What is an “eGFR,” and Why and When Does it Matter?

This blog post was made by Dr. John Agar on April 12th, 2018.
What is an “eGFR,” and Why and When Does it Matter?

I often wonder why we tend to make kidney disease seem so mystical, so hard to understand…and so frightening. Of course, it can be all of those things, but many are unnecessarily frightened if explanations are too complex and a simple explanation is always the best. So, let me have a shot at unpacking the “mysteries” of kidney function, if or as it declines. What follows is the discussion I have about diminishing kidney function with my patients.

Rather fortuitously, a normal eGFR—a term that stands for estimated glomerular fltration rate, but that really means “effective kidney function”—is about 100. Forget the “units,” forget all that ‘mL/minute’ stuff: just think of a percentage (%) scale. In percentage terms, 100% means a “full house,” while 0% means “damn all of nothing.” As 100% dwindles to 0%, whatever is being measured (it doesn’t matter—it can be your finances, your kidney function, a town water supply—anything), it falls from ideal to nothing. So, as the eGFR dwindles for 100 to zero, kidney function falls from normal to nil.

Right. Now, imagine a factory with 100 workers making a product, an output. Next, just like on the Apprentice, fire 50 workers: halve the workforce. Those who remain at work will all have to work a bit harder. They will get a bit more overtime, they will go home a bit later. They will get more tired, but they will manage. Some may even be chuffed that they are getting more overtime pay, and work a little harder. In kidney function terms, that’s called functional up-regulation! In a word, they will “cope.” They will sustain the factory output (maybe with some grumbling at the water-cooler), without any major or sustained disruption.

But, fire another half, and things begin to unravel. Maybe if just a few more workers could have been retained, even as few as 1/3 of the original workforce... With only 25% of the workforce left of the original workers still on the factory floor (1 in 4), it is all too much! Too few are left to do the work.Those who remain are now clearly both over-worked and (likely) under-paid. They begin to leave. They jump ship. They fall ill, and can’t be replaced. Or, they fall away from sheer exhaustion. A point of no return has been passed. The “factory” begins to implode, as its workers quit, either by choice—or by death. A self-destructive pattern is established; A vicious cycle into factory implosion is guaranteed. The factory (and its output) is doomed.

And so it is with kidney disease, and, to be honest, it doesn’t really matter what the cause was. As functioning nephrons are lost and the eGFR dwindles and is lost, it is no different to the failing factory as its workers are fired, or quit. Eventually, the collapse of kidney function becomes an inevitable, self-fulfilling prophecy. So, if you have kidney disease of any cause, once about 2 in every 3 of your original full nephron workforce has been “taken out” by that disease, those that remain are destined to fail.

Even then, there is commonly lots that can be done to keep the struggling workforce afloat. This is the realm of good CKD management. Ultimate functional loss may not be averted—but it can be delayed and made much easier to tolerate. That said, the real battle is way back when the eGFR is greater than 50: that’s when the fight to preserve and protect really counts.

There is one caveat to this principle: age. As we humans age, our eGFR progressively diminishes in us all, from about the time we enter our fourth decade of life. Just as we age on the outside: our hair goes grey, we get wrinkles, our joints begin to ache in the mornings when we get up…we age inside too. Part of that ageing process affects kidneys and kidney function. The average human loses kidney function (eGFR) at around 8-10 ml/min per decade, each decade, after the early 30’s. This is a factor of ageing.

At that rate—assuming a starting eGFR of 100—we would have to live to and beyond 130 years of age before we ran out from age-related loss. Of course, none of us live that long. Perish the thought! But, by the time we reach 80, for most of us, our eGFR will have roughly halved. But, so too has our solute load: we eat less, we do less, we generate less, and we don’t need as much eGFR as we might have done as an healthy active younger adult. To be truthful, an 80+ year old with an eGFR in the 25-30+ range is at little or no major risk, if all other markers of active kidney disease are absent and other health parameters are secure.

Sadly, lots of people don’t get this, or are poorly informed. Lots of elderly people have the living daylights scared out of them by being told they have “kidney failure,” when, in truth, they have appropriately aged kidneys and are in no danger at all. Many live, unfairly, under a fear of death when—really—there is little or nothing to panic about. Older people tolerate a low eGFR, and often a very low eGFR without trouble.

We, in nephrology, “spook” far too many people, when reassurance and the pulling of gentle, low-key medical levers is all that is required. Sure, it is wise to exclude real markers of trouble by ensuring normal renal anatomy with an ultrasound, and excluding nasty glomerular diseases by protein analyses. But, it is only rarely that these are found to be abnormal. If the only issue is an eGFR in an elderly person of 20-25 or so, then other than checking it now and then, nothing else is needed. Certainly not talk of dialysis.

To be truthful, the data suggests that an octogenarian does just as well, lives just as long, and is way less impacted by conservative care than those who (often quite inadvisably) are committed to dialysis. Of course there ARE exceptions, but these ARE few.

Back, then, to the eGFR. Understand that the battle must be fought early. Understand that once too much is gone, progression is inevitable. But also understand that this paradigm is altered by advancing age, as older people need less functional “grunt” to stay well. So, if and as you approach and pass 80, there is actually much less to get your knickers in a knot over!

Understanding eGFR—and all its implications, both good and bad—matters.

Comments

  • Ant

    Apr 13, 9:04 PM

    Thanks for a great article.

