Classifying Azotemia

Classifying Azotemia

• Azotemia involves elevated Blood Urea Nitrogen (BUN) and Creatinine (CREA) levels.
• Ultrasonography (USG) helps determine if azotemia is pre-renal, renal, or post-renal.

Prerenal Azotemia

• Decreased renal perfusion is the primary cause, often due to dehydration.
• Physical exam (PE) findings include tacky mucous membranes and skin tenting.
• Bloodwork indicates increased Packed Cell Volume (↑PCV), total protein (↑TP), and albumin (↑Alb).
• Urine Specific Gravity (USG) is concentrated as kidneys attempt to conserve water.

Renal Azotemia

• Intrinsic kidney disease causes nephron damage, occurring after roughly 75% nephron loss.
• Azotemia with isosthenuria (USG 1.008-1.012) is a key indicator, signifying impaired urine concentration/dilution.
• Cats can maintain some urine concentrating ability despite renal failure.
• USG assesses nephron functionality in urine concentration and dilution.

Postrenal Azotemia

• Obstruction of urine flow is the cause.
• Signalment and PE are important (e.g., castrated males more prone to obstructions).
• Clinical signs: straining to urinate, large bladder, potentially distended abdomen (uroabdomen).
• USG is variable based on obstruction duration/severity and kidney back pressure.

Differentiating Azotemias

• Thorough assessment of history, signalment, and PE findings is critical.
• Evaluate the patient's hydration status.
• Determine if factors like calcium or cortisol interfere with kidney concentration abilities.
• Azotemia + isosthenuria = renal disease unless proven otherwise.
• If urine concentration doesn't match hydration status, renal azotemia is likely.

Identifying Renal Disease - First Tier

• Initial evaluation includes:
  • BUN
  • Creatinine (CREA)
  • Urine Specific Gravity (USG)

Identifying Renal Disease - Second Tier (after confirming renal azotemia)

• Analytes include Phosphate, Calcium, Potassium, Sodium, Chloride, Bicarbonate, and Anion Gap

Phosphate (Phos)

• Look for hyperphosphatemia (↑PHOS).
• When Glomerular Filtration Rate (GFR) drops below 25% of normal, phosphorus excretion is impaired.
• High phosphorus can cause soft tissue mineralization if Ca x Phos > 70.
• Horses and cattle may or may not have hyperphosphatemia.

Calcium (Ca)

• Calcium levels vary (hypo-, normo-, hypercalcemia) based on species, cause, and renal failure stage.
• Measure ionized calcium (iCa2+); total calcium (tCa) might be elevated with normal/decreased iCa.
• Most animals with renal failure are normocalcemic, especially in early stages.
• Hypocalcemia develops as renal failure progresses due to:
  • Decreased renal calcium resorption
  • Reduced renal production of Vitamin D
  • Hyperphosphatemia
  • Tissue mineral deposition
• Renal Secondary Hyperparathyroidism (CKD-MBD): Hypocalcemia triggers PTH release, elevating calcium (primarily from bones); biochemical changes: azotemia, ↑Phos, N-↓Ca, ↑PTH.
• Hypercalcemia can occur in some patients:
  • Horses with renal failure (diet, excretion)
  • Some cats/dogs with chronic renal failure, possibly due to receptor abnormalities like "tertiary hyperparathyroidism," which is expected to cause hyposthenuria as calcium interferes with ADH receptors.
• Hypercalcemia can sometimes trigger renal disease.

Potassium (K)

• Hypokalemia occurs in chronic renal failure, mainly in cats ("hypokalemic nephropathy") and cattle, due to renal/salivary loss, anorexia, and metabolic alkalosis.
• Hyperkalemia occurs with decreased excretion in oliguria/anuria (end-stage chronic/acute renal failure) and metabolic acidosis (H+ moves intracellularly, K+ extracellularly); can be life-threatening in acute renal failure/urethral obstructions; consider spurious causes.

Sodium (Na) and Chloride (Cl)

• Typically normal in renal failure.
• Hyponatremia/hypochloremia can occur in chronic renal failure, mostly in horses/cattle (reduced intake) and dogs/cats; consistently found in uroabdomen.

