobin.
o Fever or starvation
Related Findings
Elevated liver enzymes and increased serum bilirubin supports hepatic disease, while regenerative anemia with spherocytes supports hemolytic disease.
Other Laboratory Tests
• If bilirubinuria is evident, follow-up tests include serum bilirubin, alanine aminotransferase (ALT), alkaline phosphatase, and CBC.
• If CBC indicates anemia, reticulocyte count is indicated.
UROLITHIASIS IN SMALL ANIMALS
Some mineral solutes precipitate to form crystals in urine; these crystals may aggregate and grow to macroscopic size, at which time they are known as uroliths (calculi or stones)
Urolithiasis is a general term referring to stones located anywhere within the urinary tract
Kidney NEPHROLITHS
Ureter URETEROLITHS
Bladder UROCYSTOLITHS
Urethra URETHROLITHS
Mineral Name Chemical Formula Chemical Name
Struvite MgNH
4PO
4• 6H
20 Magnesium ammonium phosphate hexahydrate
Whewellite CaC
2O
4• H
20 Calcium oxalate monohydrate Weddellite CaC
2O
4• 2H
20 Calcium oxalate dihydrate
Hydroxyapatite Ca
10(PO
4)
6(OH)
2Calcium phosphate (hydroxyl form)
Urate C
5H
4N
4O
3Urate
Ammonium urate
NH
4• C
5H
4N
4O
3Ammonium urate Sodium urate Na • C
5H
4N
4O
3×
H
2O
Sodium urate monohydrate Cystine (SCH
2CHNH
2COOH)
2Cystine
Silica SiO
2Silica
Xanthine C
5H
4N
4O
2Xanthine
Mechanisms involved in stone formation are incompletely understood in dogs and cats.
oUrinary Tract Infection oDiet
oIntestinal Absorption oUrine Volume
oFrequency Of Urination oTherapeutic Agents
oGenetics
SIGNS
oClinical signs associated with urolithiasis are seldom caused by microscopic crystals.
oMacroscopic uroliths in the lower urinary tract that interfere with the flow of urine and/or irritate the mucosal surface often results in dysuria, hematuria, and stranguria
oNephroliths often are asymptomatic unless pyelonephritis exists concurrently or they pass into the ureter.
oUreteral obstruction may produce signs of vomiting, lethargy, and/or flank and
renal pain
DIAGNOSIS
•Abdominal palpation
•Rectal palpation or located by passing a catheter
•Radiodense calculi >3 mm in diameter are usually visible on radiographs
•Urate, and occasionally cystine, uroliths may be radiolucent, requiring contrast radiography or ultrasonography to confirm their presence
•Dentification of crystals on microscopic examination of fresh, warm urine and bacterial culture and sensitivity testing
• Ultrasonography and cystoscopy may also be useful.
URETHRAL OBSTRUCTION
•Urethral obstruction is common in male dogs and cats
•It may occur suddenly or may develop throughout days or weeks
•Initially, the animal may frequently attempt to urinate and produce only a fine stream, a few drops, or nothing
•Complete obstruction causes uremia within 36–48 hr, which leads to depression, anorexia, vomiting, diarrhea, dehydration, coma, and death within ~72 hr.
•Urethral obstruction is an emergency condition, and treatment should begin
immediately.
URETHRAL OBSTRUCTION
•If the bladder is intact, it is distended, hard, and painful; care should be used when palpating the bladder to avoid iatrogenic rupture. If the bladder has ruptured, it cannot be palpated and urine can sometimes, but not always, be obtained from the abdominal cavity by paracentesis.
•Hyperkalemia and metabolic acidosis are life-threatening complications of urethral obstruction. An ECG (to record cardiac rhythm and rate) and a serum potassium are indicated.
•Initial emergency care involves immediate relief of obstruction by
catheterization and fluid therapy with normal saline.
CANINE UROLITHIASIS
Struvite Stones (MgNH4PO4 · 6H2O)
• The most common urinary stones in dogs are composed
• In most cases, struvite uroliths form in association with urinary tract infections with urease- producing Staphylococcus or Proteus spp. Although they are frequent in cats, sterile struvite uroliths rarely form in dogs. of struvite
• The choice among surgery, lithotripsy, and medical treatment may not be easy. Owner compliance, the animal’s acceptance of the diet, availability of lithotripsy, practice philosophy, and knowledge of the indications and contraindications are necessary to make a decision.
