Cell-derived extracellular vesicles (EVs) can be isolated from various body fluids, including urine. Urinary EVs have gained important recognition as potential diagnostic biomarkers in renal disease since their cargo includes nucleic acids, proteins, and other cellular components, which likely mirror the physiological and possibly pathophysiological state of cells along the nephron. Accumulating evidence highlights the feasibility of using EVs as biomarkers for diagnostic, prognostic, and therapeutic purposes in several forms of renal disease, such as acute kidney injury, glomerulonephritis, and renal transplantation. Additionally, exogenous delivery of EVs released in vitro by cells in culture may have salutary benefits for renal diseases. In this review, we introduce recent studies that attempt to identify urinary EVs as candidate biomarkers for human kidney diseases and consider their potential implication as a therapeutic option in key kidney diseases.
The aim of this study was to investigate the clinical characteristics of sepsis-induced acute kidney injury (AKI) in patients undergoing continuous renal replacement therapy (CRRT). From 2011 to 2015, we enrolled 340 patients who were treated with CRRT for sepsis at the Presbyterian Medical Center. In all patients, CRRT was performed using the PRISMA platform. We divided these patients into two groups (survivors and non-survivors) according to the 28-day all-cause mortality. We compared clinical characteristics and analyzed the predictors of mortality. The 28-day all-cause mortality was 62%. Survivors were younger than non-survivors and had higher platelet counts (178 ± 101 × 103/mL vs. 134 ± 84 × 103/mL, p < .01) and serum creatinine levels (4.2 ± 2.8 vs. 3.3 ± 2.7, p < .01). However, survivors had lower red blood cell distribution width (RDW) scores (14.9 ± 2.1 vs. 16.1 ± 3.3, p < .01) and APACHE II scores (24.5 ± 5.8 vs. 26.9 ± 5.7, p < .01) than non-survivors. Furthermore, survivors were more likely than non-survivors to have a urine output of >0.05 mL/kg/h (66% vs. 86%, p = .001) in the first day. In a multivariate logistic regression analysis, age, platelet count, RDW score, APACHE II score, serum creatinine level, and a urine output of <0.05 mL/kg/h the first day were prognostic factors for the 28-day all-cause mortality. Age, platelet count, APACHE II score, RDW score, serum creatinine level, and urine output the first day are useful predictors for the 28-day all-cause mortality in sepsis patients requiring CRRT.
Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure.
15 February 2021 in Genetic Testing and Molecular Biomarkers
Background: Urinary microRNA (miRNA)-21 is a biomarker for acute kidney injury (AKI). We conducted this study to determine if a urinary exosomal analysis for this biomarker could serve as a novel diagnostic approach for detecting kidney disease. Materials and Methods: We investigated the clinical significance of urinary exosomal miRNA-21 levels for AKI in scrub typhus patients. We collected 138 urine samples from scrub typhus patients at the time of admission. Urinary exosomal miRNA-21 was assessed in 25 age- and sex-matched scrub typhus patients with and without AKI. Results: The total leukocyte count was higher in AKI patients than in non-AKI patients (10.40 × 10 3 /mL vs. 6.40 × 10 3 /mL, p < 0.01). Urinary exosomal miRNA-21 levels were higher in the AKI group than in the non-AKI group (20.1 ± 1.2 vs. 17.8 ± 1.8 ΔCt value of miRNA-21, p < 0.01). Additionally, the miRNA-21 levels correlated directly with the total leukocyte counts and inversely with the estimated glomerular filtration rate. A receiver operating characteristic curve analysis demonstrated good discriminative power for the diagnosis of scrub typhus-associated AKI, with an area under the curve value of 0.907. Conclusion: Urinary exosomal miRNA-21 could be a surrogate marker for scrub typhus-associated AKI diagnosis.
31 May 2023 in Kidney Research and Clinical Practice
Background: In this study, we investigated the clinical characteristics of acute kidney injury (AKI) in patients with glyphosate surfactant herbicide (GSH) poisoning.Methods: This study was performed between 2008 and 2021 and included 184 patients categorized into the AKI (n = 82) and non-AKI (n = 102) groups. The incidence, clinical characteristics, and severity of AKI were compared between the groups based on the Risk of renal dysfunction, Injury to the kidney, Failure or Loss of kidney function, and End-stage kidney disease (RIFLE) classification.Results: The incidence of AKI was 44.5%, of which 25.0%, 6.5%, and 13.0% of patients were classified into the Risk, Injury, and Failure categories, respectively. Patients in the AKI group were older (63.3 ± 16.2 years vs. 57.4 ± 17.5 years, p = 0.02) and had ≥1 comorbidities (52.4% vs. 32.7%, p = 0.005) than those in the non-AKI group. The length of hospitalization was longer (10.7 ± 12.1 days vs. 6.5 ± 8.1 days, p = 0.004) and hypotensive episodes occurred more frequently in the AKI group (45.1% vs. 8.8%, p < 0.001). Electrocardiographic (ECG) abnormalities on admission were more frequently observed in the AKI group than in the non-AKI group (80.5% vs. 47.1%, p < 0.001). Patients in the AKI group had poorer renal function (estimated glomerular filtration rate at the time of admission, 62.2 ± 22.9 mL/min/1.73 m2 vs. 88.9 ± 26.1 mL/min/1.73 m2, p < 0.001) on admission. The mortality rate was higher in the AKI group than in the non-AKI group (18.3% vs. 1.0%, p < 0.001). Multiple logistic regression analysis showed that hypotension and ECG abnormalities upon admission were significant predictors of AKI in patients with GSH poisoning.Conclusion: The presence of hypotension on admission may be a useful predictor of AKI in patients with GSH intoxication.
31 March 2022 in Kidney Research and Clinical Practice
Background: Evidence of the ethical appropriateness and clinical benefits of shared decision-making (SDM) are accumulating. This study aimed to not only identify physicians’ perspectives on SDM, and practices related to end-of-life care in particular, but also to gauge the effect of SDM education on physicians in Korea.Methods: A 14-item questionnaire survey using a modified Delphi process was delivered to nephrologists and internal medicine trainees at 17 university hospitals.Results: A total of 309 physicians completed the survey. Although respondents reported that 69.9% of their practical decisions were made using SDM, 59.9% reported that it is not being applied appropriately. Only 12.3% of respondents had received education on SDM as part of their training. The main obstacles to appropriate SDM were identified as lack of time (46.0%), educational materials and tools (29.4%), and education on SDM (24.3%). Although only a few respondents had received training on SDM, the proportion of those who thought they were using SDM appropriately in actual practice was high; the proportion of those who chose lack of time and education as factors that hindered the proper application of SDM was low.Conclusion: The majority of respondents believed that SDM was not being implemented properly in Korea, despite its use in actual practice. To improve the effectiveness of SDM in the Korean medical system, appropriate training programs and supplemental policies that guarantee sufficient application time are required.