High Plasma Angiopoietin-2 Levels Predict the Need to Initiate Dialysis within Two Years in Patients with Chronic Kidney Disease.

Volume status, congestion, endothelial activation, and injury all play roles in glomerular filtration rate (GFR) decline. In this study, we aimed to determine whether the plasma endothelial and overhydration markers could serve as independent predictors for dialysis initiation in patients with chronic kidney disease (CKD) 3b-5 (GFR < 45 mL/min/1.72 m2) and preserved ejection fraction. A prospective, observational study in a single academic center was conducted from March 2019 to March 2022. Plasma levels of angiopoietin (Ang)-2, Vascular Endothelial Growth Factor-C (VEGF-C), Vascular Cell Adhesion Molecule-1 (VCAM-1), Copeptin (CPP), beta-trace protein (BTP), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) were all measured. Lung ultrasound (US) B-lines, bioimpedance, and echocardiography with global longitudinal strain (GLS) were recorded. The study outcome was the initiation of chronic dialysis (renal replacement therapy) during 24 months of follow-up. A total of 105 consecutive patients with a mean eGFR of 21.3 mL/min/1.73 m were recruited and finally analyzed. A positive correlation between Ang-2 and VCAM-1 and BTP was observed. Ang-2 correlated positively with BNP, cTnI, sCr, E/e', and the extracellular water (ECW)/intracellular water (ICW) ratio (ECW/ICW). After 24 months, a deterioration in renal function was observed in 47 patients (58%). In multivariate regression analysis, both VCAM-1 and Ang-2 showed independent influences on risk of renal replacement therapy initiation. In a Kaplan-Meier analysis, 72% of patients with Ang-2 concentrations below the median (3.15 ng/mL) survived without dialysis for two years. Such an impact was not observed for GFR, VCAM, CCP, VEGF-C, or BTP. Endothelial activation, quantified by plasma levels of Ang-2, may play a key role in GFR decline and the need for dialysis initiation in patients with CKD 3b, 4, and 5.

Antibodies in the breastmilk of COVID-19 recovered women.

OBJECTIVE: Human milk contains antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which may serve as a protective factor through passive immunization in infants. The objective of this study was to measure the levels of anti-SARS-CoV-2 IgG and IgA in human milk and serum after a SARS-CoV-2 infection. DESIGN: Breast milk and serum samples from 72 lactating mothers with confirmed SARS-CoV-2 asymptomatic or symptomatic infection were collected 1-229 days after the onset of clinical symptoms related to COVID-19. Seventeen mothers with no history of COVID-19 served as a control group. Enzyme-Linked ImmunoSorbent Assay was performed to analyze antibodies against SARS-CoV-2. RESULTS: SARS-CoV-2-IgA human milk antibodies were detected in mothers and their concentrations were consistently higher than SARS-CoV-2-IgG antibodies. The serum and breastmilk samples of women with COVID-19 was characterized by a higher concentration of anti-RBD IgA and IgG than the serum from the control group without COVID-19. No statistically significant difference was observed between the antibody levels in the serum samples obtained from symptomatic and asymptomatic women exposed to SARS-CoV-2 and between the antibody level and the time from a positive SARS-CoV-2 test result over the period studied. CONCLUSION: Our results confirm the presence of SARS-CoV-2 IgA and IgG antibodies in the breastmilk of COVID-19 recovered women and the possibility of these antibodies in providing specific immunologic benefits to breastfeeding infants such as protection against the virus transmission and severity of the acquired COVID-19 disease.

Immunity after COVID-19 Recovery and Vaccination: Similarities and Differences.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy.

