Vad är GFR?
Den glomerulära filtrationshastigheten, GFR, är den volym primärurin som produceras per tidsenhet, motsvarande den plasmavolym som filtrerats under samma tid.
Mätning av renalt inulin-clearance = ”sanningen”
Vad är sanning?
Absolut sanning finns bara i himlen eller i Platons idévärld.
Vad är då den högsta vetenskapliga sanning som kan uppnås på jorden?
Vad är jordisk sanning?
Alla artiklar som publicerats i ämnet samlas in och genomläses av
specialister inom sanningsområdet. Därefter väljs de bästa artiklarna ut enligt en kvalitets-skala och specialisterna bedömer om det finns möjlighet att dra slutsatser och graderar slutsatsernas styrka enligt:
Det finns starkt vetenskapligt underlag () för att ...
Det finns måttligt starkt vetenskapligt underlag () för att ...
Det finns begränsat vetenskapligt underlag () för att ...
Det finns otillräckligt vetenskapligt underlag () för att bedöma om ...
Olika metoder att mäta GFR jämförda med renalt inulinclearance
During 1979 - 1994 a total of eight articles on cystatin C as a GFR-marker were published, but only by the Lund group, possibly due to their use of a slow, manual method, enzyme-amplified single radial immunodiffusion, for analysis.
Kyhse-Andersen J, Schmidt C, Nordin G, Andersson B, Nilsson-Ehle P, Lindström V, Grubb A.
Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method is a better marker than serum creatinine for glomerular filtration rate
Clin Chem 40: 1921-1926, (1994)
PubMed search February 2012 for “cystatin C AND (renal OR glomerular)”
generated 1513 hits
Google search for “cystatin C” February 2012: 403000 hits
40 Å
30 Å
5 Å
Advantages of cystatin C as a GFR-marker
Demonstrates the early, potentially reversible, decrease of GFR in the “creatinine-blind” area
Independent of diet
No tubular secretion
Low influence by muscle mass, gender and race (African American)
Independent of age for children and adults above 1 year
Demonstrates the decrease of GFR in old persons
Mirrors the diurnal GFR variation
Elucidates filtration quality and life expectancy
GFR-markers for patients with muscle atrophy
Non-parametric ROC plots
for serum cystatin C (solid line)
AUC = 0.912 and
serum creatinine (dotted line)
AUC = 0.507
AUC = 0.50 equals the
diagnostic efficiency of
tossing a coin
Disadvantages of cystatin C as a GFR-marker
High doses of corticosteroids increase significantly the
P-Cystatin C level (but not low doses e.g. ointments, inhalation)
Hyperthyreosis moderately increases the P-Cystatin C level (and decreases the P-Creatinine level due to increased tubular secretion)
The cost of analysing P-Cystatin C is higher than that of analysing P-Creatinine (prices in Lund 2011: 2 versus 1 Euro)
GFR-prediction equations Relative GFR in mL/min/1.73m2
Creatinine-based for adults:
MDRDIDMS-traceable: eGFR = 175 x (creatinine/88.4)-1.154 x age-0.203
x 0.742 (if female) x 1.212 (if African American)
Cystatin C-based for adults and children: eGFR = 85 x cystatin C-1.68
Creatinine-based eGFR equations
MDRD : 186.3 x [S- creat (mol/L)/88.4]-1.154 x age - 0.203 x 0.742 (if female)
x 1.212 (if African American)
or
e10.337-1.154 x ln(creat) - 0.203 x ln(age) - 0.299 (if female) + 0.192 (if African American)
Only for adults
Schwartz: 0.55 x height (cm) x [P- creat (mol/L)/88.4]-1
Only for children
Counahan–Barratt : 0.43 x height (cm) x [P- creat (mol/L)/88.4]-1
Only for children
Lund-Malmö : e4.62 - 0.0112 x creat + 0.339 x ln(age) - 0.0124 x age - 0.226 (if female)
For children and adults
Age-related GFR-predictions at a constant creatinine level of 80
micromol/L for 3 prediction equations
Reasons for the multitude of GFR prediction equations
A Use of different calibrators
B Use of different methods with varying dose- response curves
C Use of different mathematical models
D Use of different study populations
Reduction of the multitude of GFR prediction equations
A Use of different calibrators
- Use verified international calibrators
B Use of different methods with varying dose-response curves
- Use international calibrators and commutability studies to equalize all methods
C Use of different mathematical models
- Use improved mathematical models
D Use of different study populations
- Identify the most important types of population
The cystatin C international calibrator,
ERM-DA471/IFCC, was released June 2010
Ongoing calibration work
4049 samples from patients with known GFR (iohexol clearance)
0.17 – 95 years of age
472 children below 18 years of age
1022 above 70 years of age
1943 with GFR > 60 ml/min/1.75 sqm
Use of four different commutable methods adjusted to the international calibrator for cystatin C (ERM-DA471/IFCC): Gentian, Siemens, Dako, Sentinel (Abbott)
Aims of ongoing calibration work
To arrive at method-independent cystatin C-based GFR prediction equations
To compare prediction equations for GFR above and below 60 ml/min/1.75sqm. Do we need separate equations?
