American Football Players in Preseason Training at Risk of Acute Kidney Injury Without Signs of Rhabdomyolysis.

OBJECTIVE: This study was designed to identify changes in blood biomarkers that would indicate excessive muscle breakdown during the initial 10 days of preseason training in collegiate American football players and subsequently increase their risk of acute kidney injury (AKI). DESIGN: Prospective cohort study. SETTING: Preseason, heat acclimatization period. PARTICIPANTS: Twenty-five Division I American football players. INTERVENTION: Clinical biomarkers for muscle damage were measured during a preseason training camp. Samples were obtained before camp and approximately 5 and 10 days into camp after completion of heat acclimatization training. MAIN OUTCOMES: Creatine kinase, myoglobin, lactate dehydrogenase, and creatinine were measured. Glomerular filtration rate (GFR) was calculated. Urine was collected at each blood draw to qualitatively identify hematuria and red blood cells. RESULTS: A high percentage of athletes had an asymptomatic reduction in kidney function over the 10-day period. Ten of 23 athletes did have a significant, 31.6%, mean reduction in GFR, placing each at risk of AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) classification. The plasma myoglobin for the at risk of AKI group had a mean value 8× above their baseline mean on day 5 and statistically significant mean 13× higher on day 10 than baseline. The not at risk of AKI group did not have significant differences between days 0, 5, and 10. CONCLUSIONS: A relatively high percentage of athletes had an asymptomatic reduction in kidney function during the intense preseason training period. 43.4% of athletes in this study had a significant 31.6% mean reduction in GFR over the 10 days. According to RIFLE classification, this placed each athlete "at risk" of AKI.

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC-Trial): A randomized controlled first-in-human trial.

AIMS: Increasing evidence indicates that the ATP-generating enzyme creatine kinase (CK) is involved in hypertension. CK rapidly regenerates ATP from creatine phosphate and ADP. Recently, it has been shown that beta-guanidinopropionic acid (GPA), a kidney-synthesized creatine analogue and competitive CK inhibitor, reduced blood pressure in spontaneously hypertensive rats. To further develop the substance as a potential blood pressure-lowering agent, we assessed the tolerability of a sub-therapeutic GPA dose in healthy men. METHODS: In this active and placebo-controlled, triple-blind, single-centre trial, we recruited 24 healthy men (18-50 years old, BMI 18.5-29.9 kg m-2 ) in the Netherlands. Participants were randomized (1:1:1) to one week daily oral administration of GPA 100 mg, creatine 5 g, or matching placebo. The primary outcome was the tolerability of GPA, in an intent-to-treat analysis. RESULTS: Twenty-four randomized participants received the allocated intervention and 23 completed the study. One participant in the placebo arm dropped out for personal reasons. GPA was well tolerated, without serious or severe adverse events. No abnormalities were reported with GPA use in clinical safety parameters, including physical examination, laboratory studies, or 12-Lead ECG. At day 8, mean plasma GPA was 213.88 (SE 0.07) in the GPA arm vs. 32.75 (0.00) nmol l-1 in the placebo arm, a mean difference of 181.13 (95% CI 26.53-335.72). CONCLUSION: In this first-in-human trial, low-dose GPA was safe and well-tolerated when used during 1 week in healthy men. Subsequent studies should focus on human pharmacokinetic and pharmacodynamic assessments with different doses.

Analysis of Central and Peripheral Vision Reaction Times in Patients With Postconcussion Visual Dysfunction.

OBJECTIVE: To determine whether central and peripheral vision reaction times (PVRTs) are prolonged in patients with visual dysfunction after sustaining a concussion. DESIGN: Comparison of Dynavision D2 central and PVRTs in patients with postconcussion visual dysfunction were compared with control data from a normative patient database. Concussion patients without visual dysfunction were not included in this study. SETTING: National Collegiate Athletic Association Division 1 college training room and university based, academic health center. PARTICIPANTS: Patients were selected for inclusion based on diagnosis of new visual dysfunction as indicated either by physical examination of the team physician or by patient self-report of symptoms. Patients included college athletes, college students, and concussion patient's presenting to a university based, academic health center. INTERVENTION: Measurement of central and PVRTs using a Dynavision D2 reaction time program were used as the dependent variables. Evaluations were conducted from 3 days to 11 months postconcussion, depending on the temporal development of visual symptoms after the concussion. No intervention was used. MAIN OUTCOME MEASURES: Average central and PVRTs for patients with postconcussion visual symptoms were compared with an asymptomatic control group with no history of concussion. RESULTS: Both central and PVRTs were significantly prolonged in patients with postconcussion visual symptoms compared with patients with no history of concussion. CONCLUSIONS: Central and PVRTs are both prolonged in patients with postconcussion visual dysfunction with PVRT being disproportionately prolonged. The percent change from central to PVRT was also increased in patients with postconcussion visual dysfunction.

