ChemPath: Assessment of Renal Function 1 Flashcards
3 main functions of the kidneys
- Excretion of waste
- Maintenance of extracellular volume
- Hormone synthesis
Most effective method at assessing renal function
glomerular filtration rate
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 a unit of time.
Clearance equation
= (urine concentration of marker x urine flow rate) / plasma concentration of marker
What are the ideal 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
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. It is also difficult to assay
- 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 as a marker to measure GFR
- first endogenous marker to be used to measure GFR
- By-product of protein metabolism
- Variable absorption (30-60%) by tubular cells (reducing its validity)
- Dependent on nutritional state, hepatic function and GI bleeding (reducing validity)
- Overall limited clinical value
Where does serum creatinine come from?
Myocytes
Which features of serum creatinine make it a useful marker of GFR?
- Endogenous marker
- 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.
Due to this variability what is the most effective way to interpret creatnine as a GFR marker
- Muscle mass (which is indirectly imapcted by the following below)
- Age
- Sex
- Ethinicity
Due to this variability seen amongst individuals - creatinine is best used to monitor a trend for each individal and look for a change over time.
Outline the relationship between serum creatnine and GFR
Serum creatinine concentration is inversely related to GFR (when GFR decreases, there is decreased creatinine filtration and more remains in plasma)
However GFR can reduce by 50% before a rise in creatinine serum goes above reference range of normal. Therefore serum creatinine is an insensitive marker for changes to GFR (especially early changes).
Relationship between serum creatinine levels and renal function.
Normal creatinine serum concentration does not necessarily mean normal renal function.
Raised serum concentration of creatinine does generally mean abnormal renal function.
Outline modifiable factors which may impact serum creatinine levels (outside of renal function)
Increased serum creatinine:
* large protein meal (hence why ideal sample is taken when fasting but this is rarely done)
* pregnancy
Decreased serum creatinine
* Starvation
* After surgery
* After steroid treatment
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, less reliable for those with normal kidney function or AKI as MDRD study was done only on those with CKD)
- CKD-EPI - improvement of MDRD and currently recommended
Name a better alternative endogenous marker of GFR to creatinine
Cystatin C
NOTE: it is constitutively produced by all nucleated cells, is generated at a constant rate independent of age, sex, ethnicity or muscle mass and freely filtered. It is almost completely reabsorbed and catabolised by tubular cells.
Outline in what clinical pictures is Cystin C most useful in
Most useful at initial diagnosis in patients whose serum creatinine levels may not yet reflect GFR changes or whose creatinine levels are physiologically imoacted by muscle mass (e.g. body builders, elderly women)
How can spot urine measurement be used to quantify proteinuria instead of a 24 hour collection
Using a urine protein:creatinine ratio measurement in spot urine test.
Measurement of creatnine corrects for any changes to urine concentration may have on urine protein levels - therefore effectively quantifying proteinuria.
NOTE: this has superseded 24-hour urine collection
Why is proteinuria a marker of renal damage
Renal damage = increases glomerular membrane permeability = more protein filrated into filtrate and excreted.
Normal urine protein secretion
<150mg/day
Aside from blood (intact RBCs), what else can cause a urine dipstick to be positive for blood?
Myoglobinuria (from rhabdomyolysis)
Lysed RBCs (from haemolysis)
