• All new members please introduce your self here and welcome to the board:
    http://www.professionalmuscle.com/forums/showthread.php?t=259
Buy Needles And Syringes With No Prescription
M4B Store Banner
SPC-210x65
Riptropin Store banner
Generation X Bodybuilding Forum
Buy Needles And Syringes With No Prescription
Buy Needles And Syringes With No Prescription
Mysupps Store Banner
IP Gear Store Banner
Anabolic Hormones Store Banner
Ganabol Store Banner
Spend $100 and get bonus needles free at sterile syringes
Professional Muscle Store open now
LandmarkChem Email Banner
Medtech Store Banner
Bruce Labs Store banner
gd
Professional Muscle Store open now
over 5000 supplements on sale at professional muscle store
granabolic123
Blackroids-animated-optimized-number-1
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store
over 5000 supplements on sale at professional muscle store

Maintaining kidney health while on AAS

MyNameIsJeff

Well-known member
Kilo Klub Member
Joined
Jul 18, 2017
Messages
1,725
In this thread, I will address the question of whether AAS abuse leads to kidney damage. Furthermore, I will examine through which mechanisms this happens, and speculate what preventative measures bodybuilders could take.

Let's start by reviewing the (case) studies on AAS and kidney disease in humans. There is surprisingly little information on the relationship between AAS abuse and kidney damage, with case studies popping up only recently.

1) Herlitz et al. (2010)

Anabolic steroid abuse adversely affects the endocrine system, blood lipids, and the liver, but renal injury has not been described. We identified an association of focal segmental glomerulosclerosis (FSGS) and proteinuria in a cohort of 10 bodybuilders (six white and four Hispanic; mean body mass index 34.7) after long-term abuse of anabolic steroids. The clinical presentation included proteinuria (mean 10.1 g/d; range 1.3 to 26.3 g/d) and renal insufficiency (mean serum creatinine 3.0 mg/dl; range 1.3 to 7.8 mg/dl); three (30%) patients presented with nephrotic syndrome. Renal biopsy revealed FSGS in nine patients, four of whom also had glomerulomegaly, and glomerulomegaly alone in one patient. Three biopsies revealed collapsing lesions of FSGS, four had perihilar lesions, and seven showed ≥40% tubular atrophy and interstitial fibrosis. Among eight patients with mean follow-up of 2.2 yr, one progressed to ESRD, the other seven received renin-angiotensin system blockade, and one also received corticosteroids. All seven patients discontinued anabolic steroids, leading to weight loss, stabilization or improvement in serum creatinine, and a reduction in proteinuria. One patient resumed anabolic steroid abuse and suffered relapse of proteinuria and renal insufficiency. We hypothesize that secondary FSGS results from a combination of postadaptive glomerular changes driven by increased lean body mass and potential direct nephrotoxic effects of anabolic steroids. Because of the expected rise in serum creatinine as a result of increased muscle mass in bodybuilders, this complication is likely underrecognized.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799287/

The first thing to note is that with these case studies, we cannot prove that the AAS abuse is the cause for the kidney disease. It could be that other (genetic and lifestyle factors) caused the kidney damage. After all, there are tens of thousands of bodybuilders in the US who are on similar cycles as the study subjects and don't develop symptoms severe enough to seek medical attention. That being said, these case studies do strongly suggest that the AAS abuse played a causal role, based on the changes over time observed for each individual.

Take for example the following chart detailing the creatinine and proteinuria levels of a patient. Upon cessation of AAS use (and supplements and training), both parameters improved quickly and dramatically, only to increase again once the patient resumed his regimen. Unless you suspect the training and supplements to be the culprit (which is very unlikely), you can with high confidence conclude that the AAS caused the kidney damage as measured by worse kidney filtration and leaking of protein (both are imperfect measures in bodybuilders, but the trends are clear).

asn0021042680002.jpg


All patients in this study were diagnosed with secondary Focal segmental glomerulosclerosis (FSGS) caused by a combination of high lean mass and AAS abuse.

Many diseases and conditions can affect your kidney function by attacking and damaging the glomeruli, the tiny filtering units inside your kidney where blood is cleaned. These diseases and conditions are called glomerular diseases and can have many different causes. Focal Segmental glomerulosclerosis is a type of glomerular disease and describes scarring (sclerosis) in your kidney. The scarring of FSGS only takes place in small sections of each glomerulus (filter), and only a limited number of glomeruli are damaged at first.
https://www.kidney.org/atoz/content/focal

However, the patients' clinical features and biopsy results were different than typically observed in FSGS: the degree of proteinuria was higher, there was higher levels of global (in addition to the segmental) glomerulosclerosis, more of the glomeruli were affected, and there was much more interstitial scarring. So overall more severe and characteristically unique presentation of AAS induced FSGS.

Despite this, only one out of 8 patients with follow-up developed into full blown kidney failure. The remaining 7 patients' kidney function stabilized upon ceasing AAS abuse and lowering their lean mass (plus some ACEi/ARB treatment).

2) Gollasch et al. (2018)

We present a 42-year-old man with a BMI of 32, who was referred because of proteinuria and decreased renal function. We were impressed by his markedly muscular physique. A renal biopsy was performed, which showed focal segmental glomerular sclerosis (FSGS). Is this patient merely an obese person with FSGS or is something else going on here?

[...]

