In a prospective, observational, non-interventional, single-center study, we assessed various plasma and urinary biomarkers of kidney injury (neutrophil gelatinase-associated Lipocain NGAL, ...kidney-injury molecule-1 KIM-1, and interleukin-18 IL-18); inflammation (IL-6, C-reactive protein CRP); plus angiotensin converting enzyme 2 (ACE2) in 120 COVID-19 patients (of whom 70 had chronic kidney disease (CKD) at emergency-department (ED) admission). Our aim was to correlate the biomarkers with the outcomes (death, acute kidney injury AKI). All patients had received a chest-CT scan at admission to calculate the severity score (0-5). Biomarkers were also assessed in healthy volunteers and non-COVID-19-CKD patients. These biomarkers statistically differed across subgroups, i.e., they were significantly increased in COVID-19 patients, except for urinary (u)KIM1 and uIL-18. Amongst the biomarkers, only IL-6 was independently associated with mortality, along with AKI and not using remdesivir. Regarding the prediction of AKI, only IL-6 and uKIM1 were significantly elevated in patients presenting with AKI. However, AKI could not be predicted. Having high baseline IL-6 levels was associated with subsequent ventilation requirement and death. The mortality rate was almost 90% when the chest CT-scan severity score was 3 or 4 vs. 6.8% when the severity score was 0-2 (
< 0.0001).
Post-acute sequelae of SARS-CoV-2 (PASC) is a significant health concern, particularly for patients with chronic kidney disease (CKD). This study investigates the long-term outcomes of individuals ...with CKD who were infected with COVID-19, focusing on their health status over a three-year period post-infection. Data were collected from both CKD and non-CKD patients who survived SARS-CoV-2 infection and were followed for three years as part of a research study on the impact, prognosis, and consequences of COVID-19 infection in CKD patients. In this prospective cohort study, we analyzed clinical records, laboratory findings, and patient-reported outcomes assessed at intervals during follow-up. The results indicated no permanent changes in renal function in any of the groups analyzed, although patients without CKD exhibited faster recovery over time. Furthermore, we examined the effect of RAAS-blocker therapy over time, finding no influence on PASC symptoms or renal function recovery. Regarding PASC symptoms, most patients recovered within a short period, but some required prolonged follow-up and specialized post-recovery management. Following up with patients in the post-COVID-19 period is crucial, as there is still insufficient information and evidence regarding the long-term effects, particularly in relation to CKD.
Regarding COVID-19 infection, Bulgaria has one of the lowest rates of vaccination in Europe, and its COVID-19-related mortality rate has been one of the highest in the European Union. Chronic kidney ...disease (CKD)-COVID-19 patients are at higher risk of developing acute kidney injury (AKI) and death after hospital admission. This single-center prospective cohort study from Bulgaria included 120 in-patient COVID-19 subjects of whom 70 had CKD and 50 normal renal function. Diabetes mellitus, hypertension, obesity, and cardiovascular disease were statistically more prevalent in the CKD group as compared to the non-CKD group. At admission, D-dimer, creatinine, and urea levels were significantly higher in the CKD group, whereas estimated glomerular-filtration rate was significantly lower as compared to the non-CKD patients. During hospitalization, 23 patients (19.1%) died, of which 19 were in the CKD group (p-value = 0.0096); in addition, 38 developed AKI (31.6%), of which 31 were in the CKD group (p-value = 0.0006). Using binary logistic regression, being male, having experienced AKI, and not having been treated with remdesivir were independent risk factors for COVID-19-induced mortality. Regarding risk of AKI, having had COVID-19-related symptoms for more than 6 days before admission, having CKD at baseline, and having not received remdesivir therapy were independent predictive factors for developing AKI after admission.
