Stanozolol and the kidneys: what is known about the load

When it comes to the risks of stanozolol, the liver and cholesterol are usually mentioned. The kidneys remain in the shadow — partly because there are very few direct studies specifically of stanozolol and kidney function. However, clinical observations of people who use anabolic steroids describe several mechanisms of kidney injury. Our editors examine what is known for certain, what is a supposition and how to correctly interpret tests.

What we know and what we do not know

Stanozolol is an oral and injectable anabolic steroid, a derivative of dihydrotestosterone with a pyrazole ring attached to ring A and a methyl group at position 17α. Medically it was used, in particular, to prevent attacks of hereditary angioedema, as well as in veterinary medicine. Today in most countries stanozolol products for humans are practically absent from legal circulation.

There are virtually no controlled studies that would specifically examine the effect of stanozolol on the kidneys. The available data are descriptions of clinical cases and case series, as well as reviews that summarize kidney injury in people who use anabolic steroids, often several at once. Therefore it is usually impossible to isolate the contribution of stanozolol specifically.

At the same time the body of observations is convincing enough to speak of real risks. Nephrologists’ reviews describe several different types of injury: from glomerular diseases to acute kidney injury associated with cholestasis or rhabdomyolysis.

So the honest answer is this: a direct nephrotoxic effect of stanozolol at the doses used by athletes has not been quantitatively established, but the mechanisms through which it can harm the kidneys are well described for the class of anabolic steroids.

Mechanisms of kidney injury with steroid use

The best-known work on this topic is the study by Herlitz and colleagues (2010), published in the Journal of the American Society of Nephrology. The authors described a series of bodybuilders with long-term use of anabolic steroids, in whom focal segmental glomerulosclerosis (FSGS) developed — scarring of the kidney glomeruli, which manifests as protein in the urine and a gradual decline in kidney function. Some patients had improvement after stopping steroids, in some the disease progressed.

The authors linked FSGS to a combination of several factors: a sharp increase in body weight, which raises the load on the glomeruli (hyperfiltration), a possible direct effect of androgens on kidney cells, as well as arterial hypertension. A similar mechanism is known in obesity, when the kidneys “cannot keep up” with the increase in body weight.

The second mechanism is a rise in arterial pressure. Anabolic steroids can contribute to the retention of sodium and fluid and to a change in vascular tone. Chronic hypertension is one of the main causes of chronic kidney disease in the general population, and for people who use steroids this path is also relevant.

The third mechanism is acute kidney injury not directly related to the glomeruli. This includes rhabdomyolysis after excessive training, dehydration before competitions, the use of diuretics, as well as long-term intake of non-steroidal anti-inflammatory agents for joint pain. In real life these factors are often combined.

The review by Parente Filho and colleagues (2020) summarized the described cases of kidney injury associated with steroids and excessive intake of vitamin supplements, in particular hypercalcemia due to vitamin D overdose, which is also sometimes observed in the sports community.

Peculiarities of stanozolol: the liver as a “bridge” to the kidneys

Stanozolol, as a 17α-alkylated steroid, is associated with cholestatic liver injury — a disruption of bile outflow. In severe cases the level of bilirubin and bile acids in the blood rises significantly. Nephrologists describe in this case so-called cholemic nephropathy (bile cast nephropathy): bile acids and bilirubin act toxically on the kidney tubules and form casts in them, which can cause acute kidney injury.

Such cases have been described in people who used oral anabolic steroids, including 17α-methylated drugs. For stanozolol there are reports of severe cholestasis, so theoretically this path is quite real for it. It is important that the early symptoms — itching of the skin, darkening of the urine, pale stools, jaundice — appear precisely on the part of the liver.

The second aspect is lipids. Stanozolol belongs to the steroids with the most pronounced negative effect on the lipid profile: in classic works (Applebaum-Bowden et al., 1987) a rapid decrease in HDL and an increase in the activity of hepatic lipase were shown. Dyslipidemia and atherosclerosis affect not only the heart but also the renal arteries.

Finally, unlike testosterone, stanozolol is not aromatized and is less prone to causing pronounced fluid retention. But this does not cancel the effect on pressure, and for the kidneys the total effect is more important: body weight, pressure, lipids, the state of the liver and behavioral factors.

How to read kidney tests in a person who trains

The most common measure of kidney function is blood creatinine, from which the glomerular filtration rate (GFR) is calculated. However, creatinine is formed from muscles, so in people with a large muscle mass or those who take creatine it is naturally higher. The calculated GFR in this case may be underestimated, although the kidneys are working normally.

For clarification doctors often use cystatin C — a protein whose level depends little on muscle mass. The KDIGO guidelines on chronic kidney disease describe it as a complement to creatinine in situations where creatinine can be misleading.

An extremely important measure is protein (albumin) in the urine. It was precisely proteinuria that was the main sign of FSGS in bodybuilders. At the same time intense training the day before can temporarily raise protein in the urine, so the test is better taken after days of rest and, if necessary, repeated.

The totality of measures should be interpreted by a doctor who is aware of drug use, training and supplements. Independent conclusions from a single measure are often mistaken in both directions.

Who is in the risk group and what are the warning signals

The risk of kidney injury rises in the presence of several factors at once. Special caution should be shown by people who already have kidney diseases, elevated pressure, diabetes mellitus, a hereditary burden, or who previously had episodes of acute kidney injury.

• A persistent rise in arterial pressure.
• Foamy urine (may indicate protein in the urine).
• Swelling in the legs or face.
• Darkening of the urine, jaundice, itching of the skin.
• A sharp decrease in the amount of urine, especially after a heavy workout or dehydration.
• Muscle pain with tea-colored urine — a possible sign of rhabdomyolysis.

Any of these signs requires seeing a doctor, and a combination of jaundice and a decrease in urine or tea-colored urine — emergency care.

For athletes, we remind you that stanozolol is in section S1 of the WADA Prohibited List and is banned at all times. Its classic metabolites, in particular 3'-hydroxystanozolol, have long been used as markers in doping control.

Editorial conclusions

Direct studies of the effect of stanozolol on the kidneys are few, but for anabolic steroids in general several mechanisms of injury are described: FSGS through hyperfiltration, hypertension, cholemic nephropathy against the background of cholestasis and acute kidney injury through rhabdomyolysis and dehydration.

For stanozolol the cholestatic path and the pronounced negative effect on lipids are especially relevant.

Kidney function in people with a large muscle mass should be assessed taking into account the peculiarities of creatinine; cystatin C and a urine test for albumin give a more accurate picture.

We also recommend reading our materials on the effect of stanozolol on the psyche and on the skin, as well as on the metabolites of oxandrolone.

References

1. Herlitz LC, Markowitz GS, Farris AB, et al. Development of focal segmental glomerulosclerosis after anabolic steroid abuse. J Am Soc Nephrol. 2010;21(1):163–172.
2. Parente Filho SLA, Gomes PEAC, Forte GA, et al. Kidney disease associated with androgenic-anabolic steroids and vitamin supplements abuse: Be aware! Nefrologia. 2020;40(1):26–31.
3. Applebaum-Bowden D, Haffner SM, Hazzard WR. The dyslipoproteinemia of anabolic steroid therapy: increase in hepatic triglyceride lipase precedes the decrease in high density lipoprotein2 cholesterol. Metabolism. 1987;36(10):949–952.
4. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1–150.
5. Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
6. Schänzer W. Metabolism of anabolic androgenic steroids. Clin Chem. 1996;42(7):1001–1020.