• Medical management involves dissolution and prevention of stone formation
Dissolution Protocol:
• Reduce urine pH to <6 [dietary maneuvers ]
• Dogs fed these rations generally have reduced intake of protein, phosphate, and magnesium and a high intake of sodium
• Urease-producing urinary tract infections must be treated. The choice of antibacterial should be based on sensitivity testing
• Urease inhibitor such as acetohydroxamic acid enhances the rate of struvite stone dissolution (12.5 mg/kg, PO, bid)
• After ~4 wk of treatment, a physical examination, serum chemistry profile, urinalysis, and
abdominal radiographs or ultrasonography should be repeated. The stone dissolution protocol
should be discontinued if severe adverse effects develop, although a mild degree of
hypoalbuminemia is to be expected and can be tolerated. With good compliance, the following
results can be anticipated: urine pH <6.5, urine specific gravity <1.025, serum urea <10
mg/dL.
Calcium Oxalate Stones
Hypercalciuria leading to calcium oxalate stone formation can result from increased renal clearance of calcium due to excessive intestinal absorption of calcium (absorptive hypercalciuria), impaired renal conservation of calcium (renal leak hypercalciuria), or excessive skeletal mobilization of calcium (resorptive hypercalciuria)
Routine laboratory determinations should include serum calcium, phosphate, total CO
2, and chloride to eliminate the possibility of hyperparathyroidism and renal tubular acidosis.
Dissolution of calcium oxalate stones by medical means has not currently been established.
Treatment requires surgical removal or lithotripsy followed by preventive strategies.
Prevention Protocol
Recurrence is a major problem with calcium oxalate uroliths. An “ideal” diet is considered to be low oxalate, low protein, and low sodium and would maintain urine pH at 6.5–7.5 and urine specific gravity <1.020
A few commercially available canned foods achieve these goals and may minimize the risk
of recurrence. Potassium citrate may be added as needed to assure the urine pH is within
the desired range
Urate Stones
Ammonium urate stones are most common in Dalmatians and in dogs with congenital portosystemic vascular shunts
Dalmatians do not convert most of their metabolic urate to allantoin and thus excrete the bulk of nucleic acid metabolites as relatively insoluble urate.
Dissolution Protocol:
Urine alkalinization minimizes renal ammonia production; the goal is to achieve a urine pH >7.
If required, urine alkalinization can be achieved by administering NaHCO3, 1 g (¼ tsp)/5 kg, PO, tid, with food.
Potassium citrate, administered to effect (25–50 mg/kg/day) is an alternative, more palatable alkalinizing agent.
Reduce urinary urate output
a low-purine, low-protein commercial diet
xanthine oxidase inhibitor allopurinol (15 mg/kg, PO, bid)
Urine volume should be increased to reduce the concentration of all dissolved solutes in urine. This can be
achieved by feeding canned diets restricted in protein. Adding salt, 1 g (¼ tsp)/5 kg, daily to the diet, or mixing water with the food are additional methods
FELINE LOWER URINARY TRACT DISEASE (FELINE UROLOGIC SYNDROME)
• Hematuria, pollakiuria, and stranguria are the characteristic clinical signs of feline lower urinary tract disease (FLUTD) in cats.
• the specific underlying cause of this common syndrome is often not identified
• Associated conditions include
• Urinary tract infection
• Neoplasia
• Trauma
• Urethral plugs
• Urolithiasis
• Sterile cystitis (feline interstitial cystitis)
STERILE CYSTITIS (FELINE INTERSTITIAL CYSTITIS
•
Feline interstitial cystitis is generally taken to be synonymous with sterile cystitis of unknown cause.
•
The underlying cause of this disorder is unknown, although anxiety and altered neurohormonal factors have been implicated.
•Diagnosis is by exclusion of other causes of lower urinary tract disease in cats, such as obstruction by
urethral plugs, bacterial urinary tract infection, neoplasia or other mass lesions, and urolithiasis.
•Diagnostic tests to exclude these conditions may include radiographs, ultrasonography, urinalysis, urine
culture, and cystoscopy.