Bicarbonate (HCO3) and the Anion Gap (AG)

• Metabolic acidosis is common in severe renal disease (acute/chronic).
• Mechanisms: increased urinary bicarbonate loss, reduced tubular H+ secretion, unmeasured anion production (sulfates/phosphates), leading to increased anion gap.

Proteinuria

• Protein in urine is measured via reagent strip, with color indicating protein concentration; most effective for albumin detection.
• Measurable albumin in urine can occur through glomerular leakage and/or enter after the glomerulus.
• Proteinuria categorized by source: prerenal, renal, postrenal.

Prerenal Proteinuria

• Increased small proteins in blood (hemoglobin, myoglobin, paraproteins like Bence-Jones) from physiologic conditions (hypertension, fevers, seizures, intense exercise).

Renal Proteinuria

• Glomerular: Damaged glomerular barrier (glomerulonephritis, amyloid deposition) causes filtration of larger proteins.
• Tubular: Defective proximal tubules (e.g., Fanconi's Syndrome) fail to resorb filtered proteins, usually associated with acute renal disease.

Postrenal Proteinuria

• Hemorrhage (RBCs/hematuria) or inflammation (WBCs/pyuria) in the urinary tract due to trauma, neoplasia, coagulopathy, or infections (UTIs, cystitis).

Urine Protein:Creatinine Ratio (UPCR)

• Quantifies proteinuria.
  • Normal: 0.5
  • Glomerular: >1.0 (most severe)
• Hypoalbuminemia occurs only with major glomerular proteinuria.

Glomerulonephropathy

• Signalment: Familial in some breeds (early onset), or due to chronic infectious/inflammatory issues/neoplasms (middle-aged/older dogs).
• History: Often asymptomatic; some sick with underlying disease.
• Pathogenesis: Renal glomerular damage affecting podocytes, antigen-antibody complex or amyloid deposition, podocyte retraction, filtration of larger, negatively-charged proteins.
• Look for: Moderate to marked hypoalbuminemia, moderate to marked proteinuria, +/- renal insufficiency.

Nephrotic Syndrome

• Protein-losing nephropathy (PLN) from glomerular disease leads to abdominal effusion; includes: 1. Proteinuria (glomerular), 2. Hypoalbuminemia, 3. Abdominal effusion (loss of oncotic pressure), 4. Hypercholesterolemia (mechanism unknown), 5. Hypercoagulable state (loss of antithrombin).

Acute Renal Failure (ARF)

• AKA Acute Kidney Injury (AKI).
• Presentation: Any signalment, sudden onset of signs (rapid sickness!).
• Physical Exam: Usually good Body Condition Score (BCS) at first.
  • GI: Anorexia, vomiting, diarrhea, halitosis (NH3).
  • Renal: Oliguric to anuric.
  • Neuro: Depressed to obtunded to non-responsive, seizures.
• Etiologies: Commonly toxicants (e.g., lily toxicity in cats), renal ischemia, infection (e.g., leptospirosis) that rapidly damage kidneys.
• Features: Significant drop in GFR causing azotemia; may be reversible/irreversible.
• Common Lab Findings:
  • Bloodwork: Rapidly developing azotemia, +/- hyperkalemia, +/- acidemia.
  • Urinalysis: Oliguria to anuria, USG variable, +/- proteinuria, +/- cellular casts (tubular cell damage).

Chronic Renal Failure (CRF)

• AKA Chronic Kidney Disease (CKD).
• Presentation: Usually geriatric, commonly cats, slow onset of signs.
• Etiology: Often irreversible chronic renal interstitial fibrosis in cats.
• Physical Exam: Typically poor BCS (thin, cachexic), dehydration.
  • GI: Anorexia, vomiting, diarrhea, halitosis (NH3).
  • Renal: Polyuric.
  • Neuro: Depressed.
  • Cardiovascular: Hypertension.
• End Stage: 2:1 is diagnostic.
• Azostick determination of abdominal versus blood BUN may be helpful if after-hour chemical measurements are unavailable.