Influence of Muscle Mass and Physical Activity on Serum and Urinary Creatinine and Serum Cystatin C

Background and objectives: For addressing the influence of muscle mass on serum and urinary creatinine and serum cystatin C, body composition was assessed by skinfold thickness measurement and bioelectrical impedance analyses.Design, setting, participants, & measurements: A total of 170 healthy individuals (92 women, 78 men) were classified as sedentary or with mild or moderate/intense physical activity. Blood, 24-h urine samples, and 24-h food recall were obtained from all individuals.Results: Serum and urinary creatinine correlated significantly with body weight, but the level of correlation with lean mass was even greater. There was no significant correlation between body weight and lean mass with cystatin C. Individuals with moderate/intense physical activity presented significantly lower mean body mass index (23.1 ± 2.5 versus 25.7 ± 3.9 kg/m²) and higher lean mass (55.3 ± 10.0 versus 48.5 ± 10.4%), serum creatinine (1.04 ± 0.12 versus 0.95 ± 0.17 mg/dl), urinary creatinine (1437 ± 471 versus 1231 ± 430 mg/24 h), protein intake (1.4 ± 0.6 versus 1.1 ± 0.6 g/kg per d), and meat intake (0.7 ± 0.3 versus 0.5 ± 0.4 g/kg per d) than the sedentary individuals. Conversely, mean serum cystatin did not differ between these two groups. A multivariate analysis of covariance showed that lean mass was significantly related to serum and urinary creatinine but not with cystatin, even after adjustment for protein/meat intake and physical activity.Conclusions: Cystatin C may represent a more adequate alternative to assess renal function in individuals with higher muscle mass when mild kidney impairment is suspected.Accurate renal function measurements are important in the diagnosis and treatment of kidney diseases, adjustment of drug dosages, and decision-making regarding when to initiate renal replacement therapy. Serum creatinine is the most commonly used indicator of renal function, but its measurement suffers from a variety of analytical interferences and significant standardization problems (1,2).Serum creatinine can be affected by age, gender, ethnicity, dietary protein intake, and lean mass and may remain within the reference range despite marked renal impairment in patients with low muscle mass. Consequently, the sensitivity of serum creatinine for the early detection of kidney disease is poor and not a good predictor when analyzing the elderly (3,4). Conversely, theoretically, serum creatinine may be falsely increased in individuals with higher muscle mass and normal renal function.The GFR represents the best overall assessment of kidney function, but the gold standard techniques for the measurement of GFR, such as inulin clearance, [¹²⁵I]iothalamate, ⁵¹Cr-EDTA, ^99mTc-diethylenetriaminepentaacetic acid, and iohexol are too labor-intensive and costly for routine clinical use (5,6), so creatinine clearance is used instead.To rid the need of 24-h urine collections, several serum creatinine–based prediction formulas have been proposed to predict GFR (7–16). The equations of Cockcroft and Gault (7,8) and the one derived from the Modification of Diet in Renal Disease (MDRD) study (10) are the most widely accepted; however, the competence of such formulas to predict GFR in patients with normal values of serum creatinine is debated.Despite the important influence of muscle mass on serum creatinine, the different equations used to predict GFR do not include parameters of body composition such as lean mass. Human body mass can be partitioned into two main compartments: Fat and lean (fat-free) mass. The latter comprises body cell mass (BCM), bone mass, and extracellular water. The gold standard techniques for the measurement of body composition include hydrodensitometry, computed tomography, magnetic resonance imaging, dual-photon absorptiometry, neutron activation analysis, total body potassium counting, and isotope dilution (17,18). Nevertheless, in clinical practice, the indirect, low-cost, noninvasive methods of determining human body composition, such as bioelectrical impedance and skinfold thickness, are used instead (17). Muscle mass is extremely variable among elderly individuals and in children (4,19–22) and can be substantially modified by physical exercise (23).Cystatin C, a low molecular weight basic protein (13 kD) that is freely filtered and metabolized after tubular reabsorption with only small amounts excreted in the urine, is an endogenous filtration marker that is being considered as a potential replacement for serum creatinine. Unlike serum creatinine, the serum concentration of cystatin remains constant up to 50 yr of age. It is commonly accepted that cystatin is produced at a constant rate in virtually all nucleated cells and that it is unaltered by inflammatory conditions. The advantages of using cystatin C as a filtration marker are less influence by age, gender, weight, and muscle mass than serum creatinine (24–31). An overall meta-analysis based on 46 studies performed on adults and children demonstrated, by means of receiver operating characteristic analysis, that cystatin C is superior to serum creatinine as a marker of kidney function (32). To address the influence of muscle mass on serum and urinary creatinine determination and serum cystatin C, we evaluated the body composition through bioelectrical impedance and skinfold thickness in healthy individuals with distinct levels of physical activity.     

Renal stone disease: Causes, evaluation and medical treatment

The purpose of the present review is to provide an update about the most common risk factors or medical conditions associated with renal stone formation, the current methods available for metabolic investigation, dietary recommendations and medical treatment. Laboratory investigation of hypercalciuria, hyperuricosuria, hyperoxaluria, cystinuria, hypocitraturia, renal tubular acidosis, urinary tract infection and reduction of urinary volume is based on the results of 24-hr urine collection and a spot urine for urinary sediment, culture and pH. Blood analysis for creatinine, calcium and uric acid must be obtained. Bone mineral density has to be determined mainly among hypercalciurics and primary hyperparathyroidism has to be ruled out. Current knowledge does not support calcium restriction recommendation because it can lead to secondary hyperoxaluria and bone demineralization. Reduction of animal protein and salt intake, higher fluid intake and potassium consumption should be implemented. Medical treatments involve the use of thiazides, allopurinol, potassium citrate or other drugs according to the metabolic disturbances. The correction of those metabolic abnormalities is the basic tool for prevention or reduction of recurrent stone formation.     