Focal segmental glomerulosclerosis (FSGS) involves podocyte injury. In patients with nephrotic syndrome, progression to end-stage renal disease often occurs over the course of 5 to 10 years. The diagnosis is based on a renal biopsy. It is presumed that primary FSGS is caused by an unknown plasma factor that might be responsible for the recurrence of FSGS after kidney transplantation. The nature of circulating permeability factors is not explained and particular biological molecules responsible for inducing FSGS are still unknown. Several substances have been proposed as potential circulating factors such as soluble urokinase-type plasminogen activator receptor (suPAR) and cardiolipin-like-cytokine 1 (CLC-1). Many studies have also attempted to establish which molecules are related to podocyte injury in the pathogenesis of FSGS such as plasminogen activator inhibitor type-1 (PAI-1), angiotensin II type 1 receptors (AT1R), dystroglycan(DG), microRNAs, metalloproteinases (MMPs), forkheadbox P3 (FOXP3), and poly-ADP-ribose polymerase-1 (PARP1). Some biomarkers have also been studied in the context of kidney tissue damage progression: transforming growth factor-beta (TGF-ß), human neutrophil gelatinase-associated lipocalin (NGAL), malondialdehyde (MDA), and others. This paper describes molecules that could potentially be considered as circulating factors causing primary FSGS.

Diurnal Variability of Platelet Aggregation in Patients with Myocardial Infarction Treated with Prasugrel and Ticagrelor.

BACKGROUND: Contemporary antiplatelet treatment in acute myocardial infarction (AMI) is based on one of two P2Y12 receptor inhibitors, prasugrel or ticagrelor. The aim of this study was to compare diurnal variability of platelet reactivity between patients receiving prasugrel and ticagrelor during the initial phase of maintenance treatment after AMI. METHODS: It was a prospective, two-center, pharmacodynamic, observational study. Blood for platelet testing was sampled at four time points on day four after AMI (8:00, 12:00, 16:00, 20:00). Diurnal variability of platelet reactivity was expressed as a coefficient of variation (CV) of the above-mentioned measurements. RESULTS: 73 invasively-treated patients were enrolled (ticagrelor: n = 47, prasugrel: n = 26). CV was greater in patients treated with ticagrelor compared with prasugrel according to a VASP assay (47.8 [31.6-64.6]% vs. 21.3 [12.9-25.5]%, p < 0.001), while no statistical differences were detected when the CVs of platelet aggregation according to Multiplate were compared between ticagrelor- and prasugrel-treated patients. Ticagrelor-treated patients showed more pronounced platelet inhibition than prasugrel at 16:00 and 20:00 (VASP16:00: 20.6 ± 15.0 vs. 24.9 ± 12.8 PRI, p = 0.049; VASP20:00: 18.6 ± 17.7 vs. 26.0 ± 11.7 PRI, p = 0.002). CONCLUSIONS: Ticagrelor shows greater diurnal variability in platelet aggregation than prasugrel during the initial maintenance phase of AMI treatment, and this is due to the continuous increase of platelet inhibition after the morning maintenance dose. Both drugs provide an adequate antiplatelet effect early after AMI. Evaluation of the clinical significance of these findings warrants further investigation.

Anti-ETAR and suPAR as markers of disease activity in renal ANCA-associated vasculitis.

PURPOSE: In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a lack of reliable biomarkers of disease activity. The aim of the study was to evaluate soluble urokinase plasminogen activator receptor (suPAR) and anti-endothelin-1 type A receptor (anti-ETAR) antibodies levels in active phase and remission of AAV. PATIENTS AND METHODS: We enrolled 60 patients (median age 63.0 years) with renal AAV into this study. Plasma suPAR, urine suPAR (expressed as urine suPAR/creatinine ratio) and serum anti-ETAR antibodies were assayed by ELISA. Disease activity was assessed using Birmingham Vasculitis Activity Score (BVAS) and patients were divided into 2 subgroups based on their BVAS scores, namely: active AAV subgroup (BVAS≥1) and remission subgroup (BVAS â€‹= â€‹0). Median follow-up was 12 months. RESULTS: Patients with active AAV had higher levels of all candidate biomarkers in comparison to those in remission (p â€‹< â€‹0.05). C-statistics for plasma suPAR, urine suPAR/creatinine ratio and serum anti-ETAR were 0.807, 0.713 and 0.783, respectively. In multivariable analysis, no clear associations were found between serum anti-ETAR and BVAS, while both plasma suPAR and serum anti-ETAR were independently influenced by estimated glomerular filtration rate (eGFR). CONCLUSIONS: Plasma suPAR better discriminated between active AAV and remission in comparison to urine suPAR/creatinine ratio and serum anti-ETAR antibodies.

