Development of fluorescence-linked immunosorbent assay for rapid detection of Staphylococcus aureus.

Staphylococcus aureus is a major pathogen that causes infections and life-threatening diseases. Although antibiotics, such as methicillin, have been used, methicillin-resistant S. aureus (MRSA) causes high morbidity and mortality rates, and conventional detection methods are difficult to be used because of time-consuming process. To control the spread of S. aureus, a development of a rapid and simple detection method is required. In this study, we generated a fluorescent anti-S. aureus antibody, and established a novel fluorescence-linked immunosorbent assay (FLISA)-based S. aureus detection method. The method showed high sensitivity and low limit of detection toward MRSA detection. The assay time for FLISA was 5 h, which was faster than that of conventional enzyme-linked immunosorbent assay (ELISA) or rapid ELISA. Moreover, the FLISA-based detection method was applied to diagnose clinically isolated MRSA samples that required only 5.3 h of preincubation. The FLISA method developed in this study can be widely applied as a useful tool for convenient S. aureus detection. KEY POINTS: • A fluorescence-linked immunosorbent assay-based S. aureus detection method • Simultaneous quantification of a maximum of 96 samples within 5 h • Application of the novel system to diagnosis clinical isolates.

A strategy to promote the convenient storage and direct use of polyhydroxybutyrate-degrading Bacillus sp. JY14 by lyophilization with protective reagents.

BACKGROUND: Bioplastics are attracting considerable attention, owing to the increase in non-degradable waste. Using microorganisms to degrade bioplastics is a promising strategy for reducing non-degradable plastic waste. However, maintaining bacterial viability and activity during culture and storage remains challenging. With the use of conventional methods, cell viability and activity was lost; therefore, these conditions need to be optimized for the practical application of microorganisms in bioplastic degradation. Therefore, we aimed to optimize the feasibility of the lyophilization method for convenient storage and direct use. In addition, we incoporated protective reagents to increase the viability and activity of lyophilized microorganisms. By selecting and applying the best protective reagents for the lyophilization process and the effects of additives on the growth and PHB-degrading activity of strains were analyzed after lyophilization. For developing the lyophilization method for protecting degradation activity, it may promote practical applications of bioplastic-degrading bacteria. RESULTS: In this study, the polyhydroxybutyrate (PHB)-degrading strain, Bacillus sp. JY14 was lyophilized with the use of various sugars as protective reagents. Among the carbon sources tested, raffinose was associated with the highest cell survival rate (12.1%). Moreover, 7% of raffionose showed the highest PHB degradation yield (92.1%). Therefore, raffinose was selected as the most effective protective reagent. Also, bacterial activity was successfully maintained, with raffinose, under different storage temperatures and period. CONCLUSIONS: This study highlights lyophilization as an efficient microorganism storage method to enhance the applicability of bioplastic-degrading bacterial strains. The approach developed herein can be further studied and used to promote the application of microorganisms in bioplastic degradation.

Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Bypassing Heaven's Gate Technique Using Black-Box Testing.

In recent years, the number and sophistication of malware attacks on computer systems have increased significantly. One technique employed by malware authors to evade detection and analysis, known as Heaven's Gate, enables 64-bit code to run within a 32-bit process. Heaven's Gate exploits a feature in the operating system that allows the transition from a 32-bit mode to a 64-bit mode during execution, enabling the malware to evade detection by security software designed to monitor only 32-bit processes. Heaven's Gate poses significant challenges for existing security tools, including dynamic binary instrumentation (DBI) tools, widely used for program analysis, unpacking, and de-virtualization. In this paper, we provide a comprehensive analysis of the Heaven's Gate technique. We also propose a novel approach to bypass the Heaven's Gate technique using black-box testing. Our experimental results show that the proposed approach effectively bypasses and prevents the Heaven's Gate technique and strengthens the capabilities of DBI tools in combating advanced malware threats.

Effective methods for monitoring internal contamination among workers handling radioactive materials in various fields.

