STEUP Renal and Genitourinary System: Proteinuria and Hematuria Flashcards
What is proteinuria defined as?
Urinary excretion of >150mg protein/24 hours
What are the classifications of proteinuria causes?
1) Glomerular
2) Tubular
3) Overflow proteinuria
4) Other causes of proteinuria (all of the following can affect renal blood flow)
a) UTI
b) Fever, heavy exertion/stress, CHF
c) Pregnancy
d) Orthostatic proteinuria - occurs when the patient is standing but not when recumbent; self-limited and benign
What is glomerular proteinuria due to? What can it lead to? When can it be seen? Is it severe?
1) Due to increased glomerular permeability to proteins
2) Can lead to nephrotic syndrome
3) May be seen in all types of GN
4) Protein loss tends to be more severe than in nonglomerular causes
What happens in tubular proteinuria? Is it severe? What are causes?
1) Small proteins normally filtered at the glomerulus then reabsorbed by the tubules appear in the urine because of abnormal tubules (i.e., due to decreased tubular reabsorption)
2) Proteinuria tends to be less severe
3) Causes include sickle cell disease, urinary tract obstruction, and interstitial nephritis
What is overflow proteinuria?
Increased production of small proteins overwhelms the tubules’ ability to reabsorb them (e.g., Bence Jones protein in multiple myeloma)
What are the key features of nephrotic syndrome?
1) Urine protein excretion rate > 3.5g/24 hours
2) Hypoalbuminemia
3) Edema
4) Hyperlipidemia and lipiduria
5) Hypercoagulable state
6) Increased incidence of infection
Why do you get hypoalbuminemia in nephrotic syndrome?
Hepatic albumin synthesis cannot keep up with these urinary protein losses. The result in decreased plasma oncotic pressure, which leads to edema
Why do you get edema in nephrotic syndrome?
This is often the initial complaint (from pedal edema to periorbital to anasarca, ascites, pleural effusion), and results from hypoalbuminemia. Increased aldosterone secretion exacerbates the problem (increases sodium reabsorption)
Why do you get hyperlipidemia and lipiduria in nephrotic syndrome?
Increased hepatic synthesis of LDL and VLDL because liver is revving up albumin synthesis
Why do you get a hypercoagulable state in nephrotic syndrome? What is the patient at increased risk for?
1) Hypercoagulable state due to loss of certain anticoagulants in the urine
2) Increased risk of thromboembolic events (deep venous thrombosis, pulmonary embolism, renal vein thrombosis)
Why do you get an increased incidence of infection in nephrotic syndrome?
Results from loss of immunoglobulins in the urine
What kind of disease does nephrotic syndrome usually indicate? What is the underlying cause of nephrotic syndrome?
1) Significant glomerular disease (either primary or secondary to systemic illness)
2) The underlying cause is abnormal glomerular permeability
What are different types of causes of nephrotic syndrome?
1) Primary glomerular disease (50% to 75% of cases of nephrotic syndrome)
2) Systemic disease
3) Amyloidosis, cryoglobulinemia
4) Drugs/toxins
5) Infection
6) Multiple myeloma, malignant HTN, transplant rejection
What are the primary glomerular diseases that cause nephrotic syndrome?
1) Membranous nephropathy is most common in adults (40% of cases)
2) Focal segmental glomerulosclerosis (FSGS) (35%)
3) Membranoproliferative GN (15%)
4) Minimal change disease (MCD) is the most common cause in children (75% of cases)
What are the systemic diseases that cause nephrotic syndrome?
1) Diabetes
2) Collagen vascular disease
3) SLE
4) RA
5) Henoch-Schonlein purpura
6) Polyarteritis nodosa (PAN)
7) Wegener granulomatosis
What are the drugs/toxins that cause nephrotic syndrome?
1) Captopril
2) Heroin
3) Heavy metals
4) NSAIDs
5) Penicillamine
What are the three classes of infections that cause nephrotic syndrome?
1) Bacterial
2) Viral
3) Protozoal
What is the first test that can be done in diagnosis of nephrotic syndrome? What is it specific for? How is it graded? What is a disadvantage of the test that can lead to false-negative results?
1) Urine dipstick test (read color changes)
2) Specific for albumin - detects concentrations of 30 mg/dL or higher
3) Graded 0, trace, 1+ (15 to 30 mg/dL) through 4+ (>500 mg/dL)
4) More sensitive to albumin than to immunoglobulins, thus can lead to false-negative results when predominant urinary protein is globulin (e.g., light chains in myeloma)
What is the initial test to diagnose nephrotic syndrome once proteinuria is detected by dipstick test? Why is examination of urine sediment important? What should you do if urinalysis confirms the presence of protein?
