Azotemia and Uremia

Basics

Definition

Azotemia is an excess of urea, creatinine, or other non-protein nitrogenous substances in blood, plasma, or serum.
Uremia is the polysystemic toxic syndrome that results from marked loss in kidney functions. Uremia occurs simultaneously in animals with increased quantities of urine constituents in blood (azotemia), but azotemia may occur in the absence of uremia.

Pathophysiology

Azotemia can be caused by (1) increased production of non-protein nitrogenous substances, (2) decreased glomerular filtration rate, or (3) reabsorption of urine that has escaped from the urinary tract into the bloodstream. High production of non-protein nitrogenous waste substances may result from high intake of protein (diet or gastrointestinal bleeding) or accelerated catabolism of endogenous proteins. Glomerular filtration rate may decline because of reduced renal perfusion (prerenal azotemia), acute or chronic kidney disease (renal azotemia), or urinary obstruction (post-renal azotemia). Reabsorption of urine into the systemic circulation may also result from leakage of urine from the excretory pathways (also a form of post-renal azotemia).
Pathophysiology of uremia-incompletely understood; may be related to (1) metabolic and toxic systemic effects of waste products retained because of renal excretory failure, (2) deranged renal regulation of fluids, electrolytes, and acid-base balance, and (3) impaired renal production and degradation of hormones and other substances (e.g., erythropoietin and 1,25-dihydroxycholecalciferol).

Systems Affected

Uremia affects virtually every body system.
Cardiovascular-arterial hypertension, left ventricular hypertrophy, heart murmur, cardiomegaly, cardiac rhythm disturbances.
Endocrine/Metabolic-renal secondary hyperparathyroidism, inadequate production of 1,25-dihydroxycholecalciferol (calcitriol) and erythropoietin, hypergastrinemia, weight loss.
Gastrointestinal-anorexia, nausea, vomiting, diarrhea, uremic stomatitis, xerostomia, uremic breath, constipation.
Hemic/Lymph/Immune-anemia and immunodeficiency.
Neuromuscular-dullness, drowsiness, lethargy, fatigue, irritability, tremors, gait imbalance, flaccid muscle weakness, myoclonus, behavioral changes, dementia, isolated cranial nerve deficits, seizures, stupor, coma, impaired thermoregulation (hypothermia).
Ophthalmic-scleral and conjunctival injection, retinopathy, acute-onset blindness.
Respiratory-dyspnea.
Skin/Exocrine-pallor, bruising, increased shedding, unkempt appearance, loss of normal sheen to coat.

Signalment

Dog and cat

Signs

General Comments

Azotemia may not be associated with historical or physical abnormalities. Unless patient has uremia, clinical findings are limited to the disease responsible for azotemia. Findings described here are those of uremia.

Historical Findings

Weight loss
Declining appetite or anorexia
Reduced activity
Depression
Fatigue
Weakness
Vomiting
Diarrhea
Halitosis
Constipation
Polyuria
Changes in urine volume (increase or decrease)
Poor haircoat or unkempt appearance

Physical Examination Findings

Muscle wasting: sarcopenia/cachexia
Mental depression
Dehydration
Weakness
Pallor
Petechiae and ecchymoses
Dull and unkempt haircoat
Uremic breath
Uremic stomatitis (including oral ulcers, infarctions of the tongue)
Scleral and conjunctival injection
Relative hypothermia

Causes

Prerenal Azotemia

Reduced renal perfusion due to low blood volume or low blood pressure.
Accelerated production of nitrogenous waste products because of enhanced catabolism of tissues in association with infection, fever, trauma, corticosteroid excess, or burns.
Increased gastrointestinal digestion and absorption of protein sources (diet or gastrointestinal hemorrhage).

Renal Azotemia

Acute or chronic kidney diseases (primary kidney disease affecting glomeruli, renal tubules, renal interstitium, and/or renal vasculature) that impair at least 75% of kidney function (glomerular filtration rate).

Post-renal Azotemia

Urinary obstruction; rupture of the excretory pathway.

Risk Factors

Medical conditions-kidney disease, hypoadrenocorticism, low cardiac output, hypotension, fever, sepsis, polyuria, liver disease, pyometra, hypoalbuminemia, dehydration, acidosis, exposure to nephrotoxic chemicals, gastrointestinal hemorrhage, urolithiasis, urethral plugs in cats, urethral trauma, and neoplasia.
Advanced age may be a risk factor.
Drugs-potentially nephrotoxic drugs, nonsteroidal anti-inflammatory drugs, diuretics, antihypertensive medications; failure to adjust dosage of drugs primarily eliminated by the kidneys to correspond with decline in renal function.
Toxins-ethylene glycol, grapes (dogs), lilies (cats).