Ectophosphatase activity in Candida albicans influences fungal adhesion: study between HIV‐positive and HIV‐negative isolates

Oral Diseases (2010) 16 , 431–438 Objective: This study describes the expression of acidic ectophosphatase activity on twenty isolates of C. albicans from oral cavities of HIV‐infected children (HIV+) and compares them with fifteen isolates from HIV‐negative children (HIV?), as well as the fungal adhesion to epithelial cells and medical records. Methods: The activities were measured in intact cells grown in BHI medium for 48 h at 37°C. Phosphatase activity was assayed at pH 5.5 using 4‐methylumbelliferyl phosphate. Yeast adhesion was measured using the MA 104 epithelial cell line. Results: Mean values of ectophosphatase activity were 610.27 ± 166.36 and 241.25 ± 78.96 picomoles 4‐methylumbelliferone/h/10⁷ cells for HIV+ and HIV? group, respectively (P = 0.049). No correlation between C. albicans enzyme activity from HIV children with viral load and CD4 percentual was observed. Yeasts with high enzyme activity, isolated from HIV+ children showed greater adherence than yeasts with basal levels of ectophosphatases from HIV? (Spearman correlation, r = 0.8). Surface phosphatase activity was apparently involved in the adhesion to host cells, as the enhanced attachment of C. albicans to host epithelial cells was reversed by pretreatment of yeast with sodium orthovanadate (1 mM), an acid phosphatase inhibitor. Conclusion: These results show that C. albicans from HIV+ has an ectophosphatase activity significantly higher than the other isolates. Yeasts expressing higher levels of surface phosphatase activity showed greater adhesion to epithelial cells. So, the activity of acidic surface phosphatases on these cells may contribute to the early mechanisms required for disease establishment.     

Alleviation of Pulmonary Hypertension by Cardiac Resynchronization Therapy is Associated with Improvement in Central Sleep Apnea

Background: Recent studies have demonstrated that cardiac resynchronization therapy (CRT) reduces sleep apnea in heart failure (HF); however, the mechanism of benefit remains unclear. Methods: Overnight polysomnography (PSG) was performed in consecutive HF patients who were scheduled for CRT implant. Patients with sleep apnea defined by an apnea‐hypopnea index (AHI) of >10/hour were recruited and underwent echocardiogram examination at baseline and 3 months after CRT. Results: Among 37 HF patients screened, 20 patients (54%) had sleep apnea and 15 of them consented for the study. After 3 months of CRT, there was a significant improvement in New York Heart Association functional class (3.1 ± 0.1 vs 2.1 ± 0.1, P < 0.01), quality‐of‐life (QoL) score (62.9 ± 3.3 vs 56.1 ± 4.5, P = 0.02), left ventricular ejection fraction (LVEF, 28.8 ± 2.5% vs 38.1 ± 2.3%, P < 0.01), and reduction in pulmonary artery systolic pressure (PASP, 41.0 ± 2.7 vs 28.6 ± 2.2 mmHg; P < 0.01) compared with baseline. Repeated PSG after CRT demonstrated a reduction in the duration of arterial oxygen desaturation ≤95% (251.2 ± 36.7 vs 141.0 ± 37.1 minutes), AHI (27.5 ± 4.7 vs 18.1 ± 3.0, P = 0.05), and number of central sleep apnea (CSA) (7.8 ± 2.6 vs 3.0 ± 1.3/hour, P = 0.03), but not number of obstructive sleep apnea (OSA, 8.6 ± 3.3 vs 7.2 ± 2.3/hour, P = 0.65) compared to baseline. Percentage change in PASP was significantly correlated with percentage changes in LVEF (r=?0.57, P = 0.04), AHI (r = 0.5, P = 0.05), and number of CSA episodes (r = 0.55, P = 0.02). Conclusions: The results demonstrated that CRT significantly reduces CSA in patients with HF. Importantly, we have noted a decrement of PASP correlated to drop in CSA which maybe one of the mechanisms explaining this observation. Future studies are required to confirm our finding and elucidate other possible mechanisms in this regard.     

Total Pectoral Implantation: A New Technique for Implantation of Transvenous Defibrillator Lead Systems and Implantable Cardioverter Defibrillator

We describe a new approach to tolal pectoral implantation of cardioverter defibrillators with an endocardial defibrillation lead system. Endocardial lead configuration used was an FDA approved right atrial-superior vena cavo defibriliation spring electrode, right ventricular bipolar sensing electrode, and a pectoral patch. Endocardial leads were implanted via a cephalic or an axillary venesection. Pectoral patch was placed in a sabmuscular position. In case of failure to obtain satisfactory thresholds, a small intercostal thoracofomy was performed via fhe same skin incision and patch placed over the epicardium instead of submuscular position and used with Ihe right atrial spring electrode. The device was implanted in the pectoral region, submuscularly, over the patch. Sixteen consecutive patients underwent this approach. With a submascular patch, adequate defibrillation thresholds (< 15 joules [J]) were obtained in 14 (87.5%) patients. In the other two, defibrillation thresholds of ≤ 15) were obtained with a epicardial patch. Pectoral implantation of the device was feasible in all 16 patients and none needed repositioning. Average postimplant hospital stay was 5 days. During follow-up period (average 5 months), none of the patients reported any major local symptoms and no problems have been encountered in device interrogation. Thus, total pectoral implantation of the cardioverter defibrillator including the patch, leads, and the device is feasible. Furthermore, in case of foilure to obtain adequate defibrillotjon thresholds with submuscular patch, an epicardial patch can easily be implanted and allows 100% successful defibrillation at energy levels of ≤ 15 J with right atrial patch configuration.