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
Explain why urine protein should be measured
Urine protein should be measured because:
- It has prognostic significance in CKD
- In protein-losing nephropathies, severe proteinuria may be detected prompting further investigation - It is a therapeutic target - It may allow early detection of renal disease (prior to the onset of renal azotemia)
What is the gold standard to measure proteinuria
Urine protein/creatinin ratio (UPCR) is the gold standard because:
- It is inexpensive and very sensitive - By measuring a ratio the volume of urine produced in a day is corrected for so that a spot UPC is reflective of 24-hour protein loss
What is pre-renal proteinuria
Pre-renal proteinuria is characterized by increased protein in the blood overwhelming renal reabsorptive mechanisms
Serum total protein measurement will exclude pre-renal causes
What is renal proteinuria
Renal proteinuria usually results from glomerular disease
- The amount of protein lost into the urine depends on the quality of the filtration barrier and individual glomerular hypefiltration
What is post-renal proteinuria
Post-renal proteinuria occurs when a source of protein enters the urine after the kidneys (i.e., in the bladder or genital tract)
Cystitis is the most common cause
UPC should be interpreted only after resolution of any lower urinary tract inflammation
How UPCR evaluation can help localizing the disease process
Only 20 % or less of cats with CKD have a UPCR greater than 0.4 with the majority having UPCs of less than 0.2
Severely elevated UPCR results should prompt investigation for other diseases (e.g., glomerular diseases and amyloidosis)
Give your main differentials for proteinuria according to its localization
Pre-renal causes:
- Hemoglobin
- Myoglobin
- Bence-Jones proteins
Post-renal causes
- Lower urinary tract infection/inflammation
- Genital ttract infection/inflammation
Renal causes
- AKI
- CKD
- Pyelonephritis
- Fanconi syndrome
- Benign transient proteinuria
- Stress/exertion
- Pyrexia
Why is it important to perform a urine culture in a cat with CKD
Bacterial UTI is highly unsual in healthy, young cats
Up to 30% of cats with CKD may have a UTI and not all will have an active sediment
Culture should be performed on a cystocentesis sample
What are the advantages and disadvantages of radiography for upper urinary tract disease evaluation
Radiograhy allows measurement of renal size and assessment of shape
Radiography does not allow assessment of the cortex/medulla junction or other abnormalities that do not alter shape/size of the renal outline
In cats the normal renal size is assessed on a VD view by measuring L2
- The normal range is 2.4-3 times the length of L2
Radio-opaque ureteroliths/nephroliths may be visible
Bladder size can also be assessed
Explain indications and contra-indications of excretory urography
Excretory urography can be performed to:
- assess renal size and shape
- locate filling defects in the renal pelvis or ureters
- identify congenital defects (e.g., ectopic ureters, renal agenesis)
- rupture of the urinary tract
- pyelonephritis
The IVU is dependent on GFR and the opacity of the kidney will be affected by reduced GFR
It shouldn’t be performed in dehydrated patients or those with AKI (risk of reduction in GFR and hypersensitivity reaction)
What are the advantages of ultrasonography for evaluation of the upper urinary tract
It is non invasive and easy to perform
It allows assessment of the internal renal architecture including the capsule, cortex, medulla, pelvis and ureter
Ureteral obstruction can be identified
The bladder can be examined for uroliths, size and wall thickness
What are the ultrasonographic characteristics of the kidneys
Normal kidneys are less echogenic than the liver and spleen
The medulla is less echogenic than the cortex
Normal renal length is 3-4.3 cm
Could you give example of conditions associated with a medullary rim sign (an echogenic line at the cortico-medullary junction)
Ethylene glycol toxicity
FIP
Hypercalcemic nephropathy
Chronic tubulointerstitial nephritis
Explain why a renal biopsy is not required in the majority of feline CKD
It will only reveal the chronic tubular changes observed in this condition
Clotting ability should be assessed prior to renal biopsy
What are the indications for renal biopsy
Indications would include:
- Parenchymal abnormalities of the cortex seen on imaging, not consistent with CKD (e.g., a mass)
- Severe proteinuria
- Suspicion of lymphoma or FIP
What are the complications associated with renal biopsies
Complications can be significant and include:
- Hemorrhage
- Infarction and further renal damage
- Hydronephrosis (ureteral/pelvic blood clots)
All cats should be monitored for 24-48 hours and a brisk diuresis instigated during/post-procedure
