creatine and renal function

[physioman]

hello

creatine is contraindicated in renal failure
with which mechanism creatine exacerbates renal failure?
just like eating too much protein?
or with other mechanisms too?
because if it's all about creatine acting as an aminoacid and thus exacerbating kidney failure, is this considerable? since an individual may take just 4-5g creatine per day (which would mean 4-5g of amino acids per day, so few, compared with 100g of protein intake per day)

thanks

[DJAuto]

The majority of research points to negligible renal effects from normal creatine supplementation. The possibility for renal damage or failure is grossly exaggerated.

While serum levels may increase (the increase in creatinine is often misread as renal issues), there is no real danger from moderate level acute or chronic ingestion.

[physioman]

thanks but i was talking about pre-existing renal failure

[kurious]

"Creatine should be used cautiously in persons with pre-existing renal disease that produces renal impairment or renal failure. Creatine loading generates large quantities of the metabolite creatinine, a nitrogenous compound that must be eliminated by the kidney. In diabetics with already-compromised renal function, excessive concentrations of blood urea accelerates the decline in renal function. Although both creatinine and urea are nitrogenous compounds excreted renally, generally, it is not thought that creatinine contributes the same osmotic damage that urea can. The long-term effects of creatine loading on the renal function of subjects with normal renal function are currently unclear."

Source: MDConsult Drug Monograph

[physioman]

"Creatine should be used cautiously in persons with pre-existing renal disease that produces renal impairment or renal failure. Creatine loading generates large quantities of the metabolite creatinine, a nitrogenous compound that must be eliminated by the kidney. In diabetics with already-compromised renal function, excessive concentrations of blood urea accelerates the decline in renal function. Although both creatinine and urea are nitrogenous compounds excreted renally, generally, it is not thought that creatinine contributes the same osmotic damage that urea can. The long-term effects of creatine loading on the renal function of subjects with normal renal function are currently unclear."

Source: MDConsult Drug Monograph

what is the reason for a need to remove large quantities of creatinine? this implies that creatinine is toxic so that "must be eliminated" ? I don't think this is true

how creatine interferes with urea ?

urea 's damage is mainly osmotic ? I thought urea is highly toxic, so its damage is not just osmotic
also I thought that urea passes through the membranes easily, so how does it pose osmotic damage?

[DJAuto]

thanks but i was talking about pre-existing renal failure

They did studies on mice with existing renal conditions. Normal creatine supplementation did not induce progression of the issue.

[physioman]

They did studies on mice with existing renal conditions. Normal creatine supplementation did not induce progression of the issue.

do you have reference for this?

also any study in humans?

thanks

[DJAuto]

Normal renal function:
http://www.theannals.com/cgi/content/full/39/6/1093
http://www.springerlink.com/content/x4u84jwyefm9kly3/

I can't find the one in mice.

This article suggests there may possibly induction of renal damage in those already with issues, but doesn't test for it (in humans):
http://www.ncbi.nlm.nih.gov/pubmed/15273072

There's a lot more out there, some suggesting there is furthering of damage and others stating there isn't significant increases in damage (with low to moderate creatine intake).

[physioman]

There's a lot more out there, some suggesting there is furthering of damage and others stating there isn't significant increases in damage (with low to moderate creatine intake).

these are what i am looking for, any hint?

[papagunz]

For what it's worth, I wrote a paper for my freshman nutrition class on creatine. One of my sources was about kidney function, and mice with a 2/3rds nephrectomy showed no impaired markers of renal function when administered creatine.

Don't have it on me though, sorry (laptop the paper was on died). Your search for it would be as productive as mine.

[physioman]

For what it's worth, I wrote a paper for my freshman nutrition class on creatine. One of my sources was about kidney function, and mice with a 2/3rds nephrectomy showed no impaired markers of renal function when administered creatine.

Don't have it on me though, sorry (laptop the paper was on died). Your search for it would be as productive as mine.

thanks but the hard part is to find human studies and that's what i am looking for

to be honest, either in vitro or animal studies wont say much, unless there is no human study at all, so a good in vitro or animal study would be ok

[NO HYPE]

creatine is contraindicated in renal failure

with which mechanism does creatine exacerbate renal failure?

