Barbell Medicine - From Bench to Bedside

We frequently receive questions from lifters who see their doctors and get a variety of screening tests done, including bloodwork. Interpreting lab data accurately can be a tricky endeavor, particularly for individuals who lack training in clinical medicine. Simple comparison of results against the lab reference ranges, for example, is a recipe for problems ranging from overdiagnosis, overtreatment, and unnecessary anxiety to missed diagnoses and preventable downstream harm. While we cannot fully educate the lay public in clinical lab interpretation, with these articles we hope to answer some basic questions to guide more productive conversations between you and your physician.

Early disclaimer: this article is for informational and, perhaps, entertainment purposes only. You should make all medical decisions pertaining to your laboratory test results in conjunction with a healthcare professional. We also have a podcast series coming out about this starting on Monday August 7th, 2020, so be sure to check that out. 

Kidney Function

The kidneys are remarkable organs. When healthy, they regulate the excretion of water, all of our electrolytes, and a variety of metabolites and waste products in order to precisely match our daily intake and production. They also participate in several other processes in the body that regulate blood pressure, bone metabolism, thyroid function, and blood cell production.

A useful metric of kidney function is the rate at which an individual’s kidneys are filtering the liquid portion of the blood, called plasma. This is known as the Glomerular Filtration Rate, or GFR. Healthy kidneys can filter at a rate of about 125 mL per minute; this means our typical plasma volume (about 3 liters) gets filtered 60 times per day.

The normal range for GFR varies between individuals depending on age, sex, and body size; a typical normal value might be 120 mL/min/1.73 m2 (the 1.73 m2 represents a factor to normalize for body size). It is complex and impractical to measure someone’s GFR directly, so instead we measure the rate of filtration and clearance of other substances like creatinine to calculate an estimate for GFR. Blood urea nitrogen (BUN) and creatinine are two common blood tests used to assess kidney function and are included in panels such as the Basic Metabolic Panel.

A Deeper Dive into Creatinine

Creatinine is a byproduct of the metabolism of creatine (note the spelling difference). Creatine is a compound found in skeletal muscle, dietary meat, and a variety of dietary supplements. For an individual who is in stable health and is consuming a consistent diet, creatinine is 1) released into the plasma at a relatively constant rate, and 2) filtered via the kidneys at a relatively constant rate.

In this context of metabolic equilibrium, called homeostasis, the plasma creatinine concentration should also remain constant. A typical lab reference range for creatinine is about 0.7 mg/dL to 1.2 mg/dL, although there is significant variation in this range between normal individuals and between different labs. Additionally, there are a number of limitations to this measurement, such as variations in creatinine production, secretion, and limitations to the lab tests themselves that are beyond the scope of this article. The measured creatinine value is then used, along with patient-specific factors like age and sex, to calculate an estimated GFR (eGFR) using formulas such as the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI).

If kidney impairment results in a decrease in filtration rate (with muscle mass and diet remaining constant), a decrease in the clearance of creatinine causes it to accumulate in the blood. This becomes apparent as an elevated blood level on a lab test. It should be noted that creatinine is a benign metabolic byproduct. It is not harmful or toxic itself even if it starts to accumulate when kidney function is impaired. That is why physicians get excited about it. Elevated creatinine can, but does not always, suggest kidney impairment.

Kidney function can become impaired for a variety of reasons including dehydration, decreased blood flow, infection, inflammation, autoimmune processes, toxins, drug reactions, obstruction, and many others. Many individuals who experience an initial injury to their kidneys will recover without long-term consequences. However, some who experience particularly severe or recurrent impairment, or who have conditions like high blood pressure or diabetes may develop permanent, progressive impairments known as Chronic Kidney Disease (CKD) and kidney failure. It is in the end stages of this condition that interventions including dialysis and kidney transplantation are often performed.

Note the caveat that muscle mass and diet — factors that influence creatinine production — remained constant in the above scenario. As a blood measurement, creatinine is most useful and interpretable when the patient is in homeostasis. However, this is not always the case. Let’s consider a few potentially tricky scenarios.