This study aimed to develop effective methods for monitoring internal contamination among workers handling radioactive materials in various fields. A total of 160 workers from nuclear power plants, medical institutions, military units, and educational/research institutions were included in the study. The monitoring methods included urinalysis and whole-body counting (WBC) using a mobile radio bioassay laboratory (MRL). Gamma-emitting radionuclides were monitored using the MRL WBC system, and a separate pretreatment procedure was used for tritium measurement in urine samples. Gross beta-screening was performed using a liquid scintillation counting system. The results were evaluated on the basis of the established screening criteria and compared with the dose limits. Additionally, tritium concentrations in the bodies of workers in the vicinity of a heavy-water reactor was analysed to assess the association between tritium concentration and occupation. The results showed a wide distribution of tritium concentrations. Workers involved in fuel and maintenance tasks demonstrated the maximum exposure. Workers in medical facilities showed low levels of internal contamination, which was primarily related to tasks involving radioactive isotopes. Military personnel involved in equipment repair showed significant tritium contamination due to damage during repairs. Workers in educational and research institutions in general had low levels of internal contamination.

Performance Evaluation of Bruker Biotyper, ASTA MicroIDSys, and VITEK-MS and Three Extraction Methods for Filamentous Fungal Identification in Clinical Laboratories.

Filamentous fungi are a major cause of life-threatening infections in immunocompromised patients; thus, rapid and accurate identification is critical. Filamentous fungal identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been demonstrated with high sensitivity and reproducibility; however, its wider application has been limited in clinical laboratories because of practical challenges such as database availability or lack of standardization. In this study, we compared the performance of the Bruker Biotyper, ASTA MicroIDSys, and Vitek MS for 84 clinical filamentous fungal isolates. Moreover, the sensitivity of three independent sample preparation methods (direct, on plate, in tube) was compared. Bruker Biotyper identified 71.43% (60/84) of isolates correctly (species, genus, or complex/group level). ASTA MicroIDSys and Vitek MS showed accuracy rates of 70.24% (59/84) and 55.95% (47/84), respectively. We found that any difference in sensitivity may be attributed to the database of the systems. In addition, the "in tube" method showed the highest sensitivity among the three methods; however, there was no statistical difference among them. For the broader application of MALDI-TOF MS for filamentous fungal identification, further studies from multiple perspectives are required.

Comparison of Erythrocyte and Reticulocyte Indices for Evaluation of Iron Deficiency by Two Automated Hematologic Analyzers.

The reticulocyte hemoglobin content and hypochromic erythrocyte percentage offer advantages in evaluation of iron deficiency, especially in inflammatory conditions. The aim of this study was to evaluate the correlation of reticulocyte hemoglobin content (CHr, Ret-He) and hypochromic erythrocyte percentage (%HYPO, Hypo-He) between two automated hematologic analyzers. The CHr and %HYPO values were determined using the Advia 2021i (Siemens), while the Ret-He and Hypo-He levels were assessed using the XN-3000 (Sysmex). Data from a total of 971 cases and 834 patients were collected. For reticulocyte hemoglobin content, there was a good linear correlation between CHr and Ret-He (r = 0.857, p < 0.001). For percentage of hypochromic erythrocytes, there was a better correlation between the two measures when using a second-degree polynomial equation (Hypo-He* = 0.4818 - 0.0218 x %HYPO + 0.0069 x %HYPO2) (r = 0.786, p < 0.001).

Nationwide Survey for Current Status of Laboratory Diagnosis of Clostridioides difficile Infection in Korea.