I believe one of the aspects for the contradiction of creatine supplementation in renal failure is a result of significant elevations in guanidino compounds e.g. guanidinovaleric & argininic acid [of which are already elevated in individuals with renal failure as a result of dimished glomerular filtration, and are therefore considered uremic toxins].

Nephrol Dial Transplant. 2008 Apr;23(4):1330-5. Epub 2007 Nov 29.
Taes YE, Marescau B, De Vriese A, De Deyn PP, Schepers E, Vanholder R, Delanghe JR.
Guanidino compounds after creatine supplementation in renal failure patients and their relation to inflammatory status.

BACKGROUND: Specific guanidino compounds have been described as uraemic toxins and their concentrations are increased in renal failure due to dimished glomerular filtration, whereas the guanidino compound creatine is used as a performance-enhancing substance in athletes. The present study investigates the effects of creatine supplementation on plasma guanidino compounds in a chronic haemodialysis population.

METHODS: Twenty male haemodialysis patients were included in a placebo-controlled cross-over trial. Patients were treated with creatine (2 g/day) or placebo during two treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma guanidino compounds and routine biochemical parameters were determined, as well as the prognostic inflammatory and nutritional index (PINI).

RESULTS: Upon creatine supplementation, guanidinoacetate concentrations decreased by 15%, due to inhibition of creatine synthesis. Concentrations of alpha-keto-delta-guanidinovaleric acid increased three-fold and argininic acid concentrations doubled. Guanidinosuccinate concentrations did not change, but correlated inversely with CRP (r = -0.736; P = 0.001), PINI-score (r = -0.716; P = 0.002) and correlated positively with plasma urea concentration (r = 0.54; P = 0.02).

CONCLUSIONS: Creatine supplementation in haemodialysis patients significantly altered the concentration of specific guanidino compounds. Guanidinosuccinate correlated positively with plasma urea and negatively with inflammation markers.


J Appl Physiol. 2004 Sep;97(3):852-7. Epub 2004 Apr 23.
Derave W, Marescau B, Vanden Eede E, Eijnde BO, De Deyn PP, Hespel P.
Plasma guanidino compounds are altered by oral creatine supplementation in healthy humans.

Although creatine is one of the most widely used nutritional supplements for athletes as well as for patients with neuromuscular disorders, the effects of oral creatine supplementation on endogenous creatine synthesis in humans remains largely unexplored. The aim of the present study was to investigate the metabolic consequences of a frequently used, long-term creatine ingestion protocol on the circulating creatine synthesis precursor molecules, guanidinoacetate and arginine, and their related guanidino compounds. For this purpose, 16 healthy young volunteers were randomly divided to ingest in a double-blind fashion either creatine monohydrate or placebo (maltodextrine) at a dosage of 20 g/day for the first week (loading phase) and 5 g/day for 19 subsequent wk (maintenance phase). Fasting plasma samples were taken at baseline and at 1, 10, and 20 wk of supplementation, and guanidino compounds were determined. Plasma guanidinoacetate levels were reduced by 50% after creatine loading and remained approximately 30% reduced throughout the maintenance phase. Several circulating guanidino compound levels were significantly altered after creatine loading but not during the maintenance phase: homoarginine (+35%), alpha-keto-delta-guanidinovaleric acid (+45%), and argininic acid (+75%) were increased, whereas guanidinosuccinate was reduced (-25%). The decrease in circulating guanidinoacetate levels suggests that exogenous supply of creatine chronically inhibits endogenous synthesis at the transamidinase step in humans, supporting earlier animal studies showing a powerful repressive effect of creatine on l-arginine:glycine amidinotransferase. Furthermore, these data suggest that this leads to enhanced utilization of arginine as a substrate for secondary pathways.


Pflugers Arch. 2001 Jul;442(4):558-69.
Levillain O, Marescau B, Possemiers I, Al Banchaabouchi M, De Deyn PP.
Influence of 72% injury in one kidney on several organs involved in guanidino compound metabolism: a time course study.