We can imagine an individual with extremely low skeletal muscle mass, a condition known as Sarcopenia. This decrease in muscle leads to low creatinine production. As a result, the measured plasma creatinine concentration may be low, leading to a falsely high estimated Glomerular filtration rate without any true change in GFR. In fact, we have evidence that very low plasma creatinine levels (less than 0.4 mg/dL or 35 umol/L) are associated with an increased risk of complications and death. This is likely because these numbers often reflect sarcopenia. [Thongprayoon 2016a, Thongprayoon 2016b, Ostermann 2016]

Things may not always be this simple, however. This individual with sarcopenia whose  baseline creatinine level is low due to a lack of muscle mass (less than 0.4 mg/dL) might then develop kidney impairment. This could lead to an accumulation of creatinine (e.g., up to 1.0 mg/dL), which falls in the typical normal range and might therefore not raise suspicions of an underlying problem. However, for this particular individual, a level of 1.0 mg/dL reflects a decline in kidney function! This helps to illustrate how lab interpretation can be quite tricky and is more complicated than just looking at “normal ranges”.

Another scenario may involve an individual who is very muscular. The higher level of skeletal muscle results in more creatinine production, and therefore a higher plasma creatinine level – without any change in GFR. This can be tricky in practice because the lab report may highlight the value (for example, 1.4–1.5 mg/dL) as being “out of range”, potentially raising a false alarm about a decline in kidney function. To be clear: the vast majority of individuals – even those who train – will not exceed 1.5 mg/dL or 133 umol/L in the absence of kidney impairment.

Similarly, taking dietary creatine supplements (particularly in close temporal relationship to a blood draw) may make lab interpretation challenging. After this creatine load is metabolized, an increased plasma creatinine concentration may raise concern for a decline in kidney function even if the true GFR is unchanged. While pure creatine supplementation has never been shown to cause harm to the kidneys, this situation can be even trickier since there are many tainted supplements on the market that certainly do cause kidney injury.

My Creatinine is Elevated: What Do?

The comprehensive evaluation of kidney impairment is beyond the scope of this article and should involve consultation with a medical professional. However, we can discuss a few basic considerations for generally healthy folks who train and want to understand the meaning of an abnormal lab result.

The first consideration is whether there is a prior lab value available for comparison because this helps to characterize the degree of “abnormality” as well as the time course involved. For example, if an apparently healthy patient without any medical issues has a result of 1.3 mg/dL and it was the same 1.3 mg/dL five years ago, this stability provides some reassurance. Conversely, if an individual’s last measurement was 0.8 mg/dL and it is now 1.4 mg/dL, this should prompt further evaluation. This would be true even if they have gained some muscle mass from in the interim. Levels above 1.5 mg/dL (~132 umol/L) should always be evaluated further, and should only be attributed to muscularity or dietary factors if other causes have been confidently ruled out. With that said, values below this threshold may still represent a degree of kidney impairment, so decisions about further evaluation should always be made together with a healthcare professional

Another up-front consideration should include any historical features to suggest dehydration or any new drugs or supplements. Frequent use of NSAID analgesics like Ibuprofen or Naproxen is common among lifters and can lead to kidney-related complications, particularly when used at high doses for prolonged periods of time. Other medications including a variety of antibiotics, proton-pump inhibitors, and diuretics can potentially cause kidney issues as well. As mentioned above, creatine supplementation can contribute to abnormal creatinine concentrations that do not necessarily reflect kidney injury, whereas tainted supplements and anabolic steroids can certainly cause kidney injury and organ failure.

Conclusion

While this article is primarily focused on generally healthy lifters with concerns about their lab results, it should be pointed out that chronic high blood pressure and diabetes are the most common causes of chronic kidney disease. A history of these conditions should therefore raise concern in the setting of abnormal lab values, and these values should be routinely monitored in patients with these conditions.

The next steps in assessing kidney function typically involve obtaining a urine sample for “urinalysis” and microscopic evaluation. A completely normal urinalysis in a muscular individual whose plasma creatinine concentration is mildly elevated (say, 1.3 mg/dL) and is stable over long periods of time is typically reassuring. On the other hand, these urine tests might reveal abnormalities such as glucose, protein, crystals, blood, bacteria, or other abnormal cells/casts in the urine that may reflect upstream problems in the kidney. At this point, further evaluation would be directed by the medical professional and is beyond the scope of our article.

Thank you to Tom Campitelli, DTFP, for his assistance in editing this article.


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About Austin Baraki

Dr. Austin Baraki is a practicing Internal Medicine Physician, competitive lifter, and strength coach located in San Antonio, Texas. Originally from Virginia Beach, Virginia, he completed his undergraduate degree in Chemistry at the College of William & Mary, his doctorate in medicine at Eastern Virginia Medical School, and Internal Medicine Residency at the University of Texas Health Science Center in San Antonio.

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