Influence of Virtual Reality Devices on Pain and Anxiety in Patients Undergoing Cystoscopy Performed under Local Anaesthesia.

BACKGROUND: Bladder cancer is one of the most common malignancies. Its diagnosis is based on transurethral cystoscopy. Virtual reality (VR) is a three-dimensional world generated through the projection of images, the emission of sounds and other stimuli. VR has been proven to be a very effective "distractor" and, thus, a useful tool in managing pain. The aim of this study was to determine whether the use of VR sets is technically feasible during the cystoscopy and whether the use of VR devices would reduce the degree of ailments associated with the procedure; Methods: The study prospectively included both men and women who qualified for rigid cystoscopy due to both primary and follow-up diagnostics. The study group underwent rigid cystoscopy with the VR set and the control group underwent the procedure without the VR set. Patients enrolled in both groups were subjected to blood pressure, heart rate and saturation measurements before, during and after the procedure. Additionally, the patients were asked to describe the severity of fear, pain sensations and nausea associated with the procedure. Non-verbal pain manifestations were assessed using the adult adjusted Faces, Legs, Activity, Cry and Consolability (FLACC) scale; Results: The study population included 103 patients (74M/29F; mean age 64.4 years). Pain intensity differed significantly between the groups, reaching lower values in the VR group. In all analyzed subgroups the use of the VR set was associated with higher levels of nausea. The mean FLACC score reached higher values for patients without the VR set. Blood pressure as well as heart rate increased during the procedure and decreased afterwards. The increase in systolic blood pressure and pulse rate was statistically higher in the control group; Conclusions: This study confirmed that cystoscopy is associated with considerable preprocedural fear and severe pain. Blood pressure and heart rate rise significantly during the cystoscopy. VR sets can lower pain perception during cystoscopy, but they may cause moderate nausea.

Comparing Humoral and Cellular Adaptive Immunity during Convalescent Phase of COVID-19 in Hemodialysis Patients and Kidney Transplant Recipients.

BACKGROUND: It is still unclear whether COVID-19 convalescent kidney transplant recipients (KTR) and hemodialysis (HD) patients can develop anti-SARS-CoV-2 adaptive immunity. The aim was to characterize and compare the immune response to the virus in HD patients and KTR. METHODS: The study included 26 HD patients and 54 KTR-both convalescent (14 HD, 25 KTR) and unexposed. The immune response was assessed by determining the anti-SARS-CoV-2 antibodies in serum and specific T cell response via the interferon-gamma release assay (IGRA). Moreover, blood-morphology-derived parameters, immune cell phenotypes, and acute phase reactants were evaluated. RESULTS: KRT and HD convalescents presented similar serum levels of anti-SARS-CoV-2 IgG and IgA. A negative correlation occurred between IgG and time after the infection was observed. There was a strong relationship between the prevalence of anti-SARS-CoV-2 cellular and humoral responses in both groups. Convalescent IGRA response was significantly higher in HD patients compared to KTR. CONCLUSIONS: HD patients and KTR develop humoral and cellular responses after COVID-19. The antibodies levels are similar in both groups of patients. SARS-CoV-2-reactive T cell response is stronger in HD patients compared to KTR. The SARS-CoV-2-specific IgG level decreases with time while IgA and a cellular response are maintained. IGRA proved to be a valuable test for the assessment of specific cellular immunity in immunocompromised HD patients and KTR.

Alpha-1 Acid Glycoprotein and Podocin mRNA as Novel Biomarkers for Early Glomerular Injury in Obese Children.