BACKGROUND: The interest in Clostridioides difficile infection (CDI) has increased, and the choice of assays became wider since the first national survey in Korea on CDI diagnosis in 2015. We conducted a survey of the domestic CDI assays with more varied questions to understand the current situation in Korea. METHODS: In April 2018, about 50 questions on the current status of CDI assays and details on implementation and perceptions were written, and a survey questionnaire was administered to laboratory medicine specialists in 200 institutions. RESULTS: One-hundred and fifty institutions responded to the questionnaire, of which 90 (60.0%) including one commercial laboratory, performed CDI assays. The toxin AB enzyme immunoassay (toxin AB EIA), nucleic acid amplification test (NAAT), and C. difficile culture, glutamate dehydrogenase assay, alone or in combination with other assays, were used in 75 (84.3%), 52 (58.4%), 35 (36.0%), and 23 (25.8%), respectively, and 65 (73.0%) institutions performed a combination of two or more assays. The sensitivity of toxin AB EIA was more negatively perceived, and that on specificity was more positively perceived. The perception of sensitivity and specificity of NAAT was mostly positive. Perception on the algorithm test projected it as useful but in need of countermeasures. Sixty-three (73.3%) institutions responded that they performed surveillance on CDI. CONCLUSION: This study provides useful evidence on the current status of CDI laboratory diagnosis in Korea as well as on items that require improvement and is thought to aid in standardizing and improving the CDI laboratory diagnosis in Korea.

Chest CT abnormalities in COVID-19: a systematic review.

Computed tomography (CT) of the chest is one of the main diagnositic tools for coronavirus disease 2019 (COVID-19) infection. To document the chest CT findings in patients with confirmed COVID-19 and their association with the clinical severity, we searched related literatures through PubMed, MEDLINE, Embase, Web of Science (inception to May 4, 2020) and reviewed reference lists of previous systematic reviews. A total of 31 case reports (3768 patients) on CT findings of COVID-19 were included. The most common comorbid conditions were hypertension (18.4%) and diabetes mellitus (8.3%). The most common symptom was fever (78.7%), followed by cough (60.2%). It took an average of 5.6 days from symptom onset to admission. The most common chest CT finding was vascular enlargement (84.8%), followed by ground-glass opacity (GGO) (60.1%), air-bronchogram (47.8%), and consolidation (41.4%). Most lung lesions were located in the lung periphery (72.2%) and involved bilateral lung (76%). Most patients showed normal range of laboratory findings such as white blood cell count (96.4%) and lymphocyte (87.2%). Compared to previous published meta-analyses, our study is the first to summarize the different radiologic characteristics of chest CT in a total of 3768 COVID-19 patients by compiling case series studies. A comprehensive diagnostic approach should be adopted for patients with known COVID-19, suspected cases, and for exposed individuals.

Survival Benefit of Anticoagulation Therapy in End Stage Kidney Disease Patients with Atrial Fibrillation: A Single Center Retrospective Study.

Background and Objectives: Although the need for anticoagulation to prevent thromboembolism is increasing and non-vitamin K antagonist oral anticoagulants (NOACs) have been tried, there is still controversy about the efficacy of anticoagulation in patients with dialysis. Materials and Methods: We retrospectively analyzed the risk and benefit of anticoagulation in dialysis patients with atrial fibrillation (AF). We retrospectively analyzed all data of 89 patients who received dialysis therapy and were diagnosed with AF. Among them, 27 received anticoagulation (11 warfarin and 16 apixaban 2.5 mg twice a day), while 62 received no anticoagulation. Results: In multivariate Cox regression analysis, compared to no anticoagulation treatment, anticoagulation treatment was associated with a low incidence of all-cause mortality (hazard ratios (HR) 0.36; 95% confidence interval (CI) 0.15-0.88). Compared to no anticoagulation treatment, more anticoagulation treatment patients experienced severe bleeding (HR 4.67; 95% CI 1.26-17.25) and any bleeding (HR 2.79; 95% CI 1.01-7.74). Compared to no anticoagulation, warfarin treatment patients were associated with a low incidence of all-cause mortality (HR 0.26; 95% CI 0.09-0.81) and a high incidence of severe bleeding (HR 4.85; 95% CI 1.12-21.10). All-cause mortality and bleeding were not significantly different between no anticoagulation and apixaban treatment patients. Conclusions: In dialysis patients with AF, anticoagulation therapy is associated with an increased incidence of severe bleeding, but anticoagulation therapy is associated with a low incidence of all-cause mortality. Individualized anticoagulation therapy with careful bleeding monitoring is needed in dialysis patients with AF.

Characterization of Chlamydia trachomatis ompA Genotypes Among Sexually Transmitted Disease Patients in Korea.

