Thread by @Dilushiwijay

1/ Monitoring eGFR in CKD is almost a reflex🦵!

But how did we get here?
What are we trying to assess?
And how does eGFR help?

#NephMadness #primarycare pits GFR vs proteinuria in CKD

In this tweetorial let's take a closer look at GFR

But first, who has your vote?#NephTwitter

2/ The concept of GFR as a marker of kidney function dates way back to the 1950s. (Apologies to the tubules, we do❤️you!)

But how could we measure GFR??

It was suggested that if a solute had certain characteristics its plasma clearance would = GFR

Let's briefly recap🤓

3/ The solution, INULIN, a non-toxic exogenous molecule, came through studies on aglomerular fish! #AnimalHouse

INULIN renal clearance= measured GFR
It is considered the GOLD standard🏆

But it comes with baggage
🧳It's expensive
🧳It's tedious
🧳It's hardly available anymore

4/
*⃣ Iohexol and iothalamate are cheaper alternatives to inulin
But measurements haven't been standardized, preventing widespread use

*⃣ Nuclear imaging uses tracers which are taken up by the kidney eg DTPA, MAG
Images can link function to anatomy
But accuracy is not great😞

5/ Exogenous markers are considered to yield a MEASURED GFR

So they are considered standard, even though they often do not yield comparable results!🙈

Usually a new test of GFR must be validated against mGFR

If not careful, error will beget more error!
cjasn.asnjournals.org/content/6/8/18…

6/ Measuring GFR is too costly and laborious for clinical practice

🎺Enter CREATININE (Cr)

an ENDOgenous molecule that's
freely filtered
not reabsorbed/ metabolized by the tubule
AND easy and cheap to measure

Cr based eGFR is now the most commonest test of renal function!

7/Creatinine is popular but not perfect

1. Secreted by the PCT
👉Insignificant at higher GFR. As GFR drops, contributes to higher proportion of renal Cl ➡️OVERESTIMATION of GFR
👉Competes for secretion with drugs➡️📈S Cr without change in GFR

2. Production corresponds to💪mass

8/ Ok.. So, how do we get from a serum creatinine to an eGFR?

Currently we use 3 equations to CALCULATE an eGFR based on the serum creatinine
1. Cockroft- Gault (CG)
2. MDRD
3. CKD-EPI

Which is your favourite?

9/ Most of us are familiar with the CG equation👇🏿(1976)

But DO YOU KNOW

1. It estimates CrCl not eGFR- so it estimates an estimate

2. At low GFR CrCl overestimates GFR (contribution of secreted Cr)

3. Sampled 249 veterans- 94% ♂️
Correction factor for ♀️- not validated!🤦🏿🙅🏿

10/ MDRD formula - 1999
This mere spin off of the original MDRD trial became its lasting legacy!

>1700 patients : training + validation sample
40% female
12% non-white
Mean GFR 38.5ml/min
Only demographic and serum variables
Initial 6-variable formula, later adopted with 4 👇🏿

11/ First the CG formula and later the MDRD heralded a new era in nephrology.

MDRD made eGFR everyday lingo!

MDRD derived eGFR were used by KDIGO for staging of CKD and developing prognostication tools.

Check out this VA from @AJKDonline @NephMadness

12/ But MDRD tends to UNDERestimate eGFR in those with relatively normal kidney function, inadvertently labelling them CKD 😭

Levy et al, came up with a new formula for Cr based eGFR 👉CKD-EPI suggesting to replace (their own) MDRD in everyday practice.

ncbi.nlm.nih.gov/pmc/articles/P…

13/ Serum Cystatin C is an alternative to Cr in estimating GFR

-Produced by all nucleated cells, freely filtered & metabolized in the PCT.

-similar accuracy to Cr based eGFR; correlates BETTER with CV & renal OUTCOMES!

-#KDIGO recommends it when Cr based eGFR is unreliable

14/The place of race in eGFR (MDRD and CKD-EPI) was recently questioned

Correcting for race ⬆️s the eGFR in AA vs Caucasians

But AA have⬆️risk of ESKD and have⬇️access to KTx😔

03.2021
NKF🎺"Race is a social not a biological construct and should NOT be considered in eGFR"

15/A lot of work has gone into perfecting eGFR!
But does it always reflect change in renal function?

REMEMBER

📈GFR is not always due to disease- eg ACEI, SGLT2i, diet🥩

"Normal" ranges may not be normal- eg Pregnancy

What concerns us more than the value is the OUTCOME

16/ It's been a long journey for GFR (and a long🧵)! Does it live up to the hype?
Remember to make your pick for @nephmadness

Check out ajkdblog.org/2021/03/01/nep…

🙏to @RacquelbelleMD @cjdiamantidi @Nephro_Sparks @drM_sudha @docanjuyadav @amyaimei @NSMCinternship @AJKDonline