Chronic kidney disease (CKD) is defined as structural or functional kidney abnormalities persisting for at least three months, or a reduction in glomerular filtration rate (GFR) by more than 50% from normal for the same duration.
Overview and Clinical Importance
Chronic kidney disease (CKD) is defined as structural or functional kidney abnormalities persisting for at least three months, or a reduction in glomerular filtration rate (GFR) by more than 50% from normal for the same duration. CKD affects approximately 0.5% to 1.5% of all dogs and is a leading cause of morbidity and mortality, particularly in geriatric patients. The disease is characterized by irreversible, progressive loss of functional nephrons and eventual replacement fibrosis.
| Category |
Examples |
| Acquired |
Tubulointerstitial nephritis (most common), glomerulonephritis, pyelonephritis, nephrolithiasis, neoplasia, amyloidosis |
| Congenital/Hereditary |
Renal dysplasia, polycystic kidney disease, hereditary nephropathy (glomerular basement membrane defects) |
| Toxic/Ischemic |
NSAIDs, aminoglycosides, ethylene glycol, grape/raisin toxicosis, hypoperfusion events |
| Idiopathic |
Age-related degeneration (geriatric onset CKD) - cause often unknown |
Etiology and Pathophysiology
Causes of Canine CKD
Pathophysiology of CKD Progression
Glomerular Hyperfiltration: When nephrons are lost, remaining nephrons increase their single-nephron GFR. This increases intraglomerular pressure, causing proteinuria, glomerulosclerosis, and progressive nephron destruction.
RAAS Activation: Angiotensin II vasoconstricts the efferent arteriole to maintain GFR but causes glomerular hypertension and promotes oxidative stress, inflammation, and fibrosis.
Proteinuria: Protein leakage is directly toxic to tubular cells and promotes tubulointerstitial inflammation.
Tubulointerstitial Fibrosis: The final common pathway. Loss of peritubular capillaries creates hypoxia that stimulates further fibrosis.
Renal Secondary Hyperparathyroidism: Decreased phosphorus excretion and calcitriol production trigger PTH secretion, causing bone demineralization.
High-YieldThe compensatory mechanisms of CKD (hyperfiltration, RAAS activation) may contribute MORE to disease progression than the original injury. This is why ACE inhibitors and renal diets are crucial - they interrupt this maladaptive cycle.
| Breed |
Disease |
Key Features |
| Samoyed |
X-linked hereditary nephropathy |
COL4A5 mutation. Males: proteinuria by 2-3 months, renal failure by 9-15 months. Females are carriers. |
| English Cocker Spaniel |
Autosomal recessive hereditary nephropathy |
COL4A4 mutation. Proteinuria by 4-6 months, death by 9-18 months. |
| Soft-Coated Wheaten Terrier |
Protein-losing nephropathy and enteropathy |
NPHS1/KIRREL2 mutations. Later onset (around 6 years). Often concurrent GI signs. |
| Chinese Shar-Pei |
Renal amyloidosis |
Secondary to Shar-Pei fever. Intermittent fever, hock swelling, kidney failure by 3-5 years. |
| Bull Terrier |
Polycystic kidney disease |
Autosomal dominant PKD. Screen with UPC ratio greater than 0.3. |
| Lhasa Apso, Shih Tzu |
Renal dysplasia |
Disorganized renal parenchyma with fetal glomeruli. Signs before 2 years. |
Breed Predispositions and Hereditary Nephropathies
NAVLE TipRemember 'SECS' for X-linked nephropathy: Samoyed, English Cocker Spaniel (autosomal), English Springer Spaniel. Young Samoyed male with proteinuria and rapid decline = hereditary nephropathy.
| Stage |
Creatinine (mg/dL) |
SDMA (ug/dL) |
Characteristics |
| Stage 1 |
Less than 1.4 |
Less than 18 |
Nonazotemic. May have renal abnormalities. |
| Stage 2 |
1.4 - 2.8 |
18 - 35 |
Mild azotemia. Usually no clinical signs. |
| Stage 3 |
2.9 - 5.0 |
36 - 54 |
Moderate azotemia. Systemic signs likely. |
| Stage 4 |
Greater than 5.0 |
Greater than 54 |
Severe azotemia. High uremic crisis risk. |
IRIS Staging System
The International Renal Interest Society (IRIS) staging system provides a standardized framework for classifying CKD severity. Staging should only be applied to stable, hydrated patients after excluding prerenal and postrenal causes.
IRIS CKD Staging Criteria for Dogs
Substaging Criteria
Proteinuria Substaging (UPC Ratio)
Blood Pressure Substaging
High-YieldSDMA elevates earlier than creatinine (25-40% nephron loss vs. 75%) and is NOT affected by muscle mass. Use SDMA to catch early CKD in patients with muscle wasting.