INTRODUCTION: Obesity, which is a serious problem in children, has a negative impact on many organs, including kidneys, and obesity-related glomerulopathy (ORG) is an increasingly common cause of ESKD (end-stage kidney disease) in adults. Early-detected and -treated glomerular lesions are reversible, so it is important to find a useful marker of early damage. The study aimed to evaluate the albumin-to-creatinine ratio (ACR), urinary alpha-1-acid glycoprotein (α1-AGP), and mRNA of podocyte-specific proteins as indicators of glomerular injury and their relationship with the degree of obesity and metabolic disorders. MATERIALS AND METHODS: A total of 125 obese children and 33 healthy peers were enrolled. Patients were divided into two groups, depending on SDS BMI values. ACR, α1-AGP, mRNA expression of nephrin, synaptopodin, podocin, and C2AP protein in urine sediment were measured. RESULTS: ACR values did not differ between groups and were within the normal range. α1-AGP and mRNA expression were significantly higher in obese children compared with controls. mRNA expression of the remaining podocyte proteins was similar in both groups. No significant differences concerning all examined parameters were found depending on the degree of obesity. There was a positive significant correlation between α1-AGP and ACR. CONCLUSIONS: Increased α1-AGP before the onset of albuminuria suggests its usefulness as a biomarker of early glomerular damage in obese children. An increased podocin mRNA expression also indicates podocyte damage and may be linked to ORG development. The lack of increase in expression of other podocyte proteins suggests that podocin mRNA may be a more specific and sensitive biomarker. The degree of obesity has no impact on the tested parameters, but further studies are needed to confirm it.

Immune Cells Profiling in ANCA-Associated Vasculitis Patients-Relation to Disease Activity.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of necrotizing multiorgan autoimmune vasculitides that predominantly affect small blood vessels and are associated with the presence of ANCAs. The aim was to assess regulatory and effector cell populations accompanied by the suPAR biomarker level and link the so-defined immune state to the AAV disease activity. The research involved a multicomponent description of an immune state encompassing a range of B and T cell subsets such as transitional/regulatory B cells (CD19+CD24++CD38++), naïve B cells (CD19+CD24INTCD38INT), Th17 cells, T regulatory cells (CD4+CD25+FoxP3+) and cytotoxic CD4+CD28- cells by flow cytometry. The suPAR plasma level was measured by ELISA. The results indicate that AAV is associated with an increased suPAR plasma level and immune fingerprint characterized by an expansion of Th17 cells and T cells lacking the costimulatory molecule CD28, accompanied by a decrease of regulatory populations (Tregs and transitional B cells) and NK cells. Decreased numbers of regulatory T cells and transitional B cells were shown to be linked to activation of the AAV disease while the increased suPAR plasma level-to AAV-related deterioration of kidney function. The observed immune fingerprint might be a reflection of peripheral tolerance failure responsible for development and progression of ANCA-associated vasculitides.

Immune Response to Vaccination against COVID-19 in Breastfeeding Health Workers.

BACKGROUND: Initially, there were no data on the safety of COVID-19 vaccines in lactating women. The aim of our study was to evaluate the immune response to COVID-19 vaccinations in breastfeeding women. METHODS: The study included 32 breastfeeding women who, regardless of the study, had decided to be vaccinated. Maternal serum and breast milk samples were simultaneously collected on days 8 ± 1, 22 ± 2, 29 ± 3, and 43 ± 4 after the first dose of the vaccine. The immune response was assessed by determining the presence of anti-SARS-CoV-2 IgG and IgA. RESULTS: The breast milk IgG level was detectable (6.50 ± 6.74, median 4.7, and maximum 34.2 BAU/mL) and highly correlated to serum IgG level (rS 0.89; p < 0.001). The breast milk ratio of IgA to the cut-off value was higher in serum IgA-positive (4.18 ± 3.26, median 2.8, and maximum >10) than in serum IgA-negative women (0.56 ± 0.37, median 0.5, and maximum 1.6; p < 0.001). The highest concentrations of serum and breast milk antibodies were observed on day 29 ± 3 with a decrease on day 43 ± 4. CONCLUSION: The immune response to the vaccination against SARS-CoV-2 is strongest 7 ± 3 days after the second dose of the vaccine. Lactating mothers breastfeeding their children after vaccination against SARS-CoV-2 may transfer antibodies to their infant.

