Creatina e Função Renal Em Indivíduos Em Treinamento de Resistência

7/25/2019 Creatina e Funo Renal Em Indivduos Em Treinamento de Resistncia

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Eur J Appl Physiol (2008) 103:3340

DOI 10.1007/s00421-007-0669-3

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ORIGINAL ARTICLE

EVects of creatine supplementation on renal function:

a randomized, double-blind, placebo-controlled clinical trial

Bruno Gualano Carlos Ugrinowitsch Rafael Batista Novaes

Guilherme Gianini Artioli Maria Heloisa Shimizu Antonio Carlos Seguro

Roger Charles Harris Antonio Herbert Lancha Jr

Accepted: 28 December 2007 / Published online: 11 January 2008

Springer-Verlag 2008

Abstract Creatine (CR) supplementation is commonly

used by athletes. However, its eVects on renal function

remain controversial. The aim of this study was to evaluate

the eVects of creatine supplementation on renal function in

healthy sedentary males (1835 years old) submitted to

exercise training. A randomized, double-blind, placebo-con-

trolled trial was performed. Subjects (n = 18) were randomly

allocated to receive treatment with either creatine (CR)

(10 g day1 over 3 months) or placebo (PL) (dextrose).

All subjects undertook moderate intensity aerobic training,

in three 40-min sessions per week, during 3 months. Serum

creatinine, serum and urinary sodium and potassium were

determined at baseline and at the end of the study. Cystatin

C was assessed prior to training (PRE), after 4 (POST 4) and

12 weeks (POST 12). Cystatin C levels (mg L1) (PRE CR:

0.82 0.09; PL: 0.88 0.07 vs. POST 12 CR: 0.71 0.06;

PL: 0.75 0.09, P = 0.0001) were decreased over time,

suggesting an increase in glomerular Wltration rate. Serum

creatinine decreased with training in PL but was unchanged

with training in CR. No signiWcant diVerences were

observed within or between groups in other parameters

investigated. The decrease in cystatin C indicates that high-

dose creatine supplementation over 3 months does not pro-

voke any renal dysfunction in healthy males undergoing aer-

obic training. In addition, the results suggest that moderate

aerobic training per se may improve renal function.

Keywords Adverse eVects Kidneys Cystatin C

Exercise

Introduction

Despite well documented beneWcial eVects of creatine sup-

plementation on exercise performance, neurodegenerative

disorders, musculoskeletal abnormalities and mitochondrial

cytopathies (Terjung et al. 2000), several case reports have

suggested that supplementation may impair renal function

(Kuehl et al. 1998; Pritchard and Kalra 1998; Koshy et al.

1999; Thorsteinsdottir et al. 2006). In addition, recent Wnd-

ings have demonstrated creatine-induced deleterious eVects

in rats with cystic kidney disease (Edmunds et al. 2001) and

sedentary animals (Ferreira et al. 2005). In contrast, other

studies have indicated no deleterious eVect in sedentary

(Taes et al. 2003) or exercised (Ferreira et al. 2005) rats,

and in pre-existing renal failure rats (Taes et al. 2003).

Studies in humans have indicated that creatine supplemen-

tation does not aVect renal function (Poortmans et al. 1997;

Poortmans and Francaux 1999; Poortmans et al. 2005; Rob-

inson et al. 2000). However, these studies have been criti-

cized by the absence of prospective randomization, the lack

of any uniform creatine source and dosage, the limited

study power of the studies, and particularly the low sensi-

tivity of the methods used to evaluate glomerular Wltration

B. Gualano C. Ugrinowitsch R. B. Novaes G. G. Artioli

A. H. Lancha Jr

Laboratory of Applied Nutrition and Metabolism,

School of Physical Education and Sport,

University of Sao Paulo, Sao Paulo, Brazil

M. H. Shimizu A. C. Seguro

School of Medicine, Nephrology Department,

University of Sao Paulo, Sao Paulo, Brazil

R. C. Harris

School of Sport, Exercise and Health Sciences,

University of Chichester, Chichester, UK

B. Gualano (&)

Av. Professor Mello Moraes, 65, Butant,

Sao Paulo, SP 05508-900, Brazil

e-mail: [email protected]