The patient was a German professional bodybuilder who was not fat despite a BMI of 32 that classified him as an obese person (obesity class 2). He used progressive resistance exercise to develop his musculature from the age of 18–39 years. As part of his bodybuilding regimen, he consumed anabolic steroids, muscle growth-stimulating substances, and high-protein, low-fat diets. For more than 6 months until admission to our hospital, he resumed progressive resistance exercise and also regularly used anabolic androgenic steroids, including testosterone enanthate (depot 250 mg × 2/week, i.m.), recombinant growth hormone (somatotropin 2× 2 IU/day, i.m.), and boldenone 200 mg × 2/week, i.m. In addition, he administered trenbolone enanthate (TrENOL 100) 100 mg × 1/week, i.m. and methandienone (Metabolon) 10 mg × 3/day, p.o., and consumed a high-protein, low-fat diet: protein 1,326 kcal (42.8%), carbohydrate 1,615 kcal (52.1%), fat 160 kcal (5.1%), and vitamins, spread over 6 meals a day. Our patient reported intense training sessions within the past weeks.
https://www.karger.com/Article/FullText/489087

This guy wasn't as lucky, his FSGS was too advanced and his kidney function did not recover.

963003


There's a couple of take away points from this study. First, the authors argue that his FSGS developed over years until the damage was too much to recover from. So a lesson is to continuously monitor your kidney function to if necessary pull the plug in time. Second, the authors point to the importance of genetic factors. They identify a number of risk factors in the patient's DNA that could predispose him to developing FSGS. So the reason why AAS abuse leads to FSGS in some bodybuilders but not others may come down to genetic factors. Basically, your genes determine how much AAS your organs can take before failing. However, we don't know our DNA and whether we have those (poorly understood) risk factors. Again, the lesson is to do regular check ups, given that you could be one of the people who are predisposed.

Next, the kidney biopsy revealed signs of long standing hypertension. Upon admission, the patient's BP was 146/90. This is despite the fact that he was on prescribed Telmisartan and a diuretic at the time! This is another important lesson, you have to adjust your BP meds and dosages based on your BMI and based on the AAS (dosage) you are currently taking. Furthermore, just an ARB or ACEi may be insufficient to adequately control blood pressure. Especially when on a highly androgenic drug regimen, you need to also take care of the neurohormonal pathway via beta blockers.

The authors conclude that the combination of high lean mass, PED abuse, genetic factors, and hypertension lead to the kidney failure.

3) Garcia et al. (2017)

We report the case of a 37-year-old male with hypertension known for the last 10 years, with no treatment, who regularly practised bodybuilding; took intramuscular anabolic steroids (testosterone and stanozolol), growth hormone and oral creatine; and followed a protein-rich diet. He visited the Emergency Department due to signs and symptoms of general malaise, nausea, headache and blurred vision that had lasted for one week. He was found to have high BP (250/180mmHg) and severe acute kidney failure. Complementary tests revealed anaemia and thrombocytopenia (haemoglobin 9.9g/dl, haematocrit 28.4%, platelets 91,000/mm3) as well as the above-mentioned kidney failure (urea 246mg/dl, creatinine 23.5mg/dl). An immunology study was negative (except for a slight decrease in C3 and C4 fraction), with proteinuria of 1.7g/24h and oligoalbuminuria of 491mg/l.
http://revistanefrologia.com/en-art...roids-practice-bodybuilding-S2013251417302146

Another case study that drives home the point of how important blood pressure management is when on AAS. As we will discuss later, increases in blood pressure are one of the channels through which AAS use damages the kidneys. The case study only focuses on the short term management of the hypertensive crisis, but it is reasonable to assume that the untreated hypertension and AAS abuse over years lead to kindney failure which then pushed him into hypertensive crisis.

4) El-Reshaid et al. (2018)
We report our experience of renal disease associated with bodybuilders who had been on high-protein diet, anabolic androgenic steroids (AASs), and growth hormone (GH) for years. A total of 22 adult males who volunteered information about use of high protein diet and AAS or GH were seen over a six-year period with renal disease. Kidney biopsy revealed focal segmental glomerulosclerosis (FSGS) in eight, nephroangiosclerosis in four, chronic interstitial nephritis in three, acute interstitial nephritis in two, nephrocalcinosis with chronic interstitial nephritis in two, and single patients with membranous glomerulopathy, crescentic glomerulopathy, and sclerosing glomerulonephritis. Patients with FSGS had a longer duration of exposure, late presentation, and worse prognosis. Those with interstitial disease had shorter exposure time and earlier presentation and had improved or stabilized after discontinuation of their practice. There is a need for health education for athletes and bodybuilders to inform them about the risks of renal disease involved with the use of high-protein diet, AAS, and GH.
https://www.ncbi.nlm.nih.gov/pubmed/29657200

Another very recent study that is suggestive about the development of different types of renal damage over time when abusing AAS. Only 8 of the 22 patients had developed FSGS, and those that did had a longer exposure to AAS. Interstitial fibrosis and other forms of renal damage are associated with shorter AAS exposure and have a better prognosis. This is neatly in line with Gollasch et al. (2018) who suspect that their patient's FSGS developed over many years rather than being acute onset. Also interesting is the presence of nephrocalcinosis in 2 patients. Possibly related to excess Vitamin D and calcium intake? In any case, don't overdose on VitD and do take sufficient VitK2 with it to be safe.

In the next part, I'm gonna review the animal studies available. But based on the human studies alone, one should conclude that yes, AAS leads to kidney damage, with the extent depending on genetic predisposition, the steroids used, dosages, blood pressure control, (lean) body mass, hydration, etc.
 

suppdude

Active member
Kilo Klub Member
Registered
Joined
May 1, 2016
Messages
1,746
I haven’t opened the study and it probably is in there but would be nice to know what exactly the risk factors were and what we should look out for? Would something like our 23andme results give us any clue?

“Second, the authors point to the importance of genetic factors. They identify a number of risk factors in the patient's DNA that could predispose him to developing FSGS. So the reason why AAS abuse leads to FSGS in some bodybuilders but not others may come down to genetic factors. Basically, your genes determine how much AAS your organs can take before failing. However, we don't know our DNA and whether we have those (poorly understood) risk factors. Again, the lesson is to do regular check ups, given that you could be one of the people who are predisposed.”


