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Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of malignant and non-malignant disorders. CARs are synthetic transmembrane receptors expressed on genetically modified immune effector cells, including T cells, natural killer (NK) cells, or macrophages, which are able to recognize specific surface antigens on target cells and eliminate them. CAR-modified immune cells mediate cytotoxic antitumor effects via numerous mechanisms, including the perforin and granzyme pathway, Fas and Fas Ligand (FasL) pathway, and cytokine secretion. High hopes are associated with the prospective use of the CAR-T strategy against solid cancers, especially the ones resistant to standard oncological therapies, such as pancreatic cancer (PC). Herein, we summarize the current pre-clinical and clinical studies evaluating potential tumor-associated antigens (TAA), CAR-T cell toxicities, and their efficacy in PC. [ABSTRACT FROM AUTHOR]

Abstract: Cathepsin B and L are active in several physiological processes that occur in the human body. Their synthesis and activity is detectable in several tissues and processes, including skin hyperkeratosis, insemination, and embryonic development. Proteolytic enzymes are very important cellular constituents and have been the subject of much research. The enzymes are in the limelight of scientists first of all as ECM degradation factors. Most publications describe proteolytic enzymes as tumor and metastasis factors. These proteases also have a central function as apoptosis factors. The aim of this study was to evaluate correlations between age and the enzymatic activities of the proteolytic enzymes cathepsin B and L together. This research was conducted using blood samples provided by healthy people (n =60, 30 men and 30 women). Subjects were subdivided into groups with respect to age: young (about 20 years old, n =20), middle age (about 50 years old, n =20), and elderly (about 80 years old, n =20). Fluorometric assay was used to determine proteolytic enzyme activity. Cathepsin B and L activity was measured as a total activity. The activity of cathepsin B and L significantly increases with age. [Copyright &y& Elsevier]

Long-lasting diabetes mellitus type 1 and end-stage renal disease induce severe metabolic and immunologic deterioration. Pretransplant C-reactive protein (CRP) and albumin (ALB) levels impact kidney transplantation. We evaluated the effects of preoperative CRP, ALB, neutrophils (NEU), and platelet (PLT) counts on 1- and 5-year recipient survival after simultaneous pancreas and kidney transplantation (SPK). Among 103 SPK recipients, the parameters were as follows: CRP (mean: 4.5 ± 4.97 mg/L); NEU (mean: 5.12 ± 2.13 × 103/mm3); PLT (mean: 244 ± 84 × 103/mm3); ALB (mean 4.5 ± 0.75 g/dL) were obtained before transplantation. Cox regression, uni-, multivariate analysis for 1- and 5-year survivals were performed with 95% CIs, and the area under the receiver operating characteristic (ROC) curve (AUC) was assessed. In Cox regression, ALB <3.65 g/dL significantly affected 1- and 5-year survivors with hazard ratios of 8 (95% CI, 1.5–38.28; P <.05) and 3.13 (95% CI, 1.45–6.73; P <.05), respectively. In univariate analysis, we found significantly decreased 1-year survival when PLT <180×103/mm3, ALB <3.65 g/dL, NEU >5.8×103/mm3 and CRP >2.25 mg/L with odds ratios (OR) of 6.75 (95% CI, 2.12–21.15); 4.05 (95% CI, 1.3–12.09); 2.97 (95% CI, 1.02–8.64) and 5.51 (95% CI, 1.67–18.19), respectively. Independent factors for 5-year survival were CRP, ALB, and PLT with OR of 4.72 (95% CI, 1.67–13.29), 3.31 (95% CI, 1.18–9.25), and 4.2 (95% CI, 1.39–12.68), respectively. In multivariate analysis, we built 2 models for 1-year survival. Model 1 (ALB+PLT) with ORs of 3.12 (95% CI, 0.97–10.07) and 5.55 (95% CI, 1.67–18.4); and model 2 (CRP+PLT) with ORs of 5.51 (95% CI, 1.5–17.3) and 4.3 (95% CI, 1.2–15.06), respectively. The AUC for models 1 and 2 were 0.74 and 0.759, respectively. NEU, PLT, ALB, and CRP levels assessed before transplantation are independent factors for 1- and 5-year SPK recipient survival. [ABSTRACT FROM AUTHOR]

Background: Obesity is a risk factor for many diseases, diagnosed by calculating body mass index (BMI). Methods: To find an association between BMI and mortality in adults, we searched PubMed for articles published in the 21st century. Our review included 82 original studies, comprising 2.7 million patients and 23.4 million patient years. Results: The meta-analysis showed a U-shaped relationship between BMI and all-cause mortality risk, with the lowest mortality in the BMI range of 25–30 kg/m2. Subgroup analysis showed a J-shaped relationship, with greater risk in the highest BMI range (>35 kg/m2). Among the elderly, BMI values <20 kg/m2 were associated with the highest risk. Among diabetic patients, a U-shaped relationship was noticed, again with the highest risk in the lowest (<20 kg/m2) and highest BMI range (>35 kg/m2). Among patients with cardiovascular disease, the risk increased with BMI values <25 kg/m2 but did not noticeably change for BMI exceeding that value. Among cancer patients, the relationship was less pronounced than in other subgroups, with a slightly higher risk (>35 kg/m2). Conclusions: Our results show that the lowest mortality is observed among patients with BMI 25–30 kg/m2. Reduction of body mass should not be a universal recommendation in clinical practice, but it should be individualized. [ABSTRACT FROM AUTHOR]

