1. Etiology (Causes)

Chronic Kidney Disease (CKD):

• Primary Causes:

  • Chronic Hypertension: Long-term high blood pressure damages blood vessels in the kidneys, leading to progressive nephron loss.

  • Chronic Glomerulonephritis: Progressive inflammation of the glomeruli can lead to fibrosis and scarring.

  • Pyelonephritis: Recurrent or chronic kidney infections cause scarring and fibrosis.

  • Systemic Diseases: Conditions like diabetes mellitus, hypercalcemia, and hyperthyroidism can contribute to CKD progression.

  • Chronic Tubulointerstitial Diseases: Tubular damage and fibrosis due to persistent injury (e.g., nephrotoxins).

• Congenital and Hereditary Causes:

  • Polycystic Kidney Disease (PKD) and Fanconi Syndrome in some breeds like Persians (cats) and Basenjis (dogs).

Acute Kidney Injury (AKI):

• Primary Causes:

  • Toxins: Exposure to nephrotoxic substances like ethylene glycol, NSAIDs (e.g., ibuprofen, carprofen), aminoglycosides (e.g., gentamicin, amikacin), radiocontrast agents, and mycotoxins.

  • Ischemia: Sudden reduction in renal blood flow due to hypovolemia, shock, or cardiac failure leading to ischemic tubular injury.

  • Infection: Systemic infections such as leptospirosis and pyelonephritis can cause acute renal damage.

  • Obstruction: Urinary tract blockages (e.g., urolithiasis, neoplasia, or urethral obstruction).

  • Severe Dehydration: Persistent dehydration can lead to prerenal azotemia, a reversible form of AKI if managed promptly.

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2. Pathophysiology

Chronic Kidney Disease (CKD):

• Progressive Nephron Loss: In CKD, renal interstitial fibrosis (scarring) leads to a reduction in nephron number and function over months to years.

• Decline in Glomerular Filtration Rate (GFR): Progressive decline in kidney filtration capacity results in azotemia (elevated blood urea nitrogen [BUN] and creatinine levels), electrolyte imbalances (e.g., hyperphosphatemia, hyperkalemia), and metabolic acidosis.

• Compensatory Hyperfiltration: Remaining nephrons initially compensate for loss of function, which can accelerate the damage due to increased pressure.

• Uremic Syndrome: Accumulation of uremic toxins leads to systemic signs like vomiting, anorexia, weight loss, and oral ulcers.

Acute Kidney Injury (AKI):

• Tubular Necrosis: AKI primarily involves acute tubular necrosis (ATN), where the tubular cells die due to ischemia or toxins. This leads to loss of renal function and impaired urine concentration.

• Reversibility: Unlike CKD, AKI has the potential for complete recovery if the underlying cause is treated and kidney function is preserved during the acute phase.

• Impaired Filtration: AKI leads to sudden azotemia, hyperkalemia, and fluid overload. Urine output may decrease (oliguria) or stop (anuria).

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3. Clinical Signs

Chronic Kidney Disease (CKD):

• Early Signs:

  • Polydipsia (increased thirst) and polyuria (increased urination) due to the kidney’s inability to concentrate urine.

• Progressive Symptoms:

  • Anorexia, vomiting, lethargy, weight loss, and dehydration as kidney function worsens.

  • Oral ulcers and halitosis (uremic breath) due to toxin accumulation.

  • Hypertension is often present, leading to target organ damage.

  • Anemia (due to reduced erythropoietin production), hyperphosphatemia, and hyperkalemia in advanced stages.

Acute Kidney Injury (AKI):

• Acute Onset:

  • Vomiting, lethargy, depression, anorexia, and oliguria or anuria (low or no urine output).

  • Pain in some cases (e.g., if infection or obstruction is involved).

  • Dehydration: Often profound, with dry mucous membranes and skin tenting.

  • Azotemia and electrolyte imbalances (particularly hyperkalemia) may cause arrhythmias or seizures in severe cases.

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4. Diagnosis

Chronic Kidney Disease (CKD):

• Laboratory Tests:

  • Azotemia: Elevated BUN and creatinine concentrations (creatinine >1.6 mg/dL in dogs, >2 mg/dL in cats is concerning).

  • Urine Specific Gravity (USG): Typically below 1.030 (dogs) or 1.035 (cats) due to loss of concentrating ability.

  • Urinalysis: Proteinuria is common and can indicate glomerular involvement.

  • Electrolytes: Hyperphosphatemia, hypokalemia (due to tubular dysfunction), and metabolic acidosis (low bicarbonate).