Arginine (Arg) produced from citrulline originates mostly from kidneys. Arg is involved in guanidino compound biosynthesis, which requires interorgan co-operation. In renal insufficiency, citrulline accumulates in the plasma in proportion to renal damage. Thus, disturbances in Arg and guanidino compound metabolism are expected in several tissues. An original use of the model of nephrectomy based on ligating branches of the renal artery allowed us to investigate Arg and guanidino compound metabolism simultaneously in injured (left) and healthy (right) kidneys. The left kidney of adult rats was subjected to 72% nephrectomy. Non-operated, sham-operated and nephrectomized rats were studied for a period of 21 days. Constant renal growth was observed only in the healthy kidneys. Guanidino compound levels were modified transiently during the first 48 h. The metabolism and/or tissue content of several guanidino compounds were disturbed throughout the experimental period. Arg synthesis was greatly reduced in the injured kidney, while it increased in the healthy kidney. The renal production of guanidinoacetic acid decreased in the injured kidney and its urinary excretion was reduced. The experimentally proven toxins alpha-keto-delta-guanidinovaleric acid and guanidinosuccinic acid (GSA) accumulated only in the injured kidney. The urinary excretion of GSA and methylguanidine increased in nephrectomized rats. When the injured kidney grew again, the level of some guanidino compounds tended to normalize. Nephrectomy affected the guanidino compound levels and metabolism in muscles and liver. In conclusion, the specific accumulation of toxic guanidino compounds in the injured kidney reflects disturbances in renal metabolism and function. The healthy kidney compensates for the injured kidney's loss of metabolic functions (e.g. Arg: production). This model is excellent for investigating renal metabolism when a disease destroys a limited area in one kidney, as is observed in patients.

[physioman]

I believe one of the aspects for the contradiction of creatine supplementation in renal failure is a result of significant elevations in guanidino compounds e.g. guanidinovaleric & argininic acid [of which are already elevated in individuals with renal failure as a result of dimished glomerular filtration, and are therefore considered uremic toxins].

let's accept that elevated guanidinovaleric & argininic acid may exert toxic effects
let's accept that this elevation is more profound when creatine supplementation and renal failure co-exist

these facts do not mean that creatine supplementation that causes elevated guanidinovaleric & argininic acid may cause renal failure

[NO HYPE]

these facts do not mean that creatine supplementation that causes elevated guanidinovaleric & argininic acid may cause renal failure

Where did I ever imply that creatine use would result in renal failure? In your first post, you were asking by which mechanism of action did exogenous creatine [exacerbate] pre-existing renal failure. Now your comments pertain to creatine initiating renal failure. Confused.

[physioman]

Where did I ever imply that creatine use would result in renal failure? In your first post, you were asking by which mechanism of action did exogenous creatine [exacerbate] pre-existing renal failure. Now your comments pertain to creatine initiating renal failure. Confused.

elevated guanidinovaleric & argininic acid is a result of renal failure

elevated guanidinovaleric & argininic acid is a result of creatine supplementation

how can one conclude from these that creatine supplementation causes or exacerbates renal failure?

are guanidinovaleric & argininic acid nephrotoxic? are guanidinovaleric & argininic acid increase the effort of kidneys to clear them from the blood and thus cause energy stress to the kidneys? or is there any other mechanism with which guanidinovaleric & argininic acid are detrimental for the renal function?

because it seems that guanidinovaleric & argininic acid are the result and not the cause of (exacerbation of) renal function

[NO HYPE]

how can one conclude from these that creatine supplementation causes or exacerbates renal failure?

it seems that guanidinovaleric & argininic acid are the result and not the cause of (exacerbation of) renal function

I will be commenting further on this subject when I get some extra time however, I'd like to emphasize the fact that all of my previous comments merely pertain to the hypothetical subject of creatine-induced [exacerbation] of renal dysfunction, and have nothing to do with it's [pathogenesis].

