Acute and Chronic Kidney Disease in Horses

What is a rapid loss of renal function with or without structural changes?

AKI/ARF

What are the phases of AKI/ARF in order?

Early AKI (treatable and reversible) -> ARF (worsening azotemia; urinary volume changes; can be irreversible) -> CRF (may be subclincial)

T/F: Increases in creatinine can be significant even if still within the normal range, so you must always monitor at-risk patients.

True!

What are FIVE factors that increase the risk of AKI/ARF in horses?

1. Pre-renal conditions (hypovolemia/hypotension)

2. Post-renal conditions (LUTD)

3. Critical illness (SIRS, CV compromise)

4. Pigment nephropathy (hemoglobinuria/myoglobinuria)

5. Nephrotoxins (especially if hypovolemia/hypotension)

T/F: Prolonged post-renal azotemia increases the risk of AKI and is common in sick horses (colitis, pneumonia, etc.)

False! Prolonged PRE-renal azotemia increases the risk of AKI and is common in sick horses (colitis, pneumonia, etc.)

Name a few causes of hypotension and hypovolemia that can help contribute to AKI.

Hypotension: anesthesia, sepsis, SIRS

Hypovolemia: blood loss, diarrhea, enterogastric reflux

Post-renal conditions and AKI are more common in (adults/foals).

Foals (uroabdomen, concurrent systemic illness)

What are the TWO most common renal causes of AKI/ARF in horses?

1. Acute tubular necrosis (ATN)

2. Papillary necrosis

What are THREE rarer causes of AKI/ARF in horses or also are associated with CKD?

1. Acute interstitial nephritis

2. Pyelonephritis

3. Glomerulonephritis

What do we call direct or indirect damage to renal tubules?

Acute tubular necrosis (ATN)

What are FOUR major causes of ATN?

1. Ischemia (hypovolemia/hypotension)

2. Endogenous toxins (pigment nephropathy)

3. Drugs (aminoglycosides; oxytetracycline; polymyxin B)

4. Exogenous toxins (oak; vitamins D and K3)

Aminoglycosides bind —- on brush border of renal tubular —- cells, where cellular uptake and accumulation within the —- occurs.

Phospholipids

Epithelial

Lysosomes

What happens with appropriate dose interval vs over-accumulation of aminoglycosides?

Appropriate: no damage

Over-accumulation: tubular cell damage and death

What THREE things can worsen the risk of aminoglycoside toxicity?

1. Dehydration/hypovolemia

2. Concurrent renal injury

3. Overdose

—- is the commonly used aminoglycoside in adults while —- is common in foals, and therapeutic drug monitoring should be used in sick patients to adjust their dose intervals.

Gentamicin

Amikacin

What are the THREE pigments that can cause pigment nephropathy?

Myoglobin, hemoglobin, methemoglobin

What major cause of pigment nephropathy features myoglobinuria?

Rhabdomyolysis

What is the most nephrotoxic NSAID?

Phenylbutazone

What specific renal change is associated with NSAID toxicity? Why?

Papillary necrosis- papillae very sensitive to ischemia

Explain the pathophysiology behind NSAID papillary necrosis.

COX inhibition -> prostaglandin inhibition -> loss of blood flow protection, worsened when perfusion reduced

What will you see in early vs chronic papillary necrosis?

Early: microscopic hematuria

Chronic: nephrolithiasis

What condition is rare and hard to distinguish from ATN?

Acute interstitial nephritis (AIN)

What are the FOUR major causes of AIN?

1. Pyelonephritis (embolic/ascending infection; Lepto)

2. Immune-mediated

3. Drug reactions (beta lactams or sulfonamide antibiotics)

4. Aberrant parasitic migration (H. Gingivalis, D. Renale)

What is bacterial infection of the renal pelvis and parenchyma often leading to inflammation and necrosis of the tubulo-interstitium?

Pyelonephritis

What is the usual cause of pyelonephritis?

