Acute kidney injury

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Tubulointerstitial nephritis in a dog which died from acute renal injury associated with leptospirosis[1]

Acute kidney injury (AKI; acute renal failure; acute nephritis) is a collective term for any acute renal disease.

The term has replaced the historical term acute renal failure for renal damage occurring over a short period of time (hours to days) because it is thought to better describe the pathophysiologic changes and duration of the different phases of injury[2].

Acute kidney injury is caused by ischemia or chemical injury to the circulatory, filtration, tubulointerstitial or excretory system of the kidney, resulting in uremia and elevated levels of creatinine and other metabolic wastes and electrolyte, fluid and acid-base balance. Following ischemia, the reperfusion of the kidney results in a repair process involving proliferation of proximal tubular epithelial cells as well as cell migration and differentiation. In severe ischemia, repair progresses to scar formation and fibrosis of individual nephron with associated loss of function[3].

Renal ischemia is a common intra-operative and post-operative cause, and when the mean arterial pressure is less than 70 to 80 mm Hg, renal perfusion is compromised.

Clinically, acute renal injury can be classified into three broad stages of initiation (immediately following renal insult), maintenance (oliguria and uremia which may persist for weeks) and recovery (renal repair with marked polyuria).

Causes

There are numerous causes, including:

- Amyloidosis
- Ectopic ureter
- Ureteral stenosis[4]
- Fanconi's syndrome
- Polycystic kidney disease
- Renal agenesis
- Renal cystadenocarcinoma[5] - associated with dermatofibrosis in German Shepherds
- Renal dysplasia
- Renal hypoplasia (Ask-Upmark kidney)[6]
- X-linked hereditary nephropathy - Cocker Spaniel
- Familial juvenile glomerulonephropathy (autosomal-recessive) - French Mastiff, Bull Terrier
- Ethylene glycol[7], Zinc coins[8]
- Algal blooms[9]
- Drugs - Gentamycin, cisplatin[10], melamine and cyanuric acid feed additives[11]
- hemoglobinuria, myoglobinuria, hypercalcemia
  • Coagulopathies
- thromboembolism, DIC, cutaneous-renal vasculopathy, tumor lysis syndrome[12], heatstroke[13]
- Chronic prostatitis
- Chronic cystitis
- Leptospira spp
- Pyelonephritis
- Balamuthia mandrillaris
- Dioctophyme renale
- Pearsonema plica
  • Inflammatory
- Glomerulonephritis
- Urolithiasis
- Renal dysplasia
- Acute renal injury
- Angiomyxoma
- Lymphoma
- Oncocytoma
  • Secondary renal disease
- Psychogenic polydipsia
- Diabetes insipidus
- Diabetes mellitus
- Hyperadrenocorticism
- Hypoadrenocorticism
- Nephrotic syndrome

Diagnosis

Clinically affected dogs usually present with acute anorexia, lethargy, vomiting, oral ulcers, uremic breath and oliguria.

Physical examination findings often reveal dehydration but otherwise are usually not remarkable, although pain is occasionally elicited on palpation of the kidneys, which may be normal-sized to slightly enlarged[14]. Ultrasonography may reveal irregularly shaped or smaller kidneys. Normal sized kidneys are usually compared to vertebral length (renal:vertebral ratios usually 1.3 - 2.7[15])

Blood results usually show hyperphosphatemia and elevated levels of blood creatinine and BUN and marked proteinuria, and urine examination findings of hematuria, cylindruria with renal epithelial cells and leukocytes in the urine sediment are considered definitive findings.

Acute azotemia (elevated BUN and creatinine) and hyperphosphatemia are good prognostic indicators of survival rates, with elevated levels affording a poorer prognosis[16][17].

Acute kidney injury results in secondary diseases such as hypertension[18] and pulmonary alveolar mineralization[19], leading to greater risks of developing secondary pneumonia.

Diagnosis is usually based on evidence of exposure to toxins, presence of renal disease and hematological findings of markedly increased blood urea nitrogen and creatinine[20]. Other blood abnormalities usually reflect underlying causes of renal disease.

Staging of renal function in acute renal failure is usually based on the International Renal Interest Society (IRIS) categories:

Stage Creatinine level Blood pressure Clinical signs
Stage 1 ≤ 140 μmol/L ≤ 160 mm Hg Asymptomatic
Stage 2 140 - 200 μmol/L ~160 mm Hg Asymptomatic
Stage 3 180 - 440 μmol/L ≥160 mm Hg Uremic breath, dehydration, vomiting, dehydration
Stage 4 ≥ 440 μmol/L ≥160 mm Hg Uremic breath, dehydration, vomiting, dehydration, moribund

Renal ultrasonogrpahy or CT imaging are often employed to help visualize the physical extent of gross renal damage. Renal biopsies are indicated in patients hemodynamically stable enough to submit to general anesthesia.