Creatine transporter deficiency leads to increased whole body and cellular metabolism.

Creatine (Cr) is a guanidino compound required for rapid replenishment of ATP in cells with a high-energy demand. In humans, mutations in the Cr transporter (CRT;SLC6A8) prevent Cr entry into tissue and result in a significant intellectual impairment, epilepsy, and aphasia. The lack of Cr on both the whole body and cellular metabolism was evaluated in Crt knockout (Crt (-/y) ) mice, a high-fidelity model of human CRT deficiency. Crt (-/y) mice have reduced body mass and, however, show a twofold increase in body fat. There was increased energy expenditure in a home cage environment and during treadmill running in Crt (-/y) mice. Consistent with the increases in the whole-body metabolic function, Crt (-/y) mice show increased cellular metabolism as well. Mitochondrial respiration increased in skeletal muscle fibers and hippocampal lysates from Crt (-/y) mice. In addition, Crt (-/y) mice had increased citrate synthase activity, suggesting a higher number of mitochondria instead of an increase in mitochondrial activity. To determine if the increase in respiration was due to increased mitochondrial numbers, we measured oxygen consumption in an equal number of mitochondria from Crt (+/y) and Crt (-/y) mice. There were no changes in mitochondrial respiration when normalized to mitochondrial number, suggesting that the increase in respiration observed could be to higher mitochondrial content in Crt (-/y) mice.

Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes.

Primary care pediatricians and a variety of specialist physicians strive to define an accurate diagnosis for children presenting with impairment of expressive speech and delay in achieving developmental milestones. Within the past two decades, a group of disorders featuring this presentation have been identified as cerebral creatine deficiency syndromes (CCDS). Patients with these disorders were initially discerned using proton magnetic resonance spectroscopy of the brain within a magnetic resonance imaging (MRI) examination. The objective of this review is to provide the clinician with an overview of the current information available on identifying and treating these conditions. We explain the salient features of creatine metabolism, synthesis, and transport required for normal development. We propose diagnostic approaches for confirming a CCDS diagnosis. Finally, we describe treatment approaches for managing patients with these conditions.

Sixty minutes of what? A developing brain perspective for activating children with an integrative exercise approach.

Current recommendations for physical activity in children overlook the critical importance of motor skill acquisition early in life. Instead, they focus on the quantitative aspects of physical activity (eg, accumulate 60 min of daily moderate to vigorous physical activity) and selected health-related components of physical fitness (eg, aerobic fitness, muscular strength, muscular endurance, flexibility and body composition). This focus on exercise quantity in youth may limit considerations of qualitative aspects of programme design which include (1) skill development, (2) socialisation and (3) enjoyment of exercise. The timing of brain development and associated neuroplasticity for motor skill learning makes the preadolescence period a critical time to develop and reinforce fundamental movement skills in boys and girls. Children who do not participate regularly in structured motor skill-enriched activities during physical education classes or diverse youth sports programmes may never reach their genetic potential for motor skill control which underlies sustainable physical fitness later in life. The goals of this review are twofold: (1) challenge current dogma that is currently focused on the quantitative rather than qualitative aspects of physical activity recommendations for youth and (2) synthesise the latest evidence regarding the brain and motor control that will provide the foundation for integrative exercise programming that provide a framework sustainable activity for life.

The influence of sport goggles on visual target detection in female intercollegiate athletes.