•Therapeutic considerations include reduction of stress through environmental changes, dietary
adjustments (eg, use of canned preparations), pheromones applied topically in the environment, and
analgesics (eg, butorphanol, 0.2–0.4 mg/kg, PO, bid-tid). Other medications (eg, amitriptyline, 5–12.5
mg/cat, PO, once or twice daily; clomipramine, 0.5 mg/kg/day, PO; fluoxetine, 1 mg/kg/day, PO) have
yielded mixed results
RENAL DYSFUNCTION
IN SMALL ANIMALS
• Failure of the filtration function of the kidneys leads to the development of azotemia (an excess of nitrogenous compounds in the blood), which may be classified as prerenal, renal, postrenal, or of mixed origin.
• Prerenal azotemia develops whenever mean systemic arterial blood pressure declines to values <60 mmHg and/or when dehydration causes plasma protein concentration to increase.
• Dehydration, congestive heart failure, and shock.
• Renal azotemia refers to a reduction in glomerular filtration rate (GFR) of ~75% during acute or chronic primary renal (or intrarenal) diseases.
• Postrenal azotemia develops when the integrity of the urinary tract
is disrupted (eg, bladder rupture) or urine outflow is obstructed (eg,
urethral or bilateral ureteral obstruction). Once adequate urine flow
is restored, postrenal azotemia will resolve.
CHRONIC KIDNEY DISEASE
Chronic kidney disease (CKD) involves a loss of functional renal tissue due to a prolonged (≥2 mo), usually progressive, process.
Stagea 1 2 3 4
Nonazotemic Kidney
Disease Mild Renal
Azotemia Moderate Renal
Azotemia Severe Renal Azotemia
Stagea 1 2 3 4
Nonazotemic Kidney Disease
Mild Renal Azotemia
Moderate Renal Azotemia
Severe Renal Azotemia
Creatinine (mg/dL)
Dogs <1.4 1.4–2.0 2.1–5.0 >5.0
Cats <1.6 1.6–2.8 2.9–5.0 >5.0
Classification of Stages of Kidney Disease
Substaging Based On Blood Pressure:
Sytemic hypertension is present in ~20% of dogs and cats with CKD and is associated with target organ damage in the kidneys, eyes, CNS, and cardiovascular system. it is recommended that animals with CKD be substaged on the basis of blood pressure measurements
Substagea AP0 AP1 AP2 AP3
No or minimal risk Low risk Moderate risk High risk
Substagea AP0 AP1 AP2 AP3
No or minimal risk Low risk Moderate risk High risk Blood pressure (mmHg)
Systolic <150 150–159 160–179 >180
Diastolic <95 95–99 100–119 >120
In general, animals in substage AP3 and those in substage AP2 with preexisting target organ
damage (eg, retinal injury or CKD) should be considered candidates for antihypertensive therapy.
Substaging Based On Proteinuria:
Substagea N BP P
Nonproteinuric Borderline Proteinuric
Substagea N BP P
Nonproteinuric Borderline Proteinuric
Dogs <0.2b 0.2–0.5 >0.5
Cats <0.2 0.2–0.4 >0.4
Proteinuria is an important finding and is associated with a poor prognosis in aged
animals and in those with CKD. Changes in the magnitude of proteinuria represent a
good marker for the efficacy of antihypertensive therapy. Animals with CKD should also
be substaged on the basis of proteinuria (see Table: Substages of Chronic Kidney
Disease Based on Proteinuria), using the protein:creatinine ratio.
ETIOLOGY
macrovascular compartment
• Systemic hypertension
• Coagulopathies
• Chronic hypoperfusion
microvascular compartment
• Systemic and glomerular hypertension
• Glomerulonephritis
• Developmental disorders
• Congenital collagen defects
• Amyloidosis
interstitial compartment
• Pyelonephritis
• Neoplasia
• Obstructive uropathy
• Allergic and immune-mediated nephritis
tubular compartment
• Tubular reabsorptive defects
• Chronic low-grade nephrotoxicity
• Obstructive uropathy
Clinical Findings
•No clinical signs are seen as a direct result of disease until ≥75% of nephron function has been impaired (Stages 3 and 4)
• Polydipsia and polyuria (late Stage 2 or early Stage 3)
• Azotemia
• Uremic syndrome in Stage 4
• Anorexia, weight loss, dehydration, oral ulceration, vomiting, and diarrhea
• Loose teeth, deformable maxilla and mandible, or pathologic fractures may be seen with renal secondary osteodystrophy (Renal Secondary Hyperparathyroidism)
• Nonregenerative, normocytic, normochromic anemia.
Diagnosis
• In Stages 1 and 2, diagnosis is often missed or made incidentally during imaging studies or urinalyses conducted for other purposes.
