A claim you hear on longevity podcasts

Is cystatin C better than creatinine for muscular people?

Leaning for. Of 5 studies that test it, 3 agree, 1 partly agrees and 1 disagrees.

Best for:
people with a lot of muscle whose creatinine or eGFR came back outside the lab range, weighing cystatin C vs creatinine as the kidney test.
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The claim checked: In muscular people, a high creatinine does not mean weak kidneys, and cystatin C gives the corrected reading Hear it at 2:10:08

What do the studies say?

Leaning for

Three studies found cystatin C was less tied to muscle mass than creatinine and backed it as the more reliable test, one of them in muscular men on testosterone. A study of hospital patients with heart failure found cystatin C less accurate than creatinine in the patients with more muscle. One study was mixed: it saw the expected pattern but measured no true GFR.

Computed from 5 studies that test this point, each judged by two readers, in full. 10 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“many of my patients are uh large and buff as I would say and they almost all have higher levels of creatinin that doesn't mean that your kidney function is suffering uh one thing that one would do clinically would uh get a cattin C to correct and get a corrected GFR to see if it's within the normal range”
Gabrielle Lyon, a guest on Huberman Lab · How to Exercise & Eat for Optimal Health & Longevity | Dr. Gabrielle Lyon · 2:10:08 on YouTube
No study named on tape; she describes her own clinical practice.
Point 1 of 2 Leaning for

In people with a lot of muscle mass, a cystatin C test gives a more accurate (corrected) estimate of kidney function (GFR) than creatinine

Agree 3

other primary study · 2008 · landmark

“This study showed that muscle mass affects serum and urinary creatinine but not cystatin C; therefore, the use of cystatin may represent a more adequate alternative to assess renal function in healthy individuals with higher muscle mass and potential mild kidney impairment.”

Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol
Who: 170 healthy adults (92 women, 78 men; aged 18-75, mean 36.6) recruited from hospital staff and gymnastics schools in Sao Paulo, grouped as sedentary, mild or moderate/intense physical activity; anabolic steroid, creatine and supplement users excluded
PMID 18235143

other primary study · 2024 · landmark

“Conversely, serum cystatin C demonstrates minimal association with muscle mass, supporting its increased use in routine clinical practice as a more reliable alternative.”

Creatinine, cystatin C, muscle mass, and mortality: Findings from a primary and replication population-based cohort. J Cachexia Sarcopenia Muscle
Who: Community adults from the Dutch PREVEND cohort (primary; mean age 49.8, 50% male) and the US NHANES 2001-2002 cycle (replication; mean age 48.7, 48% male)
PMID 38898741

other primary study · 2024

“Overall, we demonstrate Cys C as the marker less influenced by BMI and, therefore, more accurately reflective of renal function in this patient population.”

Creatinine and Cystatin C: A Measure of Renal Function in Men With Testosterone-Induced Muscle Hypertrophy. Am J Mens Health
Who: 227 male self-identified elite athletes (professional or amateur competitors) with testosterone-induced muscle hypertrophy at a single men's health tertiary clinic; median age 41, median BMI 30.6, median body fat 15.6%
PMID 39402920

Partly agree 1

other primary study · 2022

“Higher CER index was associated with lower eGFR Cr and higher eGFR Cys ( Figure 2A,B ).”

Muscle mass and estimates of renal function: a longitudinal cohort study. J Cachexia Sarcopenia Muscle
Who: 7943 community-dwelling adults from the Dutch PREVEND cohort (mean age 49.7, 49.7% male, 95.5% Caucasian)
PMID 35596604

Disagree 1

other primary study · 2021

“Accuracy was statistically better with eGFRcys compared with eGFRcr in patients with lower muscle mass, though both performed poorly (1-P30, 48.3%, vs 70.0%, respectively, P < .001); on the contrary, accuracy was worse with eGFRcys compared with eGFRcr in higher muscle mass (1-P30, 42.5%, vs 26.0%, respectively, P < .001).”

