Title: The Relationship Between Apelin And Cardiac Parameters In Patients On Peritoneal Dialysis: Is There A New Cardiac Marker?

Transcription

1 Author's response to reviews Title: The Relationship Between Apelin And Cardiac Parameters In Patients On Peritoneal Dialysis: Is There A New Cardiac Marker? Authors: Serhat Karadag (serhatkaradag@gmail.com) Savas Ozturk (savasozturkdr@yahoo.com) Meltem Gursu (drmeltemgursu@gmail.com) Ahmet Gurdal (gurdal27@hotmail.com) Filiz Basinoglu (filizbasinoglu@yahoo.com) Servet Yigit (servetyigit@gmail.com) Zeki Aydin (zekiaydindr@yahoo.com) Sami Uzun (drsamiuzun@gmail.com) Abdullah Sumnu (abdullahsumnu@yahoo.com) Huseyin Oflaz (hoflaz@hotmail.com) Rumeyza Kazancioglu (drkazancioglu@yahoo.com) Version: 3 Date: 15 August 2013 Author's response to reviews: see over

2 Dear Editor, We have received the comments of the reviewers about our paper. We thank you and both of the reviewers for their nice comments. Below are the point to point answers to the comments. The changes that have been made in the paper have been signed as colored. We hope that the paper in its revised form would be appropriate for publication. King regards. Meltem Gursu, MD. 1. REVIEWER'S REPORT MAJOR COMMENTS * Apelin is a peptide with different isoforms. So, please, identify in the abstract and in whole paper the isoform measured (in this case, apelin-36). "Apelin" was changed as "apelin-36" throughout the paper. * Conclusion (abstract and whole paper) - The authors wrote that apelin may be a treatment alternative for some disorders (cardiovascular, lipid, bone mineral) in the future. However, the study design is cross-sectional and, because of that, this conclusion is not adequate. Conclusions (abstract and whole paper) were changed accordingly. * Please, give the diagnostic criteria for diabetes, hypertension and hyperlipidemia. These clinical conditions are cited in results (1st paragraph page 9) but their diagnostic criteria are not explicit. Diagnostic criteria of the comorbidities were added to methods. * Methods ELISAs can be relatively imprecise, so, assay precision for apelin measurement should be reported. It is added to the methods. * The r values for correlations were weak (except for alkaline fosfatase) and, although the authors found a positive correlation between LDL-c and apelin, the apelin levels were not different between patients with or without hyperlipidemia. Moreover, in the

3 discussion, the authors wrote that some differences between the present study and previous studies can be justified due to small number of patients (2nd paragraph - Page 12). My question is: Was the sample size adequate for paper proposal? The diagnosis of hyperlipidemia was based on the criteria of National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III. Elevated LDL cholesterol level is only one of these criteria. Levels of triglyceride, total cholesterol and HDL cholesterol are also used for the diagnosis. The number of peritoneal dialysis patients all over the world is not so much; so there are not much studies carried on with huge numbers of patients. That is why it may be acceptable for a study about a new marker like apelin in this small group of population. Regarding the study as a whole sample size would be appreciated as acceptable for paper proposal. * In the statistical section, the authors wrote that Pearson test was used for numeric variables and Sperman s rho correlation for nonnumeric variables. The correct would be parametric and nonparametric variables, respectively. The changes needed have been done in the 'methods' section. * Data are presented as mean ± standard deviation (SD) and minimum and maximum. For parametric data, only the mean ± SD presentation are sufficient. For nonparametric data, is adequate to present median (interquartile range). MINOR COMMENTS * The table 2 is duplicated. * Please, give a more complete title (Tables 2 and 3) and insert the legends for variables that were abbreviated in the tables 2, 3 and 4 (e.g., AST, ALT). * Findings that were not cited in objectives, methods and results were cited in the discussion section (Page 13 Apelin and hscrp). The changes needed have been done about hscrp in 'methods' and 'results' sections.

4 DISCRETIONARY REVISIONS * The statistical package used could be removed from abstract. This information is not too important to be in the abstract. The statistical package used has been removed from abstract 2. REVIEWER'S REPORT * This work deals with the (plasma? serum?) apelin level among CKD patients treated with peritoneal dialysis (PD). Apelin levels were studied in plasma. This knowledge has been to the 'methods' section. * Major Compulsory Revisions: * 1. The pathophysiological role of apelin is not clear, as the authors mentioned in this article. The authors should mention clearly their working hypothesis regarding the relationship between apelin and CKD patients treated with PD. As stated in "introduction" section cardiovascular mortality rate of dialysis patients is markedly elevated compared with the general population. Apelinergic system is also implicated in cardiovascular functions, volume regulation, vascular tonus, inhibition of antidiuretic hormone release, heart failure, vascular calcification etc. all of which have been related to cardiovascular mortality. Although there are some studies in hemodialysis patients, there are limited studies in peritoneal dialysis patients on role of this new apelinergic system. For this reason herein we aim to study relationship of blood apelin levels with some important cardiovascular parameter as well as some important laboratory markers which have been implicated in morbidity and mortality in peritoneal dialysis patients. * 2. I am afraid that the strong relationship between apelin and ALP might be due to only one outlier on right-upper portion of the square of Figure 1d. As well known, the correlation between extreme values has great importance in correlation analyses as well as high number of patients. Besides, formulas of correlation coefficient involve also "distance" of variables to "the mean". On the other hand, in our study,

5 when the pointed case has been excluded from the analysis, correlation was still significant although it has lost its power (r=0.196; p=0.016).