• In Stages 3 and 4, the BUN, serum creatinine, and inorganic phosphorus concentrations are increased
• Potassium depletion, due to renal potassium wasting combined with inadequate intake and the kaliuretic effects of acidosis, is frequently seen in cats and occasionally in dogs
• Hyperkalemia associated with oliguria and anuria may be noted in terminal
Stage 4
Treatment
• Recommended treatment varies with the stage of the disease
• identify and treat the primary cause of the disease should be thorough
• The identification and supportive treatment of developing complications
• Systemic hypertension
• Potassium homeostasis disorders
• Metabolic acidosis
• Bacterial urinary tract infection
Antihypertensive medications (AP2 and AP3)
Calcium-channel blocker:amlodipine besylate (0.25–0.5 mg/kg/day, PO)
Angiotensin-converting enzyme (ACE) inhibitor: enalapril or benazepril (0.5 mg/kg, once daily in cats and bid in dogs)
Angiotensin-receptor blocker (ARB): telmisartan (1 mg/kg, once daily in cats and bid in dogs)
If an ACE inhibitor is used in conjunction with a renal diet, potassium should be carefully monitored. Hyperkalemia may develop, particularly in Stage 4, and dietary change or dosage adjustment should be considered if serum potassium exceeds 6.5 mEq/L
While ACE inhibitors (or ARBs) and calcium-channel blockers may be administered
together, a calcium-channel blocker is usually recommended as initial therapy in cats
and an ACE inhibitor (or ARB) in dogs.
•
Dietary restriction of phosphate and acid load
•
specialized diets for management of kidney disease should be fed.
•
Potassium citrate or sodium bicarbonate, given PO, may be indicated if the animal is severely acidotic (plasma bicarbonate <15 mEq/L) or remains acidotic 2–3 wk after diet change.
•
phosphate-binding gels containing calcium acetate, calcium carbonate, calcium carbonate plus chitosan, lanthanum carbonate, or aluminum hydroxide
•
Dietary restriction of protein may relieve some of the signs of uremia. High-quality protein (eg, egg protein) should be fed at a level of 2–2.8 g/kg/day for dogs and 2.8–3.8 g/kg/day for cats.
•
proton pump inhibitor such as omeprazole (0.5–1 mg/kg/day, PO) or an H2-receptor antagonist such as famotidine (5 mg/kg, PO, tid-qid) decreases gastric acidity and vomiting.
Anabolic steroids, such as oxymethalone or nandrolone, have been administered to stimulate
RBC production in anemic animals, but this is not effective.
• Erythropoietin and other erythropoiesis-stimulating agents (eg, darbopoietin, continuous erythropoietin receptor activator) may stimulate RBC production, but antierythropoietin antibodies develop in ~50% of animals treated with the human recombinant erythropoietin, epoetin alfa, and may result in refractory anemia
• Fluid therapy with polyionic solutions, given IV or SC in the hospital or SC by owners at home, is often beneficial in animals with intermittent signs of uremia
• Oral vitamin D administration may reduce uremic signs and prolong survival, particularly
in dogs. However, vitamin D administration requires prior resolution of
hyperphosphatemia (goal is serum phosphorus <6 mg/dL), and it may induce
hypercalcemia.
ACUTE KIDNEY INJURY(ACUTE RENAL FAILURE)
Causes
• Toxins (eg, ethylene glycol, aminoglycoside antibiotics, hypercalcemia, hemoglobinuria, melamine-cyanuric acid, grapes or raisins, NSAIDs)
• Ischemia (eg, embolic showers from disseminated intravascular coagulation or severe prolonged hypoperfusion)
• Infection (eg, leptospirosis, borreliosis).
Clinical Findings
• Mild AKI often goes unrecognized; severe initial or repeated bouts may lead to CKD.
• AKI is recognized in advanced stages and is characterized clinically by anorexia, depression, dehydration, oral ulceration, vomiting and/or diarrhea, or oliguria.
• Physical examination findings often reveal dehydration but otherwise are usually
not remarkable, although pain is occasionally elicited on palpation of the kidneys,
which may be normal in size to slightly enlarged.
DIAGNOSIS
•
History of hypotension, shock, or recent exposure to known nephrotoxins
•
Poorly concentrated urine (specific gravity 1.007–1.030) despite dehydration and/or azotemia suggests renal dysfunction.
