Proteinuria Flashcards
Normal protein handling
Glomerular protein filtration
- size and shape (>40 kDa retained; only small proteins e.g. retinol binding protein, beta-2 microglobulin)
- electrical charge (negative charge of membranes repels proteins)
Proximal tubular reabsorption
- most filtered proteins
==> normally <150 mg/day protein in urine
Definition of Proteinuria
Proteinuria = >150 mg/day
Microalbuminuria = 30-300 mg/day but not detectable by conventional urine dipstick
Nephrotic syndrome = >3.5 g/day with hypoalbuminaemia, oedema, hyperlipidaemia
Clinical significance of proteinuria
- Sign of kidney damage
- Direct pathogenic role in the progression of renal and CVS diseases
Assessment for:
- screening kidney damage
- marker for progressive renal dysfunction
- prognostic factor of CKD
- independent risk factor for CVS morbidity and mortality
Classification of Proteinuria
Physiological
- transient
- orthostatic
Pathological
- overflow
- tubular
- glomerular
Transient proteinuria causes
Causes:
- fever
- exercise
- concentrated spot urine e.g. early morning sample
- contamination e.g. from vagina
Orthostatic proteinuria
Children and young adults, usually benign
- upright posture (absent when urine collected after sleep)
May indicate underlying renal disease and should be followed up 6-12 monthly
Overflow proteinuria
Massive excretion of systemic low molecular weight protein
- light chains/ Bence Jones proteins (myeloma)
- myoglobin (rhabomyolysis, crush injury)
- haemoglobin (haemolysis)
- lysozyme (myelo-monocytic leukemia)
==> high load exceeds tubular reabsorption capacity
Tubular proteinuria
Tubular dysfunction
- mainly cause low molecular weight proteinuria
e. g. Retinol-binding protein, beta-2 microglobulin, lysozyme, light chains, haemoglobin, myoglobin
Causes:
- pyelonephritis
- ATN
- papillary necrosis e.g. analogies nephropathy
- heavy metal intoxications
- SLE
- Fanconi’s syndrome (also glucosuria, aminoaciduria, RTA)
Usually <3g/day
Glomerular proteinuria
Most common form
Glomerular dysfunction = proteins >40 kDa can escape into urine
Classified as:
- selective proteinuria – only <100 kDa e.g. albumin, transferrin
- non-selective – range of different sized e.g. IgG also
- microalbuminuria
Causes:
- GN
- DM, HT
- Myeloma
- Amyloidosis
- SLE
- Drugs and toxins
- Pre-eclampsia
Albuminuria
All levels of albumin that’s found in the urine
–> marker of kidney damage! (increased glomerular permeability)
Microalbuminuria
- urine albumin excretion 30-300 mg/day or excretion rate 20-200 mcg/min
==> greater than normal but NOT DETECTED BY URINE DIPSTICK
3 categories of albuminuria
KDIGO guidelines
A1 = ACR < 3mg/mmol
A2 = ACR 3-30 mg/mmol
A3 = ACR >30 mg/mmol
A2 and A3 a/w significantly increased CVS risk even in patients with GFR >60
Cutoffs used in PWH (UACR)
- first void spot urine
- sex specific cut offs
Microalbuminuria
- men 2.5-25 mg/mmol
- women 3.5-35 mg/mmol
or 30-300 mg/day (24 hr)
Clinical significance of microalbuminuria
Correlates with mortality in patients with DM and HT
Predicts development of nephropathy in DM
Treat promptly and adequately to prevent or postpone diabetic nephropathy
Treatment involves BP control, with ACEi and strict diabetic control
Assessment of Proteinuria: choice of test, timing, patient variables
- Choice of test
- urine dipsticks for total protein or albumin
- lab testing for urinary total protein, albumins or specific proteins - Time of urine collection
- spot urine vs timed
- random vs first morning void - Patient variables
- should be free from UTI, fever, intense exercise within 24 hrs, menstruation - Reporting units
- Interpretation
Urine dipsticks: use, sensitivity, false positives and false negatives
SCREENING of proteinuria
- colour changes in presence of protein due to pH change
- intensity correlates with concentration
Detects albumin ==> GLOMERULAR PROTEINURIA
Sensitivity: 0.1 g/L (100 mg/L) of urine albumin –> NOT MICROALBUMINURIA
(have albumin specific dipsticks)
False positives:
- alkaline urine e.g. UTI
- pigmented urine
- concentrated urine
- drug/ chemical interference
- contamination with vaginal secretions
- egg white
False negatives:
- protein not albumin e.g. overflow proteiunuria
- urine too dilute
Lab test for urinary proteins
UACR as surrogate of 24 hr urine
- 24 hr inconvenient, inaccurate collections
DM and HT – UACR
Myeloma – urine protein electrophoresis
Spot doesn’t mean random!!
- first morning urine preferred (least variable, best correlation; required for dx of orthostatic/exercise proteinuria)
- random urine acceptable if first morning not available
- utility improved by using ratio with Cr (standardise to urine concentration)
