ChemPath: Assessment of Renal Function 1
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What is normal GFR?
120 mL/min (7.2 L/hour)
At what rate does age affect GFR?
Declines by 1ml/min per year
Define clearance.
The volume of plasma that can be completely cleared of a marker substance per unit time.
What are the three criteria for a marker to be used to measure GFR?
• Marker is not bound to serum proteins • Freely filtered by the glomerulus • Not secreted or absorbed by tubular cells
State the equation that links clearance with urine and plasma concentration.
C = (U x V/P)
What is inulin and what is its main purpose?
• Neutral, freely filtered fructose polymer that is technically the perfect marker • However, measurement of inulin concentrations is difficult and it requires a steady-state infusion • So, it is only used as a research tool
Name three single injection plasma clearance markers/
• 51Cr-EDTA • 99Tc-DTPA • Iohexol
Describe how single injection plasma clearance markers are used.
The injection is administered followed by measurement of urine collection using a Geiger counter or blood samples can be taken to look for a progressive reduction in radioactivity. NOTE: this is only used under specific circumstances (e.g. when accurate estimation of GFR is necessary before chemotherapy)
Describe the key features of plasma urea.
• By-product of protein metabolism • Variable absorption (30-60%) by tubular cells • Dependent on nutritional state, hepatic function and GI bleeding • Limited clinical value
Where does serum creatinine come from?
Muscle cells
Which features of serum creatinine make it a useful marker of GFR?
• Freely filtered • Produced at a constant rate NOTE: it is actively secreted into the urine by tubular cells
List some factors that affect the rate of generation of creatinine.
• Muscularity • Age • Sex • Ethinicity
Name and briefly describe three equations that are used to estimate creatinine clearance or GFR.
• Cockcroft-Gault - estimates creatinine clearance by taking into account weight, age and sex (may overestimate when GFR <30ml/min) • MDRD - estimates GFR from creatinine clearance and takes into account age, sex, serum creatinine and ethnicity (may underestimate in overweight and young people) • CKD-EPI - improvement of MDRD and currently recommended
Name an alternative endogenous marker of GFR.
Cystatin C NOTE: it is constitutively produced by all nucleated cells, is generated at a constant rate and freely filtered. It is almost completely reabsorbed and catabolised by tubular cells.
What is urine protein: creatinine ratio?
• Quantitative assessment of proteinuria • Measurement of creatinine corrects for urine concentration
How is proteinuria estimated?
• Spot urine protein: creatinine ratio (PCR) NOTE: this has superseded 24-hour urine collection
Aside from blood, what else can cause a urine dipstick to be positive for blood?
Myoglobinuria (from rhabdomyolysis)
What is specific gravity?
A measure of urine concentration
What can urine microscopy be used to look for?
• Crystals • RBCs • WBCs • Casts • Bacteria
How can ethylene glycol poisoning cause AKI?
It gets converted to oxalic acid which precipitates with calcium to form calcium oxalate stones