    If I picture a nephron with its specialized regions I wonder about the status of the cells that are no longer performing their function. Are they dead or just inactive? Do they still have oxygen and nutrient requirements (i.e. have turned into passengers)? If dead what prevents them from decomposing and polluting the system?

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    • John Agar

      Apr 14, 3:22 AM

      Nice question, Ant.
      You may have heard the term glomerulosclerosis ... sclerosis being a scarring process where the cells ‘harden’ as they are replacedby connective tissue — micro-gristle, if you like. It is essentially inactive, bloodless tissue that loses funtion and structure.
      Now this ‘gristling’ process occurs, cell by cell, and bit by bit, across each glomerulus and across collective groups of glomeruli ... the glomerulus is the individual filter unit that is the filtration ‘head’ of each nephron.
      Concurrently, interstitial fibrosis - often actually the more defining factor that determines the ultimate fate of renal function - scars and replaces the tubules and the surrounding structural architecture - the interstitium - of the kidney, laying down more collagen, more fibrosis, more ‘scar’ tissue due to overgrowth and overexpression of tissue fibtoblasts ... well, you did ask!
      As each tubule receives its blood supply ‘downstream’ from its ‘parent’ glomerulus, in simplistic terms, if a glomerulus is in blood supply trouble, its’ tubule will be in even greater ischaemic (blood supply) distress. And again, simplistically, as the cells of the glomerulus ‘steal’ the last remaning oxygen and nutrients that are being supplied to it by its failing, sclerosing, fibrosing microscopic artery (the glomerular afferent arteriole), the tubule that is downstream of the glomerulus stands no chance! It will be in even greater distress, will be even more starved of oxygen, and deprived of nutrients.
      All this leads to a spiralling loss of nephrons through fibrosis, effectively the final common pathway of all renal diseases, regardless of the primary disease. The initial disease may begin, develop, and damage in different ways, but their end pathways converges into a final common process: fibrosis.
      Much of the current research effort in renal disease is to understand this fibrotic process and develop ways to inhibit the expression (production) of collagen by fibroblasts, or directly control fibroblast function.
      They dont decompose (rot) and thus pollute: rather they thicken into bloodless clumps and strands of fibrous collagen - scar tissue. Perhaps that is a nicer ending, but an ending it is, all the same.

      Ok ... there is a bit of poetic licence in all that as I have tried to simplify it down to a few key steps, but, hopefully you can follow it through.

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      • Ant

        Apr 14, 7:58 AM

        That makes things clear, but I'm afraid begs more queries.

        "as the cells of the glomerulus ‘steal’ the last remaining oxygen and nutrients that are being supplied to it by its failing, sclerosing, fibrosing microscopic artery (the glomerular afferent arteriole),.."
        I'm trying to picture how the blood supply, progressively hindered from its journey by sclerosing, will be able to make its way back to the renal vein. The unpleasant (and no doubt simplistic thought) is blood backing up and stagnating in the branched extensions of the renal artery and eventually the artery itself.

        Further, for those of us with RRF (1400 ml urine) but an eGFR of 5, implies osmo-regulatory function is +- OK. How does water make its way through the fibrous, dead cells of the tubules into the surrounding capillaries?

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      • ant

        Apr 14, 5:16 AM

        Thank you. The terms came back to me...background in Zoology

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  • John Agar

    Apr 13, 8:03 PM

    Just to briefly extend the theme: patients often express surprise, concern, consternation, or befuddlement when their serum creatinine jumps up (or down) and thus changes their calculated eGFR.

    “.... my eGFR has dropped 27 —> 25 ...oh no! ... but the next is 28, and the ones after are 26, then 27! ... how can that be?”

    I remind them that the human body is not a stable and unchanging machine. We alter. Our diet alters, day on day. Our hydration state changes, day on day. Our exercise patterns change, day on day. We are physiologic, not metronomic. Eat red meat —-> absorb a bit of animal muscle creatinine. Exercise ++ —-> make a bit more creatinine. Do both on a hot day when you fall a bit behind on fluid —-> an increase in creatinine concentration. Some drugs can affect creatinine measurements —-> non-sustained or sustained change. Even lab measurements vary, lab to lab, and even in the same lab, such that there is an ‘error’ component to the test itself.

    I liken the creatinine to a share price ... people buy and sell shares in a company and, as they do, the share price will rise and fall such that any one price may differ from the price before, and the price after. Over time, though, what really matters is whether there is a SUSTAINED change, or whether the ‘wobbles’ are just wobbles around a stable mean.

    Another example might be the average temperature of a Victorian winters day (Victoria is my home Australian state) ... let’s say it is 17C. Is 16C different? ... no. Is 18C different? ... no. Then is 16C different to 18C. ... well, just a little and if sustained, then ... maybe. But it would take a few more readings over time to know. And, over a reasonable length of time, too. Hence, the repeated lab tests!

    What all this means is ... don’t get too hung up about numbers. They count ... yes! But their interpretation is the key. Lots of things can wobble a creatinine, and thus an eGFR (which is calculated from the creatinine). Small ups and downs signify little. Its all in the interpretation, and a trained nephrologist should be able to recognise the difference between a wobble and a whoops.

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  • Sheila Broydell

    Apr 12, 6:41 PM

    What a wonderful explanation, Dr. Agar.
    Thanks so much.
    Can this somehow be made into a pamphlet so every new (and old!!) kidney "patient" gets a copy.

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