A patient comes to me with a lab report showing a rise in creatinine, along with a chilling sentence her doctor told her: your kidneys are failing. She also has a two-page supplement protocol.

By the time she is in my chair, this patient has been frightened for weeks. She’s also confused about what might be causing her kidney problem, and what she should and shouldn’t be taking.

Cases like this are not uncommon in my functional medicine nephrology clinic. These patients come in after being told they’re in some stage of kidney failure. But in many of these cases, nothing is failing. Certainly, not the kidneys.

So, why the mistaken, panic-inducing diagnosis? All too often, doctors are taking a muscle metabolite and reading it as a kidney measurement, and the two are not the same thing.

A Muscle Number

I’m talking about creatinine. The creatinine level is a muscle number before it is a kidney number. Creatinine is the breakdown product of creatine in muscle. Anything that raises the amount of creatine going through that system raises the serum value, but none of it necessarily means the renal filters are damaged.

This is especially true for patients who are exercising intensively and/or who are on supplementation protocols that include creatine—which is very popular these days.

Creatine supplementation raises serum creatinine without impairing kidney function in healthy people. This was shown in a randomized controlled trial (Gualano, European Journal of Applied Physiology, 2008), and has long been the position iterated in the sports nutrition literature more broadly (Kreider, Journal of the International Society of Sports Nutrition, 2017).

The creatinine level is a muscle number before it is a kidney number. Anything that raises the amount of creatine going through that system raises the serum value, but none of it necessarily means the renal filters are damaged.

This means that your patient who started lifting weights and added five grams of creatine a day will run a higher creatinine level that looks new, and her eGFR will look worse. Yet her kidneys are fine.

Protein does the same thing on a smaller scale. In healthy adults, higher protein intake does not change measured kidney function. A meta-analysis put this matter to rest some years ago (Devries, Journal of Nutrition, 2018).

In established chronic kidney disease, however, the conversation about protein intake is different and worth having properly (Ko, Journal of the American Society of Nephrology, 2020). But a normal kidney is not injured by the protein your patient eats.

There’s the reverse phenomenon: a patient with low muscle mass produces less creatinine, so her creatinine number looks reassuring, while her filtration is genuinely reduced. This often gets missed clinically.

Sarcopenia and adiposity both drive large discordance between creatinine and cystatin C-based estimates (Hanna, Journal of Cachexia, Sarcopenia and Muscle, 2024). The frail 78-year-old with a creatinine of 0.9 is the patient I worry about, not the athlete at 1.4.

Consider the Whole Picture

So, before you scare someone by telling her that her test results show a high creatinine, and that this means kidney injury or renal failure, and before you send the patient to a specialist like me, consider the whole picture:

Ask about what may have changed in the eight weeks before the blood draw. A new creatine supplement? New protein intake target? A training block? Weight loss? Dehydration on the day of the blood test? Any of those is a more likely explanation for a high creatinine reading than the development of kidney failure in an organ that was healthy at the last panel.

A Role for Cystatin C Testing

We also need to consider Cystatin C. It is made by every nucleated cell and is not driven by muscle, which is exactly why it often settles these arguments. Combined creatinine and cystatin C equations estimate GFR more accurately than either marker alone (Inker, New England Journal of Medicine, 2021). Further, cystatin C carries stronger prognostic information for the outcomes we actually care about: end-stage renal disease, cardiovascular mortality, and overall mortality (Shlipak, New England Journal of Medicine, 2013).

The 2024 KDIGO guideline suggests a confirmatory cystatin C when the creatinine estimate is likely to be wrong (KDIGO, Kidney International, 2024). I recommend ordering a cystatin C test in four situations:

1) When the number and the patient disagree.

2) When muscle mass is at either extreme– the bodybuilder or the frail elder.

3) When you are about to make a decision that hinges on an eGFR threshold, a drug dose, a contrast study, or a referral.

4) Before you tell somebody to stop a protocol that is otherwise working well.

Cystatin C is not a perfect test either. Thyroid disease, corticosteroids, and significant adiposity can all affect the level, so read it as the second opinion that it is, not in isolation as the sole truth.

Combined creatinine and cystatin C equations estimate GFR more accurately than either marker alone

Potentially Dangerous Compounds

What actually injures kidneys, and what gets blamed instead?

Indeed, there are compounds in some foods, drugs, and dietary supplements that can cause renal injuries. But real injuries are narrower than the typical internet search would suggest, and they are specific.