Background: Advanced renal cell carcinoma (RCC) is therapeutically challenging. RCC progression is facilitated by mesenchymal stem/stromal cells (MSCs) that exert remarkable tumor tropism. The specific mechanisms mediating MSCs' migration to RCC remain unknown. Here, we aimed to comprehensively analyze RCC secretome to identify MSCs attractants. Methods: Conditioned media (CM) were collected from five RCC-derived cell lines (Caki-1, 786-O, A498, KIJ265T and KIJ308T) and non-tumorous control cell line (RPTEC/TERT1) and analyzed using cytokine arrays targeting 274 cytokines in addition to global CM proteomics. MSCs were isolated from bone marrow of patients undergoing standard orthopedic surgeries. RCC CM and the selected recombinant cytokines were used to analyze their influence on MSCs migration and microarray-targeted gene expression. The expression of genes encoding cytokines was evaluated in 100 matched-paired control-RCC tumor samples. Results: When compared with normal cells, CM from advanced RCC cell lines (Caki-1 and KIJ265T) were the strongest stimulators of MSCs migration. Targeted analysis of 274 cytokines and global proteomics of RCC CM revealed decreased DPP4 and EGF, as well as increased AREG, FN1 and MMP1, with consistently altered gene expression in RCC cell lines and tumors. AREG and FN1 stimulated, while DPP4 attenuated MSCs migration. RCC CM induced MSCs' transcriptional reprogramming, stimulating the expression of CD44, PTX3 and RAB27B. RCC cells secreted hyaluronic acid (HA), a CD44 ligand mediating MSCs' homing to the kidney. AREG emerged as an upregulator of MSCs' transcription. Conclusions: Advanced RCC cells secrete AREG, FN1 and HA to induce MSCs migration, while DPP4 loss prevents its inhibitory effect on MSCs homing. RCC secretome induces MSCs' transcriptional reprograming to facilitate their migration. The identified components of RCC secretome represent potential therapeutic targets. Highlights: Mesenchymal stem/stromal cells (MSCs) facilitate renal cell cancer (RCC) progression RCC secretes high amounts of AREG and FN1 DPP4 secretion is attenuated in RCC cells AREG and FN1 stimulate, while DPP4 attenuates MSCs migration RCC secretome reprograms MSCs transcription to facilitate their migration [ABSTRACT FROM AUTHOR]

Tobacco smoking is deleterious to the lungs because it exposes them to many toxic substances. These include transition metal ions, such as cadmium. However, there is a lack of information about the influence of endogenous metal-binding peptides, such as His-Leu (HL), on the lung distribution of transition metals in smokers. To address this, we administered HL subcutaneously to rats exposed to tobacco smoke for six weeks, then we measured the concentrations of transition metal ions in the lungs. We found that exposure to tobacco smoke elevates the concentrations of Cd(II) and Cu(II). Administration of the HL peptide, whose elevation is a consequence of angiotensin receptor blocker anti-hypertension therapy, increases the concentration of Fe in the lungs of rats exposed to smoke. These findings suggest that smoking is a risk factor for patients receiving angiotensin receptor blockers to treat hypertension. [ABSTRACT FROM AUTHOR]

Heart failure is defined as a clinical syndrome consisting of key symptoms and is due to a structural and/or functional alteration of the heart that results in increased intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise. One of the key mechanisms determining myocardial dysfunction in heart failure is oxidative stress. MicroRNAs (miRNAs, miRs) are short, endogenous, conserved, single-stranded non-coding RNAs of around 21–25 nucleotides in length that act as regulators of multiple processes. A systematic review following the PRISMA guidelines was performed on the evidence on the interplay between microRNA and oxidative stress in heart failure. A search of Pubmed, Embase, Scopus, and Scopus direct databases using the following search terms: 'heart failure' AND 'oxidative stress' AND 'microRNA' or 'heart failure' AND 'oxidative stress' AND 'miRNA' was conducted and resulted in 464 articles. Out of them, 15 full text articles were eligible for inclusion in the qualitative analysis. Multiple microRNAs are involved in the processes associated with oxidative stress leading to heart failure development including mitochondrial integrity and function, antioxidant defense, iron overload, ferroptosis, and survival pathways. [ABSTRACT FROM AUTHOR]

Introduction: The literature points to several viruses associated with brain carcinogenesis, including gliomas. Aim: The aim of this study was to assess the presence of several viruses in gliomas and plasma from patients with brain tumor and the possible association of viral positivity with the clinical course. Material and methods: The study group consisted of 37 patients with gliomas who were subjected to surgery. Mean patient age was 54.59 (SD 15.85) years. The presence of viral DNA was assessed using real-time polymerase chain reaction. Results and discussion: We did not confirm any BK virus, John Cunningham virus, or human adenovirus-positive gliomas. The percentage of patients with gliomas positive for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus (HHV) 6 and 7 was 18.9%, 8.1%, 2.7%, and 10.8%, respectively. We did not confirm the co-occurrence of glioma and plasma viral positivity. Fisher’s test did not reveal the influence of viral infection on the risk of death. We did not detect any differences regarding sex, WHO classification of gliomas, or the functional impairment evaluated by the Karnofsky scale index at admission to the hospital in the group of patients positive or negative for EBV, CMV, or HHV6. Conclusions: We cannot confirm an association of the investigated viruses with gliomas. [ABSTRACT FROM AUTHOR]

Statins are lipid-lowering medications used for the prevention of cardiovascular disease (CVD), but the pleiotropic effects of statins might be beneficial in other chronic diseases. This meta-analysis investigated the association between statin use and mortality in different chronic conditions. Eligible studies were real-world studies that compared all-cause mortality over at least 12 months between propensity score-matched statin users and non-users. Overall, 54 studies were included: 21 in CVD, 6 in chronic kidney disease, 6 in chronic inflammatory diseases, 3 in cancer, and 18 in other diseases. The risk of all-cause mortality was significantly reduced in statin users (hazard ratio: 0.72, 95% confidence interval: 0.66–0.76). The reduction in mortality risk was similar in CVD studies (0.73, 0.66–0.76) and non-CVD studies (0.70, 0.67–0.79). There were no significant differences in the risk reduction between cohorts with different diseases (p = 0.179). The greatest mortality reduction was seen in studies from Asia (0.61, 0.61–0.73) and the lowest in studies from North America (0.78, 0.73–0.83) and Australia (0.78, 0.62–0.97). There was a significant heterogeneity (I2 = 95%, tau2 = 0.029, p < 0.01). In conclusion, statin use was associated with a significantly reduced risk of all-cause mortality in real-world cohorts with CVD and non-CVD. [ABSTRACT FROM AUTHOR]