Sent from my iPhone using Tapatalk
 

MyNameIsJeff

Well-known member
Kilo Klub Member
Joined
Jul 18, 2017
Messages
1,725
I haven’t opened the study and it probably is in there but would be nice to know what exactly the risk factors were and what we should look out for? Would something like our 23andme results give us any clue?

Sent from my iPhone using Tapatalk
mutations in our patient in the FSGS genes CD2AP, PLCE1, INF2, NPHS2, NPHS1, MYO1E, ACTN4, TRPC6, WT1, LMX1B, and LAMB2
I doubt that this is something that genetic testing firms would cover. And no doctor would order those tests without some very good reason. BTW I might have misread the study there: Looks like the patient had none of those (identified) risk factors. When they say that 'We detected several common DNA variants occurring at a specific position in the FSGS genes ...' they seem to talk about their testing methodology in general, not the patient. So clearly not having those specific risk factors does not mean you are safe from FSGS.
 

little slice

Featured Member / Kilo Klub
Joined
Mar 3, 2014
Messages
12,654
well



assuming you don't develop an autoimmune disorder..




-keep blood pressure under control (lisinopril)

-don't become a diabetic

-don't abuse diuretics

-don't abuse (or even use IMO) painkillers or NSAIDS
 

Kaladryn

Featured Member / Kilo Klub
Featured Member
Kilo Klub Member
Registered
Joined
Jul 28, 2009
Messages
5,647
My observations: they keep mentioning creatine supplementation as if creatinine (a metabolite of creatine) is difficult for the kidneys to process, research shows it is not. Creatinine is only significant as a marker of kidney filtration rate, high creatinine isn't significant on its own. These studies take this into account by doing 24-hour urine collections and getting real creatinine clearance rates. BUT most people who get bloodwork done don't do this, and they get estimated GFRs based on estimated creatinine clearance rates from a single blood draw. This is going to cause panic.

I take 10g of creatine per day, which results in the following creatinine level:

CREATININE, 24 HOUR URINE - 4.86g/24h

normal range: 0.63-2.50g/24h

Now that same test without the creatine (done a week later):

CREATININE, 24HR URINE - 2.82g/24h

Neither of these values are significant, in fact the tests were just done automatically alongside other urine tests I needed to get done, there is no reason to think they impact kidney function.

When taking creatine, here is my creatinine clearance:

CREATININE CLEARANCE (mL/min) 214
normal range: 85-125

The point I'm trying to make is that creatinine itself isn't something that stresses the kidneys, it's just a marker used to measure kidney function. Jeff and many good doctors probably know this, but lots of people (and doctors) who don't do clearance testing and who just look at serum creatinine levels are going to panic when they see very high creatinine levels, unnecessarily.


I have a theory on kidney damage in bodybuilders. I think it's myoglobin. I think most of these guys are massively overtraining (as do the majority of bodybuilders, PED use keeps them from seeing symptoms) and large amounts of myoglobin are being released from the resulting muscle damage. Not enough to cause full rhabdomyolysis, but enough to cause some kidney damage. This is where excessive amounts of protein intake come into play, creating a more acid environment in the kidneys. In an acidic environment, myoglobin is more likely to crystallize in the renal tubules and cause damage (scaring). It might not even require overtraining, it could just be from being excessively strong. If muscle is being damaged, some myoglobin is being released.
 
Last edited:

MyNameIsJeff

Well-known member
Kilo Klub Member
Joined
Jul 18, 2017
Messages
1,725
My observations: they keep mentioning creatine supplementation as if creatinine (a metabolite of creatine) is difficult for the kidneys to process, research shows it is not. Creatinine is only significant as a marker of kidney filtration rate, high creatinine isn't significant on its own. These studies take this into account by doing 24-hour urine collections and getting real creatinine clearance rates. BUT most people who get bloodwork done don't do this, and they get estimated GFRs based on estimated creatinine clearance rates from a single blood draw. This is going to cause panic.

I take 10g of creatine per day, which results in the following creatinine level:

CREATININE, 24 HOUR URINE - 4.86g/24h

normal range: 0.63-2.50g/24h

Now that same test without the creatine (done a week later):

CREATININE, 24HR URINE - 2.82g/24h

Neither of these values are significant, in fact the tests were just done automatically alongside other urine tests I needed to get done, there is no reason to think they impact kidney function.

When taking creatine, here is my creatinine clearance:

CREATININE CLEARANCE (mL/min) 214
normal range: 85-125

The point I'm trying to make is that creatinine itself isn't something that stresses the kidneys, it's just a marker used to measure kidney function. Jeff and many good doctors probably know this, but lots of people (and doctors) who don't do clearance testing and who just look at serum creatinine levels are going to panic when they see very high creatinine levels, unnecessarily.


I have a theory on kidney damage in bodybuilders. I think it's myoglobin. I think most of these guys are massively overtraining (as do the majority of bodybuilders, PED use keeps them from seeing symptoms) and large amounts of myoglobin are being released from the resulting muscle damage. Not enough to cause full rhabdomyolysis, but enough to cause some kidney damage. This is where excessive amounts of protein intake come into play, creating a more acid environment in the kidneys. In an acidic environment, myoglobin is more likely to crystallize in the renal tubules and cause damage (scaring). It might not even require overtraining, it could just be from being excessively strong. If muscle is being damaged, some myoglobin is being released.
Very good point, the creatine supplementation more than likely does not cause any kidney damage. I actually left out some case studies where the doctors focused completely on creatine and protein supplements as the cause, while ignoring the blatant steroid abuse. Many doctors are uneducated on this.

