ISSN 2398-2985      

Interstitial nephritis

Jreptile
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, celioscopy, 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.
    • 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: antigen-antibody complex deposition and resultant interstitial nephritis.
  • Viral infection.
  • Fungal infection, eg Histoplasma capsulatum: lesions containing histiocytes with basophilic round or ellipsoid cytoplasmic bodies were identified in the kidneys as well as other organs.
  • Parasitic infection, eg Hexamita spp Flagellate / ciliate infection:
    • Thought to have direct life cycles, with tubulointerstitial nephritis a result of ascending infection from the cloaca.
    • Considered a significant but poorly understood pathogen.
    • Most commonly reported in chelonians but also reported in squamates.
    • Flagellated eukaryote parasite.
  • 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 Cystic calculi.
    • 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 Gentamicin and sulfonamides.
    • Heavy metals, eg lead.
  • Suboptimal husbandry Chelonia husbandry Lizard husbandry Snake husbandry:
    • Of particular importance in the development of reptilian renal disease Renal disease.
    • Chronic subclinical dehydration:
      • Inappropriate methods of delivery of water sources for the species.
      • Lack of sufficient environmental humidity.
    • Excess dietary protein Chelonia nutrition Lizard nutrition Snake nutrition:
      • Common in herbivorous species.
      • Adult omnivorous reptiles, eg Bearded dragons Bearded dragons (Pogona vitticeps) fed a largely insectivorous diet.
    • Excessive Vitamin D3 supplementation: renal mineralization.
    • Hypovitaminosis A Hypovitaminosis A: squamous metaplasia of renal epithelium and resultant loss of functional nephrons.
    • Improper temperature provision: renal metabolism slower if preferred optimal temperature zone is not achieved, impacting sufficient excretion of uric acid.

Predisposing factors

General

  • Suboptimal husbandry and sanitation.
  • Chronic dehydration.

Specific

  • Exposure to known nephrotoxins.
  • Neoplasia more common in aged animals.
 The reader is encouraged to become familiarized with normal reptilian renal anatomy and physiology Chelonia anatomy and physiology Lizard anatomy and physiology Snake anatomy and physiology, which can confer particular considerations when managing reptilian patients with renal disease.

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, 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:
      • 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.
      • Must be differentiated from nutritional secondary hyperparathyroidism Metabolic bone disease.
      • Typically manifest as signs associated with hypocalcemia.
    • Gastrointestinal disorders:
      • Anorexia Anorexia, nausea, ileus.
      • Weight loss can result from malnutrition but also from metabolic derangement and catabolic factors such as acidosis.
      • Uremic gastritis and stomatitis 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.
  • Johnson J G & Watson M K (2020) Diseases of the reptile renal system. Vet Clin North Am Exotic Anim Pract 23 (1), 115-129 PubMed.
  • Parkinson L A & Mans C (2020) Evaluation of subcutaneously administered electrolyte solutions in experimentally dehydrated inland bearded dragons (Pogona vitticeps). Am J Vet Res 81 (5), 437-441 PubMed.
  • Schmidt L, Di Girolamo N & Selleri P (2020) Diagnostic imaging of the reptile urinary system. Vet Clin North Am Exotic Anim Pract 23 (1), 131-149 SciDirect.
  • Wilkinson S L & Divers S J (2020) Clinical management of reptile renal disease. Vet Clin North Am Exotic Anim Pract 23 (1), 151-168 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.
  • Music M K & Strunk A (2016) Reptile critical care and common emergencies. Vet Clin North Am Exotic Anim Pract 19 (2), 591-612 PubMed.
    Dallwig R (2010) Allopurinol. J Exotic Pet Med 19 (3), 255-257 SciDirect.

Other sources of information

  • Divers S J & Innis C J (2019) Urology. In: Mader's Reptile and Amphibian Medicine and Surgery- E-Book. Eds: Divers S J & Stahl S. Saunders, 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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