Endothelin A Receptors Expressed in Glomeruli of Renal Transplant Patients May Be Associated with Antibody-Mediated Rejection.

BACKGROUND: Non-human leukocyte antigen (HLA) anti-endothelin A receptor antibodies are presented as being potentially important, but the expression of the endothelin A receptor in glomeruli (ETA receptor (g+)) has not yet been described. We decided to evaluate the presence and relevance of the ETA receptor in for-cause renal transplant biopsies. The aim of our study was to evaluate the immunoreactivity of the ETA receptor and its significance in patients who underwent a renal transplant biopsy due to the deterioration of transplant function, with detailed characterization of staining in glomeruli. METHODS: The immunohistochemical expression of ETA receptor (ETAR) was analyzed in renal transplant biopsies. Microscopic evaluation was performed on paraffin sections in glomeruli. The analysis was performed using a two-step scale (0: lack of ETAR expression; 1: the presence of ETAR expression-mild to moderate immunoreactivity). RESULTS: We analyzed 149 patients who underwent renal allograft biopsy after renal transplantation. Positive staining of ETA receptors in glomeruli (ETA receptor (g+)) was noticed in 13/149 (8.7%) patients. Five of these 13 (38.5%) patients with ETA receptor (g+) developed antibody-mediated rejection (AMR), while 13 of the remaining 136 (9.5%) ETA receptor (g-) patients developed AMR (p = 0.0022). Graft loss was noticed in all but one ETA receptor (g+) patient with AMR (4/5; 80%), but only in 2/13 (15%) ETA receptor (g-) patients with AMR (p = 0.009) during the first year after biopsy. CONCLUSIONS: The expression of endothelin A receptors in glomeruli seems to be a potentially important feature in the diagnosis of damage during antibody-mediated rejection. It may help to identify patients at a higher risk of allograft rejection and injury.

[Serum cytokines in ANCA-associated vasculitis: Correlation with disease-related clinical and laboratory findings]. / Citocinas séricas en la vasculitis asociada a ANCA: correlación con los hallazgos clínicos y de laboratorio relacionados con la enfermedad.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic, autoimmune disease. Cytokine dysregulation during active disease and clinical remission, reflects significant immunological activity in various disease stages, and might be responsible for the potential relapse of ANCA-vasculitis. OBJECTIVES: This study aimed to screen serological profiles in active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and to determine their associations with clinical characteristics. MATERIALS AND METHODS: Serum IL-10, IL-12, IL-17, IL-21, IL-23, B cell activating factor (BAFF) concentrations were determined by Quantikine HS ELISA in 71 patients, 47 with GPA and 24 with MPA, and compared with 16 healthy controls. Subsequently, the correlations between serum IL-10, IL-12, IL-17, IL-21, IL-23, BAFF levels, and both laboratory and clinical abnormalities were investigated. RESULTS: BAFF levels were significantly higher in GPA than MPA, and healthy controls. IL-10 and BAFF levels were elevated in GPA patients with pulmonary involvement. Higher BAFF levels might reflect severe GPA. IL-10 and IL-12 levels were higher in MPA than GPA. In MPA, IL-10 levels were highest in patients with short disease duration, and young individuals. IL-12 correlated positively with BVAS and was elevated in patients with cardiovascular involvement and nasal S. aureus carriers. CONCLUSIONS: In MPA, IL-12 correlates positively with disease activity, and is significantly increased in patients with cardiovascular involvement and nasal S. aureus carriers. Increased IL-10 is observed in young MPA patients and in those with short MPA duration. Elevated BAFF and IL-10 levels are associated with pulmonary involvement in GPA. High BAFF levels might reflect severe GPA.

Serum metabolomics approach to monitor the changes in metabolite profiles following renal transplantation.

