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Basics ⬇

Outline

BASICS

Definition!!navigator!!

  • Azotemia—the accumulation of nitrogenous waste (e.g. urea, Cr, other nitrogenous substance) in blood, plasma, or serum.
  • Uremia—the clinical manifestation of azotemia; a multisystem disorder resulting from the effects of uremic toxins on cellular metabolism and function. Cr and BUN typically are measured in serum and used as indices of azotemia

Pathophysiology!!navigator!!

  • BUN concentration is determined by the rate of urea synthesis by hepatocytes and rate of clearance by the kidneys.
  • Increased protein catabolism results in elevated BUN concentration.
  • Decreased GFR may result from decreased renal perfusion, renal disease, or urinary obstruction.
  • Azotemia results from resorption of urine following urinary tract rupture.
  • Cr is a result of muscle creatine metabolism.
  • Renal excretion of Cr is dependent on GFR.
  • Cr is not resorbed by renal tubules.
  • Low BUN concentration may result after prolonged diuresis or as a result of impaired liver function

Systems Affected!!navigator!!

  • Depend on the underlying causes.
  • Generalized effects—depression, weight loss, edema, dehydration.
  • Gastrointestinal tract—anorexia, uremic stomatitis, uriniferous breath, excessive dental tartar, oral/gastric ulceration, protein losing enteropathy, diarrhea.
  • Neuromuscular—lethargy, gait imbalance, behavioral changes, seizures.
  • Endocrine/metabolic—renal secondary hyperparathyroidism, inadequate production of erythropoietin and 1,25-dihydroxycholecalciferol (calcitriol).
  • Cardiovascular—hypertension, heart murmur, cardiac dysrhythmia.
  • Hemolymphatic—anemia

Genetics!!navigator!!

Healthy, heavily muscled Quarter Horses might have serum Cr concentrations >2.0 mg/dL.

Incidence/Prevalence!!navigator!!

N/A

Geographic Distribution!!navigator!!

N/A

Signalment!!navigator!!

  • Neonatal male foals (ruptured bladder at parturition).
  • Any breed, age, or sex

Signs!!navigator!!

General Comments

Unless the animal is uremic, clinical findings are limited to the process causing azotemia such as dehydration, urinary outflow tract obstruction, urinary outflow tract, or rupture.

Historical Findings

  • Polyuria/polydipsia.
  • Weight loss.
  • Anorexia.
  • Abnormal urination.
  • Lethargy.
  • Uriniferous breath.
  • Poor performance.
  • Lumbar pain.
  • Colic.
  • Poor hair coat.
  • Prolonged posturing to urinate.
  • Stranguria

Physical Examination Findings

  • Fever.
  • Anorexia.
  • Obtundation.
  • Poor body condition.
  • Ventral edema.
  • Oral ulceration.
  • Excessive dental tartar.
  • Scleral injection.
  • Colic.
  • Distended abdomen.
  • Urine scald.
  • Dysuria.
  • Hematuria.
  • Halitosis

Causes!!navigator!!

Prerenal Azotemia

  • Renal hypoperfusion caused by decreased circulating volume or decreased blood pressure.
  • Increased protein catabolism

Renal Azotemia

  • AKI or CRF—primary renal dysfunction affecting glomeruli, renal tubules, renal interstitium, or renal vasculature
    • Prolonged dehydration.
    • Polycystic kidney disease.
    • Pigment nephropathy (e.g. hemoglobin, myoglobin).
    • Nephrotoxic drugs (e.g. NSAIDs, aminoglycoside, tetracycline, polymyxin B).
    • Toxicities (e.g. cantharidin, red maple leaf, vitamin K3).
    • Leptospirosis.
    • Neoplasia

Postrenal Azotemia

  • Obstruction of the urinary tract (e.g. urolithiasis).
  • Rupture of urinary tract

Risk Factors!!navigator!!

  • Prolonged exposure to nephrotoxic drugs, especially with concurrent dehydration.
  • Rhabdomyolysis

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

Elevated serum Cr concentration can be seen in healthy, heavily muscled horses.

CBC/Biochemistry/Urinalysis!!navigator!!