Antibody-mediated rejection (AMR) remains challenging in kidney transplant recipients. It may negatively impact the graft survival, and its treatment is associated to relatively high expenses. The aim of our study was to assess the costs of treatment of acute AMR in the Polish settings. A total of 11 kidney transplant recipients with acute AMR diagnosed between September 2016 and August 2019 and treated in our center were included. Direct costs of inpatient and outpatient care in the first year after AMR diagnosis from the perspective of a transplant center were retrospectively calculated. The costs of treatment of acute AMR were considerably high, with a mean 1-month cost of treatment 12,718 PLN (∼€2925; ∼3307 US dollars). That means that costs of management of kidney transplant recipients with acute AMR are almost 2-fold higher than hemodialysis. Intravenous immunoglobulin was responsible for the majority (55%) of costs. Treatment of acute AMR increases the costs of post–kidney transplant care in involved patients. Therefore, efforts should be made to minimize the risk for acute AMR. Despite its potential clinical benefits, management of acute AMR is even more expensive than dialysis. Therefore, further cost-effectiveness analyses are needed to justify the spending and to establish the best treatment regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: Organ graft type is an independent risk factor for the development of PTLD. Due to small cohort sizes caused by the rarity of the disease, most studies and trials are performed on populations of recipients of various organ graft types. Our study is a first direct comparison of the effect of different risk and prognostic factors between kidney and liver transplant recipients (KTRs and LTRs, respectively). We have demonstrated that the analysis of risk factors based on the general solid organ transplant recipient population is inconsistent with the results obtained through the analysis of single organ graft type cohorts. The risk of PTLD is lower in KTRs who are female, <45 years old at transplantation, or treated with cyclosporin. Based upon our findings, we are confident that the type of organ graft is an overriding factor in PTLDs' development and course. Post-transplantation lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation (SOT). Its development risk varies among organ graft recipients. In this study, retrospective data were analyzed to compare PTLD's risk and prognostic factors between adult kidney and liver transplant recipients (KTRs and LTRs, respectively). Over 15 years, 2598 KTRs and 1378 LTRs were under observation at our center. Sixteen KTRs (0.62%) and twenty-three LTRs (1.67%) were diagnosed with PTLD. PTLD developed earlier in LTRs (p < 0.001), SOT patients > 45 years old (p = 0.002), and patients receiving tacrolimus (p < 0.001) or not receiving cyclosporin (p = 0.03) at diagnosis. Tacrolimus use, male sex, and age > 45 years old significantly affected the time of PTLD onset in KTRs (hazard ratio (HR) = 18.6, 7.9 and 5.2, respectively). Survival was longer in LTRs < 45 years old (p < 0.009). LTRs were more likely than KTRs to achieve complete remission (p = 0.039). Factors affecting PTLD development and outcome differ between KTRs and LTRs; thus, these populations should be separately evaluated in future studies. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a significant risk factor for developing chronic kidney disease and progression to end-stage renal disease in elderly patients. AKI is also a relatively common complication after kidney transplantation (KTx) associated with graft failure. Since the lifespan of a transplanted kidney is limited, the risk of the loss/deterioration of graft function (DoGF) should be estimated to apply the preventive treatment. The collection of saliva and urine is more convenient than collecting blood and can be performed at home. The study aimed to verify whether non-invasive biomarkers, determined in saliva and urine, may be useful in the prediction of DoGF in kidney transplant recipients (KTRs) (n = 92). Salivary and serum toxins (p-cresol sulfate, pCS; indoxyl sulfate, IS) concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urinary proteins, hemoglobin, and glucose were measured using a semi-quantitative strip test. Salivary IS (odds ratio (OR) = 1.19), and proteinuria (OR = 3.69) were demonstrated as independent factors for the prediction of DoGF. Satisfactory discriminatory power (area under the receiver operating characteristic curve (AUC) = 0.71 ± 0.07) and calibration of the model were obtained. The model showed that categories of the increasing probability of the risk of DoGF are associated with the decreased risk of graft survival. The non-invasive diagnostic biomarkers are a useful screening tool to identify high-risk patients for DoGF. [ABSTRACT FROM AUTHOR]

Background: For long Epstein–Barr virus (EBV) has been suspected to be involved in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to verify the association between EBV, cell-free DNA (cfDNA) and kidney disease in SLE. Methods: Blood samples were obtained from 43 SLE patients and 50 healthy individuals. EBV load was measured via real-time PCR assay. Sizing and quantification of plasma cfDNA was performed on Bioanalyzer. We proposed that the uniformity of cfDNA fragmentation can be described using cfDNA fragmentation index. Results: SLE patients with chronic kidney disease (CKD +) had higher EBV load compared to CKD(–) patients (P = 0.042). Patients with high cfDNA level had higher EBV load (P = 0.041) and higher cfDNA fragmentation index (P < 0.001) compared to patients with low cfDNA level. Among patients with high cfDNA level, EBV load was higher in CKD(+) group compared to CKD(–) group (P = 0.035). EBV load was positively correlated with the fragmentation index in all SLE patients (P = 0.028, R2 = 0.13), and the correlation was even more pronounced in CKD (+) patients (P < 0.001, R2 = 0.20). Conclusions: We showed that EBV load was associated with non-uniform cfDNA fragmentation, higher cfDNA levels, and kidney disease in SLE patients. Although the causality of this relationship could not be determined with the current study, it brings rationale for further investigations on the role of EBV and cfDNA interplay in SLE pathogenesis. [ABSTRACT FROM AUTHOR]

