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The “Ins and Outs” of
Chronic Kidney Disease in Dogs
Sabrina Clark, DVM, DACVP, PhDHeska CorporationAugust 19, 2021
Overview• Review • Diagnosis• Management Considerations• Monitoring• Future Directions• Questions
The Kidney
https://fineartamerica.com/featured/1-kidney-and-nephron-illustration-monica-schroeder.html
The Glomerulus
The glomerular filtration barrier
Ichimura K, et al., Scientific Reports, 2015
Renal Function• Glomerular filtration rate (GFR)– Most useful and sensitive test
1. Plasma iohexol clearance2. Plasma creatinine clearance
• Why use creatinine (CREA) as an indirect measurement?– Produced at a constant rate in vivo– Freely filtered by glomeruli– Minimally resorbed/secreted by tubules
[CREA]blood correlates with renal excretion
CREA
Chronic Kidney Disease (CKD)
End Stage Renal
Disease (ESRD)
Renal Fibrosis and CKD• Interstitial fibrosis is a characteristic finding– Correlates with decline of renal function
Masson’s Trichrome staining for collagen
International Renal Interest Society
www.iris-kidney.com
CKD in Dogs• Most common kidney disease• A leading cause of morbidity and
mortality• Severe disease at time of diagnosis• There is NO cure
– Focus on disease management
Causes of CKD
• Complex disease influenced by a combination of genetic, individual, and environmental factors
• Various “triggers” or risk factors– Familial Kidney Disease– Acquired Kidney Disease
• Glomerular disease**• Comorbid conditions
– Periodontal disease*• Chronic medication• Chronic infection
– Aging
Clues in the Clinical Signs• Polyuria/polydipsia
– Reported up to 6 months prior to diagnosis1
• Weight loss– Reported up to 4 months prior1
• Periodontal disease– Reported up to 1-year prior1
• Vomiting, lethargy, refusing to eat > 1 day1
1Bartlett, et al. Vet Med Int. 2010
Diagnosis of CKD• Glomerular filtration rate (GFR)• Renal biopsy• More commonly used:– Blood
• Blood urea nitrogen (BUN)• Serum creatinine (sCr)• Symmetric dimethylarginine (SDMA)
– Urine• Urine specific gravity (USG)• Urine protein:urine creatinine ratio (UPC)• Glucosuria (normoglycemic)
– Imaging
Limitations• Dehydration• BUN
– Influenced by:• Diet• Liver disease• Urinary flow rate
– GI bleeding• sCr
– Increased in heavily muscled dogs– Decreased in animals with muscle loss/cachexia– High individuality– Large variation in reference intervals– Compensatory hypertrophy of nephrons in early disease
The Diagnostic Challenge
i.e., FIBROSIS
sCr may remain within the reference interval or increase
slightly
Increase in sCr
Confirm Renal Azotemia• Differentiate:
– Pre-renal– Renal– Post-renal
• Any treatment that may influence concentrating ability?• Disorders that cause pre-renal azotemia with concomitant decreased USG
– Hypoadrenocorticism– Diabetes/DKA– Pyometra– HyperCa– Liver disease
***A urinalysis should ALWAYS be a part of the
minimum database.***
Keeping up with the CREA
• Monitor trends• Small but significant– Individual variation is minimal–
investigated• Keep it constant– Analytical variations
• Use in conjunction with SDMA to evaluate renal function
CREATININE
Symmetric dimethylarginine(SDMA)
• A methylated amino acid (arginine)– Produced in the nucleus of all cells– Eliminated by glomerular filtration
• Advantages over sCr– More sensitive to changes in GFR– Less influenced by extra-renal factors– Better suited for use in population-based reference intervals
• Must be interpreted in conjunction with hydration status
IRIS Staging
International Renal Interest Societywww.iris-kidney.com
IRIS Stage 1 CKD
• One or more of the following:– Either CREA or SDMA increasing within
the reference interval – Persistent increased in SDMA (>14 μg/dL)– Abnormal kidney imaging– Persistent renal proteinuria (UPC >0.5)
When to Biopsy• Renal Pathology
– Glomerular Disease• Persistent proteinuria
– Renomegaly (particularly a mass)– History of familial renal disease
• If results will alter treatment considerations• If results will alter prognosis• Monitoring response to treatment and determine
progression
https://vet.osu.edu/vmc/international-veterinary-renal-pathology-service-ivrps
CKD Management
• Goals:1. Control clinical signs of uremia2. Minimize disturbances
associated with fluid, electrolyte and acid-base balanceSupport adequate nutrition
4. Modify progression of CKD to prolong survival time and improve quality **Plan should be tailored to
individual needs**
CKD Management• Unlimited access to fresh water• Nutritional management is crucial– Proper diet can encompass:
• Benefits from reduced protein intake• Decrease phosphorous intake• Control Na/Cl consumption• Increased omega-• Increase antioxidants (Vitamins C and E)
– Considered at Stage 1 and when CREA >2.0 mg/dL
• Control proteinuria• Control hypertension
Monitoring• Depends on Stage of CKD
– Non-azotemia: every 6 months– Azotemia: every 2-– Uremia: every 2-4 weeks
• Any evidence of malnutrition• Should include:
– CBC (PCV/TS), Chemistry profile and UA– UPC– Blood pressure– +/- urine culture and imaging
• Trends in UPC– Decreased UPC with increased azotemia may reflect
glomerulosclerosis and obsolesence
FUTURE DIRECTIONS
microRNAs• microRNAs (miR)– Small non-coding RNAs– Important in biological
functions– Post-transcriptional gene
regulators– Highly conserved– Aberrant expression in
pathologic processes
Protein
miRNAs in Circulation miRNAs as Biomarkers
NormalAffected
miR-21
• miR-21– A crucial regulatory RNA– Vital role in fibrosis– Renal fibrosis correlates with decline of renal function
miR-21 Expression During Disease Progression
Mild azotemia
Marked azotemia(ESRD)
*= p-
Renal miR-21 Expression Correlates with Kidney Function
sCr (mg/dL)
r=0.7975
UPC
GFR (mL/min/kg)
r=-
In situ hybridization: miR-21
MS1 MS5
Unaf
fect
ed
MS1 MS5
Affe
cted
400X 400X 400X
Urinary Expression: miR-21
*= p-
*
Unaffected Affected
T1 T2T2 T1
Urinary Expression: miR-X
*
*= p-
*
Unaffected AffectedT1 T2 T1 T2
*
Urinary Expression: miR-Y
*
**
*= p-
*
Unaffected AffectedT1 T1T2 T2
Future Directions• Advance the understanding of molecular mechanisms of
disease development• Compliment traditional diagnostics tools
– Use as a supplemental tool in critically ill patients– Evaluate prognostic considerations– Improve approach to management– Monitor progression and response to treatment
• Production of potential therapeutic targets
CKD Key Points• Early detection is crucial
– You can diagnosis CKD without azotemia
• Pay attention to owner observations• Monitor trends in the individual patient• Main goal in management is improving quality and
quantity of life– Nutritional therapy is imperative– Not a “one size fits all” approachpp
Grant ID# D14CA-904
Thank you! Questions?yRemember to download the CE certificate in the handouts panel ofthe webinar control panel.NOTE: CE certificate not available for watching the recording.
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