The aim of this study was to examine the effects of sport goggles on visual target detection in female intercollegiate athletes. Participants were randomly divided into three groups that varied in goggle use (G) or no goggle use (NG) over a total of three 1-min trials during a visual target detection task. The NG-NG-NG group did not wear goggles for any of the trials, whereas the NG-G-NG group wore goggles for the second trial only, and the G-NG-G group wore goggles for the first and third trials. The task consisted of illuminated targets arranged in five concentric rings from central to peripheral visual angles. The effects of sport goggles on response time to detect targets were most evident in the peripheral rings. Those who did not wear sport goggles showed improved performance from the first to second trials. This improvement was impaired, however, in those who wore sport goggles. Moreover, there was a reversal of the performance improvements achieved without goggles in those who wore goggles on the third trial. Together, these findings suggest the sport goggles not only impaired the expected initial performance but also impaired visual target detection after performance improvements were seen. These findings suggest sport goggles may impair detection of peripheral visual stimuli in athletes.

Role of bilirubin oxidation products in the pathophysiology of DIND following SAH.

Despite intensive research efforts, by our own team and many others, the molecules responsible for acute neurological damage following subarachnoid hemorrhage (SAH) and contributing to delayed ischemic neurological deficit (DIND) have not yet been elucidated. While there are a number of candidate mechanisms, including nitric oxide (NO) scavenging, endothelin-1, protein kinase C (PKC) activation, and rho kinase activation, to name but a few, that have been investigated using animal models and human trials, we are, it seems, no closer to discovering the true nature of this complex and enigmatic pathology. Efforts in our laboratory have focused on the chemical milieu present in hemorrhagic cerebrospinal fluid (CSF) following SAH and the interaction of the environment with the molecules generated by SAH and subsequent events, including NO scavenging, immune response, and clot breakdown. We have identified and characterized a group of molecules formed by the oxidative degradation of bilirubin (a clot breakdown product) and known as BOXes (bilirubin oxidation products). We present a synopsis of the characterization of BOXes as found in human SAH patients' CSF and the multiple signaling pathways by which BOXes act. In summary, BOXes are likely to play an essential role in the etiology of acute brain injury following SAH, as well as DIND.

Training the developing brain, part I: cognitive developmental considerations for training youth.

Based on the fundamental principles of pediatric exercise science and developmental physiology, childhood provides a critical window to develop the physical readiness of youth through age-related training programs that are designed purposely to teach and reinforce fundamental movement skills to enhance preparedness for physical activity and sport. Successful implementation of developmental programs requires age-related instruction by qualified professionals who understand the physical and psychosocial uniqueness of children and adolescents. An understanding of the interaction of physical and cognitive development is needed to design and implement training strategies that optimize training outcomes. Regular training with structured and integrative modalities throughout the developmental years as part of physical education, recreation, and sports practice can improve athletic performance while reducing common sports-related injuries and can facilitate the adoption of healthy lifestyles throughout adulthood. In this commentary, we outline cognitive developmental considerations in youth that may influence the design and implementation of training programs aimed at optimizing motor skill development in youth.

Effects of Prolonged Sitting with or without Elastic Garments on Limb Volume, Arterial Blood Flow, and Muscle Oxygenation.

PURPOSE: The physiological response induced by acute prolonged sitting is not fully understood. Therefore, we examined the effects of 8-h constant sitting on microcirculation and associated factors in the lower extremity among healthy males. We also evaluated the protective effects of lower-pressure thigh-length elastic compression garments on these parameters. METHODS: Nine healthy males (age, 22.6 ± 1.4 yr; body mass index, 22.4 ± 1.8 kg·m-2) completed the 8-h constant sitting experiment. Following baseline measurements, each subject was randomized to wear a lower-pressure elastic garment on the right or left leg from the inguinal region to the ankle joint, with the noncompressed contralateral leg as a control. Circumferences of the calf and malleolus, extracellular water contents, blood flow and shear rate of the dorsal metatarsal artery, and oxygen dynamics in the gastrocnemius muscles were measured in both extremities before and during 8-h constant sitting. RESULTS: Compared with baseline values, 8-h constant sitting caused enlargement of circumferences (calf, 2.4% ± 0.7%; malleolus, 2.7% ± 1.4%), retention of extracellular water in lower extremity muscles (10.1% ± 1.78%), deterioration of the blood flow (61.4% ± 16.2% of baseline) and shear rate of the dorsal metatarsal artery, and decrease in oxygenated hemoglobin and total hemoglobin levels in the gastrocnemius muscle (P < 0.05, respectively). When subjects wore the lower-pressure thigh-length compression garment, a significant reduction of these effects was observed (P < 0.05, for all). CONCLUSIONS: Prolonged sitting for 8 h induced edema, as well as deterioration of the arterial blood flow, shear rate, and microcirculation in lower limb muscles. Conversely, application of the lower-pressure elastic garment successfully prevented the pathophysiological deterioration associated with prolonged sitting.