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

Dehydration, poor peripheral perfusion, low cardiac output, history of recent fluid loss, high protein diet, or black, tarry stools-rule out prerenal azotemia.
Recent onset of altered urine output (high or low), clinical signs consistent with uremia, exposure to possible nephrotoxicants or ischemic renal injury, or kidney size normal or enlarged-rule out acute renal failure.
Progressive weight loss, polyuria, polydipsia, small kidneys, disparate kidney size (cats-big kidney and little kidney), pallor, and signs of uremia that have developed over several weeks to months-rule out chronic renal failure.
Abrupt decline in urine output and onset of signs of uremia; disparate kidney size (cats-big kidney and little kidney), occasionally dysuria, stranguria, and hematuria; large urinary bladder or fluid-filled abdomen-rule out post-renal azotemia.

CBC/Biochemistry/Urinalysis

CBC

Nonregenerative anemia (normocytic, normochromic)-often present with chronic renal failure.
Hemoconcentration-often present with prerenal azotemia; can also be seen with acute renal failure and post-renal azotemia.

Biochemistry

Serial determinations of serum urea nitrogen and creatinine concentrations may help differentiate the cause of azotemia. Appropriate therapy to restore renal perfusion typically yields a dramatic reduction in azotemia in patients with prerenal azotemia (typically within 24–48 hours). Correcting obstruction to urine flow or a rent in the excretory pathway typically is followed by a rapid reduction in the magnitude of azotemia.
Concurrent hyperkalemia may be consistent with post-renal azotemia, primary renal azotemia due to oliguric renal failure, or prerenal azotemia associated with hypoadrenocorticism.
Increased serum albumin and globulin concentration suggest prerenal azotemia or a prerenal component.s

Urinalysis

A urine specific gravity value 1.030 in dogs and 1.035 in cats supports a diagnosis of prerenal azotemia. Administration of fluid therapy before urine collection may interfere with interpretation of low specific gravity values.
Azotemic patients that have not been treated with fluids and have urine specific gravity <1.030 in dogs and <1.035 in cats typically have primary renal azotemia. A notable exception to this rule is dogs and cats with glomerular disease. Glomerulopathy is sometimes characterized by glomerulotubular imbalance in which adequate urine- concentrating ability may persist despite sufficient renal glomerular damage to cause primary renal azotemia; these patients are recognized by moderate to marked proteinuria in the absence of hematuria and pyuria.
Urine specific gravity is not useful in identifying post-renal azotemia.

Other Laboratory Tests

Endogenous or exogenous creatinine, iohexol, or inulin clearance tests or other specific tests of glomerular filtration rate may be used to confirm that azotemia is caused by reduced glomerular filtration rate.

Imaging

Abdominal radiographs-used to determine kidney size (small kidneys consistent with chronic kidney disease; mild-to-moderate enlargement of kidneys may be consistent with acute renal failure or urinary obstruction) and to rule out urinary obstruction (marked dilation of the urinary bladder or mineral densities within the excretory pathway).
Ultrasonography-may detect changes in echogenicity of the renal parenchyma and size and shape of kidneys that support a diagnosis of primary renal azotemia; useful to rule out post-renal azotemia characterized by distension of the excretory pathway and uroliths or masses within or impinging on the excretory pathway and intra-abdominal fluid accumulation (with rupture of the excretory pathway).
Excretory urography, pyelography, or cystourethrography-may help establish the diagnosis of post-renal azotemia due to urinary obstruction or rupture of the excretory pathway.

Diagnostic Procedures

Renal biopsy can be used to confirm the diagnosis of primary kidney disease, to differentiate acute from chronic kidney disease, and to attempt to establish the underlying disease process responsible for primary kidney disease.