Here are a few factors that can definitely be problematic:

Aristolochic acid: This is one I would want every clinician to be able to recognize by name. It is a nephrotoxic phytochemical produced by plants in the Aristolochia family. These are used in Chinese medicine and other herbal traditions, and they have appeared in botanical preparations across several continents (Debelle, Kidney International, 2008). The problem is, aristolochic acid can cause progressive interstitial fibrosis and urothelial carcinoma. I strongly advise patients to completely avoid Aristolochia, and the Chinese herbs that get substituted for one another in supply chains.

Oxalate load is a second important consideration. High dose vitamin C, and star fruit can both produce oxalate nephropathy, sometimes from a single exposure (Yasawardene, Transactions of the Royal Society of Tropical Medicine and Hygiene, 2021; Marques, American Journal of Kidney Diseases, 2017).

Star fruit (aka Carambola) has an additional problem, and for the patient who already has reduced kidney function, it is the more dangerous one. It contains caramboxin, a neurotoxin that a healthy kidney will clear, but a failing one does not. Caramboxin blocks GABA and overexcites the brain, and in CKD and dialysis patients it shows up as intractable hiccups, confusion and seizures, up to status epilepticus. If your patient has any reduction in function already, star fruit is a hard no rather than a caution.

NSAIDS: Third, and least glamorous, are the non-steroidal anti-inflammatories. They are associated with progression of existing kidney disease (Nderitu, Family Practice, 2013). Especially dangerous is the combination of an ACE inhibitor or ARB, a diuretic, and an OTC anti-inflammatory in somebody who is behind on fluid intake. In Houston in August, I see cases like this that land in an emergency room every few weeks.

Potassium: One more that surprises people is potassium-based salt substitutes. They are genuinely useful for helping regulate blood pressure at a population level, but the trial that made the case for them excluded patients at high risk of hyperkalemia (Neal, New England Journal of Medicine, 2021). In people with reduced kidney function, these products are a hazard. Yet they sit on the shelf next to ordinary salt with nothing on the label to say so.

What gets unfairly blamed for causing kidney injury?

Most of the rest, especially protein (in patients with healthy kidneys) and creatine. Many doctors immediately sound the alarm and tell patients to reduce consumption, or in the case of creatine to stop taking it completely. The reflex I see most often is the impulse to stop an ACE inhibitor simply because the creatinine rose after right starting it. In reality, a temporary rise up to thirty percent is the expected hemodynamic effect of ACE inhibitors, and it usually settles down within 2 months. (Bakris and Weir, Archives of Internal Medicine, 2000).

This does not mean you should not be vigilant. There are substances in food, supplements, and drugs that can be problematic, especially in patients who are already somewhat compromised. A broad survey of supplement-associated kidney injury published by Steven Gabardi and colleagues at the Brigham and Women’s Hospital, is worth keeping close at hand (Gabardi, Clinical Journal of the American Society of Nephrology, 2007).

Working Together

How can holistic physicians like you and specialists like me improve our working relationships? Where should your workup meet mine?

First, let me say I do not want to take your patient away from you. Most of what you are doing–the diet work, the blood pressure regulation, the metabolic balancing—these are the parts that will really change a patient’s long-term health trajectory, and I cannot deliver any of that in a 20-minute nephrology visit.

My requests from referring physicians are pretty narrow: Send me the patient’s full lab panel, with a cystatin C on it, if the picture is confusing. Send me the patient’s supplement list in full, including the things she buys herself, because that is where the aristolochic acid hides.

And please refer her before stage 4, not after. My referral line is an eGFR under 30, a urine albumin to creatinine ratio over 300, a loss of more than five points a year, hypertension not controlled on three drugs, or hematuria with proteinuria.

Your job is to notice the trend and to know what is confounding the numbers in front of you. My job is to slow it down once it reaches me. At stage 3 there is a great deal I can do that I cannot do at stage 5.

Bismah Irfan, MD, is a double board-certified nephrologist (ABIM Internal Medicine and Nephrology, plus Lifestyle Medicine) practicing in Houston, TX. She completed her nephrology fellowship at Albert Einstein College of Medicine, previously served as an assistant professor at Cleveland Clinic Lerner College of Medicine, and has cared for more than 1,000 patients with kidney disease over 14 years. She is the author of Your Kidneys Can Heal.