Systemic metabolic changes after renal transplantation reflect the key processes that are related to graft accommodation. In order to describe and better understand these changes, the 1HNMR based metabolomics approach was used. The changes of 47 metabolites in the serum samples of 19 individuals were interpreted over time with respect to their levels prior to transplantation. Considering the specific repeated measures design of the experiments, data analysis was mainly focused on the multiple analyses of variance (ANOVA) methods such as ANOVA simultaneous component analysis and ANOVA-target projection. We also propose here the combined use of ANOVA and classification and regression trees (ANOVA-CART) under the assumption that a small set of metabolites the binary splits on which may better describe the graft accommodation processes over time. This assumption is very important for developing a medical protocol for evaluating a patient's health state. The results showed that besides creatinine, which is routinely used to monitor renal activity, the changes in levels of hippurate, mannitol and alanine may be associated with the changes in renal function during the post-transplantation recovery period. Specifically, the level of hippurate (or histidine) is more sensitive to any short-term changes in renal activity than creatinine.

Computed Tomography Parameters and Estimated Glomerular Filtration Rate Formulas for Peridonation Living Kidney Donor Assessment.

BACKGROUND: Renal function is usually described by the estimated glomerular filtration rate (eGFR). The standard method used for living kidney donor evaluation in our center is the 24-hour urine creatinine clearance (CrCl) and kidney morphology assessment with computed tomography (CT). The aim of the study was the analysis of the correlation of CrCl with 15 published eGFR formulas and morphologic CT parameters to choose the most accurate kidney function estimation method before and after donation. METHODS: The study included 39 living donors (18 male and 21 female, aged 32-69 years; mean age, 51.4 [SD, 9.7] years). The eGFR was estimated using Cockcroft-Gault, Modification of Diet in Renal Disease 7, Modification of Diet in Renal Disease 4, Chronic Kidney Disease Epidemiology Collaboration, Mayo Clinic, Nankivell, Bjornsson, Davis-Chandler, Edward-Whyte, Walser, Gates, Hull, Jelliffe-1, Jelliffe-2, or Mawer formulas and correlated with CrCl. CT parameters (kidney dimensions, volume, vascularization) were compared with eGFR formulas. RESULTS: The 25% to 34% (mean, 28.5% [SD, 2.3%]) decrease in eGFR after donation and its 1.5% to 5.0% (mean, 3.2% [SD, 1.0%]) increase over a year were observed. Cockcroft-Gault, Bjornsson, Hull, and Mawer equations (all including serum creatinine, age, sex, and body mass) correlated with predonation CrCl (r = 0.54, 0.53, 0.53, and 0.56, respectively; P < .001). From CT parameters, renal cortex volume correlated with CrCl (r = 0.48, P = .002) as well as the 4 abovementioned equations before donation (r = 0.65, 0.61, 0.64, and 0.74, respectively; P < .001) and during the postdonation period (12-month r = 0.59, 0.54, 0.57, and 0.70 respectively; P < .002). CONCLUSIONS: The eGFR calculated with equations combining serum creatinine, age, sex, and body mass as well as renal cortex volume are predictive of pre- and postdonation kidney function.

Systemic Inflammatory Markers Predict Detrimental Outcome of Urosepsis in Kidney Transplant Recipients.

BACKGROUND: Urosepsis is a frequent cause of hospitalization among kidney transplant recipients (KTxR). Systemic inflammatory markers may reflect disease severity; nevertheless, their predictive value has not been evaluated in KTxRs. AIMS: We sought to investigate the diagnostic and prognostic value of blood-derived systemic inflammatory markers during urosepsis in KTxR. METHODS: We retrospectively enrolled 80 transplant recipients who were hospitalized between 2014 and 2017 due to urosepsis and followed for at least 1 year. Multiple parameters were calculated from medical records. The study endpoint was defined as death, graft loss, or a more than double serum creatinine level compared with baseline. RESULTS: Seventeen patients reached an endpoint and presented at admission significantly lower total serum protein [g/dL] (5.0 ± 0.6 vs 6.0 ± 0.7) and higher urea [mg/dL] (161, 118-218 vs 80, 56-125), neutrophil-to-lymphocyte ratio (NLR) (20.0, 12.5-48.3 vs 12.9, 7.0-20.1), platelet-to-lymphocyte ratio (PLR) (447, 203-706 vs 231, 160-357), derived neutrophil-to-lymphocyte ratio (dNLR) (8.5, 5.6-10.4 vs 5.3, 2.9-8.5), and maximal Sequential Organ Failure Assessment (SOFA) score (6, 4-7 vs 3, 3-5). Among blood markers, NLR showed the strongest correlation with C-reactive protein, procalcitonin, creatinine, urea, and maximal SOFA score. The NLR cut-off value >15 predicted endpoint occurrence with 59% specificity and 75% sensitivity (area under the curve [AUC] 0.67, P = .038). The combined impact of NLR, urea, and total serum protein increased the prognostic precision (sensitivity 85% and specificity 84%, AUC = 0.88, P < .001). CONCLUSIONS: The combined impact of NLR, urea, and total serum protein identifies KTxR who are at risk of a bad outcome after urosepsis and require more meticulous care.