Membranous nephropathy is a glomerulopathy that causes nephrotic syndrome and, in at least a third of cases, lasting end-stage kidney disease (ESKD). It is also a rare case of revolutionary changes in our understanding of the disease, that translates from scientific findings to real diagnosis and treatment recommendations in less than ten years. In this review we present: (1) a short history and traditional approach to patients with membranous nephropathy, (2) current recommendations and treatment options that have emerged in recent years, (3) findings of new studies, with a particular focus on serological/immunological methods, genomic and proteomic studies, still requiring validation. With further development in this field, membranous nephropathy may become one of the first nephrological conditions that apply a truly personalized approach with the omission of invasive measures such as kidney biopsy. [ABSTRACT FROM AUTHOR]

Background: Increased level of cell-free DNA (cf-DNA) is associated with systemic lupus erythematosus (SLE) and might be related to disease activity. The aim of this study was to evaluate whether cfDNA integrity, size distribution and concentration of different cfDNA fractions is associated with lupus activity and kidney involvement. Methods: Blood samples were collected from 43 SLE patients and 50 healthy controls. Nuclear and mitochondrial fractions of cfDNA and intracellular DNA were quantified by real-time qPCR. Sizing and quantification of total cfDNA level was performed on Bioanalyzer. Results: We determined four parameters that characterized cfDNA profile: fragmentation index, ratio of intra- to extracellular mtDNA copy number, cfDNA concentration, and presence of 54–149 bp and 209–297 bp fragments. Patients with healthy-like cfDNA profile had higher eGFR (P = 0.009) and more often no indications for kidney biopsy or less advanced lupus nephritis (LN) (P = 0.037). In contrary, SLE patients with distinct cfDNA profile (characterized by increased cfDNA concentration and fragmentation, higher discrepancy between intra- to extracellular mtDNA copy number, and the presence of 54–149 bp and 209–297 bp fragments) had lower eGFR (P = 0.005) and more often advanced LN or history of renal transplantation (P = 0.001). Conclusions: We showed that cfDNA profiling may help to distinguish SLE patients with renal involvement and severe disease course from patients with more favorable outcomes. We suggest cfDNA profile a promising SLE biomarker. [ABSTRACT FROM AUTHOR]

The recurrence of hepatitis C (HCV) after liver transplant (LTX) leads to graft fibrosis and cirrhosis. Liver biopsy remains the criterion standard for their diagnosis and monitoring. Our objective was evaluation of shear wave elastography (SWE) in patients with HCV recurrence after LTX and its comparison with histopathologic fibrosis assessment scoring systems. A total of 101 LTX recipients with HCV recurrence (42 women [41.6%] and 59 men [58.4%]) were evaluated by graft biopsy specimens (Ishak, Scheurer, and meta-analysis of histologic data in viral hepatitis [Metavir] score) and SWE (liver stiffness). Median age of patients was 59.4 years; median time from LTX was 84.9 months. The study protocol conforms with the Declaration of Helsinki. Median liver stiffness was 21.3 kPa. To differentiate between liver fibrosis and cirrhosis, patients were divided into 2 subgroups: Ishak score fibrosis (1-4 [85.2%]) and cirrhosis (5-6 [13.9%]); Scheurer score fibrosis (0-3 [85.2%]) and cirrhosis (4 [12.9%]); Metavir score fibrosis (0-3 [85.2%]) and cirrhosis (4 [14.9%]). We have observed statistically significant differences between liver fibrosis and liver cirrhosis groups defined on the basis of Ishak, Scheurer, and Metavir scoring systems: 20.8 kPa vs 29.6 kPa (P =.001), 20.7 kPa vs 30.3 kPa (P =.0005), and 20.7 kPa vs 28.8 kPa (P =.002), respectively. Our results indicate that SWE may be useful in differentiating patients with advanced cirrhosis from those with fibrosis and may be helpful in the noninvasive diagnosis and monitoring of HCV recurrence after LTX. • We studied use of shear wave elastography (SWE) after liver transplant. • SWE is useful in identification of liver cirrhosis in liver transplant. • SWE as a noninvasive tool for diagnosis of cirrhosis due to hepatitis C virus recurrence. [ABSTRACT FROM AUTHOR]

Treatment with direct-acting antivirals (DAA) for hepatitis C (HCV) in liver transplant (LTX) recipients is very effective, but some studies showed that the treatment effectiveness might be impaired in patients with hepatocellular carcinoma (HCC). The study aimed to evaluate the predictors of DAA treatment failure in LTX recipients. Liver biopsy was done before the treatment in 107 of the 120 patients included. All patients had an abdominal ultrasound and liver elastography performed before and after the therapy. Blood HCV polymerase chain reaction was done before; during; and at 4, 12, and 24 weeks after the treatment. Overall sustained viral response 24 weeks after treatment (SVR24) was 96%. There were 2 patients with HCC at the start of the DAA treatment and 3 cases of HCC recurrence during a 1-year follow-up. Treatment failure was observed in 1/115 (0.9%) patients without HCC and 4/5 (80%) with active HCC (P =.0001). Liver fibrosis and previous interferon treatment had no impact on treatment efficacy. Time to viremia elimination on treatment was shorter in the responder versus nonresponder group (28 vs 58 days, P =.03). HCC is a negative predictor of DAA therapy success in LTX recipients. • The degree of liver fibrosis has no effect on the efficacy of DAA therapy. • Previous interferon treatment has no effect on the efficacy of DAA therapy. • HCC before or soon after DAA therapy is a negative predictor of treatment success. • The efficacy of DAA treatment after LTX is very high. [ABSTRACT FROM AUTHOR]

