L27 Proteinuria Flashcards
Definition of proteinuria?
protein in urine >150mg/day
What is the definition of nephrotic syndrome?
Urine protein excretion >3.5g/day, a/w
- hypoalbuminemia
- edema
- hyperlipidemia
Definition of microalbuminuria? Can it be detected by urine dipstick?
Microalbuminemia: 30-300 mg/day not detectable by conventional urine dipstick
What is the definition of macroalbuminuria?
> 300 mg/day
What is the physiology of urine protein handling - Which 2 parts of the renal system is involved? How?
- Glomerulus
- Protein filtration - protein size of >40kDa are retained (e.g. albumin)
- Negatively charged proteins and GMB - Proximal tubular reabsorption
- for most proteins that are filtered
Name the 2 types of physiological proteinuria and briefly describe.
- Orthostatic proteinuria
- MC isolated proteinuria in teenagers
- increased protein excretion in an upright posture, normal in a recumbent position
- collect early morning urine to rule out orthostatic proteinuria - Transient proteinuria
- heavy exercise/ UTI/ fever/ contamination from vaginal secretions
- increased in spot urine but normal in 24h urine
Name the 3 types of pathological proteinuria.
- Overflow proteinuria
- Tubular proteinuira
- Glomerular proteinuria
What is overflow proteinuria?
- Its level of proteinuria can be up to nephrotic range (>3.5g/day)
- List 2 possible causes.
- Concentration of one of the low molecular weight proteins that exceed the reabsorption capacity.
Examples
- Bence Jones protein in MM
- Lysozyme in chronic myelomonocytic leukemia
- Myoglobin in rhabdomyolysis
- Hemoglobin in intravascular hemolysis
What is tubular proteinuria?
- It’s level of proteinuria usually <2g/day (not reaching nephrotic range)
- List 2 possible causes
- Low MW proteins (e.g. retinol-binding protein, beta2 microglobulin) not resorbed due to tubular dysfunction (glomerular function intact)
Causes
- ATN
- Pyelonephritis
- SLE
- Fanconi’s syndrome
Which form of proteinuria is the most common?
Describe its pathophysiology.
Glomerular proteinuria
- glomerular dysfunction causing the escape of proteins >40 kDa into the urine
- levels of proteinuria can be up to nephrotic range (>3.5g/day)
Causes for glomerular proteinuria? (5)
- Glomerulonephritis
- DM
- Amyloidosis, MM
- Hypertensive glomerulosclerosis
- Pre-eclampsia
What are the subtypes of glomerular proteinuria? (3)
- Selective proteinuria - only intermediate-sized proteins (<100 kDa) like albumin, transferrin leak through the glomerulus
- Non-selective proteinuria - different sizes, including larger proteins e.g. IgG
- Microalbuminuria - albumin 30-300mg/day
What is the clinical significance of microalbuminuria in DM patients?
- Predict the development of nephropathy in DM
> treat with ACEI and strict DM control
(DM causes glycation in efferent arteriole > narrowed, ACEI dilate it)
What are them 3 KDIGO categories of albuminuria?
What is the clinical significance?
A1: urine ACR (albumin:creatinine ratio) <30mg/g
A2: urine ACR 30-300mg/g (microalbuminuria)
A3: urine ACR >300 mg/g (macroalbuminuria)
A2-A3: significantly increased CVS risk, even in patients with a GFR >60 ml/min per 1.73m^2
Which of the following are patient variables in proteinuria assessment?
A. Presence of UTI
B. Acute febrile illness
C. Intense exercise within 24 hours of test
D. Menstruation
All of the above
uACR is roughly equal to?
24-hour urine collection - albuminuria
uPCR (protein:creatinine ratio) is roughly equal to _________ at low levels of protein?
24-hour urine collection - proteinuria
How to convert mg/g to mg/mmol in uACR?
x0.113
How does urine dipsticks work?
- Measure total proteins/albumin by a pH indicator that changes color > shows the urine protein concentration
What are the limitations of urine dipstick? (2)
- Mainly detects albumin > thus glomerular proteinuria
- false negative in protein other than albumin e.g. Bence Jones protein - Sensitiviy: 0.1g/L (100mg/L) > insensitive to microalbuminuria
Give examples when urine dipstick will show false positive. (5)
- Alkaline pH
- Concentrated urine
- Pigmented urine: hematuria
- Interference: chlorhexidine (antiseptic)
- Contamination with vaginal secretions
2 examples when urine dipstick is false negative.
- Diluted urine
2. Protein other than albumin
Urine testing measures what in the urine?
Total proteins, albumin or specific proteins
What is the gold standard of timed urine collection?
24-hour urine collection
What are the 2 types of spot urine?
- First-morning urine
- diagnosis of orthostatic /exercise proteinuria
- preferred, least variable, correlates best with 24-hour urine protein - Random urine
What is measured in urine testing in patients with HT/DM?
UACR
- urine albumin: creatinine ratio
UACR is different in male and female:
e. g. microalbuminemia
- men: 2.5-25mg/mmol
- women: 3.5-35mg/mmol
why is there such a difference?
Albumin: creatitine ratio
Creatitine excretion is lower in females than men!
Give 2 intrinsic and 3 extrinsic causes for nephrotic syndrome.
Intrinsic
- Minimal change disease
- Membrane glomerulonephritis
- Focal segmental glomerulonephritis
- Membranoproliferative glomerulonephritis
Systemic
- DM
- Amyloidosis
- Multiple myeloma
- SLE
- Drugs: gold, penicillamine
Which of the following is incorrect regarding nephrotic syndrome?
A. Hypoalbuminemia causes edema due to reduced oncotic pressure and also causes RAAS from reduced ECF
B. Retention of lipoproteins causes hyperlipidemia
C. There is a compensatory hepatic synthesis of proteins
D. It will cause bleeding disorders
E. IgG deficiency due to urinary loss of immunoglobulins, causing patients to be immunocompromised
D
- should be thromboembolic disorders, due to urinary loss of anticoagulants such as antithrombin III
What investigations would you do in suspected nephrotic syndrome? (8)
- Serum electrolytes
- Serum protein
- Lipid profile
- Urea and creatinine
Further investigations
- 24-hour protein excretion
- Urine microscopy (for cast - glomerulonephritis, WBC - pyelonephritis, RBC - renal tubular damage)
- Renal biopsy (glomerular disease)
- Systemic investigation
What is the initial investigation for patients with suspected proteinuria after history taking?
Urine dipstick x2 + RFT
Further investigations for proteinuria? (8)
- 24h protein excretion to confirm proteinuria
- Creatinine clearance: the degree of renal impairment
- Urine microscopy (for cast - glomerulonephritis, WBC - pyelonephritis, RBC - renal tubular damage)
Other specific tests:
- Renal ultrasound (renal disease)
- Serum and urine electrophoresis (MM with BJP)
- Urine for myoglobin/ hemoglobin (rhabdomyolysis/ intravascular hemolysis)
- HbA1c (DM)
- Renal biopsy (glomerular disease)
When to refer a patient with proteinuria?
- eGFR <30ml/min/1.73^2
- Macroalbuminemia: persistent/ with hematuria
- CKD and HTN that is not well-controlled (even with 3 hypertensive agents)
