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Basics ⬇

Basics

Definition

Acute uremia is a clinical syndrome characterized by sudden onset of renal outflow or excretory failure; accumulation of uremic toxins; dysregulation of fluid, electrolyte, and acid–base balance; and clinical signs of uremia. Depending on the underlying cause, acute uremia is potentially reversible if diagnosed quickly and treated aggressively. This chapter refers to intrinsic acute kidney injury and ureteral obstruction.

Pathophysiology

  • AKI may be initiated by ischemia, nephrotoxins, infection, prolonged urine outflow obstruction and severe non-renal systemic diseases (e.g., pancreatitis, neoplasia).
  • AKI may be divided into four sequential stages: (1) initiation, (2) extension, (3) maintenance, and (4) recovery. Clinically, transition from one stage to the next may not be clearly evident, and not all stages need be present in an individual patient.
  • Renal excretory failure is perpetuated by multiple factors including (1) reduced glomerular surface area and permeability, (2) low renal blood flow, (3) intratubular obstruction by tubular debris, (4) cellular and interstitial edema, and (5) “backleak” of filtrate across damaged tubular epithelia. Resolution occurs by renal regeneration and repair.
  • Ureteral obstruction results from ureteroliths, inspissated blood, strictures or inflammatory debris.

Systems Affected

  • Renal/Urologic
  • Endocrine/Metabolic
  • Gastrointestinal
  • Hemic/Lymph/Immune
  • Musculoskeletal
  • Nervous
  • Respiratory

Incidence/Prevalence

  • Prevalence is lower than chronic kidney disease.
  • Prevalence may increase in the fall and winter with greater exposure to antifreeze containing ethylene glycol, and wet environments that support Leptospira.
  • Ureteral obstruction is the most common cause of severe acute uremia in cats.

Signalment

Species

Dog and cat

Breed Predilections

None

Mean Age and Range

  • 6–8 years peak prevalence in dogs and cats.
  • Older animals at greater risk due to decreased renal reserve.

Signs

Historical Findings

Sudden onset of anorexia, listlessness, depression, vomiting (± blood), diarrhea (± blood), halitosis, ataxia, seizures, known toxin or drug exposure, recent medical or surgical procedure, and oliguria/anuria.

Physical Examination Findings

Normal body condition and hair coat, depression, dehydration (or iatrogenic overhydration), scleral injection, oral ulceration, glossitis, necrosis of the tongue, uremic breath, hypothermia, fever, tachypnea, bradycardia, non-palpable urinary bladder, and asymmetrically enlarged, painful, firm, kidneys.

Causes

Hemodynamic/Hypoperfusion

Shock, trauma, thromboembolism (e.g., DIC, vasculitis, transfusion reaction), heatstroke, excessive vasoconstriction (e.g., administration of NSAIDs), adrenal insufficiency, excessive vasodilation (e.g., ACEI or antihypertensive drugs), prolonged anesthesia, significant hypertension, heart failure.

Nephrotoxic

Ethylene glycol, aminoglycoside, amphotericin B, chemotherapeutic agent (e.g., cisplatin, doxorubicin), thiacetarsamide, NSAIDs, radiographic contrast agents, heavy metals (e.g., lead, mercury, arsenic, thallium), insect or snake venom, heme pigment, calcium, grape or raisin ingestion (dogs), and lily ingestion (cats).

Intrinsic and Systemic Disease

Leptospirosis, Lyme disease, immune-mediated glomerulonephritis, pancreatitis, septicemia, DIC, hepatic failure, heat stroke, transfusion reaction, bacterial endocarditis, pyelonephritis, cortical necrosis, and lymphoma. Unilateral or bilateral ureteral obstruction.

