Clin Chem Lab Med 2010;48(3):405–408  2010 by Walter de Gruyter • Berlin • New York. DOI 10.1515/CCLM.2010.068 2010/361 Article in press - uncorrected proof Gender does not influence cystatin C concentrations in healthy volunteers Letı ´cia Schwerz Weinert*, Aline Bodanese Prates, Fernando Barcellos do Amaral, Marina Zerwes Vaccaro, Joı ´za Lins Camargo and Sandra Pinho Silveiro Endocrine Unit, Hospital de Clı ´nicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil Abstract Background: Current data are conflicting about the influ- ence of gender on cystatin C concentrations. The goal of this study was to determine the reference interval for serum cys- tatin C in normal Brazilian subjects, taking into account the influence of gender. Methods: Ninety-seven healthy volunteers, aged 18–70 years, 44% male, had glomerular filtration rate (GFR) meas- ured using a 51 Cr-EDTA method and estimated with the Modification of Diet in Renal Disease (MDRD) study equa- tion. Serum cystatin C was measured using a turbidimetric method, and creatinine by the Jaffe method. Results: Mean serum cystatin C was not significantly dif- ferent between males and females, 0.62"0.12 vs. 0.65"0.12 mg/L, respectively (ps0.26). However, median serum cre- atinine was significantly higher in men w 97 (80–115) vs. 80 (53–88) mmol/L; ps0.0001x . There were also no signif- icant differences between genders with respect to GFR meas- ured using 51 Cr-EDTA (103"14 for males and 106"19 mL/min/1.73 m 2 for females, ps0.47), and estimated with the MDRD equation (86"12 vs. 83"16 mL/min/1.73 m 2 , respectively, ps0.24). Conclusions: There was no effect of gender on serum cys- tatin C, as well as on measured and estimated GFR. Clin Chem Lab Med 2010;48:405–8. Keywords: creatinine; cystatin C; glomerular filtration rate; Modification of Diet in Renal Disease; 51 Cr-EDTA. Introduction Chronic kidney disease is a worldwide health problem. Esti- mation of the glomerular filtration rate (GFR) is essential for the detection and evaluation of this disease. The most reliable *Corresponding author: Letı ´cia Schwerz Weinert, Servico de ¸ Endocrinologia do Hospital de Clı ´nicas de Porto Alegre, Rua Ramiro Barcelos, 2350 – Pre ´dio 12, 48 andar, 90035-903, Porto Alegre, RS, Brazil Phone: q55 51 33598127, E-mail: leticiasweinert@yahoo.com.br Received July 13, 2009; accepted November 3, 2009; previously published online December 18, 2009 GFR measurements are based on the clearance of exogenous substances, such as insulin, iohexol, iothalamate and 51 Cr- EDTA (1, 2). However, these techniques are expensive and time-consuming. Therefore, serum creatinine has become the most commonly used marker to estimate glomerular func- tion. However, it is known that creatinine can be affected by other serum chromogens and changes in muscle mass, such as those brought by age, race and gender. In addition, it is not sensitive enough to detect small changes in renal function (1, 2). Serum cystatin C is a cysteine proteinase inhibitor pro- duced at a constant rate by all nucleated cells. It is freely filtered across the glomerular membrane and is metabolized in the proximal tubule. It has been extensively studied as a new marker of GFR (3). Recent studies suggest that it is more accurate than serum creatinine (1, 2). Age, body mass index (BMI), smoking, hypertension, higher levels of C-reac- tive protein and triglycerides have been described to be inde- pendently and positively associated with higher serum cystatin C concentrations (3, 4). Current data are conflicting about the influence of gender on cystatin C. Thus, the goal of this study was to determine the reference interval for serum cystatin C in healthy subjects, taking into account the possible influence of gender, and using a gold standard meth- od for measurement of GFR to determine kidney status. Materials and methods This is a cross-sectional study. Ninety-seven healthy volunteers were selected among students and professors from a medical college, as well as from the community of Porto Alegre, South Brazil. The protocol was approved by the Hospital Ethics Committee, and all volunteers signed written informed consent. They filled out a ques- tionnaire to provide information about their past and present medical condition. The participants were healthy volunteers aged 18–70 years, 44% were men, and 91% were Caucasian. All presented with normal fasting plasma glucose, arterial blood pressure was -140/90 mm Hg, BMI was below 40 kg/m 2 , and none were taking medica- tions that might affect renal function. Exclusion criteria were thy- roid-stimulating hormone (TSH) )10 mIU/L, pregnancy, blood donation or surgery in the last 3 months, and history of cancer in the last 5 years. Serum cystatin C concentrations were measured using a particle enhanced turbidimetric immunoassay (Dako- Cytomation Denmark A/S, Glostrup, Denmark) on the Cobas Mira  analyzer (Roche Diagnostics, Basel, Switzerland). Intra and interas- say coefficients of variation were 2.2% and 5.3%, respectively; pre- dicted linearity was up to 7.5 mg/L, and the limit of detection was 0.4 mg/L. Plasma was collected following an overnight fast, and samples were frozen at –708C until analyses. Measurements were performed in duplicate for quality control. GFR was estimated from a single 51 Cr-EDTA intravenous injection, with three collections of