L81: Biochemical Investigation Of Urogenital Disease 2 Flashcards
Proteinuria
- Small proteins (β2-microglobulin, Lysozyme) are freely filter and completely reabsorbed
- Normal excretion of protein < 150mg/day
- 50% albumin (% ↑ with severity of proteinuria)
- Albumin: 66kDa predominantly retained in circulation due to size and charge
- Albuminuria should be confirmed on at least two occasions using spot urine (UACR)
5 causes of proteinuria
- Glomerular (↑ glomerular permeability)
- Tubular
- proximal tubular damage —> ↓ tubular reabsorption + release of intracellular components
- ↓ nephron number —> ↑ filtered load per nephron
- distal tubular damage - Overflow (too much blood flow —> presence of protein in urine)
- Orthostatic: prolonged upright posture (morning urine to eliminate effect)
- Transient: systemic illnesses e.g. high fever OR strenuous exercise OR UTI
Serum creatinine vs Proteinuria
Serum creatinine: marker of renal function
Proteinuria: marker of renal damage
Measurement of urine protein
Situations:
- raised serum creatinine / ↓ GFR
- new haematuria
- initial assessment with hypertension / type 2 diabetes
- unexplained oedema
- etc.
Collection:
- 24 hour (first void discarded, remaining collected), 12 hour overnight, 4 hour
—> inconvenient, significant inaccuracies due to incomplete collection, timing errors
OR
- Urine protein to Creatinine ratio with random sample (UPCR / UACR)
—> spot urine specimen, most accurate when performed on early morning
Measurement:
- Dipstick method (most sensitive to albumin)
- tetrabromphenol blue + citrate pH 3 buffer
- green: presence of protein, yellow: absence
- less sensitive to globulins, Bence Jones protein
- interference by abnormal urine pH - Sulfosalicylic acid
Influence to UPCR and UACR
- Heavily influenced by urine creatinine concentration / creatinine production
- large muscle mass —> small UPCR/UACR —> underestimate proteinuria
- small muscle mass —> large UPCR/UACR —> overestimate proteinuria
Factors affecting UACR/UPCR
- transient elevation in albuminuria (exercise, menstruation)
- intra-individual variability
- variability in creatinine excretion (age, race, muscle mass)
- non-steady state change in creatinine (AKI)
- degradation of albumin before analysis
- prozone effect (very high albumin falsely reported as low/normal using some assay)
Microalbuminuria
- ↑ urinary excretion of albumin above reference interval
- but at an excretion not generally detectable by less sensitive clinical tests e.g. dip stick (designed to measure total protein)
- marker of risk of development of renal damage
- marker of CVD risk
- ↑ album excretion rate long before GFR start to ↓
Realationship between eGFR, serum Cr, microalbuminuria
Serum Creatinine: only ↑ above upper limits of normal when eGFR < 60
Microalbuminuria: constantly ↓ throughout all stages of CKD / eGFR
Myoglobulinuria
- Small, heme-containing protein
- catabolised by proximal tubule
- Rhabdomyolysis, large amount of myoglobin released and saturate tubules —> directly toxic —> acute tubular necrosis
- positive reaction with haemoglobin reagent strip test
Diagnosis: plasma creatine kinase, urine myoglobin, red brown urine (look for presence of RBC to distinguish haematuria from myoglobinuria)
Subjects at high risk for recurrent renal stone
- Uric acid
- Residual stone fragments
- Hyperparathyroidism
- Nephrocalcinosis
- Solitary kidneys
- Children and teenagers
- Family history
- Genetic determined (Cystinuria)
*Types of renal stone
- Calcium oxalate: Most common, idiopathic hypercalciuria
- Calcium phosphate/carbonate (results of primary hyperparathyroidism / tubular acidosis)
- Uric acid: hyperuricaemia (Gout)
- Magnesium, ammonium, phosphate (Struvite: UTI with urease-producing organisms)
- Cystine: cystinuria
Factors affecting stone formation
- Ca
- phosphate
- amino acids
- pH
- bacteria
- blood volume
- uric acid
- PTH
Treatment for renal stone
- High Ca: ↓ calcium supplement, protein intake, Na intake, Thiazide diuretics
- High oxalate: avoid high of late food, avoid vitamin C
- High uric acid: ↓ purine intake (meat), Xanthine oxidase inhibitor (allopurinol)
- Low citrate: ↑ intake of fruits and vegetables, ↓ animal protein, citrate supplment
- Low volume: ↑ fluid intake
