Introduction

• Cause: infectious agents, inflammation/immune-mediated, urinary obstruction, toxins.
• Signs: dysrexia/anorexia, lethargy, polyuria or oliguria/anuria, weight loss.
• Diagnosis: clinical examination, CBC/biochemistry, urinalysis, blood pressure (BP) examination, abdominal imaging, renal biopsy.
• Treatment: parenteral fluid therapy, nutritional support, antimicrobials if indicated, management of associated uremic signs.
• Prognosis: dependent on etiology, generally guarded to poor.

Pathogenesis

Etiology

• Bacterial infection:
  • Bacterial pyelonephritis Pyelonephritis; typically from ascending spread: hemolytic Escherichia coli and Staphylococcus aureus most common causative agents in ferrets.
  • Hematogenous spread of bacteria.
  • Leptospira spp: infection is associated with rapid bacteremia with disseminated infection. Multifocal hemorrhages are found in multiple organs including the kidneys. Renal tubular necrosis and hematuria are also often identified.
  • Borrelia burgdorferi:
    • Lyme borreliosis in ferrets.
    • Antigen-antibody complex deposition and resultant interstitial nephritis.
• Viral infection:
  • Aleutian disease Aleutian disease:
    • Immune complex deposition in the kidneys can result in glomerulonephritis and tubular interstitial nephritis.
    • Many ferrets are asymptomatic carriers.
    • Parvovirus.
  • Systemic coronavirus Ferret systemic coronavirus: renomegaly and renal granulomatous inflammation.
• Fungal infection:
  • Encephalitozoon cuniculi.
  • Histoplasma capsulatum Histoplasmosis.
• Parasitic infection: Klossiella cobayae:
  • Relatively rare occurrence.
  • Transmission is via urine-oral route.
  • Clinical signs are usually absent.
  • Diagnosis achieved via demonstration of the schizogonous stage in glomerular capillaries or schizonts and gametogenous stages in the cytoplasm of epithelial cells lining renal tubules.
• Inflammatory/immune-mediated conditions:
  • Vasculitis, sepsis, systemic inflammatory response syndrome: extension of inflammation to the kidneys.
  • Certain neoplastic conditions, eg multiple myeloma:
    • Neoplastic plasma cells in multiple myeloma secrete abnormal amounts of single whole or partial immunoglobulin (M component/paraprotein).
    • Some M components are filtered by the glomerulus and precipitate in the renal tubule, causing tubulointerstitial nephritis.
• Obstructive conditions:
  • Urolithiasis Cystitis and urolithiasis.
  • Prostatic disease Prostatic disease in male ferrets, secondary to adrenal disease.
  • Renal clearance is decreased by a combination of neurohumoral events and increased back-pressure to the kidney(s), which reduces GFR.
  • Ischemia and release of inflammatory factors contribute to the development of chronic tubulointerstitial nephritis.
  • Bacterial pyelonephritis Pyelonephritis secondary to urolithiasis can also occur.
• Toxin:
  • Ethylene glycol, drugs such as gentamicin and sulfonamides.
  • Heavy metals, eg lead Toxicosis overview.

Predisposing factors

General

• Suboptimal husbandry and sanitation.

Specific

• Exposure to known nephrotoxins.
• Neoplasia more common in aged animals

Pathophysiology

• Initiation phase:
  • Renal insult and parenchymal injury.
  • Clinical signs may not be present until there is a definable change in renal function.
• Extension phase:
  • Sustained insult results in cellular apoptosis and/or necrosis.
  • Progressive decline in glomerular filtration rate (GFR), loss of urine concentrating ability, and development of oliguria/polyuria and azotemia.
  • Renal tubular cells and casts may be identified in urine sediment examination.
• Maintenance phase:
  • Critical amount of irreversible epithelial damage.
  • GFR and renal blood flow continue to be decreased.
  • Urine output may be diminished.
  • Complications associated with uremia.
• Uremic syndrome:
  • Alteration in fluid homeostasis:
    • Hypovolemia and dehydration occur due to inadequate fluid intake and excessive fluid loss associated with vomiting, and/or polyuria.
    • Azotemia is often exacerbated.
    • Predisposes the kidneys to further ischemic injury.
  • Electrolyte and acid-base imbalances:
    • Hyperkalemia due to inadequate potassium excretion; more common with oliguria and/or anuria.
    • Hypokalemia may be seen with polyuria together with vomiting and diarrhea.
    • Hyperphosphatemia from reduced excretion.
    • Hypocalcemia Hypocalcemia can occur as a result of hyperphosphatemia.
    • Metabolic acidosis often develops in acute presentations due to impaired filtration of acid load and decreased resorption of bicarbonate; severity may be exacerbated by concurrent ethylene glycol toxicity.
  • Anemia Anemia overview:
    • Typically in chronic presentations.
    • Associated with reduced erythropoietin synthesis by renal peritubular capillary endothelial cells.
    • Gastrointestinal blood loss from ulcerative uremic stomatitis and gastritis may also be a contributing factor.
  • Renal secondary hyperparathyroidism:
    • Typically identified in advanced chronic disease associated with hyperphosphatemia and low circulating 1,25-dihydroxycholecalciferal levels, and reduced serum ionized calcium.
    • Often manifests as osteodystrophy in mammals.
  • Gastrointestinal disorders:
    • Anorexia Anorexia, nausea, vomiting, ileus.
    • Weight loss can result from malnutrition but also from metabolic derangement and catabolic factors such as acidosis.
    • Uremic gastritis and stomatitis and ulcers may contribute to vomiting and dysphagia.
  • Arterial hypertension: associated with fluid retention, activation of the renin-angiotensin-aldosterone system, and increased activity of the sympathetic nervous system.
  • Uremic neuropathy:
    • Sequelae to metabolic derangements.
    • Manifesting as altered mentation or consciousness, muscle weakness, seizure activity.

Timecourse

• Varies with etiology: can range from days (nephrotoxins and bacterial interstitial nephritis), to months or years (renal amyloidosis).

Diagnosis

Treatment

Prevention

Outcomes