•Differentiating between chronic and acute kidney disease (and establishing a specific cause in acute kidney
disease) is important, because the prognosis and specific therapy may differ
•
marked cylindruria, a large number of renal epithelial cells and leukocytes in the urine sediment, glucosuria, crystalluria, enzymuria, and/or myoglobinuria/hemoglobinuria.
•increased serum urea nitrogen, creatinine, and inorganic phosphorus concentrations and
metabolic acidosis.
•
Oliguria or anuria after rehydration, which is often associated with hyperkalemia, is a poor prognostic sign;
in contrast, polyuric animals have a better prognosis although they may become hypokalemic
Treatment
• Fluid therapy is indicated for all dehydrated and inappetant animals.
• A polyionic fluid such as lactated Ringer’s solution is satisfactory unless hyperkalemia is present, in which case normal saline is recommended.
• Sodium bicarbonate may be cautiously added to the fluids to correct acidosis
• In oliguric or anuric animals, therapy to promote increased urine volume is often recommended if the animal is well hydrated and urine production is <0.5 mL/kg/hr.
• Administration of excess fluid to an animal in the maintenance phase of oliguric
renal failure may result in life-threatening pulmonary and cerebral edema
• Overhydration by administration of a test dosage of polyionic solution IV at 50 mL/kg
• If this fails to yield adequate urine flow within 3 hr, further measures include osmotic diuresis (10% or 20% mannitol or dextrose, 0.5–1 g/kg, IV, as a slow bolus throughout 15– 30 min, alternated with infusion of lactated Ringer’s solution, 30 mL/kg, IV, throughout 30 min).
• Subsequent measures generally include furosemide (2 mg/kg, IV, which can be doubled and then tripled at 2-hr intervals if urine production does not increase above the target of 0.5 mL/kg/hr However, furosemide may worsen the severity of AKI caused by aminoglycosides.
• Finally, renal vasodilators (dopamine diluted in 5% dextrose, IV, to provide 1–5 mcg/kg/min) plus furosemide (2 mg/kg, IV) may be tried for 2 hr. Dopamine may lead to ventricular
arrhythmias, and high doses of dopamine may cause renal
vasoconstriction. Dopamine produces minimal renal vasodilation in cats and calcium channel
blockade (eg, amlodipine besylate, 0.25–0.5 mg/kg, or diltiazem, 1–3 mg/kg) may be
preferred.
• If attempts to restore urine flow fail, aggressive measures should be discontinued to avoid overhydration. Daily fluid therapy based on maintenance and rehydration needs is continued until renal function and clinical condition improve.
• Feeding tube placement greatly facilitates patient management at this stage and should be implemented for any animal with marked renal azotemia (serum creatinine >10 mg/dL after rehydration).
• A second therapeutic option, rather than the aggressive measures discussed above, is to proceed directly to fluid therapy with polyionic solutions while waiting for renal regeneration.
• Again, feeding tube placement for parenteral nutrition should be implemented in
anorectic animals with marked azotemia. Peritoneal dialysis or hemodialysis may
be necessary if none of the above measures restores urine productio
GLOMERULAR DISEASE IN SMALL ANIMALS
• Glomerular disease is a well-recognized cause of chronic kidney disease (CKD) in dogs, may produce acute kidney injury in dogs, and is also occasionally seen in cats with CKD
• Animals with primary glomerular disease as a cause of CKD may have
somewhat different clinical and laboratory abnormalities than those with
primary tubulointerstitial disease.
Glomerular Diseases In Dogs And Cats
Amyloidosis
Glomerulonephritis
Crescentic (rare)
Membranoproliferative (mesangiocapillary)
Membranous*
Proliferative (mesangial and endocapillary)
Immunoglobulin A nephropathy
Glomerulosclerosis
Focal and segmental glomerulosclerosis Global glomerulosclerosis
Familial glomerulopathies Hereditary nephritis Lupus nephritis
Minimal change glomerulopathy
*Membranous nephropathy is the most common
glomerular disease in cats; other forms appear to
be less common.