To compare cystatin C-based GFR prediction equations for adults and children. Do we need separate equations?
To determine diagnostic performance at different GFR levels
P30%-värdet för en GFR-prediktions-ekvation anger det procenttal av alla estimeringar som faller inom +/- 30% av det uppmätta GFR (med invasiv “Gold Standard” clearance-metod). De bästa kreatinin- och cystatin C-baserade ekvationerna når P30%-värden på 85-90%. Ekvationer baserade på både cystatin C- och kreatinin-baserade ekvationer når P30%-värden på 90-95%.
Suggestion for optimal diagnostic use of eGFR
Run both cystatin C and creatinine and calculate eGFR(cystatin C) and eGFR(creatinine)
at the initial patient contact.
If they agree: GFR is correct, no invasive clearance determination is required.
If they do not agree: Try to find a biomedical explanation (low muscle mass, high dose of glucocorticoid). If an obvious explanation is found no invasive clearance determination is required. The non-affected eGFR is used.
P/S-Creatinine can be used to follow a “correct” eGFR as defined above.
If the two eGFRs do not agree and no obvious explanation for the difference can be found: An invasive clearance determination is justified (iohexol clearance).
Site: egfr.se
BMI: 15
eGFR-verktyg och information
www.egfr.se
http://www.egfr.se/eGFRStrategy.pdf
http://informahealthcare.com/doi/pdf 10.3109/00365513.2011.634023
http://informahealthcare.com/doi/pdf/10.3109/00365513.2010.546879
It is more dangerous to have a reduced
eGFR(cystatin C) than a reduced eGFR(creatinine),
because you have a higher risk to die or develop end-stage renal disease.
Why?
It has been suggested that the inreased risk of having a reduced eGFR(cystatin C) compared to that of having a reduced eGFR(creatinine) is due to that not only reduced GFR, but also inflammation, increase the cystatin C level. This suggestion is based upon that some large cohort studies have shown a significant correlation between cystatin C and CRP levels.
Elective surgery to obtain elfin ears
Does systemic inflammation influence cystatin C?
20 persons with normal levels of CRP, SAA, orosomucoid and haptoglobin were subjected to elective surgery and the levels of these inflammatory markers and cystatin C and creatinine followed for 7 consecutive postoperative days
Grubb et al. Scand J Clin Lab Invest 71: 145-149 (2011)
N
o
r
m
a
l
I
n
d
i
s
e
a
s
e
?
I
n
d
i
s
e
a
s
e
!
No passage
Passage
Functional glomerular pore size
GFR/filtration quality regulated levels of LMW-proteins/peptides
Glucagon 3.5 kDa
Insulin 6 kDa
2-microglobulin 11 kDa
ProBNP 12 kDa
IL1- 17 kDa
TNF- 17 kDa
FGF-2 18 kDa
Growth Hormone 22 kDa
Light Ig-chains 23 kDa
TGF- 25 kDa
IL-6 26 kDa
Cystatin C, kreatinin och liv och död och obehag
eGFR används för att kunna:
1.Följa utvecklingen av njursjukdomar
2.Dosera läkemedel och kontrastmedel
3.Förutsäga utveckling av förvärrad njursjukdom (dialys, transplantation), behov av sjukhusvård och annat lidande
4.Förutsäga död