Bilirubin oxidation products seen post subarachnoid hemorrhage have greater effects on aged rat brain compared to young.

INTRODUCTION: We have previously shown that novel oxidation products of Bilirubin, called Bilirubin oxidation products (BOXes), are found in humans and animal models post subarachnoid hemorrhage. We have also proposed that BOXes may play a role in the pathogenesis and clinical complications post SAH. In this study we report on the direct toxicity effects of BOXes on rat brain. METHODS: Identical volumes of either vehicle (normal saline) or BOXes (30 µl of a 20 µM solution) were applied above the dura through a cranial window of young (approximately 7-13 weeks) and aged (approximately 12-18 months) adult male Sprague Dawley rats (Charles River, Wilmington, MA, USA). To determine the extent of BOX-mediated injury, histology and immunocytochemistry were performed at 1, 2, 4, and 7 days post-surgical application of BOXes. We assessed the area of stress gene induction of HSP25/27 and HSP32. Immunohistochemistry was performed using standard avidin-biotin techniques. A monoclonal antibody to HSP25/27 (StressGen, Victoria, British Columbia, Canada), a monoclonal antibody to HSP32/HO-1 (StressGen), and a polyclonal HSP 32/HO-1 antibody were used for the immunocytochemistry. RESULTS: A single dose of BOXes produced substantial increases in HSP25 and HO-1 in the aged rats at all early time points (≤4 days). After 7 days all groups were not significantly different than saline control. Young rats were resistant to BOXes effects compared to saline control with trends towards increased stress gene expression caused by BOXes that did not reach statistical significance. CONCLUSION: We conclude from these studies that BOXes have direct effects on stress gene expression of the cortex post single dose application and that this can be seen for several days with apparent resolution at about 7 days. If BOXes are produced at similar levels in patients, the latency and duration of some SAH complications are consistent with these results.

Physiological Monitoring Detected Changes During Women's Soccer Anterior Cruciate Ligament Injury.

A growing number of studies utilizing wearable technologies are examining the influence of the autonomic nervous system (ANS) on intense training, recovery, and injury risk. Exercise biometric (EB) data were collected on collegiate, female soccer players during a preseason camp. One player sustained an anterior cruciate ligament (ACL) injury. Baseline anthropometric and EB data were compared to non-injured, position-matched teammates. All players had similar baseline testing. The injured athlete had a higher body mass index (BMI) and slower vision reaction time (RT). On the day of her injury (DOI), relative percentage heart rate recovery (tHRR) between intense training sets was calculated. Relative percentage tHRR was much lower for the injured athlete, indicating reduced recovery between training sets immediately prior to the injury. Also on DOI, the injured athlete had a lower glomerular filtration rate (GFR). In addition to BMI and RT differences, the lower relative percentage tHRR and GFR on the DOI observed for the injured athlete may reflect an imbalanced ANS recovery, and potentially to risk factors leading to her ACL injury.

Intra-arterial iodinated radiographic contrast material injection administration in a rat middle cerebral artery occlusion and reperfusion model: possible effects on intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Observations in human interventional stroke treatment led us to hypothesize that iodinated radiographic contrast material use may contribute to intracerebral hemorrhage. Effects of intra-arterial iodinated radiographic contrast material on hemorrhagic transformation after middle cerebral artery occlusion and reperfusion were studied in a placebo-controlled, blinded preclinical study in rats. METHODS: Four groups of male Sprague-Dawley rats were studied: saline group (n=8), contrast group (n=12), heparin group (n=9), and contrast+heparin group (n=9). The middle cerebral artery was occluded for 5 hours using suture placement. Heparin was infused before suture removal and reperfusion. Saline and/or contrast were infused immediately during reperfusion. Incidence, location, and size of hemorrhage were determined by brain necropsy inspection at 24 hours. RESULTS: There was a significant increase in incidence of cortical hemorrhage from control (37.5%), contrast (75.0%), heparin (77.8%) to contrast+heparin (100%; Cochran-Mantel-Haenszel correlation, P<0.01). Both pooled contrast groups (85.7%) and pooled heparin groups (88.9%) had higher rates of cortical intracerebral hemorrhage compared with the control group (P<0.05). Similar trends for increased cortical intracerebral hemorrhage were seen in the contrast-only (P=0.18) and heparin-only (P=0.18) groups. There was a trend for decreased infarct edema in rats receiving contrast versus those without (P=0.06). CONCLUSIONS: Intraarterial iodinated radiographic contrast material may increase cortical intracerebral hemorrhage, similar to heparin. Iodinated radiographic contrast material effect may be additive to heparin effect on the incidence of cortical intracerebral hemorrhage.