But I think that serum creatinine is much less responsive to creatine supplementation than the 24 hour urine clearance. So maybe serum creatinine will be 10% higher in someone supplementing. Add to that a the effect of higher body mass, and out of range creatinine does actually ot imply any reduction in actual GFR. But: the patients in these case studies had creatinine levels 2 or 3 times higher than the upper range, so then it can clearly be interpreted as indication of impaired kidney function. Also, the studies look at proteinuria and Cystatin C as additional markers which don't suffer from these issues, and the conclusions are the same.

I think you are definitely onto something with the myoglobin! i'm gonna write more on that and how it relates to AAS use later.
 

Marvin Martian

Well-known member
Kilo Klub Member
Registered
Joined
Jul 13, 2008
Messages
2,747
well



assuming you don't develop an autoimmune disorder..




-keep blood pressure under control (lisinopril)

-don't become a diabetic

-don't abuse diuretics

-don't abuse (or even use IMO) painkillers or NSAIDS


Do (or don't do) these things - and you are better off than most. I have known 6 people in my life that have had kidney transplants. No one ever used AAS

As Kal said there are some things we can use to help, but from what I have experienced there are some people who simply have kidney issues regardless of doing none of the "risky"... Does that mean we shouldn't be aware? Hell no - doesn't matter if a pilot JUST landed - he is going to do a full flight check before next take off..
 

MyNameIsJeff

Well-known member
Kilo Klub Member
Joined
Jul 18, 2017
Messages
1,725
Onto the animal studies.

1) Antus et al. (2001)

Testosterone treatment resulted in an increased proteinuria as well as profound glomerulosclerosis, tubulointerstitial fibrosis, and mononuclear cell infiltration that paralleled enhanced intragraft mRNA levels of transforming growth factor-Β (TGF-Β) and platelet-derived growth factor-A and -B chain (PDGF-A and -B). In contrast, flutamide and finasteride reduced glomerulosclerosis as well as the inflammatory cell infiltration associated with decreased TGF-Β, PDGF-A, and -B chain mRNA expression. No gender-related donor differences were noted between the groups.

Conclusions
Our data suggest that dihydrotestosterone mediates the adverse effects of androgens on chronic allograft nephropathy. The inhibition of androgens improves long-term allograft outcome after kidney transplantation.
https://www.sciencedirect.com/science/article/pii/S0085253815480780

This one is a bit tricky. The researchers look at the effect of AAS on chronic allograft nephropathy, which develops in transplanted kidneys due to an autoimmune reaction. So what they did is to transplant 'donated':eek: rat kidneys into other rats. They then gave some of them Testosterone, some Finasteride, and some nothing but a placebo vehicle. Finally, they compare the degree of kindey damage between the groups. What they find is that Testosterone treatment markedly increases the degree of glomerular sclerosis as well as interstitial fibrosis. In contrast, Finasteride treatment reduced the severity of all aspects of kidney damage compared to vehicle.
Furthermore, TGF-Β1 was elevated by testosterone treatment and reduced in the Finasteride group. The authors argue that the observed effects are due to androgens promoting renal injury, something that is consistent with earlier studies showing that castration of rats decreases glomerulosclerosis and proteinuria. the take away here should be that AAS cause the detrimental effect on the kidney via the androgen receptor. The more androgenic activity an AAS has, (trenbolone, DHT, would be examples of high activity), the more damage done to the kidneys. Also, just because testosterone is 'natural' and because 'your body knows it' does not mean that it will do any less damage.

2) Frankenfeld et al. (2014)

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g−1 body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.
The Anabolic Androgenic Steroid Nandrolone Decanoate Disrupts Redox Homeostasis in Liver, Heart and Kidney of Male Wistar Rats

The main point of this study is that AAS can disrupt the redox balance and thereby lead to oxidative stress. This is a potential mechanism through which pathological changes in the kidney are induced by AAS.

3) Alm-Eldeen et al. (2012)

Boldenone is an anabolic steroid developed for veterinary use. Recently, it is used by bodybuilders in both off-season and precontest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. However, the side effect of this steroid on the human health is still unclear. Therefore, the present study was designed to investigate the possible effect of the growth promoter, boldenone undecylenate, on the function and structure of the rabbit's kidneys. A total of 36 adult New Zealand rabbits were divided into 4 groups. Control group includes animals that were injected intramuscularly with olive oil and dissected after 3 weeks. Three experimental groups include animals that receive one, two and three intramuscular injections of 5 mg/kg body weight boldenone, and dissected after 3, 6, and 9 weeks, respectively, and the interval of each dose of boldenone was 3 weeks. The biochemical analysis of the blood serum of treated rabbit showed a significant increase in the total protein, urea and creatinine concentrations, with a significant decrease in albumin/globulin (A/G) ratio. At the same time, a significant glomerulus mass reduction that accompanied with the expression of CD34, a marker for endothelial cells deterioration, was also determined. The incidence of the glomerulosclerosis was significantly increased compared with the control group (0.46 ± 0.05, p < 0.05). The glomerulosclerosis scores were 1.32 ± 0.10, 2.14 ± 0.11 and 3.02 ± 0.09 in groups 2, 3 and 4, respectively. These findings suggest that misuse of the boldenone undecylenate may contribute to the occurrence of a chronic renal injury that may lead to a progressive renal failure.
https://www.ncbi.nlm.nih.gov/pubmed/21878449

One of the many animal studies on Boldenone and kidney damage. These prompted people on lots of forums to claim that Boldenone is particularly kidney toxic. This is nonsense. it is just that at the time, Boldenone was the first steroid whose effect was studied in animals (which makes sense since it's a veterinarian product). if the same study was performed with other steroids, similar detrimental effect on kidney function would be observed.