Treatment ⬆ ⬇

Treatment

Prerenal azotemia caused by impaired renal perfusion-correct the underlying cause of renal hypoperfusion; aggressiveness of treatment depends on the severity of the underlying condition and the probability that persistent renal hypoperfusion will lead to primary renal injury or failure.
Primary renal azotemia and associated uremia-(1) specific therapy directed at halting or reversing the primary disease process affecting the kidneys, and (2) symptomatic, supportive, and palliative therapies that ameliorate clinical signs of uremia; minimize the clinical impact of deficits and excesses in fluid, electrolyte, acid-base balances; minimize the effects of inadequate renal biosynthesis of hormones and other substances, and maintain adequate nutrition.
Post-renal azotemia-eliminate urinary obstruction or repair rents in the excretory pathway; supplemental fluid administration is often required to prevent dehydration that may develop during the solute diuresis that follows correction of post-renal azotemia.
Fluid therapy-indicated for most azotemic patients; preferred fluids include 0.9% saline or lactated Ringer's solution. Determine fluid volume to administer on the basis of severity of dehydration or volume depletion. If no clinical dehydration is evident, cautiously assume that the patient is less than 5% dehydrated and administer a corresponding volume of fluid. Generally provide 25% of calculated fluid deficit in the first hour. Thereafter, serially monitor perfusion (capillary refill time, pulse pressure, heart rate, and temperature of feet), blood pressure and urine output to assess adequacy of fluid therapy. If perfusion has not improved, additional fluid should be administered. Provide the remaining fluid deficit over the next 12–24 hours. Fluid therapy should be cautiously administered to patients with overt or suspected cardiac failure and patients that are oliguric or anuric.
Treat patients in shock appropriately.
Consider feeding diets formulated for kidney disease to reduce the magnitude of azotemia, hyperphosphatemia, and acidosis.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Symptomatic therapy may be indicated for uremia in patients with kidney disease.
Famotidine (0.5–1.0 mg/kg PO, SC, IM, IV q12–24h) or other H₂-receptor antagonists may be used to reduce gastric hyperacidity and nausea (dogs).
Antiemetics such as maropitant (1 mg/kg q24h PO or SC for 5 days) are indicated for vomiting.

Contraindications

Administration of nephrotoxic drugs

Precautions

Use caution when administering drugs requiring renal excretion. Consult appropriate references concerning dose-reduction schedules or adjustments of maintenance intervals.
Use caution in administering fluids to patients that are oliguric or anuric. Monitor urine production rates and body weight during fluid therapy to minimize the likelihood of inducing overhydration.
Stop fluid therapy in overhydrated oliguric/anuric patients. Use caution in administering drugs that may promote hypovolemia or hypotension (e.g., diuretics); carefully monitor the response to such drugs by assessing hydration status, peripheral perfusion, and blood pressure, with serial evaluation of renal function tests.
Corticosteroids may worsen azotemia by increasing catabolism of endogenous proteins.

Alternative Drug(s)

N/A

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

Serum urea nitrogen and creatinine concentrations 24 hours after initiating fluid administration; also urine production, body weight, and hydration status.

Possible Complications

Failure to correct prerenal azotemia caused by renal hypoperfusion rapidly could result in ischemic primary kidney disease.
Primary renal azotemia can progress to uremia.
Failure to restore normal urine flow in patients with post-renal azotemia can result in progressive renal damage or death due to hyperkalemia and uremia.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

An association may exist between hypokalemia and azotemia in cats. Preliminary findings suggest that hypokalemia may be associated with functional or structural renal changes leading to azotemia.

Age-Related Factors

Primary renal failure may occur in animals of any age, but geriatric dogs and cats appear to be at substantially higher risk for both acute and chronic kidney disease. However, do not assume that azotemia in geriatric dogs and cats indicates primary kidney disease; these patients are also at higher risk for prerenal and post-renal causes for azotemia.

Zoonotic Potential

Leptospirosis

Pregnancy/Fertility/Breeding

Data on azotemia and pregnancy in dogs and cats are very limited. Humans may tolerate minimal renal disease well during pregnancy; however, ability to sustain a viable pregnancy declines as renal function declines.
Pregnant azotemic animals-pharmacologic agents excreted by non-renal pathways are preferred.

See Also

Chapters on acute and chronic kidney disease
Urinary Tract Obstruction

Internet Resources

International Renal Interest Society (IRIS): www.iris-kidney.com.

Author David J. Polzin

Consulting Editor Carl A. Osborne

Suggested Reading

Polzin D.Chronic kidney disease. In: Ettinger SJ, Feldman EC, eds., Textbook of Veterinary Internal Medicine, 7th ed. Philadelphia: Saunders, 2010, pp. 2036–2067.

Ross L. Acute renal failure. In: Bonagura JD, Twedt DC, Kirk's Veterinary Therapy XIV. Philadelphia: Saunders, 2009, pp. 879–882.

section name header

Basics ⬇

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

Medications ⬆ ⬇

Follow-Up ⬆ ⬇

Miscellaneous ⬆