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34 Eur J Appl Physiol (2008) 103:3340

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rate (GFR) (Kuehl et al. 2000). The relevance of the rat or

other animal models to the human is also questionable

(Kreider 2003; Tarnopolsky et al. 2003) given that creatine

is not a normal nutrient in such species and may not be

absorbed to any great extent from the gut, as for example in

the horse (Sewell and Harris 1995). This contrasts with

humans where creatine is rapidly absorbed and intake

(expressed as g monohydrate) may routinely be 12 g daily,and in some diets as high as 57 g daily. Still higher daily

intakes, which on a g per kg body weight basis may exceed

on even those taken by athletes, are found in carnivorous

animals with no apparent eVect on renal function.

The glomerular Wltration rate is widely accepted as the

best overall measure of kidney function (Dharnidharka

et al. 2002). While inulin clearance and 51Chromium-ethy-

lenediamine tetraacetic acid (Cr-EDTA) are traditionally

considered as the gold standard for estimation of GFR,

these methods are highly specialized and take several hours

to perform. In addition, a number of practical consider-

ations (i.e. cumbersome methods of determination, use of

radioactive isotopes, and high costs) limit their use in clini-

cal practice. In the last 40 years, serum creatinine has

become the most commonly used marker of renal function.

However, since creatine is converted spontaneously to cre-

atinine (Wyss and Kaddurah-Daouk 2000), the use of crea-

tine supplements to increase tissue creatine levels will

invariably increase creatinine production, falsely suggest-

ing renal function impairment. Therefore, the use of creati-

nine related parameters alone to estimate GFR is largely

inadequate in creatine supplementation trials (Pline and

Smith 2005). As an alternative, several studies (Kazama

et al. 2002; Stevens et al. 2006) including some meta-ana-

lyzes (Dharnidharka et al. 2002; Roos et al. 2007) have

suggested that cystatin C (13.3 kDa), a novel and speciWc

marker of GFR, has a role in the assessment of renal func-

tion in certain groups of patient where creatinine cannot be

used. These studies have demonstrated in several popula-

tions that serum cystatin C is more sensitive than creatinine

in the detection of early and less-severe changes in kidney

function. The validity and diagnostic accuracy of cystatin C

were investigated by Kazama et al. (2002). In addition,

Taes et al. (2003) reported cystatin C to be signiWcantly

correlated to inulin clearance in pre-existing renal failure

and control rats (r= 0.82;P = 0.001), despite 4 weeks crea-

tine supplementation. Thus, cystatin C appear to be a poten-

tially useful marker for the estimation of GFR particularlyin creatine supplementation trials.

We performed a double blind, randomized, placebo-con-

trolled trial that aimed to investigate the eVects of high-

dose creatine supplementation on renal function in seden-

tary healthy males submitted to 3 months of moderate

intensity aerobic training.

Methods and materials

Subjects

Participants were recruited between August and December

2005 from Sao Paulo, Brazil, through advertisement in

local newspapers and through the distribution of leaXets to

private homes. Respondents were invited to take part if

they were male (1835 years old) and had lead a sedentary

life for at least the past 7 years, did not have any pre-exist-

ing renal or cardiovascular diseases, were eutrophic, non-

smokers, and non-vegetarians. Subject characteristics are

presented in Table 1.

The study was approved by the local Ethics and

Research Committee. Subjects were informed of the exper-

imental procedures and of any possible risks before giving

their written informed consent to participate.

Experimental protocol

A 12-week, double-blind, randomized, placebo-controlled

trial was conducted between 1 March and 1 June 2006.