CBC

Nonregenerative anemia caused by decreased erythropoietin production can occur with CRF.

Biochemistry

  • Elevations in serum Cr and BUN concentrations indicate azotemia. In horses, BUN:Cr ratio is unreliable in differentiating AKI and CRF.
  • Hyponatremia and hypochloremia are common in horses with renal disease and can occur with third-compartment spacing of urine.
  • Hyperkalemia is a common finding in AKI and uroperitoneum.
  • Hypercalcemia and hypophosphatemia are often found with CRF; hypocalcemia and hyperphosphatemia can be found with AKI.
  • Hypercalcemia in renal failure depends upon dietary content and intake of calcium

Urinalysis

  • USG >1.020 and urine osmolality >500 mOsm/kg are consistent with prerenal azotemia.
  • Fluid therapy and some medications (e.g. furosemide, α2-receptor agonists, corticosteroids) may render the USG value inconclusive.
  • Dehydrated horses with primary renal disease usually lose the ability to concentrate urine; USG and osmolality are <1.020 and <500 mOsm/kg, respectively

Other Laboratory Tests!!navigator!!

  • Blood gas analysis—metabolic acidosis might be present with uremia.
  • Urine PCR for Leptospira sp.

Imaging!!navigator!!

Ultrasonography

  • The urinary tract can be examined either transrectally or transabdominally.
  • Bladder ultrasonography is best performed transrectally using a 5 MHz probe.
  • Transabdominal ultrasonography of the kidneys is best performed with a 2.5–3 MHz probe.
  • Assess the size and shape of both kidneys and architecture and echogenicity of the parenchyma.
  • The renal medulla is more echolucent than the renal cortex. The renal pelvis varies in echogenicity.
  • With AKI, kidneys may be normal, enlarged, or hydronephrotic, and parenchymal abnormalities are often not detected.
  • With CRF, kidneys are usually smaller and more echogenic than normal.
  • Cystic or mineralized areas are more often associated with CRF or congenital anomalies.
  • Acoustic shadowing represents calculi formation

Renal Scintigraphy

May be used to document renal function but is not commonly performed.

Other Diagnostic Procedures!!navigator!!

Urine GGT:Cr Ratio

  • Reflects GGT leakage from damaged renal tubular epithelium compared with the normal excretion of Cr.
  • Calculated as (urine GGT/urine Cr) × 100.
  • A ratio of >25 suggests proximal tubular damage; this elevation may occur before azotemia develops.
  • Finding an elevated ratio depends on having enough remaining tubules that can leak GGT; severe renal fibrosis may yield normal values

Fractional Excretion of Electrolytes !!calculator!!

  • Measurement of electrolytes in serum and urine can be compared to assess renal damage.
  • Calculated as (urine [electrolyte] × serum Cr/serum [electrolyte] × urine Cr).
  • Reported reference intervals for sodium fractional excretion range from 0.01 to 0.70.
  • Poor indicator of renal function

Rectal Examination

  • Bladder—determine size, wall thickness, and presence of calculi or mural mass.
  • Left kidney—determine size and texture.
  • Ureter—usually not detectable upon palpation, may be enlarged in association with pyelonephritis or ureterolithiasis

Ultrasonography-Guided Renal Biopsy

Can be used to confirm the diagnosis of primary renal disease, differentiate AKI from CRF, and identify a specific cause.

Urethrocystoscopy

  • To evaluate abnormal urination.
  • In adult males, a flexible endoscope with an outside diameter of <12 mm and a length of ≥1 m is adequate to evaluate the urethra and urinary bladder.
  • Normal urethral mucosa is pale pink, with longitudinal folds.
  • If the urethra is dilated with air (e.g. to aid passage of the endoscope), the mucosa may appear reddened, and a prominent vascular pattern may appear.
  • The ischial arch and colliculus seminalis are the most common sites of posturination or postbreeding hemorrhage in geldings and stallions.
  • In the dorsal aspect of the bladder trigone, the ureteral openings can be visualized to determine the source of hematuria or pyuria.
  • Biopsy of a bladder mass or collection of a sterile urine sample can be obtained

Pathologic Findings!!navigator!!

Dependent on the underlying cause.