Cystatin C and Muscle Mass in Patients With Heart Failure. J Card Fail
Who: 293 patients admitted to Yale New Haven Hospital for decompensated heart failure receiving IV loop diuretics; median BMI in the obese range
PMID 32750487

Point 2 of 2 Strong consensus for

People with a lot of muscle mass have higher blood creatinine, and that does not mean their kidney function is worse

Five studies found more muscle went with higher creatinine or a lower creatinine-based eGFR, and the ones that also measured cystatin C found it did not fall with more muscle. A study of elite athletes found creatinine rose with body size, but it measured neither muscle nor kidney function.

Computed from 6 studies that test this point, each judged by two readers, in full. 10 more studies are waiting for a full read and do not count yet.

Agree 5

other primary study · 2008 · landmark

“This study showed that muscle mass affects serum and urinary creatinine but not cystatin C; therefore, the use of cystatin may represent a more adequate alternative to assess renal function in healthy individuals with higher muscle mass and potential mild kidney impairment.”

Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol
Who: 170 healthy adults (92 women, 78 men) aged 18-75, sedentary or with mild or moderate/intense physical activity, recruited from hospital staff and gymnastics schools; kidney disease, anabolic steroids, creatine and supplements excluded
PMID 18235143

other primary study · 2024

“Concordantly, our study confirms that elevated Cr is expected in men with high muscle mass, indicated by relatively high BMI and lean PBF.”

Creatinine and Cystatin C: A Measure of Renal Function in Men With Testosterone-Induced Muscle Hypertrophy. Am J Mens Health
Who: 227 self-identified male elite athletes on testosterone therapy with testosterone-induced muscle hypertrophy at a single men's health tertiary clinic; no renal disease history apart from well-controlled diabetes, hypertension or treated nephrolithiasis
PMID 39402920

other primary study · 2022

“Higher CER index was associated with lower eGFR Cr and higher eGFR Cys ( Figure 2A,B ).”

Muscle mass and estimates of renal function: a longitudinal cohort study. J Cachexia Sarcopenia Muscle
Who: 7943 community-dwelling adults from the PREVEND cohort in Groningen, the Netherlands (mean age 49.7, 49.7% male, 95.5% Caucasian); muscle mass approximated by height-indexed 24-h urinary creatinine excretion rate
PMID 35596604

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other primary study · 2017

“Lean mass percentage and fat mass percentage are associated with creatinine-based eGFR, but not with cystatin C-based eGFR.”

Childhood Estimates of Glomerular Filtration Rate Based on Creatinine and Cystatin C: Importance of Body Composition. Am J Nephrol
Who: 4,305 healthy children aged about 6 years (95% range 5.7-8.0) in the Generation R population-based cohort, Rotterdam; body composition by DXA
PMID 28245441

other primary study · 2025

“We found significant negative correlations between CER and eGFRcr for all equations, with β coefficient ranging from −0.2 [−0.23 to −0.17] for MDRD to −0.14 [−0.17 to −0.12] for EKFC.”

Impact of Muscle Mass on the Performance of Creatinine-Based eGFR Equations and Mortality Risk Assessment After Kidney Transplantation. J Cachexia Sarcopenia Muscle
Who: 1829 adult kidney transplant recipients at Necker Hospital, Paris, with GFR measured by iohexol plasma clearance and muscle mass by timed creatinine excretion rate
PMID 41021368

Partly agree 1

other primary study · 2006

“The correlation between creatinine and BMI is not necessarily only connected with muscle mass.”

Relation between serum creatinine and body mass index in elite athletes of different sport disciplines. Br J Sports Med
Who: 151 elite male Italian athletes from five sports (rugby 44, soccer 27, alpine skiing 34, sailing 22, cycling 24), measured before the competitive season
PMID 16723402

Disagree 0

None.

What else was said but not tested?

  • Almost all of her large, muscular patients have higher creatinine
  • People on higher protein diets have higher blood creatinine

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