Thanks! I’m primarily an outpatient physician, so mainly use it do get a more accurate measurement of GFR in patients with CKD. From my reading of the literature — can be useful in AKI as well. Any inpatient clinicians out there use Cystatin C for AKI?
A bit of much ado about nothing. If I’ve learned anything about renal function it’s that it’s always changing and trying to split hairs on how to view today’s lab test is a waste of time. The clinician’s job is to see today’s result, compare it with as many previous tests as she can, and try to put it into clinical perspective. One number tells me almost nothing. A great example is a guy brought in with a creatine of 17 and a BUN of 242. No one had seen him in two weeks and he was found on his bedroom floor. We gave him a lot of fluids and he left the hospital with a creatine of 1.6, BUN 34. Would cystatin C have made any difference?
Thx for comment! I agree “less is more” often when it comes to testing. When learning about the combined equation, I was particularly surprised by data about how using it reclassified patients with CKD (which, on a population level, would signficantly change management and use of resources), as well as dose-adjustments in chemo. For your routine patient with AKI and dehydration, would a slightly more precise lab matter? As you note, probably not. This feels similar to ordering urine electrolytes, which was extremely exciting as an intern, though functionally useless in my experience.
Thanks for this article. A lot of older folks are now taking supplemental creatine to increase their muscle mass and maybe preserve cognitive function (poor evidence for the latter). Since taking supplemental creatine may bump up their serum creatinine levels, cystatine C levels can be useful to determine whether this rise in creatinine is of concern or not.
As we learned from my favorite real-world philosopher:
‘Well, it just goes to show you, it’s always something! If it’s not one thing, it’s another! If you did one test you ought to learn about the new one…’
Thank you for an excellent article. Could you clarify your point about reclassified patients doing poorly—I assume you meant the 18% who were worse and not all of the reclassified patients?
Thx for astute comment — couldn’t fit all the nuances of the study in the short piece. Here’s some more details: In the analysis of the PARADIGM-HF heart failure trial (Tolomeo et al, 2023), switching from Crt based GFR to combined equation led to 11% of patients being reclassified to better GFR, and 18% to worse GFR. Of those reclassified to worse GFR, these patient were found to have higher mortality, higher troponin, and worse quality of life. In other words, the reclassification revealed patients who were sicker and higher risk of bad outcomes.
In cases where the creatinine eGFR and cystatin C eGFR are wildly discrepant (as in the above example), is the proper approach to just "split the difference" or is it to try and determine which estimate might be closer to correct given the patient characteristics, and weigh that one higher?
Great question! Per my favorite colleague Open Evidence, here is one stepwise approach when values are discrepant: 1) Use the combined equation (this is modeled to most accurately predict the gold standard GFR). 2) Consider whether there are factors that would clearly distort one of the values — for example, in the case of Crt, if a patient has profound sarcopenia or paraplegia, eGFRcys may be more appropriate. If patient on high-dose steroids, has osteomyelitis with high inflammatory burden, GFR derived from Crt would be more appropriate. Short story is that in extreme cases, you would go with “better” marker, but in most cases, the combined equation will do its magic and cancel out discrepancies from each of the single markers
At present, is it fair to say that a reasonable approach is to continue with creatinine-based estimate for routine use, but then add a cystatin C for select patients where that estimate is likely to be poor (e.g., muscle wasting, cirrhotic patients) or when the estimate needs to be a bit more precise (oncology, transplant)? Or does the author propose using the creatinine-cystatin C on all patients?
Great question! I have a somewhat skewed clinical population — patients with paraplegia, obesity (BMI over 40), nursing home patients with sarcopenia, and patients on border of GFR of 30 where combined equation would impact clinical management. So, these are people I am adding on Cystatin C. Other clinical subpopulations where can be useful would be renal transplant patients and cancer patients undergoing chemotherapy. From my reading, it’s a relatively cheap test and pretty accessible. For your routine patient (not on extreme of muscle mass or without above conditions), I still use GFR calculated based on Creatinine. Again, if they border on CKD, I consider getting Cystatin C. Hope this is helpful!
This got me into a rabbit-hole… Per Open evidence, “The hemodynamic GFR reduction is real — and cystatin C should reflect it too.ACE/ARBs dilate the efferent arteriole, reducing intraglomerular pressure and truly lowering filtration. Both creatinine and cystatin C are freely filtered, so both should rise proportionally. In this scenario, eGFRcr-cys would show the same decline as eGFRcr, and would not reclassify the patient.” So, short story is at present, I don’t think there is great evidence for benefit of combined equation in this context (most of my reading focused on cancer patients, patient at extremes of muscle mass, and also at border of CKD). So, if patient is truly at border of GFR of 30, may be useful, but don’t think there is lots of data on this
I’m interested in your book. When will it be available?
Thanks for message… slowly trying to get it done!! Hopefully in 2027
Hello - What effect would having one kidney from birth have on this result ? Thanks !
Thanks for this. Squarely in the “learn something new everyday” category. And also “I need to read more” box as well.
Is this something more relevant in stable CKD (out)patients? Or is it applicable to AKI (in)patients as well?