Treatment ⬆ ⬇

TREATMENT

Prerenal Azotemia

Correct the underlying cause of renal hypoperfusion and/or correct the dehydration.

Renal Azotemia

  • Dependent on the underlying cause.
  • Supportive care to alleviate clinical signs of uremia; correct fluid, electrolyte, and acid–base abnormalities

Postrenal Azotemia

  • Eliminate urinary obstruction or correct cause of urine leakage
    • Surgical intervention often is required, but correction of any metabolic derangements is paramount

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

Dependent on the underlying cause.

Fluids

  • IV fluid therapy is indicated for most azotemic patients.
  • Commonly used fluids—0.9% saline, Plasmalyte, lactated Ringer's solution.
  • Base the amount of fluid administration on dehydration or volume deficit.
  • Correction of the fluid deficit can occur during the first 6 h without untoward effects, except in patients with hypoproteinemia/hypoalbuminemia and with signs of cardiac disease

Contraindications!!navigator!!

  • Use nephrotoxic drugs (e.g. NSAIDs, aminoglycosides) with caution in patients with azotemia.
  • K+-containing IV fluid solutions (e.g. Plasmalyte, lactated Ringer's solution) in the presence of hyperkalemia

Precautions!!navigator!!

  • Use caution when administering fluids to horses with AKI and CRF because they may develop significant peripheral and pulmonary edema.
  • Use IV fluids cautiously in oliguric or anuric patients to minimize overhydration.
  • Use NSAIDs and corticosteroids with caution. Although they can limit renal inflammation, they can also nonselectively block vasodilatory mediators of renal blood flow under conditions of renal hypoperfusion and are not recommended for CRF.
  • Horses should be well hydrated when using NSAIDs and aminoglycosides

Possible Interactions!!navigator!!

Be aware of additive effects of nephrotoxic drugs.

Alternative Drugs!!navigator!!

N/A

Follow-up ⬆ ⬇

Outline

FOLLOW-UP

Patient Monitoring!!navigator!!

  • Serum Cr, BUN and electrolyte concentrations within 24 h after initiating fluid therapy, hydration status, and urine outflow.
  • Monitoring body weight of foals and adult horses may be helpful.
  • With severe electrolyte or acid-base derangements, more frequent monitoring may be required

Possible Complications!!navigator!!

  • Failure to promptly correct prerenal azotemia caused by renal hypoperfusion may result in AKI.
  • Failure to correct renal azotemia may result in uremia.
  • Failure to correct postrenal azotemia may result in renal damage or death caused by hyperkalemia and uremia

Expected Course and Prognosis!!navigator!!

  • Dependent on the underlying cause.
  • With CRF, serum Cr concentrations >5 mg/dL indicates a marked decline in GFR. A grave prognosis is associated with serum Cr concentrations >10 mg/dL

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

Dependent on the underlying cause.

Age-Related Factors!!navigator!!

  • AKI may occur at any age, but older horses may be at higher risk for azotemia regardless of the cause.
  • Ruptured bladder is more common in male neonatal foals

Pregnancy/Fertility/Breeding!!navigator!!

The ability of a mare to maintain a viable pregnancy decreases as renal function decreases.

Synonyms!!navigator!!

Acute renal failure

Abbreviations!!navigator!!

  • AKI = acute kidney injury.
  • BUN = blood urea nitrogen.
  • Cr = creatinine.
  • CRF = chronic renal failure.
  • GFR = glomerular filtration rate.
  • GGT = γ-glutamyltransferase.
  • NSAID = nonsteroidal anti-inflammatory drug.
  • PCR = polymerase chain reaction.
  • USG = urine specific gravity

Suggested Reading ⬆ ⬇

Van Metre DC, Soto DR. Diseases of the renal system. In: Smith B, ed. Large Animal Internal Medicine, 5e. St. Louis, MO: Elsevier Mosby, 2015:873–895.

Author(s) ⬆ ⬇

Author: Sandra D. Taylor

Consulting Editor: Sandra D. Taylor

Acknowledgment: The author/editor acknowledges the prior contribution of Terry C. Gerros.

Additional Further Reading ⬆

Click here for Additional Further Reading