Calcineurin inhibitors (CNIs), tacrolimus and cyclosporine, undergo pharmacokinetic processes. Enzymes and transport proteins found in various organs are involved. It is possible that genetic polymorphisms of these proteins influence CNIs pharmacokinetics and the generation of CNIs metabolites. CNIs may be nephrotoxic, and it is thought that some CNIs' metabolites may have a similar effect. The study was aimed at the assessment of the relationship between selected gene polymorphisms for enzymes and transport proteins and change of estimated glomerular filtration rate (eGFR) during a 2-year follow-up in kidney transplant (KTX) patients. The study involved 366 patients after KTX (160 women; 43.7%) receiving tacrolimus (62.57%) and cyclosporine (37.43%). The mean age was 50.1 years, and the median time after KTX was 60.5 months. The study protocol conformed with the Declaration of Helsinki. The percent of difference between eGFR at baseline and at 24 months (ΔeGFR) was calculated. We evaluated selected genetic polymorphisms of CYP3A4, CYP3A5, MDR1, UGT1A9, UGT2B7, UGT1A8, and MRP2. In the tacrolimus group, there were no significant differences of ΔeGFR between groups distinguished based on analyzed genotypes. In the cyclosporine group, differences were found for CYP3A4∗22 C/C -12.3 (-26.8 to -1.8) versus C/T 13.2 (12.4 to 13.9), P =.034; MDR1 3435C>T C/T -18.2 (-31.5 to -5.7) versus C/C -1.8 (-17.1 to 6.9) vs T/T -8.1 (-18.4 to 12.4), P =.031; and UGT1A9 2152C>T C/C -9.0 (-25.5 to 2.8) versus C/T -26.8 (-31.9 to -24.1), P =.017. The study results suggest that in KTX metabolic transformations and transport, especially of cyclosporine, dependence on the genetic variability of CYP3A4, UGT1A9, and MDR1 may contribute to kidney damage. • During CsA therapy, there was deterioration of kidney graft function associated with CYP3A4∗22. • During CsA therapy, there was deterioration of kidney graft function associated with MDR13435C>T. • During CsA therapy, there was deterioration of kidney graft associated with UGT1A92152C>T. [ABSTRACT FROM AUTHOR]

The prolonged survival time after liver transplantation (LTX) creates the possibility of the occurrence and development of complications in the late post-transplantation period. Deterioration of renal function is 1 of these complications. The nephrotoxicity of calcineurin inhibitors (CNIs) and their metabolites produced during pharmacokinetic processes in the body is also postulated. The study was aimed at assessment of the relationship between selected single gene polymorphisms (SNPs) for enzymes and transport proteins and change of estimated glomerular filtration rate (ΔeGFR) during 2-year follow-up in LTX patients. The study involved 244 patients after LTX (105 women [43.0%] and 139 men [57.0%]) receiving tacrolimus (191; 78.3%) or cyclosporine A (53; 21.7%). The study protocol conforms with the Declaration of Helsinki. We have not observed significant differences of ΔeGFR between groups distinguished based on analyzed genotypes in patients treated with cyclosporine or tacrolimus. Genetic variations of CYP3A4, CYP3A5, MDR1, MRP2, UGT1A9, UGT2B7, and UGT2B7 tested in LTX recipients are not associated with kidney function during the 24-month follow-up. • There was no association of kidney function after LTX with recipient CYP3A5 variants, recipient CYP3A4 variants, recipient MDR1 variants, recipient MRP2 variants, recipient UGT1A9 variants, recipient UGT1A8 variants, or recipient UGT2B7 variants. [ABSTRACT FROM AUTHOR]

Although several analytical techniques are known for their ability to detect fluorine and its compounds, the investigation of its biotransformation in living organisms is not a trivial task. Therefore, much attention is given to the development of new analytical strategies that can trace the metabolism of fluorine-containing compounds. Molecular absorption and mass spectrometry were used as tools to collect complementary information for the investigation of the biotransformation of the fluorine-containing compounds in animal model organisms. The study aimed to examine the effectiveness of the adsorption of fluorine by animal tissues, which was done by measuring the molecular absorption of gallium monofluoride (GaF) using high-resolution continuum source graphite furnace absorption spectrometry (HR-CS GF MAS). The limit of detection (LOD) was 6 μg L−1. Then, the distribution of fluorine-containing compunds was obtained by measuring the studied drug concentrations in animal tissues using high-performance liquid chromatography with electrospray ionisation (ESI) tandem mass spectrometry (HPLC-ESI-MS/MS). The LOD for compounds containing fluorine was 0.05 μg kg−1. Finally, proteins containing fluorine modifications bound in a covalent way were studied using ultra-high performance liquid chromatography coupled to an electrospray mass spectrometer equipped with a high resolution Orbitrap mass analyzer (nano-UHPLC-ESI-(Orbitrap)-MS/MS). The developed analytical protocol contributes to considerable progress in understanding the molecular basis of the influence of fluorine-containing compounds on aminal organisms. [ABSTRACT FROM AUTHOR]