Table 1 Subject characteristics

measured at baseline and week

12

Creatine group Placebo group

Baseline Week 12 Baseline Week 12

Age (years) 24.2 5.0 NA 24.6 4.2 NA

VO2peak (ml kg1 min1) 37.6 4.6 NA 37.1 4.1 NA

VT (ml kg1 min1) 30.7 6.1 NA 28.9 5.9 NA

BMI (kg m2) 23.1 4.5 23.2 2.3 24.0 3.2 23.9 2.2

Body fat content (%) 17.9 3.1 13.1 5.1 17.2 2.8 12.75 4.9*

Waist-to-hip ratio (cm) 0.83 0.06 0.82 0.09 0.83 0.05 0.82 0.07

Waist circumference (cm) 80.1 8.2 79.9 7.2 79.9 9.6 79.2 4.2

Resting HR (beats min1) 64.1 6.1 58.2 2.3 65.1 6.5 59.4 3.1*

Running distance per

training session (km)

3.8 0.8 5.4 0.2 3.8 0.4 5.2 0.8*

No signiWcant diVerences were

observed between creatine

(n = 9) and placebo (n = 9)

groups at baseline and at 12th

week (unpaired ttest). * versus

baseline (P 0.05). VTventila-

tory gas exchange threshold;HR

heart rate; NAnot assessed at

this time


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Eur J Appl Physiol (2008) 103:3340 35

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Subjects were randomly assigned to receive either crea-

tine (CR; n = 9) or placebo (PL; n = 9) in a double-blind

fashion. As the majority of creatine consumers are physi-

cally active, both groups undertook a program of moderate

intensity aerobic training for 3 months. At baseline (PRE)

and after 4 (POST 4) and 12 weeks (POST 12) subjects

underwent renal function tests. Blood samples were

obtained 48 h after the last training session from an antecu-bital vein following 12 h overnight fast, at all time points

(PRE, POST 4 and POST 12). Twenty-four-hour urine col-

lection was also obtained 48 h after the last training session

at baseline and at the end of creatine supplementation. Pos-

sible diVerences in dietary intake were assessed by a 24-h

dietary recall at PRE and POST 12. The experimental

design is illustrated in Fig. 1.

Creatine supplementation protocol and blinding

The CR group received 0.3 g day1 kg1 of body weight for

the Wrst week, and 0.15 g day1 kg1 of body weight for the

next 11 weeks; the PL group was given dextrose in place of

creatine, at the same dose. During the loading phase, indi-

viduals received the supplement in four packages, with

equal content, and were instructed to ingest one supplement

package at breakfast, lunch and dinner and the fourth at

10 pm. During the maintenance phase, subjects consumed

the supplement as two equally divided doses, one during

lunch and the second during dinner. These packages were

coded so that neither the investigators nor the participants

were aware of the contents until completion of the analyses.

All subjects were instructed to dissolve the supplements,

preferably in juice, in order to mask both the low solubility

of creatine and the taste of dextrose. The compliance to cre-

atine supplementation was monitored weekly by personal

communication. The subjects completed a weekly question-

naire, adapted from Volek et al. 2000, to ascertain any pos-

sible adverse eVects of creatine supplementation.

In order to verify the purity of the creatine used, a sam-

ple was analyzed by HPLC. This established 99.9% of

purity, with no other peaks detected (creatinine, dicyandia-

mide and cyclocreatine < 0.01%).

VO2peaktest

Peak oxygen uptake capacity was determined at the startof the study using a treadmill exercise test (Bruce et al.

1973). This test is conducted in 3 min stages. The Bruce

protocol starts at 4.6 METS of work, at a speed of 2.7 km/

h and a grade of 10 degrees. Every 3 min, the workload is

increased by a combination of increasing speed and the

gradient of the treadmill. VO2peak was obtained when two

of three criteria were met, namely a plateau in VO2, a

respiratory exchange ratio (RER) > 1.1, and volitional

exhaustion.