• Many of the glomerular diseases that occur in dogs and cats are believed to develop secondary to sys- temic disease processes, specifically neoplastic, infectious, or noninfectious inflammatory (NIN) disorders
• A NIN disorder may not be obvious at first presentation because it is either
resolved or it is occult
NIN DISORDERS REPORTED IN ASSOCIATION WITH GLOMERULAR DISEASES IN DOGS AND CATS
Dogs Leukemia
Lymphosarcoma Mastocytosis
Primary erythrocytosis Systemic histiocytosis Other neoplasms
Cats
Leukemia
Lymphosarcoma Mastocytosis
Other neoplasms NEOPLASTİC
Dogs
Borreliosis Bartonellosis Brucellosis Endocarditis Pyelonephritis Pyometra
Pyoderma
Other chronic
bacterial infections
Cats
Leukemia
Lymphosarcoma Mastocytosis
Other neoplasms
INFECTIOUS BACTERİAL
NIN DISORDERS REPORTED IN ASSOCIATION WITH GLOMERULAR DISEASES IN DOGS AND CATS
Dogs
Babesiosis
Hepatozoonosis Leishmaniasis Trypanosomiasis
PROTOZOAL
Dogs
Ehrlichiosis
Canine adenovirus type
Dirofilariasis Blastomycosis Coccidiomycosis
Cats Viral
Feline immunodeficiency virüs Feline infectious peritonitis Feline leukemia virus
Parasitic
Dirofilariasis (?
Fungal
RİCKETTSİAL
NIN DISORDERS REPORTED IN ASSOCIATION WITH GLOMERULAR DISEASES IN DOGS AND CATS
Dogs Chronic
dermatitis
Inflammatory bowel disease Pancreatitis Periodontal disease
Polyarthritis
Cats
Pancreatitis
Cholangiohepatitis Chronic
progressive polyarthritis
Systemic lupus erythematosus Other immune-
mediated diseases Non-infectious Inflammatory
Dogs
Corticosteroid excess
Trimethoprim- sulfa
Hyperlipidemia Chronic insulin infusion
Congenital C3 deficiency Cyclic hematopoiesis in grey collies
Over-vaccination Idiopathic
Cats
Acromegaly (?) Mercury toxicity Idiopathic
Miscellaneous
Clinical Findings
Proteinuria
Hypoproteinemia, ascites, dyspnea (due to pleural effusion or pulmonary edema), and/or peripheral edema,
Result in loss of antithrombin III through the glomerular basement membrane, leading to a hypercoagulable state in dogs
Mild thrombocytosis and platelet hypersensitivity, which contribute to coagulation abnormalities in affected dogs, generally when plasma albumin levels are ≤1 g/dL
Severe dyspnea secondary to pulmonary thromboembolism or other sequelae of thrombotic disease
Diagnosis
• BUN, creatinine, and phosphorus concentrations are usually increased
•Proteinuria
• Ascites, pleural effusion, and/or peripheral, pitting, nonpainful, subcutaneous edemea
• Protein:creatinine ratio >2 suggests a glomerular origin
•Renal imaging findings in dogs with glomerular diseases are relatively nonspecific
• Renal biopsy provides a definitive diagnosis of glomerular disease
• Dogs and cats with proteinuria should be thoroughly evaluated for underlying NIN
disorders
Nonspecific Medical Management Of Glomerular Disease
1) Treatment of NIN disorders 2) Management of proteinuria
3) Management of uremia and other complications of glomerular
disease and CKD.
Management Of Proteinura
The renin-angiotensin-aldosterone system (RAAS) has been the major target system for this approach to reducing proteinuria
ACEi may reduce proteinuria and preserve renal function by several possible mechanisms in addition to decreased
efferent glomerular arteriolar resistanceleading to
decreased (normalized) glomerular transcapillary hydraulic pressure.Reduced loss of glomerular heparan sulfate, decreased size of the glomerular capillary endothelial pores, improved lipoprotein metabolism, slowed glomerular mesangial growth and proliferation, and inhibition of bradykinin degradation.
Although the serum creatinine concentration should be monitored, it seems to be
uncommon for dogs and cats to have severe worsening of azotemia due to ACEi
administration alone.
• Serum aldosterone increases over time (i.e., aldosterone escape) in people treated even with maximal doses of ACEi and ARB. Prolonged hyperaldosteronism may have adverse effects on the heart, systemic blood vessels, and glomeruli.
•Aldosterone-receptor antagonists have been shown to reduce proteinuria and stabilize kidney function in an additive fash- ion to ACEi and ARB in people.
Spironolactone has been used most commonly in veterinary medicine; however, there are little published data supporting efficacy of this drug in dogs and cats.