  • Imaging: Small, irregular kidneys on ultrasound or radiographs in advanced stages.

  • Blood Pressure: Monitoring for hypertension (e.g., >160 mmHg in cats and dogs).

Acute Kidney Injury (AKI):

• Laboratory Tests:

  • Azotemia: Elevated BUN and creatinine (sharp rise within hours to days of the insult).

  • Urine Specific Gravity (USG): May be <1.030, indicating impaired concentrating ability.

  • Urinalysis: Presence of renal tubular epithelial cells, casts, and possibly hematuria.

  • Electrolytes: Hyperkalemia is common in AKI and may be life-threatening.

  • Imaging: Normal or mildly enlarged kidneys on ultrasound or radiographs.

  • Biopsy: May be required in severe cases to determine the exact cause of injury.

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5. Treatment

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Treatment for Chronic Kidney Disease (CKD)

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Fluid Therapy:

• Goal: Maintain hydration, manage electrolyte imbalances, and support kidney function.

  • Subcutaneous Fluids: Often used in mild to moderate CKD cases to maintain hydration.

    • Lactated Ringer's Solution or Plasma-Lyte A (used for long-term subcutaneous administration) can be given at 50-100 mL/kg/week, depending on the patient’s hydration status and clinical condition.

  • IV Fluids: In severe cases or during an acute crisis, IV fluids may be required to correct dehydration and stabilize the animal.

    • Lactated Ringer's or Plasma-Lyte at 20-40 mL/kg bolus followed by maintenance rate (typically 2-3 mL/kg/hr).

    • Monitor PCV/TP, urine output, and electrolyte levels closely during administration.

Phosphate Management:

• Goal: Control hyperphosphatemia, which can worsen CKD and cause mineral bone disorders.

  • Phosphate Binders: Essential for preventing hyperphosphatemia.

    • Phosbind® (calcium carbonate): 40-60 mg/kg PO BID.

    • Epakitin® (chitosan-based binder): 1-2 teaspoons/5 kg of body weight per day mixed with food.

  • Dietary Management: Renal-specific diets have lower phosphorus content, which helps manage hyperphosphatemia.

    • Hill's Prescription Diet k/d, Royal Canin Renal Support, or Purina Pro Plan Veterinary Diets NF Kidney Function.

Blood Pressure Control:

• Goal: Control hypertension to slow the progression of kidney disease.

  • ACE Inhibitors:

    • Enalapril: 0.25-0.5 mg/kg PO q12-24h.

    • Benazepril: 0.25-0.5 mg/kg PO q12-24h.

  • Angiotensin II Receptor Blockers (ARBs):

    • Telmisartan: 1-2 mg/kg PO once daily (preferred for cats with proteinuria and hypertension).

  • Calcium Channel Blockers:

    • Amlodipine: 0.1-0.2 mg/kg PO once daily, particularly useful for managing systemic hypertension in cats.

Potassium Supplementation:

• Goal: Correct hypokalemia, which is common in CKD.

  • Oral Potassium:

    • Potassium gluconate: 10-20 mEq/animal/day for oral supplementation, divided into 2-3 doses per day.

    • K-Dur® or Kaon® tablets: Available for use if potassium levels are critically low.

  • Monitor for hyperkalemia in cases of oliguric renal failure or if the animal is on potassium-sparing diuretics.

Erythropoiesis-Stimulating Agents (ESAs):

• Goal: Treat anemia secondary to CKD by stimulating erythropoiesis.

  • Darbepoetin alfa: 0.25-0.5 μg/kg subcutaneously every 2 weeks. Start with a lower dose, and adjust according to response.

  • Epoetin alfa: 100-200 IU/kg subcutaneously 2-3 times per week (less commonly used now due to a longer-acting alternative).

Managing Acidosis:

• Goal: Correct metabolic acidosis, common in CKD due to impaired renal acid excretion.

  • Sodium bicarbonate: 0.5-1 mEq/kg PO q8-12h for moderate acidosis.

  • Alternatively, potassium citrate (1 mEq/kg PO BID) can be used for mild cases.

Appetite Stimulants and Nausea Control:

• Goal: Improve appetite and reduce uremic nausea/vomiting.

  • Appetite Stimulants:

    • Mirtazapine: 0.1-0.3 mg/kg PO every 24 hours.

  • Anti-emetics:

    • Maropitant (Cerenia®): 1 mg/kg SC q24h for nausea/vomiting.

    • Ondansetron: 0.1-0.3 mg/kg IV or SC every 8-12 hours.

Dietary Management:

• Goal: Provide kidney-friendly nutrients and reduce renal workload.

