Renal Toxicity Associated with Steroid Use

Historically, anabolic androgenic steroids were employed in treating anemia in individuals with chronic kidney disease (CKD). Due to inconsistent erythropoietic responses and the subsequent emergence of recombinant erythropoietin, these were discontinued for this purpose. Unlike other well-known side effects of androgens, like acne, virilization, testicular atrophy, gynecomastia, and liver dysfunction, renal side effects have only been described recently. To understand the damage caused by anabolic steroids, some basic renal physiology concepts are needed.

The kidneys can excrete substances in urine and eliminate excess water, regulating the osmolality of bodily fluids and concentrations of electrolytes. Waste products are also removed, thanks to functional units called nephrons, each composed of a renal corpuscle and a renal tubule.

The renal corpuscle is where blood is initially filtered, via a structure called the glomerulus. Blood is filtered through three layers that prevent blood cells, most plasma proteins, and platelets from becoming part of the filtrate. This filtrate is then collected in a cup-shaped sac called Bowman's capsule. Around 20% of the fluid that flows through the glomerulus ends up in the Bowman's capsule as part of the filtrate.

This filtrate then enters the renal tubule of the nephron. Here, reabsorption of some filtrate substances can occur. A commonly used measure to assess kidney function is the Glomerular Filtration Rate (GFR), specifically, the estimated Glomerular Filtration Rate (eGFR).

The glomerulus is particularly relevant in steroid-induced nephrotoxicity. If these filtration layers are damaged, molecules that should not normally be present, like proteins, leak into the urine, causing proteinuria - an early sign of kidney damage.

One of the first to report on steroid-induced nephrotoxicity was Herlitz et al. in 2010. Several case studies of bodybuilders presenting renal abnormalities, such as proteinuria and FSGS, were compiled. Of the seven patients with long-term follow-ups, steroid discontinuation, along with the use of RAAS cascade blockers and/or corticosteroids, resulted in improved or stabilized serum creatinine, weight loss, and reduced proteinuria.

The authors proposed that secondary FSGS in AAS users could be related to different pathways, such as increased lean body mass leading to glomerular hyperfiltration, regulation of renal blood pressure, oxidative stress, apoptosis, and inflammatory cytokines.

Other factors, such as a high-protein diet and hypertension, can have additive/synergistic adverse effects on the glomeruli.

FSGS is a term for diseases where there are glomerular injuries mediated by various aggressions targeted or inherent to the podocyte. In FSGS, these podocytes begin to change shape, their foot processes flatten, and they eventually die. They cannot regenerate as they are terminally differentiated cells, meaning they cannot proliferate. Once a podocyte is dead, it cannot be replaced with a new podocyte, and it is replaced with connective tissue (sclerosis). As a result, the kidney begins to lose filtering capacity.

Since then, the number of dated cases in the medical literature of nephropathies associated with AAS use has been increasing, going from a virtually unknown problem to a major concern within the medical community.

Unfortunately, regarding kidney problems, the only solution is to delay evolution. In the case of AAS use, it's not so much a question of whether it will occur, but rather when it will happen in a particular case.

Massive blockade of the previously described RAAS cascade with the use of drugs such as ACE inhibitors, ARBs, MRAs, etc., tends to work quite well, especially if combined with a low sodium diet. This is due to the fact that if daily sodium intake exceeds 2.5 grams, these drugs begin to lose their effectiveness over time, reaching a point, in approximately 6-12 months, where they completely stop having any renal protective effect.