Major urinary proteins?
IAABRC
- IgG
- Albumin
- a1-Microglobulin
-Retinol Binding
Protein (RBP)
- Cystatin C
- B2-Microglobulin
Filtration of protein in down to which metrics?
molecular size (20 - 40A)
protein molecular mass ( 30 - 70kDa)
Charge
How does charge influence protein filtration?
Negatively charged molecules have lower permeability
Proportion of Albumin relationship with severity of proteinuria?
proportion of Albumin increases with increasing severity of proteinuria
Normal daily excretion of protein? What protein makes up 40-50% excretion?
< 150 mg;
about 40 - 50% is Albumin
3 types of proteinuria?
Glomerular
Tubular
Overflow
What causes glomerular proteinuria?
Increased glomerular permeability
What causes overflow proteinuria?
Increased plasma concentration of
relatively freely filtered proteins
What is the consequence of glomerular proteinuria?
Progressively increasing excretion
of higher molecular weight proteins
because permeability increases
Give 5 CAUSES of tubular proteinuria?
1) PCT damage
2) DCT damage
3) Decreased nephron number
4) Orthostatic proteinuria
5) Transient proteinuria
What is the consequence of PCT damage in Tubular proteinuria?
decreased tubular reabsorptive capacity and/or release of intracellular components
What is the consequence of damaged nephron number in Tubular proteinuria?
Decreased nephron number:
increased filtered load per nephron
Give examples of proteins excreted due to overflow proteinuria?
- Bence Jones protein (BJP)
- Lysozyme
- Myoglobin (not haematuria but due to breakdown)
What is orthostatic proteinuria?
Protein excretion varies with posture,
increasing on standing/
prolonged upright posture
What is transient proteinuria?
Mild to moderate proteinuria
due to systemic illnesses apparently not related to the kidneys
Give examples of causes of transient proteinuria?
- high fever,
- congestive heart failure,
- seizures
- strenuous exercise
- urinary tract infection
What is the normal urinary albumin: creatinine ratio in male and female?
≤2.5 (males)
≤3.5 (females)
Normal Urine Reagent
Strip (‘dipstick’) reading?
Negative
Normal Urine Protein:
Creatinine ratio mg/mmol?
<15 mg/mmol
Normal Urine Total
Protein Excretion g/24h?
<0.15 g/24h
Urinary protein measurements should be taken in What new discovered changes in blood metrics?
raised serum creatinine / reduced GFR
haematuria (esp. microscopic haematuria)
What is urinary protein measurement for?
Assessment of severity of known kidney disease
e.g.Structural renal tract disease, recurrent renal calculi
Urinary protein measurement should be included when initially assessing which patients?
patients with hypertension
patients with newly diagnosed type 2 diabetes
Family history/ hereditary stage 5 CKD
Suspected multisystem disease, e.g., SLE
2 methods to collect urine protein specimen? (think timing)
Timed: 24-hour, 12-hour overnight, 4-hour
Random: assess Urine Protein / Creatinine ratio
Dipstick method for urrine protein is sensitive to what protein? The dipstick is poort for detecting what?
- Most sensitive to albumin
* Poor method for detecting tubular proteinuria
Name of reagent in dipstick and colour change in detecting protein?
Tetrabromphenol blue
green in the presence
of protein
yellow in its absence
Why is Dipstick a Poor method for detecting tubular proteinuria?
less sensitive to globulins, Bence Jones protein, mucoproteins, and hemoglobin
How does Sulfosalicylic acid change with increasing protein concentration?
Increasing turbidity/ opaqueness
More and more precipitated until Flocculent precipitate
Name some drug that can cause false positive proteinuria in urine dipstick or Sulfosalicylic acid?
Sulfonamide
High levels of penicillin or cephalosporin
Radiocontrast media
Urine pH > 8
How to collect 24h urine sample?
First void of the day should be discarded
all urine passed in the next 24 hours collected
2 main Disadvantages of timed urine collection?
inconvenient for patients
significant inaccuracies: incomplete collection, timing errors, intra-individual
variation
Spot urine specimen usually done when?
Can choose random spot specimen or first morning spot specimen
UACR test most accurate with morning spot test
Which method is used: timed 24 hours or Spot urine Pr/Cr ratio ?
Spot urine Pr/Cr ratio
In individuals with large muscle mass, how does the UPCR or UACR test result chnage?
creatinine excretion may be much higher than
average population
> > UPCR (or UACR) will
underestimate proteinuria
Cachectic patient or a patient with small muscle mass, how does the UPCR or UACR test result chnage?
creatinine excretion may be much lower than average population
> > UPCR (or UACR)
will overestimate proteinuria
What is UPCR and UACR?