1) Urinalysis
2) Examination of urine sediment is important because:
a) RBC casts suggest GN
b) WBC casts suggest pyelonephritis and interstitial nephritis
c) Fatty casts suggest nephrotic syndrome (lipiduria)
3) A 24-hour urine collection (for albumin and Cr) is appropriate to establish the presence of significant proteinuria
What does a test for microalbuminuria correspond to (in terms of amount of albumin excretion)? Why is this better than a standard dipstick? What should you do if the test is positive? What can microalbuminuria be an early sign of?
1) Corresponds to albumin excretion of 30 to 300mg/day
2) This is below the range of sensitivity of standard dipsticks. Special dipsticks can detect microgram amounts of albumin
3) If the test result is positive, perform a radioimmunoassay (the most sensitive and specific test for microalbuminuria)
4) Microalbuminuria can be an early sign of diabetic nephropathy
What are some other tests besides urine dipstick test, urinalysis, and microalbuminuria that can be used to determine the etiology (may or may not be necessary depending on the case) of nephrotic syndrome? Which is the best test of renal function? What is a CBC used for in renal failure?
1) Cr clearance - best test of renal function
2) Serum BUN and Cr
3) CBC - to detect anemia due to renal failure
4) Serum albumin level - varies inversely with degree of proteinuria
5) Renal ultrasound - to detect obstruction, masses, and cystic disease
6) Intravenous pyelogram (IVP) - to detect chronic pyelonephritis
7) ANA levels (lupus), antiglomerular basement membrane, hepatitis serology, antistreptococal antibody titers, complement levels, cryoglobulin studies
8) Serum and urine electrophoresis (myeloma)
9) Renal biopsy - if no cause is identified by less invasive means
What is the treatment of asymptomatic proteinuria in nephrotic syndrome?
1) If it is transient, no further workup or treatment is necessary
2) If it is persistent, further testing is indicated. Start by checking BP and examining urine sediment. Treat the underlying condition and associated problems (e.g., hyperlipidemia)
What should you first treat in someone with symptomatic proteinuria in nephrotic syndrome? What drug can be used to reduce proteinuria? What drug can be used if edema is present? What should be limited in the diet? What component of the serum that is elevated should be treated and how? What vaccinations should be given and why?
1) Further testing is always required
2) Treat the underlying disease (diabetes, multiple myeloma, SLE, minimal change disease)
3) ACE inhibitors (ARB cannot tolerate ACE) - these decrease urinary albumin loss. They are an essential part of treatment for diabetics with HTN and should be started before fixed albuminuria is present
4) Diuretics - if edema is present
5) Limit dietary protein and sodium
6) Treat hypercholesterolemia (using diet or a lipid-lowering agent)
7) Vaccinate against influenza and pneumococcus - there is an increased risk of infection in these patients
What is the different between asymptomatic transient and persistent protenuria?
1) Asymptomatic transient proteinuria has an excellent prognosis (no further evaluation necessary)
2) Asymptomatic persistent proteinuria and symptomatic proteinuria require further workup (high chance of renal disease in these patients)
What are three key features of nephrotic syndrome?
1) Proteinuria
2) Hypoalbuminemia
3) Hyperlipidemia
How should a urine sample be collected?
A clean-catch, midstream urine sample (after cleaning urethral meatus) is usually adequate for urinalysis and urine culture in adults
What steps does urinalysis consist of?
1) Visual inspection of urine - examine color, clarity
2) Dipstick reactions
3) Microscopic examination of urine sediment
What are the different components of a urine dipstick?
1) pH - this depends on acid-base status. The average is about 6, but can range from 4.5 to 8.0
2) Specific gravity - this is directly proportional to urine osmolality (and therefore solute concentration in urine). Normal is 1.002 to 1.035. It increases with volume depletion and decreases with volume overload. Appropriate changes in specific gravity with volume status of the patient indicate adequate tubular function (i.e., renal concentrating ability)
3) Protein - proteinuria is defined as > 150mg/day; nephrotic syndrome, >3.5g/day. The following are rough guidelines: Trace = 50 to 150mg/day; 1+ = 150 to 500mg/day; 2+ = 0.5 to 1.5g/day; 3+ = 2 to 5g/day; 4+ = >5g/day
4) Glucose - excessive glucose indicates diabetes. Absence of glucosuria does not rule out diabetes, however
5) Blood - hematuria
6) Ketones - DKA, starvation
7) Nitrite - suggests presence of bacteria in urine
8) Leukocyte esterase - suggests presence of WBC in urine; if negative, infection is unlikely
What should you look for in microscopic examination of urine sediment for urinalysis?