4) Shabir et al. (2015)

The present study was designed to assess the effects of Nandrolone Decanoate (ND), Boldenone Undecylenate (BOL) and combination of both (ND+BOL) on renal system of male rabbits. Thirty five adult rabbits were divided into four groups. Group A served as control group and group B received 4.5mg/kg body wt ND, group C 10mg/kg body wt received BOL and group D 14.5 mg/kg body wt received ND+BOL. Rabbits were injected intramuscularly twice a week for a period of six weeks. ND, BOL and ND+BOL treatments had no significant effects on body weight. Whereas Urea, Creatinine, Total Protein, Albumin, Globulin, Bilirubin and Triglyceride concentrations had increased significantly (p < 0.05), While in contrast Cortisol concentration significantly (p > 0.05) decreased in treated groups compared to control group. It is concluded that administration of ND, BOL and ND+BOL exerts a significant effect on the renal system of adult rabbits.
https://www.researchgate.net/profil...l-Status-of-Rabbits-Oryctolagus-cuniculus.pdf

This study compares the effect of Boldenone, Nandrolone, or a combination on markers of renal function. Despite the Boldenone dosage being more than twice as high, the creatinine and urea values were very similar to those of the Nandrolone group. So if anything, nandrolone is more nephrotoxic than boldenone. The combination of the two lead as expected to even higher values of serum creatinine. Note that the increases in creatinine are way too high to be due to increases in lean mass, the latter of which actually did not increase much.

5) Bakarat et al. (2015)
Although anabolic androgenic steroids like boldenone may increase lean muscle mass, strength, and the ability to train longer and harder, the serious side effects of steroid are many and may not be reversible. So, the present study was designed to investigate the role of propolis in improving hepatic and renal damage in boldenone in male rats. 40 adult rats were equally divided into four groups. 1st Control group includes animals that injected intramuscularly with olive oil for 12 weeks. 2nd group were rats receive propolis (intragastrically, 400 mg/kg body weight). 3rd experimental group include animals that receive intramuscular injections of boldenone (5 mg/Kg body weight) for 12 weeks. 4th group were co-treated group where rats receive boldenone (intramuscular injections, 5 mg/Kg body weight) and Proplis (intragastrically, 400 mg/kg body weight). Intramuscular injection of rats with boldenone showed a significant increased in GOT, GPT, urea, creatinine, cholesterol, triglycerides, HDL, albumin, total protein, sodium (Na), calcium (Ca), magnesium (Mg), malondialdehyde (MDA), nitric oxide (NO), total protein, total thiol, catalase activity and superoxide dismutase activity (SOD) in liver and kidney tissues when compared with the control group. On the other hand a significant decrease in LDL, alkaline phosphatase (ALP), potassium (K), total lipid and glutathione (GSH) in boldenone group when compared with the control group. These findings suggested that misuse of boldenone may contribute to a continuously damage of the hepatic and renal diseases so young people especially should be careful if they want to use such steroids to enhance their strength and endurance. This shows that the desired dose of boldenone can safely be used with propolis in improving hepatic and renal damage in boldenone in male rats.
Open Science - Journal - Archive

First off, their conclusion that you can use boldenone 'safely' as long as you take propolis is of course an exaggeration, seems they got a little too excited by their results. That being said, the study provides further evidence that some of the kidney damage induced by AAS is due to oxidative stress. Note in particular the Glutathione depletion resulting from this.

The authors find that increases in creatinine and urea due to Boldenone use are diminished when adding in propolis, which is attributed to the latters potent antioxidant activity. Histological findings confirm this, propolis treatment ameliorates Boldenone induced focal necrosis and interstitial inflammation.

6) Aparicio et al. (2017)

Results: Urinary pH was more acidic in the AAS compared to the placebo group (p<0.05). Kidney weight was 15% higher in the AAS compared to the placebo group (p<0.001). Renal glomerular area was
12% higher
in the AAS compared to the placebo group (p=0.001). Animals injected with AAS also displayed a no significant but clinically relevant ~20% higher kidney interstitial connective tissue, glomerular tufts and mesangiums.

Conclusion: Overall, AAS negatively affected urinary pH and kidney morphology leading to a worse renal status. More attention should be taken to the use of AAS among populations at high risk for kidney disease.
https://www.peertechz.com/articles/...enic-steroids-on-renal-morphology-in-rats.pdf

in this study, rats were given Stanozolol. Despite the acceptable sample size of 20 animals, no statistically significant differences in serum creatinine. Still, histological changes were partially significant and very noticable in the following picture. There seems to be significant interstitial fibrosis (compare C and D) and pathological changes in the capillary system (A and B). Overall, the higher kidney weight and volume indicate increases demands for filtration due to AAS. Whenever there is need for (quick) adaptation, maladaptation can occur, which seems to be the case here given the histopathology. Lastly, the increased urine acidity may potentially lead to kidney damage as well, we will come back to this shortly.


All in all, there is now significant evidence from across different species that AAS cause kidney damage. This assessment is based both on blood markers of kidney damage and histological findings. Furthermore, the studies suggest a number of potential mechanisms for this maladaptation to AAS. In the next part, I will describe the most prominent mechanisms through which AAS impact renal function.
 

MyNameIsJeff

Well-known member
Kilo Klub Member
Joined
Jul 18, 2017
Messages
1,725
The following is my speculation based on the above studies as well as additional information I will post along. The most likely channels through which AAs cause kidney damage are:


1) Increased blood pressure
2) Oxidative stress
3) Exacerbated myoglobin toxicity
4) Angiotensin II
5) Endothelin-1

6) Increased lean body mass
7) Increased protein consumption
8) Insufficient hydration


Let's look at each in turn and discuss what preventative measures we can take as AAS abusers.