This drug would be most likely to be effective in animals that have high serum
aldosterone concentrations and persistent proteinuria despite treatment with an
ACEi, ARB, or both.
Hyperkalemia appears to be a common side effect of RAAS
inhibition in dogs with renal disease. Pseudohyperkalemia due to
thrombocytosis, which is common in dogs with glomerular disease,
should be eliminated as a cause before modifying therapy. True
hyperkalemia can be managed by reducing the dosage of ACEi,
ARB, or spironolactone, by feeding diets that are reduced in
potassium, or by administering a potassium binder
Platelets and thromboxane may play an important role in the pathogenesis of glomerulonephritis. Thromboxane is an inducer of platelet aggregation and a chemotactic factor for neutrophils. Neutrophils induce damage to the GBM through release of proteolytic enzymes
Aspirin is a nonspecific cyclooxygenase inhibitor that may be used to reduce
glomerular inflammation and inhibit platelet aggregation, which may have an
added benefit of preventing thromboembolism
• Feeding a diet formulated for renal failure has several potentially beneficial effects in dogs with glomerular disease. In most cases, diets should not be supplemented with protein, because this has the potential to aggravate urinary protein losses.
• The enhanced omega-3 to omega-6 polyunsaturated fatty acid ratio and restriction in salt and phosphorus found in canine renal diets can also be of benefit to dogs with glomerulopathies.
• Plasma volume is often reduced in animals with hypoalbuminemia and edema, the
use of diuretics should be avoided unless these drugs are needed to control
respiratory distress.
Management Of Uremia And Other Complications Of Glomerular Disease and CKD
Advanced azotemia resulting from either severe glomerular lesions or generalized renal disease may eventually develop in dogs with glomerular disease.
Uremia: anorexia, oral ulcerations, vomiting, diarrhea, metabolic acidosis, anemia, and volume depletion.
Each of these needs to be managed as individual problems as the need arises in a similar fashion to other dogs with CKD.
Fluid therapy in the patient with nephrotic syndrome can present a particular challenge
because of reduced plasma oncotic pressure and the tendency for fluid to move into the
interstitial spaces
• Thromboembolism and fluid retention are complications of glomerular disease more frequently found in dogs with nephrotic syndrome.
• Inhibitors of platelet aggregation (i.e., aspirin, clopidogrel) are generally recommended for the prevention and treatment of thromboembolism in dogs with glomerular disease.
• Preventative therapy is generally instituted when serum albumin concentrations are
less than 2.0 to 2.5 mg/dL, because dogs with serum albumin concentrations below
this range appear to be at higher risk for thromboembolic disease.
Nephrotic Syndrome (NS)
• Nephrotic syndrome (NS), defined as the concurrent presence of hypoalbuminemia, proteinuria, hyperlipidemia, and fluid accumulation in interstitial spaces and/or body cavities, is a rare complication of glomerular disease in dogs, cats, and people.
• Hypoalbuminemia develops when the rate of urinary protein loss is greater than that of de novo hepatic albumin synthesis.
• Hypercholesterolemia may develop secondary to a nonspecific upregulation of hepatic biosynthesis induced by hypoalbuminemia or as a compensatory mechanism for low plasma oncotic pressure or changes in plasma viscosity
• Extravascular accumulation of fluid associated with NS may occur in any body cavity or
throughout the interstitium
The resultant hypovolemia and hypotension should stimulate renin-
angiotensin-aldo- sterone system (RAAS) activation to increase
distal nephron sodium reabsorption and water retention
RENAL TUBULAR DEFECTS IN
SMALL ANIMALS
Renal Acidosis
•The form of metabolic acidosis that occurs in acute kidney injury and Stages 2–4 of chronic kidney disease, referred to as uremic acidosis, is due to reduced urine-acidifying ability of diseased kidneys
•Renal tubular defects in dogs and cats may result in hyperchloremic metabolic acidosis, referred to as renal tubular acidosis. Two types of renal tubular acidosis have been described in dogs and one in cats.
•In Type I (distal), the ability of the distal tubule to secrete hydrogen ions against a concentration gradient is defective;
•In Type II (proximal), the ability to reabsorb bicarbonate in the proximal tubule is reduced.
•Type I has been reported in both species; Type II has also been described in dogs in conjunction with other proximal tubular defects in acquired (gentamicin nephrotoxicosis and an idiopathic form) and heritable (Fanconi syndrome, see Fanconi Syndrome) forms.