Angiotensin II Type 1 Receptor Expression in Renal Transplant Biopsies and Anti-AT1R Antibodies in Serum Indicates the Risk of Transplant Loss.

The manifestation of anti-angiotensin II type 1 receptor (AT1R) antibodies is considered a risk factor for transplant injury; however, the occurrence of angiotensin II type 1 (AT1)-Receptor expression in renal transplant biopsy may help to predict transplant loss. The aim of our study was to evaluate the expression of AT1-Receptors together with their antibodies and assess the risk of transplant loss in patients who had a renal transplant indication biopsy. METHODS: AT1-Receptor immunoreactivity was analyzed in renal transplant biopsies. Additionally, we analyzed the presence of anti-AT1R antibodies in these patients using the enzyme-linked immunosorbent assay (ELISA) method. A result ≥ 10 was assessed as positive. An immunohistochemical evaluation of AT1-Receptor expression was performed on 4 µm-thick paraffin sections mounted on salinized slides. RESULTS: We checked 156 samples of biopsies for the immunoreactivity of the AT1-Receptor. Additionally, we analyzed the presence of anti-AT1R antibodies in these patients using the ELISA method. A group of 67 patients had positive AT1-Receptor expression, and 16 patients had positive anti-AT1R antibodies (R+Ab+) results. A group of 89 patients had no expression of AT1-Receptor, among which 51 had also no anti-AT1R (R-Ab-). One-year postbiopsy graft loss in the R+Ab+ patients was 37% (6/16) compared to 10% (7/69) in the R-Ab- patients (P = .006). Two-year and 3-year graft loss was 43% versus 17% and 50% versus 21%, respectively. CONCLUSIONS: The presence of anti-AT1R antibodies in serum together with the expression of AT1-Receptor in transplant biopsies was associated with a significantly higher graft loss. The relevance of AT1-Receptor expression analyzed together with anti-AT1R antibodies should be considered for better transplant immunologic risk assessment.

Effect of Perioperative Optimization of Arterial Oxygen Content and Perfusion Pressure on the Function of the Transplanted Kidney in the Retrospective Study of Excretory Function and Assessment of New Markers of Kidney Damage: IL-18, Neutrophil Gelatinase-Associated Lipocalin, and Clusterin.

INTRODUCTION: The concept of anesthesia, in which kidney perfusion is optimized, the use of nephrotoxic drugs is avoided, and general anesthesia with protective and preconditioning properties of the graft is applied, is a key element of the therapeutic strategy in kidney transplantation (KTx). MATERIAL AND METHOD: A total of 86 patients (mean age: 49.4 ± 14.0 years, 66% men) with end-stage renal disease who underwent KTx between 2012 and 2015 were included in this retrospective study. Our aim was to assess the effect of oxygen content in arterial blood and selected hemodynamic parameters on the graft function and the occurrence of delayed graft failure. RESULTS: No differences were found in baseline characteristics, indication for transplantation, and surgical technique used among study population. No correlation was found between oxygen delivery exponents and both standard markers of renal function and new biochemical markers (eg, IL-18, clusterin, and neutrophil gelatinase-associated lipocalin [NGAL]). DISCUSSION: In our study, hemodynamic parameters measured at scheduled intervals did not exceed the physiological range, which might have been the reason for the lack of correlation between the function of graft and the described hemodynamic conditions. At the same time, in the observed ranges of perfusion pressure during optimization of the oxygen content, no correlations were found with the postoperative function of the transplanted kidney. That observation could be a valuable conclusion for reducing the tendency of maintaining high blood pressure with the abuse of catecholamines, especially vasoconstrictors, and volume therapy, whose negative effect on tissue perfusion is unequivocal.