Thanks! I’m primarily an outpatient physician, so mainly use it do get a more accurate measurement of GFR in patients with CKD. From my reading of the literature — can be useful in AKI as well. Any inpatient clinicians out there use Cystatin C for AKI?
A bit of much ado about nothing. If I’ve learned anything about renal function it’s that it’s always changing and trying to split hairs on how to view today’s lab test is a waste of time. The clinician’s job is to see today’s result, compare it with as many previous tests as she can, and try to put it into clinical perspective. One number tells me almost nothing. A great example is a guy brought in with a creatine of 17 and a BUN of 242. No one had seen him in two weeks and he was found on his bedroom floor. We gave him a lot of fluids and he left the hospital with a creatine of 1.6, BUN 34. Would cystatin C have made any difference?
Thx for comment! I agree “less is more” often when it comes to testing. When learning about the combined equation, I was particularly surprised by data about how using it reclassified patients with CKD (which, on a population level, would signficantly change management and use of resources), as well as dose-adjustments in chemo. For your routine patient with AKI and dehydration, would a slightly more precise lab matter? As you note, probably not. This feels similar to ordering urine electrolytes, which was extremely exciting as an intern, though functionally useless in my experience.
Thanks for this article. A lot of older folks are now taking supplemental creatine to increase their muscle mass and maybe preserve cognitive function (poor evidence for the latter). Since taking supplemental creatine may bump up their serum creatinine levels, cystatine C levels can be useful to determine whether this rise in creatinine is of concern or not.
Thanks for pointing this out! I may have to start asking my 90 year-old ladies if they take Creatine now :)
As we learned from my favorite real-world philosopher:
‘Well, it just goes to show you, it’s always something! If it’s not one thing, it’s another! If you did one test you ought to learn about the new one…’
Roseanne Roseannadanna
Nana Roseannadanna
Reminds me of a quote from first week of medical school: “In twenty years half of what you learn will be wrong — you just don’t know which half”
Thank you for an excellent article. Could you clarify your point about reclassified patients doing poorly—I assume you meant the 18% who were worse and not all of the reclassified patients?
Thx for astute comment — couldn’t fit all the nuances of the study in the short piece. Here’s some more details: In the analysis of the PARADIGM-HF heart failure trial (Tolomeo et al, 2023), switching from Crt based GFR to combined equation led to 11% of patients being reclassified to better GFR, and 18% to worse GFR. Of those reclassified to worse GFR, these patient were found to have higher mortality, higher troponin, and worse quality of life. In other words, the reclassification revealed patients who were sicker and higher risk of bad outcomes.
Thank you! I assumed so but just in case. Appreciate the clarification.
In cases where the creatinine eGFR and cystatin C eGFR are wildly discrepant (as in the above example), is the proper approach to just "split the difference" or is it to try and determine which estimate might be closer to correct given the patient characteristics, and weigh that one higher?
Great question! Per my favorite colleague Open Evidence, here is one stepwise approach when values are discrepant: 1) Use the combined equation (this is modeled to most accurately predict the gold standard GFR). 2) Consider whether there are factors that would clearly distort one of the values — for example, in the case of Crt, if a patient has profound sarcopenia or paraplegia, eGFRcys may be more appropriate. If patient on high-dose steroids, has osteomyelitis with high inflammatory burden, GFR derived from Crt would be more appropriate. Short story is that in extreme cases, you would go with “better” marker, but in most cases, the combined equation will do its magic and cancel out discrepancies from each of the single markers
At present, is it fair to say that a reasonable approach is to continue with creatinine-based estimate for routine use, but then add a cystatin C for select patients where that estimate is likely to be poor (e.g., muscle wasting, cirrhotic patients) or when the estimate needs to be a bit more precise (oncology, transplant)? Or does the author propose using the creatinine-cystatin C on all patients?
Great question! I have a somewhat skewed clinical population — patients with paraplegia, obesity (BMI over 40), nursing home patients with sarcopenia, and patients on border of GFR of 30 where combined equation would impact clinical management. So, these are people I am adding on Cystatin C. Other clinical subpopulations where can be useful would be renal transplant patients and cancer patients undergoing chemotherapy. From my reading, it’s a relatively cheap test and pretty accessible. For your routine patient (not on extreme of muscle mass or without above conditions), I still use GFR calculated based on Creatinine. Again, if they border on CKD, I consider getting Cystatin C. Hope this is helpful!
Wondering if the “combo GFR” equation would reclassify patients who suddenly “develop CRF “ after starting an ACE/ARB ?
This got me into a rabbit-hole… Per Open evidence, “The hemodynamic GFR reduction is real — and cystatin C should reflect it too.ACE/ARBs dilate the efferent arteriole, reducing intraglomerular pressure and truly lowering filtration. Both creatinine and cystatin C are freely filtered, so both should rise proportionally. In this scenario, eGFRcr-cys would show the same decline as eGFRcr, and would not reclassify the patient.” So, short story is at present, I don’t think there is great evidence for benefit of combined equation in this context (most of my reading focused on cancer patients, patient at extremes of muscle mass, and also at border of CKD). So, if patient is truly at border of GFR of 30, may be useful, but don’t think there is lots of data on this