1) Increased blood pressure

This one is pretty self-explanatory. The evidence that high blood pressure leads to kidney damage (especially over long periods of time) is overwhelming. Similarly, there is now a pretty good understanding of how AAS lead to increases in blood pressure, see this thread: http://www.professionalmuscle.com/f...42419-maintaining-heart-health-while-aas.html
The same thread also contains information on how to manage AAS induced increases in blood pressure. it is important that you regularly check your BP throughout your cycle. Just because your blood pressure is under control with certain medications while taking one anabolic steroid does not mean it will also be the case when taking other steroids. For example, extremely androgenic steroids like trenbolone may require higher dosages of BP meds in general, and higher doses of beta blockers in particular. Conversely, steroids that lead to extreme bloat may require use of a diuretic (and/or diet changes). Constantly monitor your blood pressure and adjust medication accordingly. the bodybuilder from the Gollasch et al. (2018) case studyis a good example. he was taking blood pressure meds but they failed to adequately control his BP given his cycle at the time.


2) Oxidative stress

We have seen in several animal studies above that AAS induce oxidative stress that may overwhelm the body's antioxidative capacity. Supplementation of compounds with antioxidative activity may ameliorate the damage caused by it. In particular, we have seen that Glutathione levels in both liver and kidney are depleted due to AAS administration. In order to combat this, one should take NAC. There isn't too much research on this, but one study found beneficial effects of NAC supplementation.

RESULTS:
Mean daily NAC and spironolactone ingestion was comparable among the treated groups. Mean weight gain was higher in NAC-treated rats than in untreated rats. A significant decrease in urinary thiobarbituric acid reactive substances (TBARS) concentrations, a lipid peroxidation marker, was observed in NAC-treated rats. By day 120, glomerular filtration rate (GFR), which dropped dramatically in untreated rats, was stable (albeit below normal) in NAC-treated rats, which also presented lower proteinuria, glomerulosclerosis index, and blood pressure, together with attenuated cardiac and adrenal hypertrophy. These beneficial effects, observed even when NAC was initiated on postnephrectomy day 60, were accompanied by a significant reduction in plasma aldosterone and urinary potassium sodium [corrected] ratio. The NAC-spironolactone combination lowered blood pressure and improved GFR protection.

CONCLUSION:
The NAC-spironolactone combination improves renal function more than does NAC alone. In the remnant kidney model, early or late NAC administration has a protective effect attributable to decreased plasma aldosterone and lower levels of lipid peroxidation.

See https://academic.oup.com/ndt/article/19/8/1951/1918231 for a review on the potential role for Glutathione in kidney disease.

In addition to this supplementation, a healthy diet with lots of veggies (and moderate fruit) is recommended. Supplements with antioxidants, such as propolis is another promising avenue.


3) Exacerbated myoglobin toxicity


When people hear myoglobin, they probably think of rhabdomyolysis. The latter occurs when damaged muscle tissue breaks down and releases myoglobin into the blood stream, which then damages the kidneys while being filtered and excreted by them.

However, myoglobin is not just released in the case of extreme muscle damage that would lead to the condition of rhabdomyolysis. Even moderate intensity exercise causes sufficient muscle damage to increase serum myoglobin levels!

The purpose of this study was to measure serum creatine kinase (CK) activity and serum myoglobin (MG) concentrations in women after two unilateral isometric knee extension exercises. Forty maximal voluntary contractions (MVC) were held for 10 s, with either a 5 s (10∶5) or 20 s 10∶20 exercise (349.4±66.1 mU · ml−1) and 6 h and MG values were measured pre, 0, 3, 6, and 18 h post exercise. For CK, the highest post exercise values were observed at 6 h following the 10∶20 exercise (349.4±66.1 mU · ml−1) and 6 h following the 10∶5 exercise (194.1±18.6 mU · ml−1). For MG, the highest values were found 3 h after the 10∶20 exercise (148.9±61.7 ng · ml−1) and 6 h after the 10∶5 exercise (67.3±10.9 ng · ml−1). Serum CK and MG levels were significantly greater (p<0.01) after the 10∶20 exercise bout. The data demonstrate that CK and MG values for women increase significantly after isometric exercise. Since greater tension levels were maintained during the 10∶20 exercise it is hypothesized that increased serum CK and MG values after isometric exercise may be related to the tension generated by the contracting muscle.
https://link.springer.com/article/10.1007/BF02343808

To determine the influence of exercise on serum levels of myoglobin, serum levels of this protein were determined by RIA in 90 healthy men, divided as follows: (1) Basal control (no exercise) 25 cases; (2) Moderate exercise (after subject had been working for 12 h in Medicine Emergency Service) 19 cases, and (3) Intensive exercise: (a) football professional (45-min match) 10 cases; (b) football amateur (45-min match) 10 cases; (c) basketball professional (45-min match) 10 cases, and (d) basketball professional (90-min training) 16 cases. Our results led us to the following conclusions. (1) Moderate exercise, such as the usual daily work, does not modify myoglobin levels; (2) Myoglobin serum levels after exercise increase in nearly all individuals. They are higher in untrained people; (3) There seems to be a correlation between exercise intensity and increase of myoglobin serum levels, and (4) The detection of serum myoglobin by RIA may have a wide field of application for sport medicine.
https://www.ncbi.nlm.nih.gov/pubmed/6861785

OK, so we know that a bodybuilding-style workout will release quite some myoglobin into the bloodstream. Here is how it then damages the kidney:

