this subject for body builders and nephrologist to be aware about the effect of Anabolic steroids on the kidney

1. Anabolic Steroids And kidney
Dr. Hayam H. Mansour
Assistant Prof. Of Internal Medicine & Nephrology
Al-Azhar University

2. •History of AAS
•Epidemiology of AAS use
•How are the anabolic steroids abused??
•General side effects of AAS
•AAS and kidney

3. Performance Enhancing Drugs
(PED)
Anabolic Steroids
Human Growth Hormone.
Creatine.
 Erythropoitin
Beta 2 Agonists.
Stimulants.
Beta Blockers.
 Diuretics.
Tamoxifen.
Thyroxin
insulin

4.  Anabolic-androgenic steroids(AAS) are the man-
made derivative of the male sex hormone
testosterone.
 The goal of altering an AAS is to increase its
anabolic characteristics & to decrease its
androgenic features.
Anabolic Steroids History

5.  1935 – Testosterone identified and synthesized
 1937 – Clinical trials on humans with testosterone
began
 WWII – German scientist synthesized other
anabolic steroids and experimented on
concentration camp inmates to treat chronic
wasting.
 Also given to German soldiers hoping to increase
their aggression.
Anabolic Steroids History

6.  However, as early as the 1940s, weightlifters started
using testosterone for its anabolic effects to enhance
athletic performance.
 The United States Drug Enforcement Agency classified
them as scheduled drugs in 1991.
Anabolic Steroids History

7. The Global Epidemiology of Anabolic Steroid Use
The worldwide prevalence of anabolic-androgenic steroid
use is poorly documented, and geographical distribution of
studies concerning AAS use is mostly limited to the USA,
Canada, Brazil and some European countries.

8. The Global Epidemiology of Anabolic Steroid Use
• An estimated 2.9 to 4.0 million Americans have used
supraphysiologic doses of illicit AAS, including
testosterone and its synthetic relatives, to gain muscle
mass for athletics or personal appearance.
Endocrine Society scientific statement. Endocr Rev. 2014;
;

9. The Global Epidemiology of Anabolic Steroid Use
• The prevalence of AAS in Jazan was 31.0 %
• Its prevalence was also significantly higher among athletes
who received higher education 37.4%.
• The most common types of AAS used are Deca-Durabolin
(57.6 %) and testosterone (52 %).

10. The Global Epidemiology of Anabolic Steroid Use
• Thirty percent of the participants who used AAS
suffered from depression and aggressive behavior while
18 % of them were hypertensive.
• The participants were not well aware of the adverse
effects of anabolic steroids use.

11. Mechanism of Action of Anabolic Steroids

12. • By far the most important use of AAS is in the treatment of male
hypogonadism.
• Other medical disorders, such as certain types of anemia, prophylactic
in hereditary angioedema, and occasionally breast cancer in women.
• Testosterone has also been found effective for the wasting syndrome
associated with HIV infection.
Parkinson etal.Med Sci Sports Exerc. 2006;38(4):644–51. 57.
Therapeutic Uses of AAS

13. Anabolic Steroids Adverse Effects

14.  In addition, because steroids are often injected, users who
share needles or use non sterile techniques when they inject
steroids are at risk for contracting dangerous infections, such
as HIV and hepatitis.
Anabolic Steroids Adverse Effects

17.  AAS users often take a combination of both injectable and
oral agents simultaneously, a practice called “stacking”
and sometimes even including compounds that are
designed for veterinary use.
 Characteristically, AAS are taken for courses of time,
called “cycles,” typically ranging from 4 to 16 weeks,
interspersed with off-drug periods.
Pope etal.,American Psychiatric Press; 2003. p. 331–58.
How are anabolic steroids abused?

18.  “Pyramiding’’ This is a process in which users slowly escalate
steroid abuse (increasing the number of steroids or the dose and
frequency of one or more steroids used at one time), reaching a
peak amount at mid-cycle and gradually tapering the dose toward
the end of the cycle.
How are anabolic steroids abused?

19. How are anabolic steroids abused?
 By using the drugs in cycles, therefore, a
user can allow his own HPT axis to
rebound to normal function during the
drug-free intervals.
Fudala etal.,Annu Clin
Psychiatry.2003

20.  Focal segmental glomerulosclerosis(FSGS).
 Rhabdomyolysis (Diffuse or Localized)
 Bile cast Nephropathy/ Cholemic Nephrosis
 Interstitial Nephritis.
 Acute Tubular Necrosis.
How are Anabolic Steroids Affecting
The Kidneys??

21. Focal segmental glomerulosclerosis
(FSGN )

22.  Anabolic steroids promote growth of skeletal
muscle and increase lean body mass.
 Increased body mass requires an increase in
glomerular filtration.
 In an attempt to meet these demands, individual
glomeruli adapt to hyper-filtration through
hypertrophy.
Mechanism Of FSGS In AAS Users

23.  Podocytes are terminally differentiated cells that cannot
proliferate, and in the process of compensatory
glomerular hypertrophy, podocyte connections to the
GBM become mechanically strained.
 If these conditions persist, then podocytes eventually
detach from the GBM, leading to development of a
segmental scar and post adaptive FSGS.
Hodgin etal.,Clin JAm Soc Nephrol 2009.
Mechanism Of FSGS In AAS Users

24. • Development of Focal Segmental Glomerulosclerosis after
Anabolic Steroid Abuse. Leal C. Herlitz,Glen S. Markowitz,
Alton B. Farris, Joshua A. Schwimmer, Michael B. Stokes,
Cheryl Kunis,Robert B. Colvin, and Vivette D. D'Agati. J Am
Soc Nephrol. 2010 Jan; 21(1): 163–172.
• Relatively high incidence of full nephrotic syndrome, presence of
collapsing or cellular lesions of FSGS, advanced fibrosis and
glomerulosclerosis, and the high degree of FPE in some patients.