Background: Increased formation of reactive oxygen species may be caused by the ion release of the metal alloys used in prosthetic dental restorations due to the corrosion process. As products of ...lipid peroxidation, isoprostanes can be used as a marker for oxidative stress in the body. There are two significant advantages of using isoprostanes as an oxidative stress marker - presence in all fluids in the body and low reactivity. Saliva provides noninvasive, painless, and cost-effective sample collection and can be used as an alternative testing medium of blood and urine. Methods: This study presents the development and validation of a sample LC-MS/MS method to quantify 8-isoprostaglandin F2-a in human saliva using salt-out assisted liquid-liquid extraction (SALLE). Results: The selected sample preparation procedure optimized chromatographic separation and mass detection provided high recovery and sensitivity of the analysis. The calibration curve was obtained in the predefined range 25-329 ng/L with R2 larger than 0.995. Normalized matrix varied between 89.7 % and 113.5%. The method showed sufficient accuracy and precision - accuracy in the range 89.7 %-113.9 %, and precision between 2.3% and 5.4%. Conclusions: The proposed method is validated according to current EMA/FDA industrial guidance for bioanalysis and offers an appropriate level of sensitivity and sufficient accuracy and precision.
Polymorphisms in the genes of drug-metabolizing enzymes have the potential to contribute to inter-individual differences in drug pharmacokinetics and toxicity. A custom next-generation sequencing ...(NGS) panel was used in 71 kidney transplanted patients to study the polymorphisms of 11 genes relevant to the metabolism of immunosuppressive drugs. Cyclosporine A and tacrolimus concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. More than 1000 polymorphisms were found in the studied 11 genes, and 45% of them were different non-synonymous variants. Eleven missense mutations were observed in the CYP3A7 gene, resulting in increased metabolism of tacrolimus at day 21 post-transplantation (6.7 µg/L vs. 10.3 µg/L; p = 0.048). Two alleles encoding a cytochrome P450 2D6 enzyme with impaired function-CYP2D6*4 (non-functional) and CYP2D6*10 (decreased function), were found in the studied group and both of them were associated with higher levels of tacrolimus at day 14 (10.1 µg/L; p = 0.021 and 9.7 µg/L; p = 0.036, vs. 7.7 µg/L respectively). Altered function of ABC transporters C3 and C2 was also associated with increased TAC concentration. ABCC3 significantly influenced TAC metabolism by itself, but polymorphisms affecting both ABCC3 and ABCC2 resulted in higher changes: 13.6 µg/L vs. 7.9 µg/L, day 14 (p = 0.003) and 20 µg/L versus 9.3 µg/L, day 21 (p = 0.019). All associations were also checked for variants affecting the activity of CYP3A4 and CYP3A5. Despite its small size, the study points out that the pharmacogenetics of calcineurin inhibitors may also be influenced by other genes besides CYP3A4 and CYP3A5.
Reactive oxygen species (ROS) are produced in the body during normal metabolism by means of enzymes and non-enzymatic chemical reduction of molecular oxygen. In case of the prevalence of ROS ...formation over their elimination, highly reactive free radicals can be accumulated and can cause multiple damages to the biomolecules and cells. Determination of isoprostanes in biological matrices is most often used to register free radical damage and requires selective, sensitive and specific techniques.
This study presents the development and validation of the LC-MS/MS method for the determination of 8-iso-Prostaglandin F2α in human plasma utilising a modified liquid-liquid extraction procedure with phase separation.
Modified sample preparation procedure assured higher extraction yield, clear separation of organic layer from the plasma water phase and protein precipitates, and better-purified product for instrumental analysis. Linearity was validated in the range 0.1-5.0 µg/L with R2 > 0.996; normalised matrix varied between 86.0% and 108.3%, accuracy ranged from 90.4 % to 113.9% and precision both within runs and between runs was less than 7%. With a run time of 10 min, a throughput of over 50 samples per working day could be performed.
The method meets all the current industrial validation criteria and allows the accurate and precise determination of 8-iso-PGF2α in human plasma at diagnostically significant concentration range.
Nutritional status was evaluated by prealbumin, retinol binding protein (RBP), fat-soluble vitamins A, D, E; magnesium and BMI in addition to routine biochemical markers; imaging morphological data ...by Cambridge classification for CT/MRCP (grade I-IV). Conclusion: Proper follow-up and correction of suboptimal PERT reduce the risk of severe malnutrition complications, associated morbidity and mortality and ensures better quality of life for patients with PEI.