Exercise training protocol

The exercise training protocol has been described previ-

ously (Gualano et al. 2008). BrieXy, both groups were sub-

mitted to aerobic training, three times a week, for 40 min

per session, for 3 months. Running intensity was set at the

heart rate corresponding to 70% of VO2peak. Subjects were

requested to run at the pre-set heart rate during the whole of

the training session. Thus, the total amount of exercise

undertaken during training increased in both running dis-

tance and intensity in response to the training. All sessions

were monitored by a Wtness-professional. From the outset it

was ruled that subjects would be dropped from the study if

they missed three non-consecutives training sessions, or

two consecutives sessions. One subject from the PL group

was excluded for this reason.

Food intake assessment

Food intake was assessed by means of three 24-h dietary

recalls undertaken on separate days (2 weekdays and

1 weekend day) using a visual aid photo album of real

foods. The 24-h dietary recall consists of the listing of

foods and beverages consumed during 24 h prior to the

recall. The interviews were conducted face to face by a

trained dietitian, using the multiple-pass method developed

by USDA (Conway et al. 2004). Energy and macronutrient

intakes were analyzed by the Brazilian software, Virtual

Nutri, based on Handbook number 8 of the USDA Human

Nutrition Information Service (Composition of food: raw;

processed; prepared, series 116, revised 19761986).

Additional information was obtained from the Brazilian

Table of Food Composition (version 1.0, 1997, University

of So Paulo, Sao Paulo, SP). The nutrient database was

complete for all the nutrients studied.

Fig. 1 Experimental design. The subjects were randomly allocated to

receive creatine supplementation (0.3 g day1 kg1 of body weight for

the Wrst week, and 0.15 g day1 kg1 of body weight for the next

11 weeks, n = 9) or placebo (dextrose, n = 9) in a double-blind fashion.

Blood samples were obtained at baseline and after 4, 8 and 12 weeks.

The 24-h urine collections were performed at baseline and at the end of

the study. Renal parameters analyzed include serum cystatin C, creati-

nine, sodium and potassium and urinary sodium and potassium. See

Methods and materials section for more details. supplsupplementa-

tion; HPLChigh-performance liquid chromatography


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Blood and urinary analyses

All samples were analyzed in duplicate and the average

value was used for data analysis. The intra-class coeY-

cient (ICC) were 0.869, 0.953, 0.967 and 0.805 (P < 0.001)

and the coeYcient of variation (CV) were 2, 0.4, 1.1, 2.8%

for creatinine, sodium, potassium and cystatin C, respec-

tively.Creatinine was determined in plasma and urine using an

enzymatic colorimetric test PAP (Labtest, So Paulo,

Brazil).

Serum and urinary sodium, and potassium were assessed

using a Xame photometer (model 143: Instrumentation Lab-

oratory, Lexington, MA, USA).

Cystatin C was measured using a BN II Nephelometer

(Dade Behring) and a particle-enhanced turbidimetric

immunoassay (N Latex Cystatin C).

Statistical analysis

Renal parameters were tested by a two-way ANOVA

(mixed model) with repeated measures. Group (CR and PL)

and time (pre, 4 and 12 weeks) were considered Wxed fac-

tors and subjects were deWned as a random factor. A post

hoc test adjusted by Tukey was used for multicomparison

purposes. Baseline characteristics between groups were

compared using Students ttest for unpaired data. SigniW-

cance level was set at P < 0.05. Data are presented as

mean standard deviation. SAS proc IML was used to

perform a simulation to determine the power of the statisti-

cal tests (Ugrinowitsch et al. 2004) as suggested by Littell

et al. (2006). Expected means and variance were used as

input to simulate cystatin C data using an autoregressive

correlation structure within subjects measurements. Nine

subjects produced a power of 0.95 in the comparison

between groups for cystatin C, the most important depen-

dent variable.

