ISSN 2398-2985      

Interstitial nephritis

4ferrets
Contributor(s):

Joanne Sheen

Sarah Brown

Synonym(s): Renal disease, Glomerulonephritis, Pyelonephritis


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:
  • 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

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Hallman R M & & Brandão J (2020) Diagnostic imaging of the renal system in exotic companion mammals. Vet Clin North Am Exotic Anim Pract 23 (1), 195-214 PubMed.
  • Reaveill D R & Lennox A M (2020) Disease overview of the urinary tract in exotic companion mammals and tips on clinical management. Vet Clin North Am Exotic Anim Pract 23 (1), 169-193 PubMed.
  • Mineres J, Yang X, Knights K & Zhang L (2017) The role of the kidney in drug elimination: transport, metabolism, and the impact of kidney disease on drug clearance. Clin Pharm Therap 102 (3), 436-449 WileyOnline.
  • Van Zeeland Y R A, Wilde A, Bosman I H et al (2017) Non-invasive blood pressure measurement in ferrets (Mustela putorius furo) using high definition oscillometry. Vet J 228, 53-62 PubMed.

Other sources of information

  • Di Girolamo N & Huynh M (2020) Disorders of the Urinary and Reproductive Systems in Ferrets. In: Ferrets, Rabbits and Rodents E-Book: Clinical Medicine and Surgery. 4th edn. Eds: Quesenberry K, Mans C, Orcutt C & Carpenter J W. Elsevier, USA.
  • Langston C E (2017) Acute Kidney Injury. In: Text of Veterinary Internal Medicine. 8th edn. Eds: Ettinger S J, Feldman E C & Cote E. Elsevier, USA.
  • Polzin D J (2017) Chronic Renal Disease. In: Textbook of Veterinary Internal Medicine. 8th ed. Eds: Ettinger S J, Feldman E C & Cote E. Elsevier, USA.

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