Risk Factors

  • Endogenous-preexisting CKD, dehydration, sepsis, hypovolemia, hypotension, advanced age, concurrent disease, hyponatremia, hypokalemia, hypocalcemia, and acidosis.
  • Exogenous-drugs (e.g., furosemide, NSAIDs, ACEI, aminoglycoside), prolonged anesthesia, acidifying diets, trauma, multiple organ disease, and high environmental temperature.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Prerenal azotemia-oliguria, concentrated USG (dogs, 1.030; cats, 1.035), correctable with fluid repletion.
  • Post-renal azotemia-anuria, dysuria, stranguria, large bladder, urethral obstruction, enlarged prostate, urethral tear, uroperitoneum.
  • CKD-polyuria, polydipsia, history of chronic illness, loss of body condition, anemia.
  • Prerenal on CKD-clinical and laboratory features of CKD but partially correctable with fluid repletion.
  • Prerenal on AKI-acute onset uremia, partially correctable with fluid repletion.
  • Hypoadrenocorticism-hyponatremia, hyperkalemia, low serum cortisol.
  • Pancreatitis-cranial abdominal pain, high trypsin-like immunoreactivity, hyperbilirubinemia, and increase in liver enzyme activity.

CBC/Biochemistry/Urinalysis

  • Normal or high PCV, variable leukocytosis, and lymphopenia.
  • Progressive (moderate to severe) increases in SUN, creatinine, and phosphorus; variably high potassium and glucose; and variably low bicarbonate and calcium concentration.
  • USG 1.020, mild-to-moderate proteinuria, glucosuria; variable number of cellular, and/or granular casts, WBCs, RBCs, and tubular epithelial cells; variable bacteriuria and calcium oxalate monohydrate crystalluria (sometimes seen in association with ethylene glycol toxicosis).

Other Laboratory Tests

  • Metabolic acidosis common; mixed disorders may occur.
  • Leptospira titer 1:800 to non-vaccinal serovar, or rising titers.
  • Ethylene glycol concentration-“spot test” positive if ingested, increased serum osmolality and/or osmolar or anion gap.

Imaging

  • Survey and contrast radiography-kidneys are normal to large, with bilateral smooth contours; asymmetric kidneys in cats (“big kidney-little kidney” syndrome) with ureteral obstruction-small radiodense uroliths may be visible in the retroperitoneum.
  • Percutaneous nephropyleography or contrast CT for ureteral obstruction.
  • Ultrasonography-severe cortical hyperechogenicity suggests ethylene glycol toxicosis. Moderate cortical hyperechogenicity suggests glomerulonephritis or nephrosis. Pelvic and/or ureteral dilation or calcific densities suggest outflow obstruction.

Diagnostic Procedures

  • Monitor urine output-helps establish diagnosis and helps in formulation of therapy and prognosis: anuria; oliguria, 0.25 mL/kg/h ( 1 mL/kg/h during fluid administration); non-oliguria, 2 mL/kg/h.
  • Fine-needle aspiration-may establish lymphoma as cause of renomegaly.
  • Percutaneous renal biopsy-helps establish the cause, severity, and potential reversibility of injury; later in the course of disease (4–6 weeks) it may help predict ongoing renal repair and permanence of renal damage.

Pathologic Findings

Nephrosis or nephritis, glomerulonephritis, calcium oxalate crystals, interstitial edema, and lack of interstitial fibrosis; the subacute stage is characterized by attenuated tubular epithelium, interstitial fibrosis and mineralization, cellular infiltration, and variable tubular regeneration.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

Inpatient management; eliminate inciting causes; discontinue nephrotoxic drugs; establish and maintain hemodynamic stability; ameliorate life-threatening fluid imbalances, biochemical abnormalities, and uremic toxicities; initiate gastric lavage, induce emesis and administer activated charcoal, cathartics, and specific antidotes to patients with acute poisoning; early hemodialysis/hemoperfusion can eliminate many toxins.