Results

The number of subjects recruited to the study is shown in

Fig. 2. Of the 103 people who responded to the initial

request for volunteers, 81 were excluded because they

performed regular physical activity or expressed self-

reported chronic disease. The remaining 22 subjects were

randomly assigned to the CR or PL groups. Four subjects

were subsequently lost: three withdrew for personal rea-

sons (two in CR and one in PL) and one was excluded

because they missed two consecutive training sessions

(PL). The compliance to creatine or placebo supplementa-

tion was 100%.

As mentioned earlier, creatine purity was assessed by

HPLC as 99.9%. Moreover, there was no diVerence

between or within groups in nutrient or energy intake

(Table 2). Hence, it is probable that neither the presence of

trace contaminants in the creatine or diVerences in dietary

intake were a factor in the study. Despite the high dose of

creatine ingested (compared with ACSM recommenda-

tions, Terjung et al. 2000), there was no report of any del-

eterious eVects assessed through subjective questionnaire.

The compliance to creatine supplementation was 100%.

The blinding was considered successful because the ability

of participants to accurately guess their group assignment

was no better than chance in both groups and was not diVer-

ent between groups (CR: 33% and PL: 44%; P = 0.78).

Twelve weeks of aerobic training signiWcantly increased

the running distance per session. There was also a time

main eVect for body fat content measured by skinfold thick-

ness and resting heart rate; other measured variables

remained unaltered (Table 1).

Cystatin C (Fig. 3) decreased at the same rate in both

groups from the beginning to the end of the training proto-

col (main time eVect) (PRE CR: 0.82 0.09; PL:

0.88 0.07 vs. POST 12 CR: 0.71 0.06; PL:

0.75 0.09 mg L1; P = 0.0001). With the exception of

one subject from PL group, all subjects showed a decrease

in serum cystatin C after 12 weeks.

PL showed a decrease in serum creatinine at weeks 4 and

12 (main time eVect, P = 0.004 and 0.003, respectively)

while CR did not (Fig. 4). The diVerence in response to the

treatment between groups was signiWcant at weeks 4 and 12

(P = 0.0001 and 0.0004, respectively). Unfortunately, it

was not possible to calculate the creatinine clearance

because most of the subjects failed to adequately collect the

24-h urine samples.

Fig. 2 Flow diagram of participants


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Eur J Appl Physiol (2008) 103:3340 37

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No signiWcant diVerences within or between groups were

found in serum and urinary sodium and potassium concen-

tration at the start and end of the study.

Discussion

The aim of the study was to investigate the eVects of crea-

tine supplementation on renal function in sedentary healthy

males submitted to aerobic training. To our knowledge, this

is the Wrst randomized, double-blind, placebo-controlled

trial to demonstrate that high-dose long-term creatine sup-

plementation (10 g over 3 months) does not impair renal

function in healthy subjects, initially sedentary but under-

going a period of moderate training. In addition, we believe

that this is the Wrst study to use cystatin C as a marker of

GFR in humans supplemented with creatine.

The eVects of creatine supplementation on renal function

have been intensely discussed in the literature. Some case

reports suggested that creatine supplementation could cause

deterioration in renal function in healthy individuals (Thor-

steinsdottir et al. 2006), and in subjects with pre-existing

renal failure (Pritchard and Kalra 1998). On the other hand,

longitudinal data have indicated otherwise for healthy indi-

viduals (Poortmans et al. 1997, 2005; Poortmans and

Francaux 1999; Kreider et al. 2003). Long-term studies

with creatine supplementation in humans have presented

severe limitations such as a lack of prospective randomiza-

tion, the absence of any uniform creatine source and dos-age, limited statistical power and, most frequently, the

absence of a marker of renal function other than creatinine

(Kuehl et al. 2000).