Extracorporeal circulation during cardiac surgery is characterized with increased risk for hypercoagulation because blood is exposed to foreign, nonendothelial cell surfaces. Thus, the usage of ...extracorporeal circulation is essentially not possible without anticoagulation. Open-heart surgery as well as many perioperative factors, such as acidosis, hypocalcemia, hypothermia, and hemodilution, might affect hemostasis and lead to coagulopathy and bleeding. A new insight into the effectiveness of anticoagulant therapy is applied to modify the dosing regimen with respect to the genetic CYP2C9 and VKORC1allelic variants. A systematic literature search was performed for VKORC1 and CYP2C9 and their association with coumarin anticoagulant therapy and bleeding risk in postoperative period of cardiac surgery with extracorporeal circulation.
Proteinuria is associated with decreased graft and patient survival after kidney transplantation. Increasing evidence shows that vitamin D has antiproteinuric and renoprotective effects. The aim of ...our study was to assess the influence of 25-hydroxyvitamin D levels on proteinuria after kidney transplantation.
Between May 1, 2012, and November 30, 2012, we tested 395 kidney transplant recipients for 25-hydroxyvitamin D levels during their regular visits to our transplant center together with routine blood sampling and proteinuria testing. Patients within 12 months of transplant, who had undergone parathyroidectomy, had unstable graft function, had concomitant intake of calcineurin inhibitors and mammalian target of rapamycin inhibitors were not included in the study. Subjects with advanced liver disease, or receiving vitamin D supplementation were also excluded. All laboratory, clinical, and therapeutic factors for proteinuria were taken into consideration. Statistical analyses included descriptive statistics and univariate and multivariate log-log regression with backward selection (SPSS version 22.0; SPSS Inc., Chicago, IL, USA), with significance at P < .05. Determination of total 25-hydroxyvitamin D levels was performed by a validated liquid chromatography-tandem mass spectrometry method.
Our study group included 230 patients (148 men, 82 women). Positive association was established between proteinuria and history of diabetes mellitus, rejection episode 12 months within testing for 25-hydroxyvitamin D levels, and use of mammalian target of rapamycin inhibitors (P < .05). Significant negative relations were detected for patient age, graft function, and 25-hydroxyvitamin D concentrations (P < .05).
Our study established that better vitamin D status is associated with lower proteinuria. However, further research is needed to clarify the possible renoprotective properties of vitamin D.
To compare the prevalence of vitamin D deficiency and fracture history in nursing home residents and community-dwelling elderly subjects and to explore the association of vitamin D levels with ...various characteristics.
Sixty-six nursing home residents and 139 community-dwelling elderly subjects participated. Marital status, medical history, medication including vitamin D supplements, smoking, past fractures were assessed. Weight and height were measured and body mass index calculated. Serum 25-hydroxyvitamin D (25-OHD), PTH, Ca, phosphate, creatinine and eGFR were determined.
In the nursing home residents 25-OHD was lower (17.8 nmol/l, 9.4-28.6 vs. 36.7 nmol/l, 26.9-50, p < 0.001), PTH was higher (5.6 pmol/l, 3.9-8.9 vs. 4.7 pmol/l 3.6-5.8, P = 0.003) and 25-OHD deficiency was more prevalent (65.2% 53.7-76.7 vs. 22.3% 15.4-29.2, p < 0.001) as was elevated PTH (23% 12.8-33 vs. 5.8% 2-10, p = 0.001). 25-OHD correlated negatively with PTH (institutionalized r = -0.28, p = 0.025 and community-dwelling r = -0.36, p < 0.001). Hip fractures were reported by 8% of the residents and 2% of the independent elderly. The only predictor for hip fracture was elevated PTH (OR = 7.6 (1.5-36.9), p = 0.013).
The prevalence of vitamin D deficiency and secondary hyperparathyroidism was high in the institutionalized subjects. Hip fracture risk was associated with elevated PTH and not directly with vitamin D levels or the residency status.
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