  • Low-protein, low-phosphorus diet: Reduces renal stress and accumulation of nitrogenous waste.

  • Use of omega-3 fatty acids from fish oil (2-3 g per 5 kg of body weight) to help reduce inflammation.

Renal Transplantation:

• Consideration: In specialized referral centers, renal transplantation may be an option for suitable candidates (although rare and expensive).

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Treatment for Acute Kidney Injury (AKI)

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Fluid Therapy:

• Goal: Restore normal hydration status, support renal perfusion, and manage fluid balance.

  • Initial Resuscitation:

    • Lactated Ringer's or Plasma-Lyte at 20-40 mL/kg IV bolus for rapid resuscitation in dehydrated or shocky patients.

    • Subsequent Fluids: Maintenance rate of 2-3 mL/kg/hr depending on hydration status and clinical response.

  • Monitor urine output, PCV/TP, electrolytes, and blood pressure during fluid therapy.

Diuretics:

• Goal: Stimulate urine production and prevent fluid overload.

  • Furosemide (Loop diuretic):

    • 1-2 mg/kg IV or SC q12h initially. May need to increase the dose up to 4 mg/kg in some cases, but monitor for signs of dehydration or electrolyte imbalances.

  • Mannitol (Osmotic diuretic):

    • 0.5-1 g/kg IV as a bolus, followed by continuous infusion if necessary.

  • Monitor for overdiuresis (e.g., hypotension, electrolyte disturbances).

Addressing the Underlying Cause:

• Nephrotoxins: If AKI is due to toxin exposure (e.g., ethylene glycol, NSAIDs), rapid decontamination is crucial:

  • Activated Charcoal: Administer at 1-3 g/kg PO if ingestion was recent (within 1-2 hours).

  • Antidotes: For ethylene glycol toxicity, use fomepizole (20 mg/kg IV bolus, followed by 10 mg/kg IV q12h) or ethanol (5-10 mL/kg IV initially).

• Infection:

  • If infection (e.g., Leptospirosis or pyelonephritis) is suspected, initiate appropriate antibiotics.

    • Leptospirosis: Doxycycline (5-10 mg/kg PO or IV q12h) for 2-3 weeks.

Blood Pressure Management:

• Goal: Control blood pressure to prevent further kidney damage.

  • ACE Inhibitors (if hypertension is present):

    • Enalapril: 0.25-0.5 mg/kg PO q12-24h.

  • Hydralazine (for acute hypertensive crisis):

    • 0.5-1 mg/kg PO q8-12h, adjusting based on clinical response.

Electrolyte and Acid-Base Management:

• Goal: Correct electrolyte imbalances (especially hyperkalemia) and maintain acid-base balance.

  • Hyperkalemia: If potassium is elevated, use calcium gluconate (10-20 mg/kg IV slow push) and insulin/glucose therapy (regular insulin 0.25-0.5 U/kg IV + 2.5-5 g of dextrose IV).

  • Sodium Bicarbonate: For metabolic acidosis, administer 0.5-1 mEq/kg IV as needed.

Dialysis:

• Indication: If kidney function does not improve with medical management, consider hemodialysis or peritoneal dialysis in referral centers.

  • Dialysis can remove toxins, manage fluid balance, and correct electrolyte disturbances in severe cases of AKI.

Nutritional Support:

• Goal: Provide easily digestible, low-protein, high-calorie food to prevent malnutrition.

  • Enteral feeding (e.g., Hill's a/d or Royal Canin Recovery), via a feeding tube if the patient is anorexic.

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6. Prevention

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Chronic Kidney Disease (CKD):

• Management of Underlying Conditions:

  • Control hypertension and diabetes to slow the progression of CKD.

  • Regular monitoring of kidney function (especially in high-risk breeds and older animals).

• Dietary Adjustments:

  • Early dietary intervention with renal-supportive foods can help slow the progression of CKD.

• Hydration:

  • Ensure adequate water intake to support kidney function and manage polyuria.

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Acute Kidney Injury (AKI):

• Avoidance of Nephrotoxic Drugs:

  • Minimize the use of nephrotoxic drugs (e.g., NSAIDs, aminoglycosides) and radiocontrast agents.

• Early Intervention:

  • Treat underlying causes of AKI promptly, such as dehydration, infection, or toxin exposure.

• Hydration:

  • Ensure proper hydration in animals at risk, particularly during surgery or in critically ill animals.

• Regular Monitoring:

  • Monitor kidney function (BUN, creatinine, USG) in animals receiving potentially nephrotoxic drugs.