The classic way to estimate renal function in humans is

through creatinine clearance. However, creatine is con-

verted spontaneously to creatinine (Ferreira et al. 2005;

Pline and Smith 2005) and elevation of tissue creatine lev-

els in supplemented subjects will inevitably increase serum

creatinine levels (Wyss and Kaddurah-Daouk 2000), falsely

suggesting renal dysfunction. In order to avoid this, non-

creatinine related markers of GFR are needed of which the

use of inulin clearance and Cr-EDTA are considered to be

the most reliable (Dharnidharka et al. 2002). These tech-

niques, however, are time-consuming, labour-intensive,

expensive, and require administration of substances that

make them incompatible with the routine monitoring of

subjects. Human cystatin C, a basic low molecular mass

protein, with 120 amino acid residues, is freely Wltered by

the glomerulus and almost completely reabsorbed and

catabolized by the proximal tubular cells. The use of serum

cystatin C to estimate GFR is based on the same logic as the

use of creatinine, but because it does not return to blood-

stream and is not secreted by renal tubules, it has been sug-

gested to be closer to an ideal endogenous marker.

Several studies have pointed out the advantages of cystatin

C in estimating GFR compared to creatinine (Dharnidharka

et al. 2002; Kazama et al. 2002). Perhaps the main advan-

tage of cystatin C over creatinine is that the former protein

is unaVected by food ingestion (Preiss et al. 2007). As a

result cystatin C is an attractive marker of renal function in

creatine trials and clinical practice. However, caution needs

to be exercised as there is currently only one study that

evaluates the correlation between cystatin C and inulin

Fig. 3 Serum cystatin C concentration at baseline and after 4 and

12 weeks in creatine (CR; n = 9) and placebo (PL; n = 9) groups. Main

time eVect: * versus week 4 (P = 0.001); # versus baseline

(P = 0.0001). aIndividual data; bMean standard deviation

Fig. 4 Serum creatinine concentration at baseline, after 4 and

12 weeks in creatine (CR; n = 9) and placebo (PL; n = 9) groups.

*Interaction eVect: PL versus CR (P < 0.005) and #time eVect: PL

versus baseline (P < 0.0001). a Individual data; b Mean standard

deviation

Table 2 Food intake assessed

by three 24-h dietary recalls at

baseline and after 12 weeks in

creatine (n = 9) and placebo

(n = 9) groups

CR group PL group

PRE POST 12 PRE POST 12

Energy (kcal) 2728 238 2833 201 2844 201 2899 287

Protein (%) 28.0 4.3 30.0 3.1 29.8 4.3 31.1 3.9

Lipid (%) 25.5 4.9 24.5 4.5 24.9 4.1 26 3.1

Carbohydrate (%) 46.3

3.9 43.3

5.3 45.3

4.9 42.9

5.1Protein/body weight (g/kg) 1.1 0.3 1.2 0.3 1.1 0.2 1.2 0.3

No signiWcant diVerences werefound


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clearance in creatine supplemented rats. Thus, further stud-

ies need to be conducted in order to determine the diagnos-

tic eYcacy of cystatin C when compared with other

established markers.

Serum creatinine was signiWcantly lower in PL than in

CR subjects after creatine supplementation, which might

suggest renal function impairment. However, in contrast

cystatin C was reduced in both groups, which suggests oth-erwise. The higher concentrations of serum creatinine in the

CR group are most probably a reXection of the increase in

tissue creatine levels brought about by creatine supplemen-

tation, and the non-enzymic Wrst-order conversion of this to

creatinine at the rate of 1.7% per day (Wyss and Kaddu-

rah-Daouk 2000; Pline and Smith 2005). A similar conclu-

sion was reached by Taes et al. (2003).

However, the eVect of creatine supplementation on renal

function remains controversial even in controlled studies in

rats, which used established methods to evaluate GFR. Taes

et al. (2003) failed to demonstrate any deleterious eVects in

rats with either renal failure or normal renal function. In

contrast, Ferreira et al. (2005) suggested that creatine sup-

plementation induced renal dysfunction in sedentary

healthy rats. In the latter study, the authors believed that

renal impairment was provoked by creatine-induced vaso-

constriction and/or cytotoxic compounds. Unfortunately,

only Taes et al. 2003 reported the purity of the creatine

administered. Hence, trace contaminants associated with

the creatine could also have been partially responsible for

the opposing Wndings in the literature. In the present study,

creatine purity was assessed by HPLC and no trace contam-

inants were found.