Juvenile rheumatoid arthritis (JRA) is an immune-mediated disease characterized by articular inflammation and subsequent tissue damage that may result in severe disability. Several combinations of drugs, including immunosuppressive agents have been used to control disease progression. Although there is no information available on rapamycin efficacy in JRA, it has demonstrated a potential to inhibit inflammatory processes observed in adult rheumatoid arthritis (RA). We present a 21 years old renal transplant recipient with JRA, primarily treated with tacrolimus and steroids, who achieved a long-term disease remission after introduction of rapamycin. As long as pathogenesis of JRA and RA is similar, we conclude that rapamycin could be promising immunosuppressant for patients after renal transplantation suffering from both JRA and RA. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein X (LpX) is an abnormal lipoprotein fraction, which can be detected in patients with severe hypercholesterolaemia and cholestatic liver disease. LpX is composed largely of phospholipid and free cholesterol, with small amounts of triglyceride, cholesteryl ester and protein. There are no widely available methods for direct measurement of LpX in routine laboratory practice. We present the heterogeneity of clinical and laboratory manifestations of the presence of LpX, a phenomenon which hinders LpX detection. Methods: The study was conducted on a 26-year-old female after liver transplantation (LTx) with severely elevated total cholesterol (TC) of 38 mmol/L and increased cholestatic liver enzymes. TC, free cholesterol (FC), cholesteryl esters (CE), triglycerides, phospholipids, HDL-C, LDL-C, and apolipoproteins Al and B were measured. TC/apoB and FC:CE ratios were calculated. Lipoprotein electrophoresis was performed using a commercially available kit and laboratory-prepared agarose gel. Results: Commercially available electrophoresis failed to demonstrate the presence of LpX. Laboratory-prepared gel clearly revealed the presence of lipoproteins with y mobility characteristic of LpX. The TC/apoB ratio was elevated and the CE level was reduced, confirming the presence of LpX. Regular lipoprotein apheresis was applied as the method of choice in LpX disease and a bridge to reLTx due to chronic liver insufficiency. Conclusions: The detection of LpX is crucial as it may influence the method of treatment. As routinely available biochemical laboratory tests do not always indicate the presence of LpX, in severe hypercholesterolaemia with cholestasis, any discrepancy between electrophoresis and biochemical tests should raise suspicions of LpX disease. [ABSTRACT FROM AUTHOR]

Background. Copper belongs to the essential trace metals that play a key role in the course of cellular processes maintaining the whole body's homeostasis. As there is a growing interest in transplanting mesenchymal stromal cells (MSCs) into the site of injury to improve the regeneration of damaged tendons, the purpose of the study was to verify whether copper supplementation may have a positive effect on the properties of human adipose tissue-derived MSCs (hASCs) which potentially can contribute to improvement of tendon healing. Results. Cellular respiration of hASCs decreased with increasing cupric sulfate concentrations after 5 days of incubation. The treatment with CuSO4 did not positively affect the expression of genes associated with tenogenesis (COL1α1, COL3α1, MKX, and SCX). However, the level of COL1α1 protein, whose transcript was decreased in comparison to a control, was elevated after a 5-day exposition to 25 μM CuSO4. The content of the MKX and SCX protein in hASCs exposed to cupric sulfate was reduced compared to that of untreated control cells, and the level of the COL3α1 protein remained unchanged. The addition of cupric sulfate to hASCs' medium increased the activity of lysyl oxidase which was positively correlated with concentration of CuSO4. Moreover, a high level of CuSO4 stimulated the action of intracellular superoxide dysmutase. The hASC secretion profile after a 5-day exposure to 50 μM cupric sulfate differed from that of untreated cells and was similar to the secretion profile of human tenocytes. Additionally, cupric sulfate increased secretion of CXCL12 in hASCs. Furthermore, the exposition to the CuSO4 significantly increased directed migration of human ASCs in a dose-dependent manner. Conclusion. Copper sulfate supplementation can have a beneficial effect on tendon regeneration not by inducing tenogenic differentiation, but by improving the recruitment of MSCs to the site of injury, where they can secrete growth factors, cytokines and chemokines, and prevent the effects of oxidative stress at the site of inflammation, as well as improve the stabilization of collagen fibers, thereby accelerating the process of tendon healing. [ABSTRACT FROM AUTHOR]

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic renal disease with a prevalence of 1:1,000 births and it is the 4th most common cause of dialysis-dependent end-stage renal disease (ESDR). Recent reports suggest an association between APDKD and metabolic derangements, particularly impaired glucose metabolism. Methods: In this cross-sectional study we analyzed data obtained from case records of 189 patients with ADPKD, including kidney transplant recipients, managed in an outpatient department. Results: The mean BMI was 25.4 ± 3.9; 25.25 before and 27.7 after transplan-tation. A fasting glucose level above 100 mg/dL (5.6 mmol/L) was observed in 60 patients (29%) – 27% without transplantation and 41% kidney transplant recipients. Diabetes mellitus was diagnosed in 17 patients (8.9%), including 3 (2.3%) without a history of transplantation and 14 (24.1%) after kidney transplantation (p < 0.01). We observed dyslipidemia in 30% and hyperuricemia in 53% of patients. Conclusion: Demonstrated metabolic abnormalities should be considered in maintenance of ADPKD patients, including kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background and purpose: Therapeutic drug monitoring is a valuable tool supporting immunosuppressive therapy. Significant variation of immunosuppressive drug (ISD) concentrations during their use at similar doses is the basis of dose-normalization strategy. The strategy of dose-adjustment is proposed to identify variability in the rate of ISD metabolism. While the parent drug-to-metabolite ratio (metabolic ratio, MR) represents the rate of formation of individual metabolites. The present study was aimed at evaluation of associations between ISDs' metabolism rate expressed as dose-adjusted concentrations (C/D) and dose/kg-adjusted concentrations (C/D/kg) and MRs of individual metabolites of tacrolimus, cyclosporine A and MPA precursors. Experimental approach: 506 patients have participated: 284 males (56.13%) and 222 females (43.87%); 318 after kidney (62.85%) and 188 after liver transplantation; median age was 51.34 (39.32-59.95) years and median time after transplantation 78.92 (33.87-138.4) months. Key results: Generally, we have not observed significant relationships between dose-adjusted and dose/kg-adjusted concentrations and MRs of cyclosporine and tacrolimus. Significant correlations were found for: AM9/CsA and dMC-CsA/CsA in kidney transplant recipients and MIII/Tac, AM1/CsA and AM4N/CsA in liver transplant recipients. In contrast, MRs of mycophenolic acid (MPA) metabolites correlated significantly with MPA C/D and C/D/kg both in kidney and liver transplant recipients. Conclusion and implications: In conclusion, easily available and easy to use in clinical practice C/D and C/D/kg ratios cannot be considered as parameters directly reflecting the rate of generation of major metabolites of cyclosporine and tacrolimus both in liver and kidney transplant recipients. [ABSTRACT FROM AUTHOR]

