Proteinuria Flashcards
describe renal handling of protein
majority of proteins never filtered!!
in health, there is a negligible amount of protein in the urine
but if glomerular disease compromises the filtration barrier or if tubular disease compromises reabsorption, then there will be an increased amount of protein in the urine!
compare and contrast proteinuria and protein-losing nephropathy
proteinuria: abnormally high amount of protein in the urine regardless of origin/cause
protein-losing nephropathy: a GLOMERULAR disease that causes proteinuria
how does proteinuria result from CKD?
the maladaptations that result in elevated intraglomerular pressure also compromise the filtration barrier, allowing proteinuria!
then proteinuria triggers and inflammatory cascade which results in tubulointerstitial fibrosis and FURTHER progresses CKD
what does proteinuria cause/is associated with?
- accelerated progression of kidney disease
- decreased survival
- hypoalbunemia which decreases plasma oncotic pressure which causes edema and cavitary effusions
- imbalance in pro-coagulant and anticoagulant factors that can result in thromboembolic disease
- imbalance in lipoproteins that can result in hypercholesterolemia
- muscle wasting/muscle loss
describe screening tests for proteinuria
- urine dipstick result is influenced by urine concentration so the UPC is used to quantify proteinuria more objectively, taking away the influence of urine concentration
- negative result of dipstick = proteinuria unlikely!
- dipstick showing or greater than trace, may warrant UPC
describe the diagnostic workup/ main 3 questions when see proteinuria
- persistence: if I recheck, is it still there?
- localization: where is it coming from?
- magnitude: how much protein is there?
decribe proteinuria persistence
- rechecking to document persistence aims to distinguish between
-functional renal proteinuria: results from altered renal physiology during or in response to a transient phenomenon; mild and transient
–could be due to strenuous exercise, fever, seizure, exposure to extreme temperatures
-pathological renal proteinuria: caused by structural or functional lesions within the kidney; can be of any magnitude and duration
–if renal, could be due to glomerular, tubular, or interstitial causes
may skip this step if animal is presenting convincingly for persistent, pathologic proteinuria: severe or overt consequenes
describe proteinuria localization
prerenal: abnormal plasma content of proteins or systemic hypertension
renal: if you rule out prerenal and postrenal, THEN you can assume it’s renal; other evidence of renal disease may not be present!
-suggests pathological renal proteinuria and is the kind we worry about most in CKD
postrenal: protein is added to urine after it enters the renal pelvis, due to inflammation, infection, or neoplasia anywhere at or below the renal pelvis (including the repro tract)
just because there’s protein in the urine, it doesn’t mean it’s coming from the kidneys!
describe quantifying magnitude of proteinuria
only need to know magnitude if you think the proteinuria is of renal origin!
if the animal has a lower UTI, it needs antibiotics no matter how much protein in the urine!
(eval UPC for this)
- the higher the UPC, the more proactive you must be with investigation and therapy; you should also be very proactive in azotemic animals (higher protein load per nephron)
describe the goal of standard antiproteinuric therapy
aims to reduce glomerular filtration of plasma proteins by decreasing (normalizing) intraglomerular pressure via
- nutrition: modified protein content, omega-3 polyunsaturated fatty acid supplementation
- RAAS inhibitors: angiotensin converting enzyme inhibition or angiotensin receptor blockade
- anti-hypertensive therapy (if needed): RAAS inhibitors or calcium channel blockers
describe nutrition as an antiproteinuric therapy
- modified protein content:
-decreases the amount of protein presented to the glomerular filtration barrier
-decreases intraglomerular capillary pressure - omega-3 polyunsaturated fatty acids
-reduces generation of thromboxane A2, which resists the net increase in efferent arteriolar vascular resistance by producing more thromboxane A3 which causes vasodilation instead
describe antiproteinuric pharmacotherapy
- angiotensin II is the major contributor to increasing efferent arteriolar resistance, so therapy is aimed at decreasing (normalizing) glomerular capillary pressure by favoring efferent arteriolar dilation instead
- angiotensin converting enzyme inhibitors (end in -pril): inhibit the generation of angiotensin II via competitive inhibition of angiotensin I at the active site
- most ACE inhibitors are administered as pro-drugs: transformed in the liver into active metabolites (-pril to -prilat)
-enalapril is primary excreted by kidneys but benazepril is primary biliary excretion - angiotensin receptor blockers (-sartan) selectively bind to the angiotensin type I receptor to block binding of angiotensin II
-some administered as prodrugs (Losartan) but some (Telmisartan) are administered as active metabolites
-Losartan: both renal and biliary excretion
-Telmisartan: largely biliary excretion
-antiproteinuric efficacy: telmisartan more effective than ace inhibitors in dogs
describe ACE inhibitors and ARB use in kidney disease
- indications:
-renal proteinuria
-systemic arterial hypertension - possible adverse reactions:
-uncommon at starting dosages and in non-azotemic but
-GI: anorexia/vomiting
-azotemia
-hyperkalemia (less aldosterone = less secretion of potassium in the distal nephron)
-systemic hypotension
-monitor systemic blood pressure, serum creatinine and potassium for safety
-monitor UPC/BP for efficacy!
- contraindications:
-volume depletion or dehydration
-systemic hypotension
-severe hyperkalemia
-pregnancy (birth defects) - use carefully if/when:
-pre-existing azotemia (consider starting at lower dose)
-using concurrently with other drugs that interfere with systemic/renal hemodynamics or promote volume depletion (diuretics) - combining ACEi and ARB improves proteinuria reduction BUT increases the likelihood of adverse reactions- Dr. Lourenco does not recommend so DONT DO IT
in terms of monitoring your therapy of proteinuria, what is your goal?
at least a 50% reduction in UPC (ideally back to non-proteinuric) and no or minimal increase in creatinine and K+
HOWEVER there is a day-day variation in UPC in dogs with stable disease that could result in a greater change in higher magnitude of UPC elevation, so average 3 serial UPC or pool samples from 3 collections to monitor!
describe glomerular proteinuric kidney diseases presentation
- can present with renal azotemia and an intact concentrating ability!!
- almost always present with proteinuria though