Notwithstanding the observations made in rats, the rele-

vance of these results to humans which routinely encounter

creatine in the diet is also open to question. As noted earlier

the typical non-vegetarian diet may contain 12 g creatine

(expressed as the monohydrate) daily, reaching a maximum

of 57 g. Still higher levels are found in the diets of carniv-

orous animals of equivalent body weight. It would be sur-

prising if, given the span of human evolution, some

adaptation to creatine intake had not occurred. Indeed the

rapid and complete absorption of creatine supplied in the

diet (Harris et al. 1992, 2002), in contrast to the lack of

absorption in a herbivorous animal such as the horse

(Sewell and Harris 1995), suggests that adaptation has

occurred at least at one level. The elegant study conducted

by Tarnopolsky et al. (2003) highlighted the species- and

tissue-speciWc response to creatine intake. These authors

demonstrated that creatine administration can induce

chronic hepatitis in mice, but not in rats. Interestingly, nei-

ther the mice nor rats showed renal dysfunction after long-

term supplementation, supporting our Wndings.

Another relevant Wnding of this study refers to the eVects

of exercise training per se on renal function. We observed

that 3 months of moderate aerobic training reduced serum

cystatin C and serum creatinine (only in the placebo group),

suggesting improvement in renal function. Despite the rele-

vance of our Wnding, we cannot provide any comparative

discussion with other studies because, to the best of our

knowledge, there are none that have investigated the eVects

of exercise training on GFR. In fact, Finkelstein et al.

(2006) showed a strong positive association between physi-cal activity and GFR in a cross-sectional review of The

Third National Health and Nutrition Examination Survey

(NHANES III). However, the authors concluded that a lon-

gitudinal study would be necessary to clearly deWne this

relationship. Although the mechanism(s) responsible for

the renal function improvement observed in our study

remains unknown, it should be noted that there is strong

evidence in literature to indicate that intensive glycemic

control, blood pressure control (Klahr et al. 1994), lipid

lowering strategies (Fried et al. 2001), oxidative stress

decrease (Gaede et al. 2001) and weight management

(Stengel et al. 2003) are important factors in arresting or

even to preventing chronic kidney disease progression.

According to Jaber and Madias (2005), it is possible to

achieve regression in the age-related decline in renal func-

tion through the control of these factors, all of which are

beneWcially improved by moderate intensity exercise train-

ing. We have previously shown (Gualano et al. 2006, 2008)

that the exercise protocol used in this study was capable of

improving glucose tolerance and the lipid proWle, as well as

reducing markers of oxidative stress. In the absence of a

suitable control group, however, we cannot conclude a

cause-and-eVect relationship in this case.

Shao and Hathcock (2006) reviewed the available data

and suggested a safe limit for creatine monohydrate intake

of 5 g day1 although creatine users frequently consume

higher doses than this (Harris et al. 1992). In their opinion

this was a dose which avoided any side eVects. However,

their conclusion was inXuenced by the fact that there were

only three studies in existence that used 10 g day1 in the

maintenance phase. Two of these did not report side eVects

but neither was not controlled or randomized. The third

study investigated patients with amyotrophic lateral sclero-

ses for 310 days did not Wnd signiWcant changes in serum

urea or urinary albumin levels with creatine supplementa-

tion (Groeneveld et al. 2005). However, because of the dis-

ease nature of the population studied, this did not allow

further extrapolation to healthy subjects. Our data contrib-

ute to the hypothesis that 10 g day1of creatine is safe and

has no eVect on renal function in healthy subjects undergo-

ing moderate intensity exercise training.

Although our study presents some important positive

points, such as well-controlled design, satisfactory statisti-

cal power and a GFR estimate marker not related to creati-

nine, we also recognize that there were some limitations.


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Creatina e Função Renal Em Indivíduos Em Treinamento de Resistência

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