1) Casts
2) Cells
3) Bacteria
4) WBCs
5) RBCs (number, shape)
6) Crystals
What is hematuria defined as?
> 3 erythrocytes/HPF on urinalysis
What is microscopic hematuria more commonly due to? What is gross hematuria more commonly due to?
1) Glomerular in origin
2) Nonglomerular or urologic in origin
What should you consider gross painless hematuria to be a sign of?
Bladder or kidney cancer until proven otherwise
What can gross hematuria lead to?
1) Obstruction if large clots form in the lower GU tract
2) Excessive blood loss can lead to iron deficiency anemia
What are causes of hematuria?
1) Kidney stones
2) Infection (UTI, urethritis, pyelonephritis)
3) Bladder or kidney cancer
4) Glomerular disease, immunoglobulin (Ig) A nephropathy
5) Trauma (Foley catheter placement, blunt trauma, invasive procedures)
6) Strenuous exercise (marathon running), fever - hematuria is generally harmless
7) Systemic diseases (SLE, rheumatic fever, Henoch-Schonlein purpura, Wegener granulomatosis, HUS, Goodpasture syndrome, PAN)
8) Bleeding disorders (e.g., hemophilia, thrombocytopenia)
9) Sickle cell disease
10) Medications (cyclophosphamide, anticoagulants, salicylates, sulfonamides)
11) Analgesic nephropathy
12) Polycystic kidney disease, simple cysts
13) BPH - rarely causes isolated hematuria
What is the first step to diagnosing hematuria?
Urine dipstick - sensitivity in identifying hematuria is > 90%
What is the next crucial step in evaluation of hematuria after urine dipstick? What is important to do in this test? What is most likely present if RBC casts and proteinuria are also present? What should you do if pyuria is present? If the dipstick is positive for blood, but urinalysis does not reveal microscopic hematuria, what is likely present?
1) Urinalysis
2) Examine urine sediment - this is very important in identifying possible renal disease
3) If RBC casts and proteinuria are also present, a glomerular cause is almost always present (usually GN)
4) If pyuria is present, send for urine culture
5) If dipstick is positive for blood, but urinalysis does not reveal microscopic hematuria (no RBCs), hemoglobinuria or myoglobinuria is likely present
What should a urine specimen be sent for? What should you do if the suspicion for malignancy is high?
1) For cytology
2) To detect cancers (bladder cancer is the main concern)
3) If suspicion for malignancy is high, perform a cystoscopy to evaluate the bladder regardless of cytology results
In hematuria, what should a 24-hour urine test be done for? When should this test be done?
1) Twenty-four-hour urine test for Cr and protein to assess renal function
2) Collect if proteinuria is present (if it is heavy, glomerular disease is likely)
What blood tests should be done in hematuria?
1) Coagulation studies
2) CBC
3) BUN/Cr
If no cause for hematuria is identified by most urine tests, what should you look for? What tests can you do to look for these causes?
1) Stones, tumors, cysts, ureteral strictures, or vascular malformations
2) IVP, CT scan, ultrasound
When should a renal biopsy be done for hematuria?
If there is suspicion of glomerular disease
How do you treat hematuria?
Treat the underlying cause; maintain urine volume
When is gross hematuria common?
It is a common presenting sign in patients with bladder cancer (up to 85% of cases) and patients with renal cell carcinoma (up to 40% of cases)
What are very common causes of atraumatic hematuria?
1) Infection (cystitis, urethritis, prostatitis) accounts for 25% of all cases of atraumatic hematuria
2) Stones account for 20%
How can menstrual blood affect a urine sample?
It may contaminate it and lead to a false-positive dipstick reading for hematuria
If hematuria is microscopic, what should you think about as causal disease? What if it is gross hematuria? Does infection cause microscopic or gross hematuria?
1) Glomerular disease
2) Postrenal causes (trauma, stones, malignancy)
3) Infection can cause either gross or microscopic hematuria
If a patient has no other symptoms associated with hematuria and thorough workup fails to reveal a cause, what is the prognosis?
Excellent (there is usually mild glomerular/interstitial disease)