Urine protein: creatinine ratio
Urine albumin: creatinine ratio
Factors affecting urinary albumin: creatinine ratio?
Transient elevation in
albuminuria (e.g. exercise, posture, UTI)
Intraindividual variability
Non-renal causes of
variability (e.g. age, race, gender)
What is urine albumin a marker for?
marker of the risk of development of renal damage in diabetic patients
Elevated urine albumin is an established marker of What?
cardiovascular risk in the diabetic and nondiabetic
populations
What does microalbuminuria indicate?
increase in urinary excretion of
albumin
above the reference interval for healthy
nondiabetic subjects
What is the 24h urinary albumin for microalbuminuria and macroalbuminuria?
Micro = 30-300mg/day
Macro = >300mg/day
How does albumin exretion rate change with time for a type I DM patient?
Steadily increases until it overtakes GFR which steadily drops»_space; renal failure
What is the initial compensation mechanism of increased albumin loss?
Hyperfiltration
Serum creatinine starts rising at which stage of CKD?
After stage 2
When eGFR is lower than 60
Microalbuminuria starts at which stage of CKD?
Stage 1
> 90 eGFR
Why should albuminuria be confirmed on at least 2 occasions?
high biological variability and nonrenal influences
Measurement of what allows the use of spot sample?
Urine albumin-to-creatinine ratio
What is the triad of nephrotic syndromes in relation to serum protein?
triad of heavy proteinuria, hypoalbuminemia,
and edema
Criteria of proteinuria for nephrotic syndrome?
Proteinuria > 3.5 gm/day/1.73 m2
Explain what occurs in rhabdomyolysis?
Large amounts of myoglobin are released into the plasma,
saturating the tubular reabsorptive mechanism
What happens to myoglobin in kidney normally?
catabolized by endocytosis and proteolysis
in PCT
What can myoglobinuria cuase?
directly toxic to the renal tubules
acute tubular necrosis with acute kidney injury
What are the 2 diagnostic tests for myoglobinuria?
plasma creatine kinase, urine myoglobin
(Positive reaction with hemoglobin reagent
strip tests)
What are some physical and chemical promoters of renal stone formation?
Chemical = calcium, urate, sodium
Physical = urinary tract obstruction, stasis
What 3 factors cause supersaturated solution of salt which can form renal stone?
Urinary volume decrease
Excess excretion of stone components
pH increase
What are some predisposing factors for renal stones?
Metabolic disorders
Hot climate
Protein rich diet
Why know the type of renal tone helps?
helps delineate
the best treatment option + identification of risk factors = prevent
recurrence
e.g. Targeted therapeutic intervention or medical prophylaxis for recurrence
Does renal stone analysis reflect the functional status of the
kidneys?
no
Name some high risk conditions for recurrent renal stone formation?
Residual stone fragments
Uric acid and urate stones
Hyperparathyroidism
Nephrocalcinosis (increase Ca)
Family history of stones/ genetic determined stones
Name some genetic determined stones?
- Xanthine
- Cystic fibrosis
- Cystinuria
What are the 3 analysis needed for treating renal stones?
Renal stone analysis
Blood and urine analysis
What are the 5 common types of stones?
CPC MAP CUACO
Calcium Phosphate/Carbonate
Magnesium, Ammonium and Phosphate (Struvite
stones)
Calcium Oxalate
Uric acid
Cystine
What causes Calcium Phosphate/Carbonate stones?
primary hyperparathyroidism or renal tubular acidosis
What causes Magnesium, Ammonium and Phosphate (Struvite
stones) stones?
urinary tract infections»_space; urease-producing organisms
> > (e.g. staghorn
calculus)
What causes Calcium Oxalate stones?
aetiology often obscure
e.g. idiopathic hypercalciuria, excess calcium ingestion, hyperparathyroidism
Which renal stone is the most common?
Calcium oxalate
What causes Uric acid stones?
consequence of hyperuricaemia
What causes Cystine stones?
very rare, associated with cystinuria
What biochemical markers are checked in lab investigation of renal stones?
24h Urine sample:
check volume, and all the ions in diff. types of stones
Early morning urine: pH, amino acids, microscopy and culture
Blood:
check ions in stones
What techniques are replacing biochemical investigation of renal stones?
infrared spectroscopic study and diffraction
crystallography