9. Assessment of renal function / acute and chronic renal failure Flashcards
What is normal GFR?
120 ml/min (7.2 L/hr)
What is the age-related decline of kidney function?
1mL/min per year
What is clearance and what is it used for?
Clearance is the volume of plasma that can be completely cleared of a marker substance per unit time. Clearance can be used to calculate GFR.
What are three criteria that need to be fulfilled for a marker to be used to measure GFR?
- Marker is NOT bound to serum proteins. 2. Freely filtered by the glomerulus 3. NOT secreted or reabsorbed by tubular cells. If these conditions are fulfilled, then clearance = GFR
At any one point, clearance =
C = (U x V)/P where U = urinary concentration, P = plasma concentration.
Describe inulin
5.2 kDa fructose polymer, neutral charge, freely filtered, not processed by tubular cells
Why is inulin only used as a research tool?
This is technically the ‘perfect marker’. However, measurement of inulin concentrations is quite difficult and it requires a steady-state infusion.
What is a clinically viable measure of GFR?
Single injection plasma clearance measurements using: 51Cr-EDTA, 99Tc-DTPA, lohexol
How to measure GFR using single injection plasma clarance measurements?
You administer the injection, then you can either measure the urine collection using a gamma counter or you can take blood samples and look at the progressive reduction in radioactivity. This is still NOT how GFR is measured on a day to day basis. This test is only used under certain circumstances (e.g. if you want to have a good estimate of GFR before starting chemotherapy)
• You would ideally like to use endogenous markers that have similar characteristics to the ideal injectable marker. What are these three charactersitics?
Not plasma protein bound, freely filtered by the glomerulus, not modified by the tubules.
Blood urea was the first endogenous marker of GFR and is a by-product of protein metabolism. What are some issues with blood urea as a marker for GFR?
- Variable (30-60%) reabsorption by tubular cells
- Dependent on nutritional state, hepatic function, GI bleeding
- Very limited clinical value
Where is serum creatinine derived from, how is it filtered and how is it affected by tubular cells?
Derived from muscle cells (small amount from intestinal absorption), freely filtered, actively secreted into the urine by tubular cells.
What is the rate of generation of creatinine affected by?
Muscularity, age, sex, ethnicity
What is the Cockcroft-Gault equation?
• Derived equation to estimate creatinine clearance (NOT GFR directly).
May overestimate GFR, especially when < 30 mL/min
What is the estimated GFR equation?
Complex equation derived from cohort studies (MDRD). Requires information about age, sex, serum creatinine and ethnicity. May underestimate GFR if above average weight and young.
What are current recommendations for GFR?
CKD-Epidemiology Collaboration (CKD-EPI). The equation is based on the same four variables as MDRD but models the relationship between GFR and serum creatinine, age, sex and race differently. It is an improvement on MDRD but it is still imprecise at higher GFRs.
What is cystatin C? How is it produced? How is it generated? How is it filtered? How is it affected by tubular cells? What do NICE guidelines say?
- This is an alternative endogenous marker.
- This is constitutively produced by all nucleated cells
- It is generated at a constant rate
- Freely filtered
- Almost completely reabsorbed and catabolised by tubular cells
- NOTE: CKD NICE guidelines have included cystatin C, however, it is not used that frequently
Serum creatinine is an insensitive marker of GFR and other endogenous markers (cystatin C) are better, true or false?
true
Should GFR be used on a daily basis?
No, single injection GFR measurement is reserved for specific situations
What is the best compromise to measure GFR?
In practice, estimated GFR/creatinine clearance is the best compromise.
Constant rate infusion GFR measurement is a research tool.
What is the most useful purpose of serum creatinine measurement?
to determine change in kidney function within an individual over time
What is urine protein: creatinine ratio?
Quantitative assessment of the amount of proteinuria. Measurement of creatinine corrects for urinary concentration.
Spot PCR or 24 hr urine collecction?
Spot urine PCR correlates pretty well with 24 hr urine collection. 24 hr Urine Collection is cumbersome and messy. Highly inaccurate without specific patient education. The estimation of proteinuria by 24 hr urine collection has been superseded by PCR.
Types of single sample urine exams:
Dipstick testing, microscopic examination, proteinuria quantification, electrolyte estimation
Types of 24 hour collection urine exams:
Creatinine clearance estimation, stone forming elements, (proteinuria quantification and electrolyte estimation)
If the dipstick is negative for blood, it reliably excludes haematuria. Haematuria is NOT the only cause of a positive dipstick for blood, what else can be a cause?
Haematuria can also be caused by myoglobinuria in cases of rhabdomyolysis
What is specific gracity?
a measure of the concentration of the urine (ranges between 1.003 to 1.035 in urine dipstick testing)
How does centrifuge occur in urine microscopy?
Centrifuge at 3000 rpm for 5-10 mins
What to look at the sediment for in urine microscopy and centrifuge?
Crystals, red blood cell, white blood cells, casts, bacteria
Clinical case: A 50 y/o, known alcoholic, presents generally unwell, seemingly intoxicated, with acute kidney injury. Urine microscopy reveals calcium oxalate crystals, what diagnosis do you expect and explain findings?
This is a classic case of ethylene glycol poisoning (anti-freeze). It gets converted to oxalic acid which will then precipitate with calcium in the renal tubules and the ureters.
What are examples of renal imaging?
- Plain KUB films
- IV urogram (Tends to be done more in paediatrics to look for anatomical defects) 3. Ultrasound KUB
- CT KUB (FIRST CHOICE for kidney stones)
- MRI KUB
- Functional imaging (static and dynamic renograms)
NOTE: renal biopsy is often necessary for various diagnoses which can be ultrasound or CT guided.
Differences between AKI and CKD in terms of decline, reversibility, and treatment target
In AKI there is an abrupt decline in GFR and in CKD there is a longstanding decline in GFR. AKI is potentially reversible, CKD is irreversible. Treatment for AKI is targeted to precise diagnosis and reversal of disease. Treatment for CKD is targeted to prevention of complications of CKD and limitation of progression.
What is the definition of an AKI?
Rapid reduction in kidney function, leading to inability to maintain electrolyte, acid-base and fluid homeostasis. (It is a MEDICAL EMERGENCY needing referral to a nephrologist for diagnosis and treatment).
What is the standardised definition of AKI?
NHS England standardised the definitions of AKI based on serial measurements of serum Creatinine (sCr) as follows:
- AKI Stage 1: Increase in sCr by >= 26 μmol/L, or by 1.5 to 1.9x the references sCr
- AKI Stage 2: Increase in sCr by 2.0 to 2.9x the reference sCr
- AKI Stage 3: Increase in sCr by >=3x the reference sCr, or increase by >=354 μmol/L
Why is one-off creatinine measurements not very useful?
You need to see how creatinine changes because it is a relative measure
What is the hallmark of pre-renal AKI?
Reduced renal perfusion. This could occur as a generalised reduction over the whole body (e.g. shock) or it could be selective renal ischaemia.