• Serum VCAM1, TNF and IL-6 were significantly higher in more advanced CKD stages. • IL-6 correlated significantly with calcium score, age, renal function and CRP. • IL-6 and calcium score were associated with 5-year mortality risk in CKD patients. • Chronic inflammation may contribute to cardiovascular mortality in CKD patients. Patients with chronic kidney disease (CKD) have a high risk of death mainly due to cardiovascular diseases (CVD). Early risk identification may allow interventions and prevention of fatal events. The study aim was to assess the usefulness of selected CVD biomarkers as predictors of 5-year mortality in patients with different CKD stages. Study included 57 CKD patients: 38 in stage 5 (ESRD), 19 in stage 3 and 4 (CKD3-4), and 19 healthy controls. Blood samples were obtained once to measure fetuin A, adiponectin, leptin, tumor necrosis factor (TNF), interleukin-6 (IL-6), metalloproteinase-9 (MMP9), intracellular-1 (ICAM1) and vascular-1 (VCAM1) adhesion molecules (ELISA or Luminex platform). Computed tomography was performed to assess the calcium score (CS). Patients were prospectively followed for 5 years to evaluate their all-cause mortality. Serum VCAM1, TNF and IL-6 were significantly higher in more advanced CKD stages. VCAM1 correlated significantly with ICAM1, TNF and IL-6. TNF and IL-6 were also significantly correlated with each other. No significant changes were detected for other markers. IL-6 correlated significantly with CS, age, renal function and CRP. Elevated CS and IL-6 increased over 3 times the 5-year all-cause and cardiovascular mortality risks in patients with CKD or ESRD at baseline. IL-6 and CS were significantly associated with 5-year risk of all-cause mortality in CKD patients. Our study suggests an involvement of chronic inflammation linked to coronary artery calcification that is likely to contribute to the cardiovascular mortality in patients with impaired renal function. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is associated with increased levels of creatinine and other uremic toxins (UTs), which impaired kidneys cannot filtrate. Typically, CKD is diagnosed by calculating the estimated glomerular filtration rate using serum creatinine or cystatin C levels. In pursuit of more sensitive and reliable biomarkers of kidney dysfunction, scientific attention has turned towards other UTs, such as trimethylamine N-oxide (TMAO), successfully quantified in standard matrices, blood and urine. However, less invasive monitoring of kidney function can be performed using an alternative diagnostic biofluid, saliva, which has been shown to contain clinically relevant concentrations of renal function markers. Accurate quantitative estimation of serum biomarkers using saliva measurements can only be achieved provided that there is a tight saliva-serum correlation for the analyte of interest. Therefore, we aimed to verify the correlation between saliva and serum levels of TMAO in CKD patients using newly developed and validated quantitative liquid chromatography coupled to mass spectrometry (LC-MS) method for simultaneous detection of TMAO, and creatinine – the conventional marker of renal impairment. Secondly, we applied this method to quantify TMAO and creatinine levels in the resting saliva of CKD patients collected with a standardised method involving swab-based collectors. A good linear correlation was obtained between the concentration of creatinine in serum and resting saliva of CKD patients (r = 0.72, p = 0.029) and even better in the case of TMAO (r = 0.81, p = 0.008). The analysed validation criteria were fulfilled. No significant influence of the type of swab in the Salivette® device on creatinine and TMAO concentrations in saliva was detected. Our study indicates that saliva can be successfully used in the non-invasive monitoring of renal failure in CKD by measuring salivary TMAO concentrations. • Novel reliable method for simultaneous determination of TMAO and creatinine in saliva. • No influence of the type of swab on saliva's creatinine and TMAO level. • Strong correlation between salivary and serum's TMAO concentrations. • Salivary TMAO differs more than salivary creatinine across different stages of CKD. • Saliva can be used in the noninvasive monitoring of renal failure in CKD. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 74-year-old white male with sensory neuropathy of unknown origination. Topics discussed include him being treated with pregabalin and tremadol for idiopathic sensory neuropathy; diagnosed with vitamin E deficiency which led to peripheral neuropathy along with low-density lipoprotein cholesterol, and familial hypobetalipoproteinemia; and oral supplements of vitamin E might be profitable.

Background. Cellular therapy is proposed for tendinopathy treatment. Bone marrow- (BM-MSC) and adipose tissue- (ASC) derived mesenchymal stromal cells are candidate populations for such a therapy. The first aim of the study was to compare human BM-MSCs and ASCs for their basal expression of factors associated with tenogenesis as well as chemotaxis. The additional aim was to evaluate if the donor age influences these features. Methods. Cells were isolated from 24 human donors, 8 for each group: hASC, hBM-MSC Y (age≤45), and hBM-MSC A (age>45). The microarray analysis was performed on RNA isolated from hASC and hBM-MSC A cells. Based on microarray results, 8 factors were chosen for further evaluation. Two genes were additionally included in the analysis: SCLERAXIS and PPARγ. All these 10 factors were tested for gene expression by the qRT-PCR method, and all except of RUNX2 were additionally evaluated for protein expression or secretion. Results. Microarray analysis showed over 1,400 genes with a significantly different expression between hASC and hBM-MSC groups. Eight of these genes were selected for further analysis: CXCL6, CXCL12, CXCL16, TGF-β2, SMAD3, COLLAGEN 14A1, MOHAWK, and RUNX2. In the subsequent qRT-PCR analysis, hBM-MSCs showed a significantly higher expression than did hASCs in following genes: CXCL12, CXCL16, TGF-β2, SMAD3, COLLAGEN 14A1, and SCLERAXIS (p<0.05, regardless of BM donor age). In the case of CXCL12, the difference between hASC and hBM-MSC was significant only for younger BM donors, whereas for COLLAGEN 14A1—only for elder BM donors. PPARγ displayed a higher expression in hASCs compared to hBM-MSCs. In regard to CXCL6, MOHAWK, and RUNX2 gene expression, no statistically significant differences between groups were observed. Conclusions. In the context of cell-based therapy for tendinopathies, bone marrow appears to be a more attractive source of MSCs than does adipose tissue. The age of cell donors seems to be less important than cell source, although cells from elder donors show slightly higher basal tenogenic potential than do cells from younger donors. [ABSTRACT FROM AUTHOR]

