Thread by @medrants

#UncleBob - eGFR Tweetorial

eGFR - estimated GFR
mGFR - measured GFR

@UnremarkableLab

1/ So what is GFR? Glomerular Filtration Rate - how much blood do the kidneys filter per minute

Perfect mGFR -> stable measurable molecule that is perfectly filtered and neither reabsorbed nor secreted

2/ mGFR continued

Measure the plasma value of the molecule and measure the quantity in urine over a specific number of minutes.

Clearance formula - (Um*V/time)/Pm

Since Um is cc and V/time (# of minutes)
The result is cc/ min.

3/ Early research into mGFR used inulin
britannica.com/science/inulin…

This works well for research, but is not usable for clinical purposes. There are several molecules that are used for mGFR - but all are rather complex

For years we used creatinine as reasonable molecule.

4/ Creatinine clearance involved a 24 hour urine collection with measurement of Pcr and Ucr

Ucr*V/(Pcr * 1440 minutes) - creatinine clearance

But collecting urine for 24 hours is challenging for many patients & the amount of creatinine produced daily is actually very variable.

5/ "Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass)."

The key here is "fairly constant rate"

The challenge of 24 hour collections led researchers to develop eGFR

6/ eGFR is not a number but rather an estimated number. Since the produced creatinine is excreted each day (at least that is the assumption), if we can estimate production we can substitute "creatinine production" for Ucr*Volume.

6/ The first effort at estimating GFR is know as the Cockroft-Gault equation - Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41

7/ They took 24 hour urine collections from male veterans and determined how much creatinine was produced and excreted as a function of age and weight. They then suggested taking 85% for women due to less muscle mass on average.

8/ While this is a reasonable formula (needs adjustments for obesity), one could not automate it, because you need weight in kg.

Creatinine clearance ~ (140 - age)*wt in kg/ (Scr*72)

9/ In order to estimate GFR using computerized medical record, formulas based on age, gender and race (many are now appropriately excluding race from the equation) have appeared. The first of these MDRD came from the Modifying Diet in Renal Disease studies.

10/ More recently we have a variety of CKD-Epi equations using the same variables. These all come for collections of 24 hour urine collections.

11/ For reasons we will discuss below sometimes we substitute (or add) cystatin C to the estimation equations.

All eGFR equations that use creatinine have the same problem - how can we accurately estimate muscle mass?

Cystatin C avoids that problem but is not widely available

12/ Since the creatinine based eGFR equations are assuming standard muscle mass for age and gender, we will have problems with either increased muscle mass or decreased muscle mass.

13/Weightlifters, many football players, etc. will have more creatinine produced and excreted than predicted - thus estimating a lower eGFR

Patients with significant cord injuries, amputations, and sarcopenia (cachexia, anorexia nervosa) will have too high an eGFR estimate.

14/ The next big problem is that the equations assume a stable creatinine. If the creatinine is increasing we should not us eGFR - likewise if the creatinine is decreasing we will have a much too large eGFR.

15/ So what should we do w/ eGFR. First, remember that it is an estimate & beware obvious errors. Second, avoid eGFR w/ changing creatinines. Third, do not base CKD estimates w/o considering other factors. Fourth, consider cystatin C if think muscle mass is too great or low

16/ For more on this topic I recommend these articles:
GFR as the “Gold Standard”: Estimated, Measured, and True ajkd.org/article/S0272-…

17/ Elise Boele-Schutte, Ron T. Gansevoort, Measured GFR: not a gold, but a gold-plated standard, Nephrology Dialysis Transplantation, Volume 32, Issue suppl_2, April 2017, Pages ii180–ii184, doi.org/10.1093/ndt/gf…

18/ Levey, A.S., Coresh, J., Tighiouart, H. et al. Strengths and limitations of estimated and measured GFR. Nat Rev Nephrol 15, 784 (2019). doi.org/10.1038/s41581…

19/ I hope this helps learners and practicing physicians. I will try to answer questions. I ask @kidney_boy @hswapnil @jordy_bc @Joe_Vassalotti and @UAB_NRTC to comment and clarify anything I made unclear