Here's how kidney injury can cause changes in kidney function, beginning with causes, phases, and signs of AKI, and how to assess kidney health after AKI.

  A first-of-its-kind veterinary test to detect kidney injury. Learn more about the IDEXX Cystatin B Test.

Kidney Injury vs. Kidney Function

Glomerular filtration rate (GFR) is most accurately used to measure kidney function. Veterinarians measure surrogate markers, such as symmetric dimethylarginine (SDMA), creatinine, and blood urea nitrogen (BUN), to facilitate the assessment. Kidney function measurement is similar to liver function measurement, with veterinarians using indicators of function such as bile acids, glucose, albumin, and BUN. When injury or destruction occurs to liver cells, alanine aminotransferase (ALT) levels increase, alerting the veterinarian to the problem.

When renal tubular epithelial cells are injured or destroyed, they release an intracellular protein called "cystatin B" into the urine. Cystatin B has been identified as a biomarker for kidney injury,²⁴ and since a test for kidney injury is not commercially available yet for use in veterinary patients, veterinarians must rely upon functional markers alone to determine whether injury has occurred. However, kidney function provides an incomplete picture; kidney injury may be subclinical or occur before changes in functional markers become evident. Cystatin B⁴² concentrations in urine may provide an opportunity to identify kidney injury irrespective of changes in functional markers.^43-44

Potential Causes of Kidney Injury in Pets

Prerenal

Prerenal causes refer to conditions that affect blood flow upstream to the kidney. These might include dehydration, hemorrhage, prolonged anesthesia, congestive heart failure (CHF), heatstroke, systemic inflammatory response syndrome (SIRS)/multiple organ dysfunction syndrome (MODS), and decreased renal perfusion caused by gastric dilatation and volvulus (GDV).

Renal

Renal causes refer to injuries that directly affect the kidneys and can be further categorized as:

• Infectious causes include leptospirosis, ehrlichiosis, Lyme disease, and sepsis.
• Noninfectious causes include neoplasia, trauma, drugs (such as nonsteroidal anti-inflammatories [NSAIDs], chemotherapeutic drugs, and aminoglycosides), and toxins (such as ethylene glycol, lilies in cats, grapes/raisins, and vitamin D).

Postrenal

Postrenal refers to causes downstream from the kidney such as urinary obstruction resulting from issues such as urethral plugs, urolithiasis, urethral stricture, or neoplasia.

Pathophysiology: Acute Kidney Injury in Pets

Acute kidney injury (AKI) typically refers to a sudden and severe event involving renal cellular damage and necrosis, resulting in an abrupt decline in kidney filtration rate. An AKI progresses through four disease phases.⁴²

1. Initiation
2. Extension
3. Maintenance
4. Recovery

Initiation Phase

The initiation phase occurs during or immediately after a kidney insult. At this time, the GFR decreases but obvious clinical signs of AKI aren't typically present. If the cause of the injury can be identified and removed during this stage, further disease progression may be prevented.

Extension Phase

In the extension phase, hypoxia, ischemia, and an ongoing inflammatory response result in continued insult to the kidney. During this phase, the GFR continues to decrease as renal tubular cells undergo apoptosis and necrosis. It is believed this stage lasts about one to two days.

Maintenance Phase

During the maintenance phase, the GFR stabilizes as kidney blood flow improves and cellular repair begins. Azotemia and potential uremic complications, such as vomiting, diarrhea, and polyuria/polydipsia can occur, explaining why AKI is typically diagnosed during this phase.

Recovery Phase

The final stage of AKI may last months to years while cellular repair occurs and GFR improves, albeit rarely to baseline prior to the initial insult. Depending upon severity of the insult, fibrosis may occur leading the patient to develop chronic kidney disease. Avoiding additional injury during this period is critical to preventing a relapse or further functional impairment.

Clinical Signs

Clinical signs are typically absent during the initiation and extension phases. When signs start to manifest, they are usually nonspecific and may include lethargy, vomiting, diarrhea, and anorexia. Oliguria, anuria, or polyuria may also be reported. If a patient is polyuric, they may also exhibit compensatory polydipsia. In severe cases, seizures may occur. Physical examination findings aren't usually specific to AKI and may include dehydration, halitosis, bradycardia, and scleral injection. Enlarged, painful kidneys may also be appreciated.

Early Detection

Early detection of kidney injury is critical to facilitate appropriate intervention to arrest or minimize renal tubular cell damage. Detection is difficult because clinical signs and laboratory changes in functional values such as SDMA and creatinine don't typically occur until maintenance phase of kidney injury, when significant insult to the kidney has already occurred.⁴² If injury is identified in the initiation or extension phases, an improved outcome may be possible, and this is why a novel injury marker, such as cystatin B, would be extremely helpful. Armed with this information, clinicians may be able to offer more timely and effective treatment that improves the prognosis for dogs and cats that have kidney injury.

Assessing Kidney Health

Ideally, a comprehensive assessment of a patient's kidney health should include kidney function, kidney injury evaluation, and ongoing monitoring, so the management plan can be adjusted as a patient's condition changes. Relevant kidney biomarkers include:

• Proteinuria. Increased macromolecule (i.e., predominantly albumin) filtration across the glomerulus results in proteinuria. Persistent proteinuria in the absence of lower urinary or reproductive tract disease typically indicates renal damage or dysfunction.

• GFR. GFR is the most accurate way to assess renal function, but the procedure is labor-intensive, time-consuming, and impractical in daily clinical practice.

• Creatinine. Creatinine is the most widely used indirect renal function biomarker, but creatinine levels do not increase until 75% of kidney function has been lost.^1,2,5

• SDMA. SDMA indicates kidney function decline earlier than other biomarkers, increasing on average with a 40% kidney function loss and with as little as a 25% function loss.^1,2,5

• Cystatin B. A cystatin B test may detect renal tubular epithelial cell injury with or without changes in functional markers^43,44 occur, offering an opportunity to intervene and potentially change the outcome for patients that have experienced kidney injury.

Kidney injury can range from mild with few or no clinical signs to severe with complete loss of function. Early detection and intervention are essential to provide the best prognosis for cats and dogs that experience kidney injury. Diagnostic tests of cystatin B may further improve and expand upon the care that veterinarians are able to provide for their patients.

 

References: IDEXX Kidney Health citations