When the protein reaches the kidneys it causes a strain on the anatomical structures reducing its effectiveness as a filter for the body. The protein acts like a dam as it forms into tight aggregates when it enters the renal tubules.[9] In addition, the increased intracellular calcium has greater time to bind due to the blockage allowing for renal calculi to form.[10] As a result this causes urine output to decrease allowing for the uric acid to build up inside the organ. The increased acid concentration allows the iron from the aggregate protein to be released into the surrounding renal tissue.[11] Iron then strips away molecular bonds of the surrounding tissue which eventually will lead to renal failure if the tissue damage is too great.
[...]
the released myoglobin is filtered by the kidneys but is toxic to the renal tubular epithelium and so may cause acute kidney injury.[15] It is not the myoglobin itself that is toxic (it is a protoxin) but the ferrihemate portion that is dissociated from myoglobin in acidic environments (e.g., acidic urine, lysosomes).
https://en.wikipedia.org/wiki/Myoglobin
https://en.wikipedia.org/wiki/Exertional_rhabdomyolysis

Thus the amount of damage done by myoglobin to the kidneys depends on the amount released, as well as the acidity of urine/the surrounding renal tissue. Rhabdomyolysis only occurs if too much myoglobin is released such that there is acute kidney failure. But even smaller amounts of myoglobin will do damage to the kidneys, in particular in case of chronic exposure.

Now, AAS abuse has a twofold impact here.

1) Increased myoglobin release. AAS allow for higher training volume and frequency. Furthermore, androgens lead to sizable strength increases, so that the mechanical tension on each set is higher, leading to more release on myoglobin per set. In addition, more sets are performed due to the ability to recover faster post exercise. Lastly, someone on juice will have less rest days to make the most of their cycle. As a result, total myoglobin load for the kidneys is higher, potentially leading to accumulated damage over time that culminates in FSGS.

2) Increased urine acidity. As described in the Aparicio et al. (2017) paper, urine acidity is increased after AAS treatment. We have also learned above that the nephrotoxicity of myoglobin depends on the acidity of the environment. Thus, i would speculate that for a given serum level of myoglobin, AAS induced acidity increases the damage done to the kidneys.
Note that there is also a potential interaction between AAS-induced antioxidant depletion and kidney damage due to myoglobin. In fact, all the channels are likely to interact in various ways and potentially exacerbate each other's effects.

In any case, this proposed increased myoglobin toxicity due to AAS abuse would lead to an accumulation of damage over time that could culminate is FSGS. Note that FSGS has only been observed in the human studies, whereas the animal studies showed more global glomerulosclerosis. This difference could be explained by the absence of resistance exercise in the animal subjects. This is pretty wild speculation on my part though.

So what can we do about this as AAS abusing bodybuilders? Unfortunately not much. My main recommendation would be to have at least some rest days and to not go ape shit on the volume. Occlusion training should be avoided. Similarly, forced reps, drop sets etc. should be used sparingly (so not almost every set). A good gauge of whether your training is too intense would be creatine kinase levels ~12 hours post exercise, given that serum CK is likely correlated with exercise induced myoglobin release. i'd say that your CK should not be above 3000 12 hours post exercise.

As mentioned before, there is an interaction between channels 1-8. For example, you can probably ameliorate myoglobin induced kidney damage by maintaining proper hydration around workouts, ensuring sufficient antioxidant activity, etc.

I will continue with the remaining points later.
 

NGL34

Well-known member
Registered
Joined
Oct 20, 2013
Messages
1,150
what do you guys think of metformin?

Its nephrotoxic esp at higher doses over a gram per day. It's common practice to hold metformin 24 hours before doing diagnostic testing, imaging or treatment involving contrast dye. Both contrast dye and metformin are nephrotoxic, so eliminating metformin while using contrast dye will decrease acute kidney injury to some degree.
 

MyNameIsJeff

Well-known member
Kilo Klub Member
Joined
Jul 18, 2017
Messages
1,725
Its nephrotoxic esp at higher doses over a gram per day. It's common practice to hold metformin 24 hours before doing diagnostic testing, imaging or treatment involving contrast dye. Both contrast dye and metformin are nephrotoxic, so eliminating metformin while using contrast dye will decrease acute kidney injury to some degree.
Nonsense. Metformin is not nephrotoxic. It is just that if kidney function is severely impaired (either due to stage 4/5 CKD and/or acutely contrast-induced nephropathy), metformin clearance by the kidneys is decreased, potentially leading to lactic acidosis. So yes, Metformin is discontinued before intravenous contrast-enhanced examinations, but not because it is nephrotoxic. For anyone whose eGFR is higher than 30 mL/min/1.73 m^2, the risk of developing lactic acidosis from metformin is zero.

If anything, metformin is renoprotective in CKD:

Results: A recent review of 17 observational studies concluded that metformin use appeared associated with reduced all-cause mortality in patients with CKD. Metformin has been shown to exert positive effects on the kidney in vitro and animal models representing different types of renal diseases, from acute kidney injury to chronic kidney disease. A retrospective cohort study from the Scientific Registry of Transplant Recipients indicated that metformin was associated with lower adjusted hazards for living donor and deceased donor allograft survival at 3 years posttransplant, and with lower mortality. Conclusion: Based on experimental evidence and some relevant clinical observations, metformin seems to be a promising drug in the treatment of progressive renal damage. RCT studies are the next essential step.
https://www.karger.com/Article/FullText/481951
 

danieltx

Well-known member
Registered
Joined
Oct 30, 2014
Messages
1,288
MyNameIsJeff - thanks for all your work breaking this down for those of us who aren't as science-minded.
 