Glutathione peroxidase and subarachnoid hemorrhage: implications for the role of oxidative stress in cerebral vasospasm.

OBJECTIVE: Worldwide, cerebral vasospasm after subarachnoid hemorrhage (SAH) has an estimated morbidity and mortality of 1.2 million annually. While it has long been suspected that reactive oxygen species play a major role in the etiology of cerebral vasospasm after SAH, promising results in animal work were not borne out in human clinical trials, despite intensive research effort. The purpose of this study is to investigate the role of glutathione peroxidase in the SAH cerebrospinal fluid milieu. METHODS: We utilized commercially available kits for the quantitation of glutathione peroxidase 1 (glutathione peroxidase) activity and oxygen radical capacity and sodium dodecyl sulfate polyacrylamide gel electrophoresis with Western blotting with specific antibodies to human glutathione peroxidase to determine the enzyme content of the cerebrospinal fluid samples. Human cerebrospinal fluid was obtained in an Institutional Review Board-exempt manner for this study in the following groups: control (no SAH), CSF(C) (SAH but no vasospasm on angiography) and CSF(V) (SAH with clinical and angiographic vasospasm). RESULTS: We found that glutathione peroxidase activity is significantly higher in CSF(V) compared with CSF(C), and this is reflected in a higher total oxidative capacity in CSF(V). Despite similar levels of glutathione peroxidase protein, CSF(V) had significantly greater activity than CSF(C). DISCUSSION: These results further elucidate previous research from this laboratory, showing increased oxidative stress in CSF(V) compared with CSF(C). In conclusion, there appears to be increased glutathione peroxidase activity in CSF(V), despite there being increased levels of oxidative stress markers, suggesting overwhelming oxidative stress may play a role in cerebral vasospasm after SAH.

Down-regulation of interleukin 7 mRNA by hypoxia is calcium dependent.

OBJECTIVE: The discovery of IL-7R(alpha) polymorphisms implicated in the pathogenesis of multiple sclerosis has highlighted the importance of interleukin 7 (IL-7) in central nervous system diseases. Hypoxia affects neurological disease states in part by modulating expression of many early and late response genes. The present work used cultured PC12 cells to investigate the effect of hypoxia on IL-7 expression. METHOD: PC12 cells were cultured in Dulbecco's modified Eagle's medium (DMEM)/F12 medium. RNA was isolated and reverse transcriptase-polymerase chain reaction (RT-PCR) was run to quantify messenger RNA (mRNA) change. Western blots were used to assess IL-7 protein change in the medium. Extracellular free Ca(2+) was removed by using Ca(2+)-free DMEM/F12 with 1 mM ethylene glycol tetraacetic acid for 45 minutes before the start of hypoxia. RESULTS: Exposure of PC12 cells to 1% oxygen for 6 hours decreased IL-7 mRNA by 77% using RT-PCR (p<0.01). Exposure to 1% oxygen for 24 hours decreased IL-7 protein in the medium by 21% (p<0.05). As hypoxia duration increased (2, 4, 6 and 24 hours) or oxygen concentrations decreased (10%, 5% and 1%), IL-7 mRNA expression progressively decreased. Removal of extracellular free Ca(2+) completely prevented these hypoxia-induced decreases of IL-7 mRNA. DISCUSSION: Since IL-7 exhibits trophic properties in developing brain, down-regulation of IL-7 by hypoxia may contribute to hypoxia-induced injury to neural cells.

PKC and Rho in vascular smooth muscle: activation by BOXes and SAH CSF.

