Why a normal eGFR does not exclude early kidney disease
A normal eGFR (an estimate of kidney filtration calculated from serum creatinine) does not exclude early kidney disease, because surviving nephrons hyperfilter (each filters more than usual).
Remember
Surviving nephrons hyperfilter in mild kidney disease, so a creatinine-based eGFR can stay normal despite real damage. Albumin in the urine is another marker of damage, so look for it as well.
Memory aid
Picture a team that loses a few members: the rest work overtime, so the output looks unchanged until they can no longer keep up.
The surviving nephrons are the team working overtime, and the unchanged output is the normal eGFR.
Each nephron (a filtering unit of the kidney) has a glomerulus, which filters blood through a tuft of capillaries, and a tubule; the proximal tubule also adds creatinine to the urine. The glomerular filtration rate (GFR) is the volume of fluid that all the working nephrons filter from the blood each minute. The eGFR is not measured directly: the CKD-EPI equation (a formula that uses serum creatinine, age and sex) calculates it.
When some nephrons are lost, the survivors enlarge (hypertrophy) and each filters more than before, which is called hyperfiltration. Total filtration can therefore stay near normal even though fewer nephrons are working.
The tubules also hide early damage from a blood test. Creatinine is a muscle waste product that the glomeruli filter and the proximal tubule also adds to the urine, a process called secretion. When creatinine begins to build up, the tubules secrete more of it, which pulls the serum level back down.
If creatinine barely moves, the equation reports a normal eGFR despite genuine damage. Until significant kidney damage has occurred, the eGFR may not fall, so in mild disease it is a late signal of damage.
Compensation is only temporary, and the surviving glomeruli run at a higher pressure, which can itself damage them over time. For people at risk, such as those with diabetes or hypertension, NICE advises a urine test for protein leak, the albumin:creatinine ratio, as well as an eGFR.
Key facts
- What the equation uses
- serum creatinine, age and sex, none of which shows how many nephrons remain or how hard they are working.
- Hyperfiltration
- surviving nephrons filter more, so overall GFR may not fall until significant kidney damage has occurred.
- Creatinine secretion
- the share of creatinine added by the tubules rises as GFR falls, which helps to hold serum creatinine fairly constant in early disease.
- Limit of eGFR
- it is less accurate in mild kidney disease, so a normal value does not rule out early damage.
- Urine marker
- a urine albumin:creatinine ratio (ACR) above 3 mg/mmol is one marker of kidney damage, and it measures albumin leaking into the urine.
- Diagnosis
- chronic kidney disease (CKD) can be diagnosed from markers of damage, such as an ACR above 3 mg/mmol, even when the eGFR is normal, if they persist for at least 3 months.
Exam traps
- The age and sex terms in an eGFR equation do not correct for the early loss of nephrons, because none of them shows how many nephrons remain or how hard they are working.
- Reduced tubular secretion of creatinine would not hide a fall in filtration, because less secretion would leave more creatinine in the blood and so lower the eGFR. In chronic kidney disease the tubules secrete a larger share of creatinine, not a smaller one.
- Falling blood flow to the kidneys does not lower creatinine production, because creatinine production is set mainly by muscle mass. Less blood flow would instead reduce filtration and raise serum creatinine, which would expose kidney disease, not mask it.
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