BACKGROUND: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted diseases (STDs) world-wide. The aim of this study was to characterize the C. trachomatis genetic profiles of clinical isolates in the Korean population by sequence analysis of the ompA gene. METHODS: Endocervical specimens from patients who were confirmed as C. trachomatis infection by real-time PCR were used for ompA sequencing. The individual sequences (about 890 nucleotides) were determined by comparison with those from known C. trachomatis strains using the BLAST search tool. Sequence variations were analyzed by comparing them with sequences from prototype strains. RESULTS: Sequence analysis using BLAST similarity search of the ompA gene from the 106 clinical isolates revealed that the most prevalent genotype corresponded to E (n = 28, 26.2%), followed by F (n = 20, 18.9%), D (n = 16, 15.1%), J (n = 16, 15.1%), G (n = 9, 8.5%), H (n = 8, 7.5%), K (n = 5, 4.7%), B (n = 2, 1.9%), and I (n = 2, 1.9%). Detailed sequence analysis based on comparison with each prototype revealed that there are sequence differences in 44 specimens (41.5%). CONCLUSIONS: This study is the update on the distribution of C. trachomatis ompA genotypes in Korea in more than a decade. The genotypes have become more diversified, with genotypes K, B, and I being newly detected. C. trachomatis genotyping is crucial for regional and global epidemiological studies, as well as for vaccine development.

Magnetic resonance elastography for evaluation of renal parenchyma in chronic kidney disease: a pilot study.

OBJECTIVE: This study aimed to prospectively evaluate the difference in renal parenchymal stiffness, measured using MR elastography, between patients with chronic kidney disease (CKD) and healthy volunteers. In addition, differences in stiffness values were assessed among the five stages of CKD. MATERIALS AND METHODS: Five healthy volunteers and 25 patients with CKD (five patients in each stage) were enrolled in the study. Each patient was positioned prone in a 3-T MR scanner and imaged with an abdominal 64-channel surface coil. Calculated tissue stiffness values were compared with the corresponding stage of CKD. RESULTS: The mean stiffnesses in normal healthy volunteers and patients with CKD (regardless of stage) were 4.35 kPa and 5.10 kPa, respectively (p = 0.027). The mean stiffness in patients with CKD significantly increased with the CKD stage (p = 0.013), although it decreased in stage 5 CKD. CONCLUSION: Renal tissue stiffness measured using MR elastography can be used to distinguish between patients with CKD and healthy individuals; moreover, it can be useful in predicting the stage of CKD.

Sarcopenia in Autoimmune and Rheumatic Diseases: A Comprehensive Review.

Sarcopenia refers to a decrease in skeletal muscle mass and function. Because sarcopenia affects mortality, and causes significant disability, the clinical importance of sarcopenia is emerging. At first, sarcopenia was recognized as an age-related disease but, recently, it has been reported to be prevalent also in younger patients with autoimmune diseases. Specifically, the association of sarcopenia and autoimmune diseases such as rheumatoid arthritis has been studied in detail. Although the pathogenesis of sarcopenia in autoimmune diseases has not been elucidated, chronic inflammation is believed to contribute to sarcopenia, and moreover the pathogenesis seems to be different depending on the respective underlying disease. The definition of sarcopenia differs among studies, which limits direct comparisons. Therefore, in this review, we cover various definitions of sarcopenia used in previous studies and highlight the prevalence of sarcopenia in diverse autoimmune diseases including rheumatoid arthritis, spondyloarthritis, systemic sclerosis, inflammatory bowel disease, and autoimmune diabetes. In addition, we cover the pathogenesis and treatment of sarcopenia in autoimmune and rheumatic diseases. This review provides a comprehensive understanding of sarcopenia in various autoimmune diseases and highlights the need for a consistent definition of sarcopenia.

A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era.

Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.

A comparative evaluation of BACT/ALERT FA PLUS and FN PLUS blood culture bottles and BD BACTEC Plus Aerobic and Anaerobic blood culture bottles for antimicrobial neutralization.