Ascending bacterial infections (stasis of urine second to LUTD -> ascending)

What are THREE major causes of ascending bacterial infection?

1. Bladder paralysis and sabulous

2. Recurrent cystitis or other UTI

3. Urolithiasis

What are TWO other rarer causes of pyelonephritis?

1. CKD (scarring; nephrolith)

2. Secondary to sepsis and neoplasia

Name at least THREE of the clinical signs of pyelonephritis.

Hematuria, pyuria, fever, weight loss, depression

What would you expect to see on urinalysis and ultrasound with pyelonephritis?

Urinalysis: bacteria, WBC

Ultrasound: nephrolith, ureterolith

What can aid diagnosis and treatment in a pyelonephritis case?

Ureteral catheterization with culture

What is glomerulonephritis most often caused by?

Immune-mediated secondary to viral/bacterial infection

What is the pathophysiology of glomerulonephritis?

Immune complex in glomerulus -> inflammation and glomerular barrier damage

What are the TWO sequelae of glomerulonephritis?

1. Proteinuria

2. Secondary development with CKD

T/F: Glomerulonephritis is rarely the primary cause of CKD and is more often a component of AKI.

False! Glomerulonephritis is rarely the primary cause of AKI and is more often CKD.

What is the progressive loss of renal function over time that can be either rapid or prolonged in progression?

CKD

T/F: CKD features multiple causes that ultimately lead to destruction of entire nephron, but histopathologic changes are typically not disease specific.

True!

T/F: CKD is just as common in horses as it is in small animals.

False! CKD is INFREQUENT relative to small animal cases, but is often under-reported in horses.

CKD is usually (congenital/acquired), especially in (younger/older) horses.

Acquired

Older

Regardless of the inciting cause, what is CKD noted for?

Progressive nature of disease

T/F: The ability of remaining functional kidney to maintain GFR and tubular function contributes to disease progression.

True!

What is the final stage of CKD?

End-stage kidney disease

What does end-stage kidney disease look like grossly and microscopically?

Grossly: pale, shrunken, firm and irregular

Histo: interstitial fibrosis

Is congenital or acquired CKD most common?

Acquired

What is the most likely cause of acquired CKD and why?

Chronic interstitial nephritis (CIN)- previous event of ATN secondary to renal insult (like NSAIDs)

What are TWO rare causes of acquired CKD?

Neoplasia and amyloidosis

———— is associated with CKD typically secondary to widespread renal damage and less commonly with previous immune-mediated events.

Glomerular disease

How would a congenital CKD present?

Name at least TWO possible causes.

Young horse with no previous ARF history

Polycystic kidney disease, renal agenesis/hypoplasia/dysplasia

What is the initiating cause of a chronic interstitial nephritis (CIN)?

Previous renal insult

T/F: A specific cause is typically identified in a CIN.

False! It is NOT typically identified.

What is the hallmark feature of CIN?

Interstitial FIBROSIS

T/F: CIN presents like CKD clinically.

True!

Amyloidosis ccomes rom systemic disease and increased production of what?

Serum amyloid A

T/F: Renal amyloidosis is more common in horses than cattle and dogs.

False! UPPER AIRWAY, SKIN, AND LIVER amyloidosis is more common in horses than cattle and dogs.

Renal neoplasia is typically rare and (unilateral/bilateral).

Name the TWO most common neoplasms.

Unilateral

Renal carcinoma and lymphoma

What is the most common clinical indicator of CKD in horses?

Chronic weight loss

Name at least FIVE other clinical signs of CKD in horses.

Ventral edema, PU/PD, lethargy or poor performance, uremic halitosis, oral/gastric ulcers, small and irregular kidneys

What would you expect to see on ultrasound for CKD? (2)

1. Increased echogenicity (fibrosis)

2. Small and irregular shape

T/F: A CRF horse will always have azotemia.

True!

Describe the creatinine levels in terms of prognosis.