Conversion From a Twice-Daily to a Once-Daily Tacrolimus Formulation in Kidney Transplant Recipients.

BACKGROUND: The aim of the study was to assess bioavailability aspects of tacrolimus formulations during conversion from twice-daily (TAC BID) to once-daily (TAC OD) formulation in 89 stable kidney transplant recipients. MATERIALS AND METHODS: The study included 89 stable kidney transplant recipients transplanted between 1998 and 2008 (37 female, 52 male, aged 46.0 ± 12.4 years) and followed for 10 years. For a comprehensive comparison of the different tacrolimus formulations, dose-normalized trough levels (ng/mL/mg total daily dose, C/D ratio) and their variability were studied for 10 consecutive visits before and 6 months after conversion. RESULTS: The mean trough level decreased significantly 14 days after conversion (16%, 5.77 ± 1.94 [5.6, 4.5-6.5] ng/mL, P < .001). There was no significant difference between the tacrolimus trough levels before and 3 months after conversion (6.92 ± 1.89 [6.8, 5.9-8.0] ng/mL, P = .548). The tacrolimus daily dose 3 months after conversion (4.56 ± 1.81 [4.5, 3.5-5.5] mg/d) was significantly higher than the dose before conversion (4.16 ± 1.80 [4.0, 3.0-5.0] mg/d, P = .006). The post-conversion mean TAC trough level (10 measures) (6.6 [6.2-7.0] ng/mL) was similar to preconversion level (6.8 [5.6-7.9] ng/mL, P = .203). C/D ratio as well as C/D intrapatient variability (CV%) did not change during conversion (C/D 1.68 [1.36-2.53] vs 1.74 [1.41 vs 2.31], P = .075; CV% 19.5 [16.4-26.6] vs 24.4 [17.5-28.3], P = .114). CONCLUSIONS: Conversion from TAC BID to TAC OD is associated with a significant increase in tacrolimus dose during the first 3 months. In a long-term observation both formulations present similar dose-normalized trough levels and variability.

Liver function after transplantation in the assessment of the coagulation system and the concept of antithrombotic therapy.

INTRODUCTION: Thrombotic complications after liver transplantation limit the long-term success of the procedure. Therefore, an early and accurate diagnosis with the appropriate treatment is crucial to sustain the proper functioning of the graft. AIM: To evaluate the return of newly transplanted liver function within the first days of ICU stay after liver transplantation surgery (Ltx) observed in laboratory examination. It is important to understand the physiology of the newly transplanted liver, particularly in terms of its metabolic function and the assessment of easy-to-monitor coagulation parameters and enzyme markers. MATERIAL AND METHODS: We present our observations carried out in 27 patients, transplanted in the period 2015-2017, during their stay in the Department of Anaesthesiology and Intensive Therapy of the University Hospital in Wroclaw. We demonstrated changes in laboratory parameters within 72 h after liver transplantation and the concept of anticoagulant therapy at our institution. RESULTS: The presented results show the characteristics of aspartate transaminase, alanine transaminase, bilirubin, and standard tests evaluating the coagulation system within the first 4 days after surgery. The concept of anticoagulant therapy used in our intensive care unit is also presented. The aim of the work is an observation of physiology of the graft function in the aspect of coagulation disorders. CONCLUSIONS: The early postoperative period is considered prognostic. The characteristics of basic biochemical tests are determined by the function of the transplanted organ. Implementation of anticoagulant therapy in this period is a therapeutic challenge that requires experience.