Treatment

Dehydrated patients should be rehydrated before general anesthesia or administration of potentially nephrotoxic substances.

Aggressive use of intravenous fluids or intermittent hemodialysis are essential for renal recovery in the short-term and minimizing loss of nephron activity[21]. Use of diuretics such as furosemide are indicated in oliguric patients.

Nutritional support is critical in anorectic patients.

Response to intravenous fluids should be monitored with repeated measurements of urine output, urinalysis, and urine chemistry results[22].

Improved success rates have been noted in dogs with acute kidney injury secondary to leptospirosis[23].

Following recovery, a predisposition to developing chronic renal disease requires regular monitoring of blood creatinine levels on a 6 monthly basis.

References

  1. Iowa State Uni
  2. Ross L (2011) Acute kidney injury in dogs and cats. Vet Clin North Am Small Anim Pract 41(1):1-14
  3. Matsuda H et al (2011) HCaRG accelerates tubular repair after ischemic kidney injury. J Am Soc Nephrol 22(11):2077-2089
  4. Lam NK et al (2012) Endoscopic placement of ureteral stents for treatment of congenital bilateral ureteral stenosis in a dog. J Am Vet Med Assoc 240(8):983-990
  5. Zanatta M et al (2012) Nodular Dermatofibrosis in a Dog without a Renal Tumour or a Mutation in the Folliculin Gene. J Comp Pathol Aug 4
  6. Kolbjørnsen O et al (2008) End-stage kidney disease probably due to reflux nephropathy with segmental hypoplasia (Ask-Upmark kidney) in young Boxer dogs in Norway. A retrospective study. Vet Pathol 45(4):467-474
  7. Babski DM et al (2012) What is your diagnosis? Ethylene glycol intoxication. J Am Vet Med Assoc 240(12):1415-1417
  8. Weingart C & Kohn B (2009) Zinc intoxication in a Yorkshire Terrier due to Euro cent ingestion. Schweiz Arch Tierheilkd 151(2):75-81
  9. van der Merwe D et al (2012) Investigation of a Microcystis aeruginosa cyanobacterial freshwater harmful algal bloom associated with acute microcystin toxicosis in a dog. J Vet Diagn Invest 24(4):679-687
  10. McDuffie JE et al (2010) Urinary parameters predictive of cisplatin-induced acute renal injury in dogs. Cytokine 52(3):156-162
  11. Dorne JL et al (2012) Recent advances in the risk assessment of melamine and cyanuric acid in animal feed. Toxicol Appl Pharmacol Jan 25
  12. Martin A & Acierno MJ (2010) Continuous renal replacement therapy in the treatment of acute kidney injury and electrolyte disturbances associated with acute tumor lysis syndrome. J Vet Intern Med 24(4):986-989
  13. Acierno MJ (2011) Continuous renal replacement therapy in dogs and cats. Vet Clin North Am Small Anim Pract 41(1):135-146
  14. Merck Veterinary Manual
  15. Barella G et al (2012) A new method for ultrasonographic measurement of kidney size in healthy dogs. J Ultrasound 15(3):186-191
  16. Harison E et al (2012) Acute azotemia as a predictor of mortality in dogs and cats. J Vet Intern Med 26(5):1093-1098
  17. Lee YJ et al (2011) Prognosis of acute kidney injury in dogs using RIFLE (Risk, Injury, Failure, Loss and End-stage renal failure)-like criteria. Vet Rec 168(10):264
  18. Geigy CA et al (2011) Occurrence of systemic hypertension in dogs with acute kidney injury and treatment with amlodipine besylate. J Small Anim Pract 52(7):340-346
  19. Le Boedec K et al (2012) Pulmonary abnormalities in dogs with renal azotemia. J Vet Intern Med 26(5):1099-1106
  20. Thoen ME & Kerl ME (2011) Characterization of acute kidney injury in hospitalized dogs and evaluation of a veterinary acute kidney injury staging system. J Vet Emerg Crit Care (San Antonio) 21(6):648-57
  21. Eatroff AE et al (2012) Long-term outcome of cats and dogs with acute kidney injury treated with intermittent hemodialysis: 135 cases (1997-2010). J Am Vet Med Assoc 241(11):1471-1478
  22. Lunn KF (2011) The kidney in critically ill small animals. Vet Clin North Am Small Anim Pract 41(4):727-744
  23. Bersenas AM (2011) A clinical review of peritoneal dialysis. J Vet Emerg Crit Care (San Antonio) 21(6):605-617