Nursing Care

  • Hypovolemia-correct estimated fluid deficits with 0.9% saline or balanced polyionic solution within 2–4 hours if patient condition permits; once hydrated, ongoing fluid requirements are provided by 5% dextrose for insensible requirements (approximately 20–25 mL/kg/day) and balanced electrolyte solution equal to urinary and other losses (i.e., vomiting and diarrhea); avoid overhydration; replace blood losses by blood transfusion.
  • Hypervolemia-stop fluid administration and eliminate excess fluid by diuretics or dialysis.
  • Monitor body weight at least four times daily and adjust fluids to maintain stable weight once rehydrated. Avoid overhydration.

Diet

  • Rapid control of vomiting and early nutritional support. Endogenous fat and protein stores are consumed while patient is anorexic; resting energy requirements must be provided within 3 days using moderately protein-restricted diets, or enteral feeding solutions formulated to control azotemia and supply caloric requirements.
  • Parenteral nutrition (intractable vomiting)-provide caloric requirements by dextrose and emulsified lipid solution; protein requirements (dogs, 2–3 g/100 kcal; cats, 3–4 g/100 kcal) provided by amino acid mixtures.
  • Enteral feeding (anorectic, non-vomiting animals)-caloric and protein requirements supplied by blended renal diets, liquid enteral solutions, or formulated diets delivered by nasoesophageal, esophagostomy, gastrostomy, or enterostomy tube.

Client Education

Guarded prognosis for complete recovery; potential for morbid complications of treatment (e.g., fluid overload, sepsis, and multiple organ failure); expense of prolonged hospitalization; alternatives to conventional medical management (i.e., peritoneal dialysis, hemodialysis, and renal transplantation); zoonotic potential of leptospirosis.

Surgical Considerations

  • For acute ureteral obstruction unresponsive to medical management, consider surgical intervention via ureteral stenting, subcutaneous ureteral bypass or ureteral resection and re-implantation.
  • Renal transplantation may provide long-term survival for cats with fulminating, nonresponsive AKI.

Peritoneal or Hemodialysis

  • Dialysis can stabilize the patient until renal function is restored or corrective surgery (removal of ureteral obstruction, renal transplantation); without dialysis, most oliguric patients die before renal repair occurs.
  • Specific indications include severe oliguria or anuria, life-threatening fluid overload or acid-base/electrolyte disturbances, SUN 100 mg/dL, serum creatinine 10 mg/dL, clinical course refractory to conservative treatment, perioperative stabilization, and poisoning/overdosage with a dialyzable toxin.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Inadequate Urine Production

  • Ensure patient is fluid-volume-replete; provide additional isonatric fluid to achieve 3% volume expansion; failure to induce diuresis indicates severe parenchymal damage or underestimation of fluid deficit; if fluid-replete, administer diuretics.
  • Hypertonic mannitol (20%) 0.5 g/kg IV over 15–30 minutes; if effective, continue as intermittent IV bolus q6h; do not repeat dosage if ineffective.
  • Furosemide (alternative or subsequent to mannitol)-4 mg/kg IV; if effective, continue CRI at 0.5 mg/kg/h or 2 mg/kg q6h; discontinue if ineffective.
  • Dopamine-lack of documented efficacy and potential side effects contraindicate its use except for pressor control.
  • If these treatments fail to induce diuresis within 4–6 hours, consider dialysis.

Metabolic Disorders, Acid-Base Disorders

Administer bicarbonate if serum bicarbonate 16 mEq/L; bicarbonate replacement: mEq = bicarbonate deficit × body weight (kg) × 0.3; give half IV over 30 minutes and the remainder over 2–4 hours; then reassess.

