Flashcards in Chapter 4 Chronic Kidney Disease Deck (31)
How can chronic kidney disease be classified?
Chronic kidney disease can be classified by:
- Glomerular filtration rate (stage)
- Albuminuria category.
What is GFR?
GFR is traditionally estimated based on clearance of a solute that is 100% freely filtered.
Why do we use GFR?
* There are six listed reasons.
GFR is used to:
- Define CKD
- Evaluate CKD
- Assess CKD progression
- Manage expected complications of CKD
- Determine drug dosing
- Assess prognosis.
What is clearance?
Clearance is UV/P
U = urine concentration
V = urine volume per unit time
P = plasma concentration
What are the features of an ideal biomarker for GFR?
* There are four listed here.
- Endogenous in plasma
- Freely filtered
- Not secreted by tubules
- Not reabsorbed by tubules.
What are the limitations of creatinine?
Creatinine levels reflect dietary intake and muscle mass independent of glomerular filtration.
What circumstances lead to falsely low level of creatinine?
3. Limb amputation
4. Cirrhosis - reduced hepatic creatinine synthesis
5. Volume overload.
Why does creatinine overestimate the GFR?
Creatinine overestimates the GFR because it is freely filtered by the glomerulus but also secreted by the tubules.
Tubular secretion of creatinine results in more creatinine in the urine than if the solute were coming from filtration alone.
Why is creatinine even more unreliable in GFR estimation in advanced CKD?
In advanced CKD, tubular secretion of creatinine is upregulated, resulting in higher levels of creatinine in urine than by filtration alone, and a further overestimation of GFR in this patient population.
Why does urea underestimate the GFR?
Urea underestimates the GFR because it is freely filtered by the glomerulus but undergoes tubular reabsorption, resulting in a lower concentration of urea in the urine compared to the concentration from filtration alone.
What options are there to measure GFR in advanced CKD?
1. GFR estimates from 24 hour urine collection in advanced CKD can be calculated as the average of creatinine and urea clearances.
2. Drugs that inhibit the tubular secretion of creatinine, such as cimetidine, can be given prior to and during the 24 hour urine collection for a better assessment of GFR.
What other filtration markers can be used to calculate GFR?
4. Ethylenediaminetetraacetic acid
5. Diethylenetriainepentaacetic acid
What are the limitations of the Cockcroft-Gault formula?
Cockcroft-Gault is an estimation of creatinine clearance.
Cockcroft-Gaul overestimates creatinine clearance in overweight individuals.
Cockcroft-Gault formula is based on old creatinine measurements and may not be accurate with modern creatinine measurements.
What is notable about the MDRD formula?
The MDRD formula provides an estimated GFR.
The MDRD formula was derived from a population with CKD.
The MDRD equations were derived based on urinary clearance of 125I-iothalamate.
What are the limitations of the MDRD formula?
MDRD underestimates GFR in patients with GFR > 60 ml/min/1.73m2.
MDRD is not validated in the elderly, children and pregnant women.
MDRD is not validated in non-steady states.
MDRD is (technically) not validated for races other than white or African American.
What is notable about the CKD-EPI formula?
The CKD-EPI formula was derived from a large database of research studies' participants with diverse characteristics including those with and without CKD, diabetes and organ transplantation.
What are the advantages of CKD-EPI over MDRD?
The advantages of CKD-EPI over MDRD include:
- Similar accuracy as MDRD for GFR < 60 ml/min/1.73m2
- Better accuracy for GFR > 60 ml/min/1.73m2
- Better accuracy for risk predictions
- Applicable across more diverse populations.
What is cystatin C?
Cystatin C is a cysteine proteinase inhibitor that is produced at a constant rate by all nucleated cells.
Cystatin C is 99% filtered by the glomerulus and metabolised by proximal tubular cells.
What are the advantages of cystatin C over creatinine?
- May more accurately estimate GFR than serum creatinine in patients with reduced muscle mass.
- May detect AKI earlier than serum creatinine.
- Be a better predictor of deaths from cardiovascular causes and CKD complications.
- Correlates with a linear increase in cardiovascular risk.
What are the limitations of cystatin C?
- Cystatin C undergoes tubular secretion
- Cystatin C undergoes extra renal elimination
Both would mean GFR would be overestimated.
- It is expensive and not in widespread clinical use.
- May be altered by inflammation, obesity, older age, male gender, diabetes, lower serum albumin level, thyroid disease, malignancy, steroids.
- Standardisation of cystatin C measurement is lacking.
What is the main advantage of creatinine over cystatin C?
Creatinine-based eGFR appears to be better predictor of ESKD than cystatin C-alone eGFR.
What does KDIGO recommend when it comes to assessing kidney function?
KDIGO advises using serum creatinine and a GFR estimating equation for initial assessment.
When should cystatin C be used according to KDIGO guidelines?
Cystatin C should be used as a confirmatory/additional test when serum-based creatinine eGFR assessments are less accurate.
Cystatin C should be used for patients with eGFR 45 - 59 ml/min/1.73 m2 with no other markers of kidney damage; a eGFR(cys) or eGFR(Cr-cys) of < 60 ml/min/1.73m2 confirms the diagnosis of CKD.
According to the KDIGO guidelines when should an endogenous marker for GFR measurement be used?
When more accurate determinants of GFR are required such that they will impact on treatment decisions (kidney donation), KDIGO recommends using an endogenous filtration marker.
What are the limitations of eGFR formulas?
eGFR formulas are:
- Not validated in non-steady state
- Compromised by factors that influence creatinine level
- Influenced by population characteristics from which they were derived.
What is a limitation of dipstick urinalysis for proteinuria?
Dipstick urinalysis for proteinuria detects predominantly albuminuria.
Dipstick urinalysis for proteinuria does not detect tubular proteins or light chain immunoglobulins well.
What is the definition of CKD?
CKD is defined as kidney damage lasting 3 months or more, with or without a decrease in GFR, manifest by either pathologic abnormalities or markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests
GFR < 60ml/min/1.73m2 for 3 months or more with or without underlying kidney damage.
What factors predict CKD progression?
Factors that predict CKD progression are:
1. CKD aetiology
2. GFR category
3. Albuminuria category
4. Other risk factors and comorbid conditions
What is CKD progression?
CKD progression is defined as a drop in CKD category accompanied by >/= 25% decline from baseline eGFR.