NEPHROTOXIC EFFECTS OF ANDROGENIC ANABOLIC STEROIDS ABUSE
Introduction
The abuse of androgenic anabolic steroids (??S) adversely affects renal function through direct and indirect mechanisms. Firstly, AAS have a direct toxic effect on glomeruliand are associated with the development of focal segmental glomerulosclerosis and tubular necrosis. On the other hand, rhabdomyolysis, high protein/creatine intake, inadequate hydration, high incidence of polydrug use are other factors that contribute to a rapid decline in renal function.[1,3,6-8]
AAS metabolism burdens the kidneys through the process of glomerular filtration in the renal parenchyma. The creatinine serum level, which is a reliable indicator of renal function, increases (> 1.5mg/ dl), as well as urea (>80 mg/ dl) and uric acid (>7.5 mg/ dl). All these biochemical parameters are affected from several othernon-renal factors (state of hydration, vegan diet) and their levels will not be raised above the normal range, until 60% of total kidney function is lost. So, the most reliable indicator of renal function is the measurement of creatinine clearance (GFR) at 24hrs.
Clinical and Nephropathologic Findings in AAS Abuse
Renal effects of AAS abuse in humans are primarily described in case reports [3-5, 7] and single small series. [2, 6, 8]
Trenbolone is a highly toxic to kidneys. During a cycle with trenbolone urine turns into brownish with a characteristic heavy odor. Stanozolol (Winstrol) is a 17 alkylated AAS highly hepatotoxic, also responsible for kidney damage, as shown to cause focal segmental glomerulosclerosis (FSGS), tubular necrosis and acute renal failure (ARF). This serious complication usually requires dialysis or renal transplantation.Boldenone, Nandrolonedecanoate also represent causes of drug-induced secondary FSGS. [2, 7, 8]
Focal segmental glomerulosclerosis is a condition in which there is focal scarring of some glomeruli within the kidneys. It affects majorly the filtration process,leading to proteinuria, edema in the face and lower extremities, hypoalbuminemiaprogressing to end-stage renal disease.
Clinically, the patient presents with edema in the face and lower extremities (proteinuria, hypoalbuminemia), hypertension, oliguria or even anuria (urine volume<500ml/24h). In microscopic urinalysis proteinuria, microhematuria and cylinders are present. [2-4, 6, 7]. GFR falls, creatinine elevates and the kidney is unable to perform its normal excretory functions. This causes disruption of electrolyte regulation, leading to a further rise in potassium levels. Hyperkalemia might lead to heart arrhythmias, such as atrial fibrillation, or ventricular tachycardia.
Numerous animal models have investigated the influence of sex hormones on the development of renal disease, and they generally show a protective role for estrogens, while androgens either are permissive or accelerate injury. Men are known to be at an overall increased risk for renal disease compared with women, and prognosis in men is worse for various types of chronic kidney disease. The sources for these differences are under investigation, and there is mounting evidence that androgens may play a central role in both normal and diseased kidney function and that estrogens are protective. [2]
In rare cases, abuse of AAS has been associated with the development of kidney tumors (nephroblastoma, adenocarcinoma).[9]
Multifactorial Stress on Kidneys
Aside AAS abuse, athletes have additional factors that could exert stress on renal function, such as high protein and creatine intake,excessive over-training, elevated BMI (>30), dehydration and polydrug use (for reducing side effects and boosting AAS effects). [1-3]
Protein and creatine supplements with a high protein intake of >300 g/day increases the renal blood flow and glomerular filtration rate in an attempt to excrete the nitrogenous by-products of its catabolism. Protein ingestion seems to cause an increase in renal blood flow and GFR by a variety of mechanisms.Although this is an appropriate adaptive response to the increase in nitrogenous waste that is the byproduct of protein metabolism, chronic hyperfiltration from a high-protein diet may accelerate progression to glomerulosclerosis and is also is associated with FSGS and acute tubular necrosis. [2]
Creatine monohydrate with loading doses of 20 g/day for 5 days and then maintenance doses of 5 g/day are considered to be safe, always with proper hydration. [3] Moreover creatine consumption affects creatinine’s serum levels, since it is metabolized into it. Creatine is an ingredient of red meat; therefore its consumption will also increase creatines concentration. Protein consumption tends to be diuretic, in the absence of carbohydrates and in such cases ketosomes are detected in a biochemical analysis, leading to exhalation of ketones (rotten apple smell). During precontest preparation and glycogen depletion phase, high consumption of animal protein (>3gr/kg), leads to ammoniaimia (skin and sweat get a characteristic heavy odor of ammonia). As known, ammonia is a waste product in urea cycle, being toxic to brain’s function (hepatic encephalopathy).