What TWO lab findings are common, which is relatively common, and which is less common with CRF?

Common: Isosthenuria, hypercalcemia

Relatively common: anemia

Less common: hypoalbuminemia (impaired glomerular function)

What finding is highly specific for CKD?

Azotemia with hypercalcemia

What are the THREE major principles of treating AKI/ARF in horses?

1. Correct predisposing disorders/stop nephrotoxic medications

2. Fluid therapy

3. Monitor- weight, creatinine, electrolytes

Is IV or oral fluids preferred in AKI horses?

IV

What are the TWO major goals of AKI/ARF fluid therapy?

1. Euvolemia to maintain RENAL PERFUSION

2. Diuresis to correct UREMIA and tubular obstructions

T/F: Extra fluids can help the kidney heal faster.

False! Extra fluids DO NOT make kidneys heal faster.

T/F: Uremia makes a patient feel sick.

True!

Diuretics may facilitate removal of —- and —- in the tubules.

Casts

Pigments

In a non-oliguric/anuric AKI fluid therapy plan, you can correct deficits over ———- and diuresis over ————.

24 hours

48-72 hours

Pre-renal azotemia should improve/correct within how long?

24 hours

T/F: You can start with small boluses (10L) to avoid fluid overload.

True!

T/F: You should monitor weight gain (

True!

What are THREE outcomes of a fluid therapy plan?

1. Deficits corrected

2. Azotemia improved

3. Polyuria (

What is the prognosis if creatinine is normalized and is polyuric?

What is the prognosis if creatinine still increased but urinating?

Good

Guarded to poor

What should your next steps be if creatinine is still increased but the horse is urinating?

Monitor over few months -> if does not normalize, permanent renal damage -> manage CRF

What is the difference between oliguria and anuria?

Oliguria:

What are at least FOUR things that indicate fluid overload?

Weight gain (>5%), edema, poor/no urine output, tachycardia, jugular vein distention, hypertension, hyperkalemia

How do you treat AKI with oliguria/anuria?

What is the first choice?

Diuretic ONLY after correction of deficits

Furosemide

If oliguria or anuria persists ———, there is a grave prognosis.

>48 hours

What is not practical but has been described in horses and foals?

Peritoneal dialysis

—- improve renal perfusion and urine production.

Diuretics

What is the MOA of furosemide, the first choice diuretic?

Loop diuretic (thick ascending LoH)- inhibit Na+ resorption

What are the pros and cons of using furosemide in horses?

Pro: renal protectant; increase urine output

Con: electrolyte loss (Na, K, Mg) with repeated administration

T/F: Efficacy of furosemide may be reduced with renal disease.

True!w

What is the most important electrolyte imbalance with oliguria/anuria in AKI?

Hyperkalemia (>6)

CKD is primarily —- to prevent further loss of renal function.

Palliative

What is the goal of CKD treatment?

Maintain quality of life

What are THREE ways to maintain quality of life with CKD treatment?

1. Treat acute exacerbations and underlying disease if possible

2. Prevent complicating conditions associated with uremia (oral/gastric ulcers)

3. Supportive care

What are THREE ways to treat acute exacerbations and underlying disease if possible?

1. Intermittent diuresis to reduce uremic toxins/hypercalcemia

2. Antimicrobials if pyelonephritis

3. Remove urinary calculi if present

What are FIVE features of supportive care in CKD?

1. Palatable/good quality diet

2. Access to water

3. Monitor/prevent weight loss

4. Avoid nephrotoxic agents

5. Supplement electrolytes as needed

What are THREE good quality diet features in management of a CKD horse?

1. Avoid high protein/Ca2+ feed (ALFALFA)

2. Good grass hay

3. Carbs

T/F: CKD progression is variable and long-term prognosis is ultimately poor.

True!

What THREE things influence CKD prognosis?

1. Azotemia/Creatinine

2. Body condition

3. Appetite

Define CKD by creatinine levels and state timeline of prognosis.