Hyperkalemia

  • Correct dehydration with potassium free (0.9% NaCl) fluids.
  • Minimize potassium intake.
  • Discontinue medications that promote hyperkalemia (e.g., ACEI, potassium sparing diuretics).
  • Loop diuretics: furosemide 2–4 mg/kg IV.
  • Sodium bicarbonate, sufficient to correct existing bicarbonate deficit, if bicarbonate status unknown, 1–2 mEq/kg IV.
  • Dextrose ± insulin: 1–2 mL/kg of 50% dextrose (diluted to 25%) IV or regular insulin 0.1–0.2 U/kg IV bolus followed by 1–2 g dextrose/unit insulin.
  • Calcium gluconate: 0.5–1.0 mL/kg of 10% calcium gluconate IV over 10–15 minutes.
  • Refractory hyperkalemia-dialysis.

Vomiting

  • Reduce gastric acid production-famotidine (0.5 mg/kg IM, IV q24h) or omeprazole (0.5–1 mg/kg PO q24h [dogs]).
  • Mucosal protectant-sucralfate (0.25–1 g PO q6–8h).
  • Antiemetics-maropitant (1 mg/kg SC/IV q24h); or ondansetron (0.1–0.3 mg/kg IV q8–12h); or dolasetron (0.5 mg/kg SC, IV q24h).

Precautions

Modify dosages of all drugs that require renal metabolism or elimination.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

Fluid, electrolyte, and acid-base balances; body weight; blood pressure; urine output; and clinical status; daily.

Prevention/Avoidance

  • Anticipate the potential for AKI in aged patients or those with systemic disease, sepsis, trauma, hemodynamic instability, receiving nephrotoxic drugs, multiple organ failure, or those undergoing prolonged anesthesia.
  • Maintenance of hydration, mild saline volume expansion, and administration of mannitol may be preventive.
  • Monitor urine production, SUN, and creatinine in high-risk patients.

Possible Complications

Seizures, coma, cardiac arrhythmias, hypertension, congestive heart failure, pulmonary edema, uremic pneumonitis, aspiration pneumonia, GI bleeding, hypovolemic shock, sepsis, cardiopulmonary arrest, and death.

Expected Course and Prognosis

  • Prognosis depends on underlying cause, extent of renal injury, concomitant disease or organ failure, age of patient and response to therapy.
  • Survival rates average 50% overall for both cats and dogs, ranging from 20% for ethylene glycol toxicosis up to 80% for acute leptospirosis.
  • Infectious and obstructive etiologies have a better prognosis for recovery than toxic causes.
  • Non-oliguric AKI-typically milder than oliguric; recovery may occur over 2–6 weeks, but the prognosis remains guarded.
  • Oliguric AKI-extensive kidney injury, difficult to manage, and has a poor prognosis for recovery without dialysis; recovery signaled by a sudden (and often excessive) polyuria and a sluggish and possibly incomplete return of renal function over 4–12 weeks; dialysis extends the potential for renal regeneration and repair.
  • Anuric AKI-poor prognosis without dialysis; often incomplete recovery of renal function.

Miscellaneous ⬆

Miscellaneous

Zoonotic Potential

Leptospirosis-avoid contact with infective urine.

Pregnancy/Fertility/Breeding

A rare complication of pregnancy in animals; promoted by acute metritis, pyometra, and postpartum sepsis or hemorrhage.

Synonyms

Acute renal failure, acute tubular necrosis, acute uremia

Abbreviations

  • ACEI = angiotensin converting enzyme inhibitors
  • AKI = acute kidney injury
  • CKD = chronic kidney disease
  • CRI = constant rate infusion
  • CT = computed tomography
  • DIC = disseminated intravascular coagulation
  • GI = gastrointestinal
  • NSAID = nonsteroidal anti-inflammatory drug
  • PCV = packed cell volume
  • RBC = red blood cell
  • SUN = serum urea nitrogen
  • USG = urine specific gravity
  • WBC = white blood cell

Author Sheri Ross

Consulting Editor Carl A. Osborne

Client Education Handout Available Online

Suggested Reading

Cowgill LD, Langston C. Acute kidney injury. In: Bartges J, Polzin DJ, eds., Nephrology and Urology of Small Animals. Ames, IA: Wiley-Blackwell, 2011.