Assessing the Diagnostic Power of Cystatin C and Creatinine in Detection of Chronic Kidney Disease

 Introduction: In patients with renal disorders, a sudden decrease in glomerular filtration rate (GFR) would not result in rapid rise concentrations of Creatinine. The present study aimed to assess diagnostic accuracy of serum Cystatin C as an appropriate alternative to serum Creatinine for early detection of Chronic Kidney Disease (CKD).Materials and Methods: In this study, 72 patients, 48 female and 24 male were selected. Serum Cystatin C and serum Creatinine were assayed, using enzyme-linked immunosorbent assay (ELISA) and routine methods, respectively. Glomerular filtration rate (eGFR) was estimated by Cockcroft and Gault formula. Receiver operating characteristics (ROC) analysis was adopted to evaluate diagnostic accuracy of serum Cystatin C and serum Creatinine.Results: Using Pearson's Correlation Coefficient analysis among Creatinine, Cystatin C and eGFR showed Serum Cystatin C was better than Creatinine. The sensitivity, specificity and AUC for Serum Cystatin C were 0.88, 0.70 and 0.85, and for Serum Creatinine, they  were 0.60, 0.80 and 0.68 respectively.Conclusion: Our results showed that in early stages of CKD, Cystatin C is a more accurate biomarker for kidney function than Creatinine  

Evaluation of Neutrophil Gelatinase-Associated Lipocalin and Cystatin C in Early Diagnosis of Chronic Kidney Disease in the Absence of the Gold Standard

Background: Glomerular filtration rate (GFR) is considered as a gold standard of kidney function. However, using GFR as the gold standard is not common in clinical practice, because its direct measurement is usually expensive, cumbersome, and invasive. In the present study, we assessed the predictive power of two other biomarkers, Cystatin-C (Cys-C) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) for early detection of chronic kidney diseases (CKD) in the absence of a gold standard. Materials and Methods: In this study, 72 patients who referred to the Shohadaye Tajrish Hospital of Tehran, Iran, for measuring their kidney function were studied. The ELISA method was utilized for measuring plasma NGAL (PNGAL) and serum Cys-C (SCys-C). The Bayesian latent class modeling approach was applied to asses the predictive power of these biomarkers. Results: While both the biomarkers had rather high sensitivities (PNGAL=91%, SCys-C=89%), the specificity of SCys-C biomarker was very lower than the one of PNGAL (SCys-C=56%, PNGAL=94%). The estimated area under the receiver operating characteristic (ROC) curve for SCys-C as the single biomarker for the diagnosis of CKD was about 0.76, while a similar estimate for PNGAL was 0.93. The added value of PNGAL to SCys-C for the diagnosis of CKD in terms of the ROC curve was about 0.19, while the added value of SCys-C to PNGAL was less than 0.02. Conclusion: In general, our findings suggest that PNGAL can be utilized as a single reliable biomarker for early detection of CKD. In addition, results showed that when a perfect gold standard is not available, Bayesian approaches to latent class models could lead to more precise sensitivity and specificity estimates of imperfect tests. Keywords:Chronic Kidney Diseases; Neutrophil Gelatinase-Associated Lipocalin; Cystatin C; Bayesian Approach; Latent Class Model; Sensitivity; Specificit

Assessing sex differential in COVID-19 mortality rate by age and polymerase chain reaction test results: an Iranian multi-center study

Background The aim of this study is to evaluate the sex differential effect in the COVID-19 mortality by different age groups and polymerase chain reaction (PCR) test results. Research design In a multicenter cross-sectional study from 55 hospitals in Tehran, Iran, patients were categorized as positive, negative, and suspected cases. Results A total of 25,481 cases (14,791 males) were included in the study with a mortality rate of 12.0%. The mortality rates in positive, negative, and suspected cases were 20.55%, 9.97%, and 7.31%, respectively. Using a Cox regression model, sex had a significant effect on the hazard of death due to COVID-19 in adult and senior male patients having positive and suspected PCR test results. However, sex was not found as significant factor for mortality in patients with a negative PCR test in different age groups. Conclusions Regardless of other risk factors, we found that the effect of sex on COVID-19 mortality varied significantly in different age groups. Therefore, appropriate strategies should be designed to protect adult and senior males from this deadly infectious disease. Furthermore, owing to the considerable death rate of COVID-19 patients with negative test results, new policies should be launched to increase the accuracy of diagnosis tests