The performance of BACT/ALERT FA and FN PLUS (FA PLUS and FN PLUS) blood culture bottles with the BACT/ALERT VIRTUO (bioMérieux, Inc., Durham, NC) and BD BACTEC Plus Aerobic and Anaerobic (BD Aerobic and BD Anaerobic) blood culture bottles with the BD BACTEC FX (BD Diagnostics, Sparks, MD) for antimicrobial neutralization at peak serum concentration was evaluated. The following antibiotic agents and microbial strains were used: ampicillin, cefepime, cefotaxime, gentamicin, levofloxacin, meropenem, piperacillin-tazobactam, and vancomycin; methicillin-sensitive Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Bacteroides fragilis. The detection rate of FA PLUS bottles was 69.1% (259/375) and that of BD Aerobic bottles was 75.5% (283/375) (p = 0.050). In the case of anaerobic culture, the overall detection rate of FN PLUS bottles was 77.0% (231/300) and that of BD Anaerobic bottles was 71.3% (214/300) (p = 0.113). The time to detection (TTD) from aerobic culture was 2.8 h shorter in FA PLUS bottles (12.4 h) compared to BD Aerobic bottles (15.2 h) (p < 0.001). And the TTD from anaerobic culture was 1.6 h shorter in FN PLUS bottles (18.1 h) compared to BD Anaerobic bottles (19.7 h) (p = 0.061). The FA PLUS bottles exhibited a lower detection rate compared to BD Aerobic bottles, while FN PLUS bottles showed a higher detection rate compared to BD Anaerobic bottles. The BACT/ALERT VIRTUO system exhibited shorter TTD compared to the BD BACTEC FX system for both aerobic and anaerobic cultures.

Application of next-generation sequencing to detect variants of drug-resistant Mycobacterium tuberculosis: genotype-phenotype correlation.

BACKGROUND: Drug resistance in Mycobacterium tuberculosis (MTB) is a major health issue worldwide. Recently, next-generation sequencing (NGS) technology has begun to be used to detect resistance genes of MTB. We aimed to assess the clinical usefulness of Ion S5 NGS TB research panel for detecting MTB resistance in Korean tuberculosis patients. METHODS: Mycobacterium tuberculosis with various drug resistance profiles including susceptible strains (N = 36) were isolated from clinical specimens. Nucleic acids were extracted from inactivated culture medium and underwent amplicon-based NGS to detect resistance variants in eight genes (gyrA, rpoB, pncA, katG, eis, rpsL, embB, and inhA). Data from previous studies using the same panel were merged to yield pooled sensitivity and specificity values for detecting drug resistance compared to phenotype-based methods. RESULTS: The sequencing reactions were successful for all samples. A total of 24 variants were considered to be related to resistance, and 6 of them were novel. Agreement between the phenotypic and genotypic results was excellent for isoniazid, rifampicin, and ethambutol, and was poor for streptomycin, amikacin, and kanamycin. The negative predictive values were greater than 97% for all drug classes, while the positive predictive values varied (44% to 100%). There was a possibility that common mutations could not be detected owing to the low coverage. CONCLUSIONS: We successfully applied NGS for genetic analysis of drug resistances in MTB, as well as for susceptible strains. We obtained lists of polymorphisms and possible polymorphisms, which could be used as a guide for future tests applying NGS in mycobacteriology laboratories. When analyzing the results of NGS, coverage analysis of each samples for each gene and benign polymorphisms not related to drug resistance should be considered.

Analysis of Respiratory Viral Infections Detected Using Multiplex Real-Time PCR in Hwaseong, Korea from 2013 to 2015.

BACKGROUND: We investigated the incidences and age-related/seasonal variations of respiratory virus infections in a regional area in Korea. METHODS: A total of 3,467 respiratory specimens from patients with acute respiratory infection symptoms in a teaching hospital were tested for respiratory viruses during 2013 - 2015. RESULTS: At least one virus was detected in 2,561 of the 3,467 specimens (73.9%), and 706 patients (20.4%) were positive for two or more viruses. The most frequently detected viruses were rhinovirus (23.9%), respiratory syncytial virus B (15.5%), and adenovirus (12.5%). Most of the patients (with and without a detected virus) were children. Young children (< 5 years old) were significantly more likely to have two or more viruses compared to older individuals (p < 0.0001). Most viruses exhibited seasonal variations. CONCLUSIONS: This study revealed the incidence of respiratory virus infections. These findings can enhance our understanding of the distribution of respiratory viruses according to patient age and season.