[physioman]

I will be commenting further on this subject when I get some extra time however, I'd like to emphasize the fact that all of my previous comments merely pertain to the hypothetical subject of creatine-induced [exacerbation] of renal dysfunction, and have nothing to do with it's [pathogenesis].

ok, it's accepted, we can discuss only about creatine-induced exacerbation of renal damage and not creatine-induced initiation of renal damage

[NO HYPE]

Original topic:

creatine is contraindicated in renal failure -- with which mechanism does creatine exacerbate renal failure?

thanks but i was talking about pre-existing renal failure

Entirely new topic [following my response to the original]:

these facts do not mean that creatine supplementation that causes elevated guanidinovaleric & argininic acid may cause renal failure

how can one conclude from these that creatine supplementation causes or exacerbates renal failure?

The above hypothetical implication was never "concluded", or even suggested. Period.

ok, it's accepted, we can discuss only about creatine-induced exacerbation of renal damage and not creatine-induced initiation of renal damage

Your last comments seem to be accompanied by a degree of sarcasm.... which I find to be rather ironic since your initial comments merely pertained to pre-existing renal failure [hence my interest in the topic]. Following my response, your topic suddenly metamorphosized into creatine-induced renal failure [a hypothetical topic in which I do not believe, nor do I care to take part in]. Next time you start a thread, be sure to properly establish the topic in which you wish to discuss.

[physioman]

no, neither sarcasm, nor implying creatine can induce renal failure

the topic is about creatine exacerbating existing renal failure, which is quite logical, since every amino acid and protein does this

[NO HYPE]

no, neither sarcasm, nor implying creatine can induce renal failure

Very well. Thanks for the clarification, as your comments seemed somewhat conflicting.

the topic is about creatine exacerbating existing renal failure, which is quite logical, since every amino acid and protein does this

From what I have gathered, renal failure is accompanied by impeded arginine/guanidino compound metabolism, which is evident by the significantly elevated toxic levels of guanidino compounds demonstrated within the literature. This alteration in guanadino metabolism is accompanied by the excessive generation of univalent radicals, in addition to excessive plasma/intracellular uraemic solute retention, thus resulting in uraemic toxicity. The addition of exogenous creatine [in addition to repression of AGAT transamidination] could further upregulate the presence of toxic guanidino compounds such as guanidinovaleric acid, argininic acid, methylguanidine, creatol, ect. and ultimately result in a significantly exacerbated degree of retention toxicity, thereby leading to a hightened state of disease severity.

[FittyFive]

I had a kidney removed about 43 years ago when I was 12 y/o due to staff infection. I like to take 5g of creatine pre-workout about 3 days a week. Have been doing that for about 15 years. All my kidney function blood levels are normal, but I have had chronic, low-grade anemia for about 25 years.

Am I safe continuing to do this? Thanks

[johngoomba]

no, neither sarcasm, nor implying creatine can induce renal failure

the topic is about creatine exacerbating existing renal failure, which is quite logical, since every amino acid and protein does this

oh your sure of this are you mister professor? then explain why i was rushed to hospital after taking creatine for 4 months with back and stomach pains,sweating,swollen ankles and legs,and collapse? never had anything wrong with me in my life before taking it so you talk bs dude.
people like you should watch what advise you give on these forums,as you may be the one responsible for killing someone some day.don't take any advise from these nutcases on here they aren't professionals and even professionals cant predict what anything can do to you.you take advise from these nutters then its at your own risk.these guys who claim to know everything about what anything will do to your body need locking up,or sued.

[physioman]

oh your sure of this are you mister professor? then explain why i was rushed to hospital after taking creatine for 4 months with back and stomach pains,sweating,swollen ankles and legs,and collapse? never had anything wrong with me in my life before taking it so you talk bs dude.
people like you should watch what advise you give on these forums,as you may be the one responsible for killing someone some day.don't take any advise from these nutcases on here they aren't professionals and even professionals cant predict what anything can do to you.you take advise from these nutters then its at your own risk.these guys who claim to know everything about what anything will do to your body need locking up,or sued.

wtf?

[thruxton]

thanks but the hard part is to find human studies and that's what i am looking for

to be honest, either in vitro or animal studies wont say much, unless there is no human study at all, so a good in vitro or animal study would be ok

i've seen a million dialysis patients. none from creatine supplementation

[physioman]

i've seen a million dialysis patients. none from creatine supplementation

I bet

but I am also sure that it doesn't work this way, scientific facts are not justified like this