During intense over training, where rhabdomyolysis appears (serum CPK>1000), damaged muscle fibers release myoglobin. This protein is toxic to the renal glomeruli and tubules and may lead to acute tubular necrosis and ARF. Kidney function impairment from rhabdomyolysis presents with a dark color of the urine, microscopic hematuria (pinkish, red color), proteinuria or presence of cylinders. [2, 3, 8]
High protein consumption produces anacidic environment in the kidneys (pH<5). That, along with calcium retention from nandrolone abuse, could be responsible for the formation of kidney stones.[3]
Greater body mass (BMI> 30)leads to higher glomerular hyper-filtration, which in time leads to mechanical strain and scarring. When BMI is raised and over-training occurs, rhabdomyolysis is more risky since more myoglobin is released into plasma.
Highly nephrotoxic AAS, such as trenbolone, should not be combined with other aggravating substances for the kidney, such as non-steroidal anti-inflammatory drugs-NSAID’s (diclophenac, nimesulid), antibiotics (aminoglycosides) and diuretics (furosemide). Because kidneys contribute to systemic blood pressure (renin–angiotensin-aldosterone system), abuse of CNS stimulants such as beta-agonists (clenbuterol) or ephedrine leads to vasoconstriction of renal vessels, chronic systemic hypertension, proximal and distal tubular necrosis and acceleration of renal failure. Diuretics also have a negative impact on renal function, particularly when their abuse is accompanied by water restriction. [5]
Bodybuilders, usually exposed to forced muscle gain, diets high in protein and creatine, polydrug abuse should be considered a high?risk group in particular. Continuous renal function monitoring and early detection of kidney injury is very important for AAS users.
References:
1. Nephrotoxic effects of common and emerging drugs. Pendergraft WF, Herlitz LC, et al. Clin J Am Soc Nephrol 2014; (9): 1996–2005. (https://www.ncbi.nlm.nih.gov/pubmed/25035273).
2. Development of Focal Segmental Glomerulosclerosis after Anabolic Steroid Abuse. Leal C. Herlitz,Glen S. Markowitz, et al. J Am Soc Nephrol. 2010; 21(1): 163–172. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799287/).
3. Acute kidney injury associated with androgenic steroids and nutritional supplements in bodybuilders. Safa E. Almukhtar, Alaa A. Abbas, et al. Clinical Kidney Journal, 2015; 8 (4): 415. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515889/)
4. The development of focal segmental glomerulosclerosis secondary to anabolic steroid abuse. Patrick Harrington, Galil Ali, et al. BMJ CaseReports 2011; doi:10.1136/bcr.07.2011.4531. (https://casereports.bmj.com/content/2011/bcr.07.2011.4531.full)
5. End?stage renal disease in a bodybuilder: a multifactorial process or simply doping? Roger Hartung, Jens Gertet al. Nephrology Dialysis Transplantation2001;16 (1): 163–165. (https://academic.oup.com/ndt/article/16/1/163/1833875)
6. Complementary bodybuilding: A potential risk for permanent kidney disease. Wael El-Reshaid, Kamel El-Reshaid et al. Saudi Journal of Kidney Diseases and Transplantation 2018 ; 29 ( 2 ): 326-331. (https://www.ncbi.nlm.nih.gov/pubmed/29657200)
7. The Case: Chronic Kidney Disease Unmasked by Single-Subject Research. Gollasch B. Wischnewski O, et al. Case Rep Nephrol Dial 2018;8:90–97. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006620/)
8. Evaluation of anabolic steroid induced renal damage with sonography in bodybuilders.Kantarci UH, Punduk Z, et al. J Sports Med Phys Fitness.2018 Nov;58 (11):1681-1687
9. Anabolic steroid abuse and renal cell carcinoma.Martorana G, Concetti S, et al. J Urol.1999 Dec;162(6):2089.