Cerebral vasospasm (CV) remains a significant cause of delayed neurological deficit and ischemic damage after subarachnoid hemorrhage (SAH), despite intensive research effort. The current lack of an effective therapeutic approach is somewhat due to our lack of understanding regarding the mechanism by which this pathological constriction develops. Recent evidence implicates bilirubin oxidation products (BOXes) in the etiology of CV after SAH: BOXes are found in cerebrospinal fluid from SAH patients with symptomatic or angiographically visible vasospasm (CSFV) but not in CSF from SAH patients with no vasospasm (CSFC). We have previously published research suggesting that the etiology of CV comprises two components: a physiological stimulation to constrict and a pathological failure to relax. Both these components are elicited by CSFV, but not CSFC, and BOXes synthesized in the laboratory potentiate physiological constriction in arterial smooth muscle in vitro, and elicit contraction in pial arteries in vivo. In this paper, we will present our results concerning the action of BOXes on arterial smooth muscle constriction, compared with CSFV. We will also present evidence implicating temporal changes in PKC isoforms and Rho expression in both BOXes- and CSFV-elicited smooth muscle responses.

Chemical and biochemical oxidations in spinal fluid after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a stroke with high rates of mortality and morbidity. SAH-induced cerebral vasospasm can lead to ischemic injury or death and is a common complication of SAH. Recently there has been an accumulation of emerging evidence that oxidation of heme-derived bilirubin into bilirubin oxidation products (BOXes) may be involved in cerebral vasospasm. BOXes are produced by the oxidation of bilirubin yielding a mixture of isomers: 4-methyl-5-oxo-3-vinyl-(1,5-dihydropyrrol-2-ylidene)acetamide (BOX A) and 3-methyl-5-oxo-4-vinyl- (1,5-dihydropyrrol-2-ylidene)acetamide (BOX B). BOXes have been a subject of interest in the neurosurgical and neurological fields for several years because of their purported correlation with and or role in subarachnoid hemorrhage induced cerebral vasospasm. We believe that it is critical to understand the chemical and biochemical environment in the hemorrhagic spinal fluid after SAH that leads to the oxidation of bilirubin. There is a growing body of information concerning their putative role in vasospasm; however, there is a dearth of information concerning the chemical and biochemical characteristics of BOXes.

Hypertension risk in idiopathic hyperCKemia.

Patients with idiopathic hyperCKemia are usually reassured and discharged. However, these subjects may have increased hypertension risk, based on data from our population study, which showed that the population tertile with the highest serum creatine kinase activities had the highest systolic and diastolic blood pressure levels. Therefore, we assessed whether subjects with idiopathic hyperCKemia have greater occurrence of hypertension than controls. We included 46 participants aged 18 to 67 years, diagnosed with idiopathic hyperCKemia at the departments of Neurology of the Universities of Amsterdam and Utrecht, The Netherlands. We found that 48% of the subjects with idiopathic hyperCKemia were hypertensive, as compared to 19% of the random population controls (n = 22,612, aged 20 to 65 years), an odds ratio of 3.9 (95 % CI, 2.2 to 6.9) before, and 2.0 (1.1 to 3.8) after adjustment for sex, age, and body mass index. In accord with our previous finding of an association between creatine kinase and blood pressure in the general population, the data reported here suggest that subjects with idiopathic hyperCKemia have greater hypertension risk than controls. This may be due to relatively high tissue creatine kinase activity, resulting in greater ATP buffer capacity to create and sustain high blood pressure levels.Larger, prospective studies are needed to further assess this association, but as active case finding is important in the diagnosis of hypertension, subjects with idiopathic hyperCKemia should be screened and monitored for the presence of hypertension.

Creatine kinase and renal sodium excretion in African and European men on a high sodium diet.

Creatine kinase (CK) rapidly regenerates ATP for Na+ /K+ -ATPase driven sodium retention throughout the kidney. Therefore, we assessed whether resting plasma CK is associated with sodium retention after a high sodium diet. Sixty healthy men (29 European and 31 African ancestry) with a mean age of 37.2 years (SE 1.2) were assigned to low sodium intake (< 50 mmol/d) during 7 days, followed by 3 days of high sodium intake (> 200 mmol/d). Sodium excretion (mmol/24-h) after high sodium was 260.4 (28.3) in the high CK tertile versus 415.2 (26.3) mmol/24-h in the low CK tertile (P < .001), with a decrease in urinary sodium excretion of 98.4 mmol/24-h for each increase in log CK, adjusted for age and African ancestry. These preliminary results are in line with the energy buffering function of the CK system, but more direct assessments of kidney CK will be needed to further establish whether this enzyme enhances sodium sensitivity.