25. • The greater severity of clinical and biopsy findings in
bodybuilders which are unusual findings in postadaptive FSGS.
• So they conclude that , AAS abuse has also direct nephrotoxic
effects.

26.  Several studies suggest that androgens may exert a
direct toxic effect on glomerular cells.
 Glomerular cells have androgen receptors, which could
make them prime target for exogenous steroids
 Exogenous testosterone administration increased
androgen receptor expression, as well as levels of the
profibrotic cytokine TGF-β1, a potent proapoptotic
stimulus to podocytes, promoting FSGS.
Mechanism Of FSGS In AAS Users

27.  Bodybuilders has additional factors that could exert stress
on glomeruli.
 Diets high in protein cause marked changes in renal
hemodynamics.
 Protein ingestion seems to cause an increase in renal blood
flow and GFR.
 Chronic hyperfiltration from a high-protein diet may
accelerate progression to glomerulosclerosis.
Mechanism Of FSGS In AAS Users

28.  Androgens are also known to induce oxidative
stress and upregulate components of the RAS.
 An animal model of hypertension-induced end-
organ damage showed significant attenuation of
renal damage by androgen receptor blockade with
flutamide.
Baltatu etal., J Am Soc Nephrol 13: 2002

29. • Findings in renal biopsy:
- Glomerular hypertrophy/glomerulomegaly.
- Glomeruloscelerosis.
- Tubulointerstitial scarring.
- Podocyte foot process effacement(FPE).

31.  Secondary forms of FSGS typically have a lower incidence of
nephrotic syndrome and a better overall prognosis when compared
with primary (idiopathic) FSGS.
• Width of foot processes is significantly higher in primary FSGS,
as compared to secondary form.

32. • Whereas the mainstay of treatment for primary FSGS is
immunosuppressant, secondary (post adaptive) forms of FSGS
are treated with RAS blockade and treatment of the underlying
cause whenever possible (e.g., discontinue anabolic steroids
and supplements, reduce protein intake and decrease exercise).

33. Rhabdomyolysis

34. Rhabdomyolysis
• Cases of diffuse rhabdomyolysis associated with
excessive physical exertion are commonly
reported, especially in long-distance runners,
weight lifters, football players, and military
personnel participating in physical training.

35. Rhabdomyolysis
• Exertional rhabdomyolysis refers to muscle cell
damage caused by intense exercise, during which
the energy supply to muscles is insufficient to
meet demands.
• The exact incidence of rhabdomyolysis among
bodybuilders remains unknown.
• Many cases in the exercise setting are probably
unrecognized and diagnosed as simple muscle
strain.

36. Rhabdomyolysis
• Breakage of skeletal muscle membrane leads to
intracellular content leakage, including creatine
kinase, serum glutamic-oxaloacetic transaminase,
lactate dehydrogenase, myoglobin, electrolytes (eg,
potassium and phosphate), and purines.

37. Rhabdomyolysis
• When blood myoglobin concentrations rise to
approximately 3 mg/L, protein crosses the renal
threshold and can be found in the urine, a
condition known as myoglobinuria.
• In high amounts, myoglobin can precipitate in
kidney tubules and compromise renal function.

38. Rhabdomyolysis
• localized rhabdomyolysis associated with weight
lifting is reported infrequently, biceps, long head
of triceps, and bilateral quadriceps.
• It might be due to a toxic effect of a drug
ingredient, or it may be the result of compartment
syndrome.

39. Bile Cast Nephropathy/ Cholemic Nephrosis

40. Bile Cast Nephropathy/ Cholemic Nephrosis
• Anabolic androgenic steroids , are recently recognized cause of
hepatotoxicity and cholestaic jaundice and may lead to acute
kidney injury.
• Cholemic nephrosis represents a spectrum of kidney injury that
ranges from proximal tubulopathy due to intracellular
accumulation of bilirubin/bile acids, which may interfere with
mitochondrial function and possibly other cellular functions , to
the presence of intrarenal bile casts, which both obstruct and have
direct toxic effects on epithelial cells.
Renal pathology meeting, 2013

41. Are anabolic steroids addictive?
• An undetermined percentage of steroid abusers may become
addicted to the drugs, as evidenced by :
• Their continued abuse despite physical problems and negative effects on social
relations.
• Steroid abusers typically spend large amounts of time and money obtaining the
drugs, which is another indication that they may be addicted.
• Individuals who abuse steroids can experience withdrawal symptoms when
they stop taking steroids, such as mood swings, fatigue, restlessness, loss of
appetite, insomnia, reduced sex drive, and steroid cravings.

42. Are AAS side effects reversible??
• Most are reversible if the abuser stops taking
the drugs, but some are permanent, such as
voice deepening in females and enlarged
clitoris.

43.  Anabolic steroid use is an underrecognized cause of
kidney affection.
 We have to raise awareness of the medical community to the
ongoing and dangerous practice of AAS supplement abuse
by young individuals.
 We have to educate students about the beneficial/harmful
effects of anabolic steroids/supplements and providing
nutrition and weight-training alternatives to there use.
Home Message

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