Novel Levofloxacin-Resistant Multidrug-Resistant Streptococcus pneumoniae Serotype 11A Isolates, South Korea.

Of 608 Streptococcus pneumoniae clinical strains isolated at a hospital in South Korea during 2009-2014, sixteen (2.6%) were identified as levofloxacin resistant. The predominant serotype was 11A (9 isolates). Two novel sequence types of multidrug-resistant S. pneumoniae with serotype 11A were identified, indicating continuous diversification of resistant strains.

Direct identification of Gram-positive bacteria and resistance determinants from blood cultures using a microarray-based nucleic acid assay: in-depth analysis of microarray data for undetermined results.

BACKGROUND: The Verigene Gram-Positive Blood Culture (BC-GP) nucleic acid assay (Nanosphere, Inc., Northbrook, IL, USA) is a newly developed microarray-based test with which 12 Gram-positive bacterial genes and three resistance determinants can be detected using blood culture broths. We evaluated the performance of this assay and investigated the signal characteristics of the microarray images. METHODS: At the evaluation stage, we tested 80 blood cultures that were positive for various bacteria (68 bacteria covered and 12 not covered by the BC-GP panel) collected from the blood of 36 patients and 44 spiked samples. In instances where the automated system failed and errors were called, we manually inspected microarray images, measured the signal intensities of target spots, and reclassified the results. RESULTS: With the manual analysis of the microarray images of 14 samples for which error calls were reported, we could obtain correct identification results for 12 samples without the need for retesting, because strong signals in the target spots were clearly discriminable from background noise. With our interpretation strategy, we could obtain 97.1% sensitivity and 100% specificity for bacterial identification by using the BC-GP assay. The two unidentified bacteria were viridans group streptococci, which produced weaker target signals. During the application stage, among 25 consecutive samples positive for Gram-positive bacteria, we identified two specimens with error calls as Streptococcus spp. by using manual analysis. CONCLUSIONS: With help of the manual review of the microarray images, the BC-GP assay could successfully identify species and resistance markers for many clinically important Gram-positive bacteria.

Myeloma progression and urinary gammaglobulin affect the urinary cystatin C to diagnose acute kidney injury in multiple myeloma.

AIMS: Urinary cystatin C has been suggested as a useful biomarker for diagnosis of acute kidney injury (AKI). Multiple myeloma is often complicated by AKI. Therefore, we investigated whether the urinary cystatin C was available for diagnosis of AKI in multiple myeloma. MATERIALS AND METHODS: This study included 39 patients with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma. We reviewed the medical records retrospectively and investigated whether urinary γ-globulin and myeloma progression had effects on urinary cystatin C excretion. RESULTS: Spearman's correlation analysis showed that serum ß2-microglobulin and serum cystatin C had a significant positive correlation with the urinary cystatin C excretion (r = 0.513, p = 0.001, r = 0.659, p < 0.001) and FEcystatinC (r = 0.585, p = 0.002, r = 0.711, p < 0.001). The GFRcr also had a significant negative correlation with the urinary cystatin C excretion (r = -0.582, p < 0.001) and FEcystatinC (r = -0.474, p = 0.002). In addition, the urinary γ-globulin had a significant positive correlation with the urinary cystatin C excretion (r = 0.678, p < 0.001) and FEcystatinC (r = 0.731, p < 0.001). Urinary γ-globulin was the most significant factor to influence urinary cystatin C excretion in multiple regression test. CONCLUSION: These results indicate that urinary γ-globulin and myeloma progression can increase the fractional and total excretion of urinary cystatin C. Therefore, it is believed that the urinary cystatin C can be affected by urinary γ-globulin and myeloma progression in the diagnosis of AKI in multiple myeloma. In addition, urinary γ-globulin is believed to be the most significant factor to influence on urinary cystatin C.