Introduction

• Acute kidney injury: the term acute kidney injury or AKI is now the preferred terminology when referring to acute damage occurring to renal parenchyma or rapid decline in renal function. It is recognized that acute kidney injury represents a spectrum of disease ranging from acute changes in renal function that may be clinically imperceptible through to complete failure of the kidneys to meet excretory, metabolic and endocrine demands. This stage may appropriately be termed acute renal failure (ARF) and renal replacement therapy may be considered. Further information regarding the recently released International Renal Interest Society AKI grading scheme can be found atwww.iris-kidney.com.
• Cause: pre-renal, intrinsic renal (toxins/drugs, infection, ischemia, vascular), post-renal (obstruction).
• Signs: dependent on severity of renal injury. At mildest clinical signs may not be apparent but AKI may be detected on the basis of biochemical, urinalysis, diagnostic imaging findings compatible with AKI. At most severe, typically short duration (<1 week) with clinical signs including lethargy, weakness, vomiting, diarrhea, anorexia, dehydration, neurological signs. Patients may present with oliguria (in most cases), anuria or polyuria (less commonly).
• Treatment: prompt therapy to maintain renal perfusion, remove toxin/drug exposure, limit renal damage, resolve any post-renal obstruction, provide on-going support for kidney.
• Prognosis: prognosis is dependent on extent of initial renal insult. Extensive renal damage will result in death (unless renal replacement therapy is provided). With less extensive renal insult prognosis for patient will depend on treatment of underlying cause of AKI and recovery of renal function. Full spectrum is possible from apparent recovery of renal function (subsequently categorized as IRIS stage I CKD due to prior known renal insult) through to IRIS stage IV CKD.

Pathogenesis

Etiology

• Organic compounds: ethylene glycol, certain pesticides and herbicides.
• Drugs:
  • Antibiotics:
    • Aminoglycoside-antibiotics (especially if overdosed or used in dehydrated/hypovolemic patient), cephalosporins, penicillins, sulphonamides, tetracyclines.
  • Antifungals:
    • Amphotericin B.
  • NSAIDs Analgesia: NSAID (especially in dehydrated/hypovolemic patient).
  • Angiotensin converting enzyme inhibitors ACE inhibitor: overview , especially with concurrent diuretic administration or administration in face of dehydration.
  • Diuretics.
  • Contrast agent.
  • Chemotherapy agents Chemotherapy: general principles :
    • Cisplatin Cisplatin , carboplatin Carboplatin , doxorubicin Doxorubicin , azathioprine Azathioprine , methotrexate Methotrexate.
  • Immunosuppressive agents:
    • Cyclosporine Ciclosporin.
• Heavy metals (mercury, lead, cadmium).
• Miscellaneous toxins: mushroom toxicity Mushroom poisoning , grapes/raisin toxicity Raisin poisoning , Vitamin D3 rodenticides Vitamin D poisoning (cholecalciferol).
• Endogenous toxins: myoglobin, hemoglobin.

Renal ischemia

• Prolonged dehydration.
• Hypovolemic shock Shock.
• Hemorrhage/trauma.
• Thromboembolism Kidney: thromboembolism.
• Anesthesia/surgery.
• Diuretics/vasodilators.
• Hemoglobin/myoglobin Myoglobinuria.
• Vasculitis Cutaneous vasculitis.
• Pancreatitis Pancreatitis: acute or other causes of systemic inflammatory response syndrome Systemic inflammatory response syndrome (SIRS).

Nephritis

• Infectious:
  • Bacterial (pyelonephritis) Kidney: pyelonephritis.
  • Spirochetal (leptospirosis).
• Acute glomerulonephritis Glomerulonephritis :
  • Infectious.
  • Immune complex mediated.

Other

• Post-renal urinary tract obstruction Urinary obstruction can result in intrinsic AKI if prolonged.
• Trauma Kidney: trauma.

Predisposing factors

• Any cause of reduced renal blood flow.

Specific

• Hypoperfusion: hypovolemia, decreased cardiac output, systemic hypotension, increased blood viscosity.
• Anesthesia/surgery, especially without appropriate blood pressure monitoring and IV fluid support.
• Administration/accidental misuse of known nephrotoxic medications, eg NSAIDs.
• Access to known nephrotoxins, eg ethylene glycol/grapes or raisins.
• Exposure to infectious agents, eg Leptospirosis.
• Pre-existing disease, eg cardiac disease, chronic kidney disease Kidney: chronic kidney disease (CKD).
• Sepsis Shock: septic , systemic inflammatory response syndrome, multi-organ dysfunction Multiple organ dysfunction syndrome (MODS).

Pathophysiology

• Pre-renal: insufficient delivery of blood to functional kidneys to allow adequate clearance of solutes and waste products.
• Intrinsic renal: damage to any section of the kidney, eg glomerulus, tubular cell, interstitium or vessels. Most is the result of acute tubular damage due to ischemic or toxic injury. Prolonged pre-renal hypoperfusion may lead to intrinsic kidney damage. Prolonged post-renal obstruction may also lead to intrinsic renal injury.
• Post-renal: urine leakage or obstruction at post-renal site, eg urethral obstruction Urethra: obstruction , bilateral ureteral obstruction or unilateral obstruction with single functioning kidney.
• Four phases of AKI:Initiation phase(inciting injury),extension phase(continued hypoxia and inflammatory response extends renal damage),maintenance phase(period of 1-3 weeks during which a critical degree of damage has occurred),recovery phase(increased urine output with variable sodium loss, regeneration of impaired tissue and nephrons may take weeks to months).

• Nephrons are damaged at different sites (glomerulus, tubular cell, intercellular junction, basement membrane) depending on etiology → acute decline in glomerular filtration rate due to intrarenal vasoconstriction and/or tubule dysfunction → hypoxia particularly affecting the medulla and mitochondrial damage → decreased availability of ATP leads to energy deficit → reduced activity of active transport pumps, eg Na+ K+ ATPase → disruption to concentration gradients → cell swelling, tubular obstruction and vascular congestion → cytoskeletal damage, impaired tubular cell polarity and redistribution of Na+ K+ ATPase pumps from apical to basolateral membrane, loss of tight junction function → cell sloughing and tubular obstruction (cell necrosis and aggregation with cast formation).
• Renal recovery → survival of sub-lethally injured tubular cells, which regain polarity and function.

Timecourse

• Animals may die acutely, especially if underlying etiology unknown, specific treatment not available and oliguria/anuria persists resulting in severe metabolic derrangements (eg hyperkalemia and metabolic acidosis).
• If treated appropriately, animals may recover, but recovery phase can take >3 weeks of intensive care with ultimate outcome being long-term chronic kidney disease

Diagnosis

Treatment

Prevention

Outcomes