Kaladryn

Featured Member / Kilo Klub
Featured Member
Kilo Klub Member
Registered
Joined
Jul 28, 2009
Messages
5,647
what do you guys think of metformin?

metformin scares the shit out of me, so does berberine for the same reason, seems like a great drug until you dig deeper, it's not something I'm going to mess with again in the future. I'm not going to go into detail on it and I could be wrong, but there is a lot of research that makes the safety of metformin questionable. Google "metformin dna" and read up...
 

thethinker48

Featured Member / Kilo Klub
Kilo Klub Member
Registered
Verified Customer
Joined
Aug 22, 2015
Messages
3,912
metformin scares the shit out of me, so does berberine for the same reason, seems like a great drug until you dig deeper, it's not something I'm going to mess with again in the future. I'm not going to go into detail on it and I could be wrong, but there is a lot of research that makes the safety of metformin questionable. Google "metformin dna" and read up...
https://www.nature.com/articles/onc2016391

"Here we report that metformin induces genome-wide alterations in DNA methylation by modulating the activity of S-adenosylhomocysteine hydrolase (SAHH). Exposing cancer cells to metformin leads to hypermethylation of tumor-promoting pathway genes and concomitant inhibition of cell proliferation."

So on one hand it's turning off oncogenes.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249452/

By pushing cancer cells to use oxidative phosphorylation instead of glycolysis, metformin can rescue cell surface major histocompatibility complex class I (MHC-I) expression that is downregulated by oncogenic transformation, a crucial adaptation of tumor cells to avoid the adaptive immune response by cytotoxic T-lymphocytes (CTLs).

On another hand it's giving tumor cells a captain America shield against the body's own immunogenic T response.

[emoji52] And I just started using metformin; BG was also 79 this morning...fml

I gotta print these out and read them, they're large papers, but just like any other drugs, there's a little caveat to metformin as well

Sent from my Pixel XL using Tapatalk
 

Landmonster

Member
Registered
Joined
Aug 5, 2007
Messages
978
My observations: they keep mentioning creatine supplementation as if creatinine (a metabolite of creatine) is difficult for the kidneys to process, research shows it is not. Creatinine is only significant as a marker of kidney filtration rate, high creatinine isn't significant on its own. These studies take this into account by doing 24-hour urine collections and getting real creatinine clearance rates. BUT most people who get bloodwork done don't do this, and they get estimated GFRs based on estimated creatinine clearance rates from a single blood draw. This is going to cause panic.

I take 10g of creatine per day, which results in the following creatinine level:

CREATININE, 24 HOUR URINE - 4.86g/24h

normal range: 0.63-2.50g/24h

Now that same test without the creatine (done a week later):

CREATININE, 24HR URINE - 2.82g/24h

Neither of these values are significant, in fact the tests were just done automatically alongside other urine tests I needed to get done, there is no reason to think they impact kidney function.

When taking creatine, here is my creatinine clearance:

CREATININE CLEARANCE (mL/min) 214
normal range: 85-125

The point I'm trying to make is that creatinine itself isn't something that stresses the kidneys, it's just a marker used to measure kidney function. Jeff and many good doctors probably know this, but lots of people (and doctors) who don't do clearance testing and who just look at serum creatinine levels are going to panic when they see very high creatinine levels, unnecessarily.


I have a theory on kidney damage in bodybuilders. I think it's myoglobin. I think most of these guys are massively overtraining (as do the majority of bodybuilders, PED use keeps them from seeing symptoms) and large amounts of myoglobin are being released from the resulting muscle damage. Not enough to cause full rhabdomyolysis, but enough to cause some kidney damage. This is where excessive amounts of protein intake come into play, creating a more acid environment in the kidneys. In an acidic environment, myoglobin is more likely to crystallize in the renal tubules and cause damage (scaring). It might not even require overtraining, it could just be from being excessively strong. If muscle is being damaged, some myoglobin is being released.


So this is concerning.


You are stating that... regardless of drug use...
just the simple acts of hard training + being strong = kidney damage?

Hasn't it always been assumed that healthy eating, hard training, and trying to get as strong as possible are the SAFEST routes to adding permanent size? (Even natural guys do this)

If you can't do that safely, what is even the point?
 
Last edited:

suppdude

Active member
Kilo Klub Member
Registered
Joined
May 1, 2016
Messages
1,746
So this is concerning.


You are stating that... regardless of drug use...
just the simple acts of hard training + being strong = kidney damage?

Hasn't it always been assumed that healthy eating, hard training, and trying to get as strong as possible are the SAFEST routes to adding permanent size? (Even natural guys do this)

If you can't do that safely, what is even the point?



Everything you do in life comes with consequences


Sent from my iPhone using Tapatalk
 

Reload

Well-known member
Kilo Klub Member
Registered
Joined
Jun 10, 2004
Messages
1,365
I've never been asked by a doctor to hold off giving my patients their Metformin prior to a contrasted CT or MTI.
I think it would be fascinating if Olympia competitors had to have a full panel of labs drawn the day prior to the competition and posted for the world to see. Not a drug/toxicology test although that would be fun to read as well. I'm referring to renal, liver and cardiac markers. I know it breaks their HIPA rights but we could all make a betting pool to see who retires first.
 

Michael30

Member
Registered
Joined
Jul 16, 2015
Messages
359
well



assuming you don't develop an autoimmune disorder..




-keep blood pressure under control (lisinopril)

-don't become a diabetic

-don't abuse diuretics

-don't abuse (or even use IMO) painkillers or NSAIDS


Hey slice what were you referring to when you said "well if we dont develope an auto immune response?
 

danieltx

Well-known member
Registered
Joined
Oct 30, 2014
Messages
1,288
MyNameIsJeff - your thoughts on astragalus for maintaining kidney health?

Dante has recommended 3 - 5 grams a day.
 

Staff online

Forum statistics

Total page views
507,045,708
Threads
124,436
Messages
2,398,997
Members
155,660
Latest member
Punisher95
Top