Contrastive analysis of diagnostic tests evaluation without gold stand-ard: review article

Considering the advancement of medical sciences, diagnostic tests have been developed to distinguish patients from healthy population. Therefore, Determining and evaluation of the diagnostic accuracy tests is of great importance. The accuracy of a test under evaluation is determined through the amount of agreement between its results with the results of the gold standard, and this test accuracy can be defined based on sensitivity, specificity, positive predictive value, negative predictive value and the area under the receiver operative characteristic curve (AUC). Gold standard is an accurate and error- free method to determine the presence or absence of disease of interest and classify patients, which is not available in some diseases and situations as this method is costly or invasive. In these cases, reference standard is a best available replacement method to be used by physicians to diagnostic disease. However, in some situation, the acceptable reference standard is invasive or costly and does not exist or unreliable. It can be imperfect and results of the reference standard method are not necessarily error- free and cannot be applied to everyone in the study; all these cases point to the conditions in which the gold standard is not available. The use of reference standard including error causes to incorrect separation of patients from healthy population and thus, it cannot be a comparing measure for other diagnostic tests and its results are inaccurate. Therefore, other alternatives methods are needed for evaluation and determine the diagnostic accuracy tests when the gold standard does not exist. Imputation method, correct imperfect reference standard method, the construct reference standard method, latent class models, differential verification, composite reference standard and discrepant analysis are of these alternative methods. Each of these methods, considering its features, advantages, and limitations can be used to evaluate the accuracy of diagnostic test in the absence of gold standard. The present study gave an overview of methods to evaluation of diagnostic accuracy tests when there is no gold standard and the focus of this study was on explain the concept of these solutions, review and compare them and their strengths and weaknesses

Assessment of prognostic factors in long-term survival of male and female patients with colorectal cancer using non-mixture cure model based on the Weibull distribution

Objective: Colorectal cancer (CRC) is known as one of the malignant form of cells growing in the inner lining of colon and rectum which could seriously affect the cure rate of patients. We aimed to evaluate the effect of prognostic factors on cure fraction of CRC patients. Methods: A total of 1043 CRC patients were included to the study from December 2001 to January 2007 at the Research Center of Gastroenterology and Liver Disease in Shahid Beheshti University of Medical Sciences, Tehran, Iran. Patients� information was extracted from their medical records, then they were followed to identify their death status via phone-call. Weibull non-mixture cure model was used to evaluate the effect of the risk factors on cure fraction of CRC patients. Results: The five-years survival rate was 0.66 (males: 0.64 and female: 0.69). The median survival time for non-cured CRC patients were 3.45 years (males: 3.46; females = 3.45 years). In the single Weibull model, BMI�30 (OR = 4.61, p-value = 0.033), poorly differentiated tumor grade (OR = 0.36, p-value = 0.036), tumor size�25 mm (OR = 0.22, p-value = 0.046), and N1-stage (OR = 0.42, p-value = 0.005) had significant effect on females� cure fraction. Also, cure fraction of male CRC patients significantly affected by BMI (levels:25.0�29.9-OR = 12.13-p-value<0.001; �30-OR = 7.00-p-value = 0.017), T1-stage (OR = 0.52, p-value = 0.021), M1-stage (OR = 0.45, p-value = 0.007), IV-staging (OR = 0.36, p-value = 0.041) and IBD (OR = 0.26, p-value = 0.017). In multiple Weibull model, females were associated with tumor size�25 mm (OR = 0.20, p-value = 0.044) and N1-stage (OR = 0.45, p-value = 0.013) and males were affected by M1-stage (OR = 0.41, p-value = 0.011) and IBD (OR = 0.20, p-value = 0.022).The cure fraction of males and females CRC patients was 64 and 69, respectively. Conclusions: The prognostic factors for cure fraction of patients with CRC may be different among males and females. Further multicenter studies are required to assess the effect of common prognostic factors between males and females