Investigation of upper urinary tract disease Flashcards
What is glomerular filtration rate and how can it be influenced
Glomerular filtration rate (=GFR) is the average flow of filtered fluid through the glomerular capillaries into the Bowman’s capsule
- Average GFR for a healthy 4.5 kg cat is 9 ml/minute
GFR is influenced by the hydrostatic and oncotic pressures in the glomerular capillary
- As dictated by the vasoconstrictive tone in the afferent (inflow) arteriole, versus the vasoconstrictive tone in the efferent (outflow) arteriole (which influences the hydrostatic pressure)
- As well as the protein content of blood being delivered to the glomerulus (which influences the oncotic pressure)
Explain how afferent and efferent arteriolar tone are influenced
Afferent and efferent arteriolar tone are influenced by:
- Tubuloglomerular feedback (= increased concentration of sodium chloride in the distal tubule)
- Renin-angiotensin system
What experimental methods exist to evaluate GFR
Experimental methods are:
- quite accurate ways to measure GFR
- availability limited
- costly and technically challenging
GFR is also affected by a number of factors including food intake, age, body size and hydration status so very difficult to standardise techniques
Exogenous creatinine clearance and inulin clearance
- GFR can be determined by plasma disappearance of these substances over time (as they are not excreted or re-absorbed)
- Lack of availability of medical-grade chemicals
Radioisotope studies
- Quantitative renal scintigraphy is a “gold standard” technique but requires specialist nuclear imaging facilities
Iohexol clearance
- Also regarded as a “gold standard” method
- The main limitation to performing this test in clinical practice is that it requires high performance liquid chromatography to measure the iohexol in serum samples
What is SDMA and why is it interesting in renal function evaluation
SDMA = symmetric dimethylarginine
SDMA is the metabolic product of methylation of the arginine residues of various proteins in the nuclei of all the cells in the body
SDMA does not undergo any further metabolism, and because it is a small, positively-charged molecule it is cleared freely from the serum via glomerular filtration, and it is not reabsorbed in the renal tubules
- Thus, the serum levels are a good marker for glomerular filtration rate
SDMA does not help in identifying the cause of kidney disease, and it cannot be used to differentiate between AKI and CKD
- It should be viewed in conjunction with other indicators of renal function, particularly urine specific gravity
Studies have shown SDMA to be a more sensitive test than creatinine in detecting CRD
- Elevations above the reference range begin at a loss of approximately 40 % of normal kidney function
- Unlike serum creatinine, SDMA is unaffected by the loss of muscle mass
Why is it important to measure phosphate in cats with renal disease
Hyperphosphatemia is common in AKI and CKD
- Phosphate will increase as GFR falls
- Impaired renal phosphate excretion is the most common cause of hyperphosphatemia in cats and dogs and usually develops when GFR has dropped to < 20 % of normal
Renal secondary hyperparathyroidism occurs at an early stage of CKD
- The use of renal diets with reduced phosphate has a positive impact on survival time
How is potassium level influenced by renal disease
Hypokalemia is not common in CKD
- Occurs in approximately 25% of cases
If severe it can cause muscle weakness (hypokalemic myopathy) and inappetence
Hypokalemia may be due to:
- Loss into the urine at higher tubular flow rate
- Lower potassium intake in the diet due to inappetence
- Activation of the renin-angiotensin-aldosterone system resulting in further potassium wasting
- Acidifying diets and metabolic acidosis commonly seen in CKD (mostly with severe renal disease) will also contribute to total body deficiency in potassium
What are the characteristics of the anemia seen in CKD and how would you explain it
A non-regenerative, normocytic, normochromic anemia is typically seen in CKD
- It may suggest chronicity in a case of acute-on-chronic renal disease
- Clinical signs resulting from this anemia would only be expected if the PCV falls below 20% and this usually occurs at a late stage of CKD
The cause of anemia is multifactorial in CKD:
- EPO deficiency (cats with CKD often have a relative EPO deficiency)
- Anemia of chronic disease
- Uremic effects (e.g., gastrointestinal bleeding, shortened RBC lifespan, erythropoietic inhibitors, reduced platelets function and bleeding)
What is blood urea nitrogen and what are its advantages and limits in evaluating glomerular filtration rate
Urea is synthesized by the liver as a result of protein catabolism and ammonia production
Serum urea is inversely proportional to GFR but is passively reabsorbed by the tubules, and more is absorbed with slow tubular flow rates
- Therefore, in states of dehydration or hypovolemia, more urea will be re-absorbed
- This explains the increase in urea alone seen in dehydration
Other influences on urea include:
- Protein intake
- Hepatic disease (e.g. portosystemic shunt)
- Endogenous protein catabolism (e.g, starvation, muscle wastage, corticosteroids)
What is serum creatinine and what are its advantages and inconvenients in evaluating GFR
Serum creatinine is a breakdown product of muscle phosphocreatine and is excreted almost entirely by glomerular filtration (not excreted or re-absorbed)
- Therefore it provides an estimate of GFR
- The relationship between GFR and serum creatinine is not linear but exponential (therefore large reductions in GFR early in the course of the disease may not increase creatinine)
Other influences on creatinine include:
- Muscle mass
- Age (e.g. young animals and older cats with muscle loss have lower levels)
- Non-creatinine chromogens are measured as creatinine and cause laboratory variations
- The reference range itself may not be correct for all cats (i.e., large cats may have normal higher levels such as with Greyhounds dogs)
- Hydration/volume status will affect GFR and therefore creatinine
Does the severity of azotemia have any prognostic value
The severity of azotemia is not prognostic in acute kidney injury, post-renal azotemia or acute on chronic kidney disease
It doesn’t predict the reversibility of the reduction in GFR
Does urea/creatinine alone help distinguish the different causes of azotemia
Assessment of urea/creatinine alone does not help distinguisjh pre-renal, renal or post-renal cause of the azotemia
For this urinalysis must be performed along with a full physical examination
Explain the different categories of urine according to the specific gravity and their implication for localising the renal lesion
Urine may be defined as isothenuric (SG = 1.007-1.015, same as glomerular filtrate), hyposthenuric (SG < 1.007) or hypersthenuric (SG > 1.015)
- Normal cats have a urine SG > 1.035 and this assessment is vital in distinguishing pre/renal/post-renal azotemia
- A value < 1.035 is indicative of reduced concentrating ability and suggests renal insufficiency
Most cats with AKI will be isosthenuric but cats with pre- or post-renal azotemia often have highly concentrated urine (> 1.045)
What is the significance of struvite crystals
The presence of struvite crystals is normal in many cats and does not indicate urolithiasis or mean a special diet should be prescribed
Struvite is the most common crystals seen and in the majority of cases is an incidental findings
What is the presence of calcium oxalate monhydrate crystals suggestive of
The presence of calcium oxalate monohydrate crystals in urine is highly suggestive of ethylene glycol toxicity in cats with AKI
Explain how proteins are prevented from passing from blood to urine through the glomerular membrane
Small amounts of protein are lost into normal urine but the passage is limited by the basement membrane according to the protein’s size and charge
- Negatively charged proteins are repelled by the basement membrane
- Proteins with molecular weights > 70000 Daltons do not usually pass
Any small proteins passing through should be re-absorbed by the tubules