NAVLE Tip'1-2-5' for creatinine cutoffs: Stage 2 at 1.4, Stage 3 at 2.9 (round to 3), Stage 4 greater than 5.0. Report as: 'IRIS Stage X, P/NP/BP, AP status' (e.g., IRIS Stage 3, P, AP 2).
| Classification |
UPC (Dogs) |
Significance |
| Non-proteinuric (NP) |
Less than 0.2 |
Normal |
| Borderline (BP) |
0.2 - 0.5 |
Monitor closely |
| Proteinuric (P) |
Greater than 0.5 |
Treat with RAAS blockade |
Clinical Signs and Diagnosis
Clinical Signs by IRIS Stage
Ultrasound Findings in CKD
High-YieldSmall, irregular kidneys with hyperechoic cortices support CKD over AKI. However, ultrasound can be NORMAL in early CKD.
| Classification |
Systolic BP (mmHg) |
Risk |
| Normotensive |
Less than 140 |
Minimal |
| Prehypertensive |
140 - 159 |
Low - monitor |
| Hypertensive |
160 - 179 |
Moderate - treat |
| Severely Hypertensive |
180 or greater |
High - urgent treatment |
Treatment and Management
Stage-Based Treatment Priorities
Key Treatment Modalities
Renal diets have Grade 1 evidence: 70% reduction in uremic crisis risk and 3x longer median survival in Stage 2-3 CKD dogs. Features include phosphorus restriction, moderate protein restriction, omega-3 fatty acids, and alkalinization.
High-YieldACE inhibitors may cause mild creatinine increases (acceptable if no uremic signs). If azotemia significantly increases with clinical deterioration, reduce dose. Never start vasoactive drugs in dehydrated patients.
| Stage |
Clinical Presentation |
| Stage 1-2 |
Often subclinical. May have PU/PD (earliest sign), mild weight loss. Detection via routine screening. |
| Stage 3 |
Systemic signs: decreased appetite, nausea, intermittent vomiting, weight loss, lethargy, dehydration. |
| Stage 4 |
Uremic syndrome: persistent vomiting, anorexia, uremic breath, oral ulceration, melena, muscle tremors. |
Prognosis
Negative Prognostic Indicators: Proteinuria (UPC greater than 0.5), hypertension, anemia, low body condition score, hypoalbuminemia, calcium-phosphorus product greater than 70.
| Finding |
Significance |
| Increased cortical echogenicity |
Most common (47% Stage 2, 69% Stage 3, 91% Stage 4). Indicates fibrosis. |
| Loss of corticomedullary distinction |
Indicates chronic disease. Prevalence increases with IRIS stage. |
| Small kidney size |
Suggests advanced CKD with fibrosis exceeding compensatory hypertrophy. |
| Irregular renal margins |
Poor prognostic indicator. Associated with fibrosis, sclerosis, cysts. |
| Stage |
Treatment Priorities |
| Stage 1 |
Identify and treat underlying cause. Treat proteinuria if UPC greater than 0.5. Screen for hypertension. |
| Stage 2 |
Begin renoprotective treatments: renal diet, RAAS blockade. Phosphorus management (target less than 4.5 mg/dL). |
| Stage 3 |
Continue renoprotective treatments. Symptomatic treatment (antiemetics). Phosphate binders. Manage anemia and acidosis. |
| Stage 4 |
Focus on quality of life. Aggressive symptomatic management. Subcutaneous fluids. Consider hospice care. |
| Drug Class |
Examples |
Notes |
| ACE Inhibitors |
Enalapril, Benazepril |
First-line for proteinuria/hypertension in dogs. Monitor creatinine and potassium. |
| ARBs |
Telmisartan |
May be first-line for proteinuria per recent IRIS guidelines. |
| CCBs |
Amlodipine |
More potent antihypertensive. Often combined with ACE inhibitors. |
| Phosphate Binders |
Aluminum hydroxide, Calcium carbonate |
MUST give WITH food. Monitor calcium with calcium-based binders. |
| Antiemetics |
Maropitant, Ondansetron |
For uremic nausea/vomiting. Improves quality of life in Stage 3-4. |
| ESAs |
Darbepoetin |
For persistent anemia. Darbepoetin preferred (less immunogenic). |
| IRIS Stage |
Median Survival |
Notes |
| Stage 1 |
Greater than 400 days |
Best prognosis with early intervention |
| Stage 2 |
200-400 days |
Renal diet significantly improves survival |
| Stage 3 |
110-200 days |
Progressive; slow progression and manage symptoms |
| Stage 4 |
14-80 days |
Guarded to poor; focus on quality of life |