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; typically from ascending spread: Corynebacterium renale is commonly identified in urine of pet guinea pigs with urolithiasis Urolithiasis.
  • Hematogenous spread of bacteria.
  • Leptospira spp:
    • Natural infection rare in guinea pigs, although they are commonly used as a model for leptospirosis.
    • Natural infection of guinea pigs have been documented in Europe - thought to be due to exposure to wild rats, and in Argentina, in association with infected cattle.
    • 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: antigen-antibody complex deposition and resultant interstitial nephritis.
• Viral infection:
  • Guinea pig cytomegalovirus (Caviid herpesvirus 2) Cytomegalovirus:
    • Transmission by exposure to infected saliva, urine or transplacentally.
    • Common in conventionally housed guinea pigs.
    • Typically identified incidentally as salivary gland lesions.
    • Systemic disease seen in experimental conditions; multifocal areas of necrosis is present in the kidneys and other organs together with interstitial pneumonitis. Intranuclear and intracytoplasmic inclusion bodies may be present within the affected foci.
• Fungal infection:
  • Encephalitozoon cuniculi Encephalitozoonosis.
  • Histoplasma capsulatum:
    • An outbreak have been reported in a group of laboratory guinea pigs, thought to be infected through contaminated wild grass.
    • Lesions containing histiocytes with basophilic round or ellipsoid cytoplasmic bodies were identified in the kidneys as well as other organs.
• Parasitic infection: Klossiella cobayae:
  • Renal coccidiosis in guinea pigs.
  • 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:
  • Systemic amyloidosis in guinea pigs:
    • May an incidental finding at post-mortem.
    • Deposition of hyaline AA amyloid within the kidneys and other organs such as the liver and spleen.
    • Tend to occur in animals with chronic bacterial infection such as pododermatitis.
  • Nephrosclerosis:
    • Common in guinea pigs >1 year of age.
    • Grossly appears as irregularly pitted, granular renal cortices.
    • Lesions interpreted as a result of general vascular disturbance, causing focal areas of ischemia and necrosis.
    • Undetermined pathogenesis; currently thought to be due to deposition of antigen-antibody complexes due to an unidentified infectious agent or endogenous tissue antigen.
    • Accelerated disease and increased incidence noted in guinea pigs fed an unusually high protein diet.
    • May be an incidental finding on post-mortem, but lesions may be sufficiently extensive to result in renal disease.
  • 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 Urolithiasis.
  • 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 secondary to urolithiasis can also occur.
• Toxin:
  • Ethylene glycol, drugs such as gentamicin and sulfonamides.
  • Heavy metals, eg lead.

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/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 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:
    • 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.
    • Rare in guinea pigs.
  • Gastrointestinal disorders:
    • Anorexia Anorexia, ileus Gastrointestinal stasis.
    • 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).

Epidemiology

• Nephrosclerosis is considered common in laboratory guinea pigs >1 year of age.
• Chronic interstitial nephritis is common in guinea pigs >3 years of age.

Diagnosis

Treatment

Prevention

Outcomes