Highlights • First LC–MS/MS method of p -cresol determination in plasma. • The IDL is 50 times lower compared with existing methods. • The analyzed validation requirements were fulfilled. • The results have shown that pC is being removed from blood by dialysis. Abstract p -Cresol is a protein-bound uremic retention solute that originates in the intestine through bacterial metabolism and accumulates throughout the body in case of kidney failure. To date, there has been no method to analyze unconjugated p -cresol concentration in the blood with a limit of detection lower than 75 pg. Thus, the aim of this study was to develop and validate a novel liquid chromatography-tandem mass spectrometry method for the determination of unconjugated p -cresol in plasma with a lower detection limit than what has been determined using previously described methods. Sample preparation included derivatization of p -cresol with dansyl chloride (derivatization reagent) showed to be a better approach to analyze the compound. The method optimization involved various pH, time of the reaction, and concentration of derivatization reagent. The validation process was performed according to the procedures prescribed by the European Medicines Agency. All analyzed validation criteria were fulfilled. The novel validated method was applied to compare the level of p -cresol in patients with chronic renal failure before and after dialysis (n = 24). Additionally, the concentration of p -cresol was determined in patients with multiple organ dysfunction syndrome (n = 23). The established method can be used for determination of p -cresol in the plasma in further clinical research. [ABSTRACT FROM AUTHOR]

Background: p-Cresol sulfate (pCS) and indoxyl sulfate (IS) are uremic toxins, high concentrations of which are related to renal failure progression. Saliva could become the first-line diagnostic sample of choice, especially for monitoring purposes. Recently, a method for determination of pCS and IS in saliva was developed. Since no data exist on correlations between the levels of toxins in saliva and serum, the applicability of saliva as a diagnostic material is yet to be established. Here, we present a study on the assessment of the utility of saliva testing in the estimation of uremic toxin levels in serum. Methods: The study material included serum and unstimulated, fasting saliva obtained from healthy volunteers (n=26) and patients at all stages of chronic kidney diseases (CKD, n=93). The concentration of pCS and IS in saliva and serum (total and unbound fractions) was determined. The daytime variation of the toxins was studied. Results: A correlation was found between pCS and IS in saliva and biological active fractions in serum (0.74; 0.81). The variation of the serum/saliva ratio during the day was negligible, with a median of 10% for pCS and 6% for IS, making saliva a reliable material for the estimation of the uremic toxins in circulation at any time of the day. Significant correlations were observed between salivary toxin levels and estimated glomerular filtration rate (pCS: −0.61; IS: −0.70) as well as significant differences in toxin levels between the stages of CKD. Conclusions: Saliva could be a valuable diagnostic material for the estimation of toxin levels in circulation. [ABSTRACT FROM AUTHOR]

Several studies have suggested negative effects of trimethylamine oxide (TMAO) on the circulatory system. However, a number of studies have shown protective functions of TMAO, a piezolyte and osmolyte, in animals exposed to high hydrostatic and/or osmotic stress. We evaluated the effects of TMAO treatment on the development of hypertension and its complications in male spontaneously hypertensive rats (SHRs) maintained on water (SHR-Water) and SHRs drinking TMAO water solution from weaning (SHR-TMAO). Wistar-Kyoto (WKY) rats were used as normotensive controls to discriminate between agedependent and hypertension-dependent changes. Telemetry measurements of blood pressure were performed in rats between the 7th and 16th weeks of life. Anesthetized rats underwent echocardiographic, electrocardiographic, and direct left ventricular end-diastolic pressure (LVEDP) measurements. Hematoxylin and eosin as well as van Gieson staining for histopathological evaluation were performed. Plasma TMAO measured by chromatography coupled with mass spectrometry was significantly higher in the SHR-Water group compared with the WKY group (~20%). TMAO treatment increased plasma TMAO by four- to fivefold and did not affect the development of hypertension in SHRs. Sixteen-week-old rats in the SHR-Water and SHR-TMAO groups (12-wk TMAO treatment) showed similar blood pressures, angiopathy, and cardiac hypertrophy. However, the SHRTMAO group had lower plasma NH2-terminal pro-B-type natriuretic peptide, LVEDP, and cardiac fibrosis. In contrast to age-matched WKY rats, 60-wk-old SHRs showed hypertensive angiopathy and heart failure with preserved ejection fraction. Compared with the SHR-Water group, the SHR-TMAO group (56-wk TMAO treatment) showed significantly lower plasma NH2-terminal pro-B-type natriuretic peptide and vasopressin, significantly lower LVEDP, and cardiac fibrosis. In conclusion, a four- to fivefold increase in plasma TMAO does not exert negative effects on the circulatory system. In contrast, increased dietary TMAO seems to reduce diastolic dysfunction in pressure-overloaded hearts in rats. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was assessment of four selected macromolecules level: osteopontin, calgranulin, uromodulin and bikunin in fresh morning urine sample in children with nephrolithiasis in the course of idiopathic hypercalciuria. Materials and Methods: The study included 90 subjects aged from 12 months to 18 years. The study group comprised 57 subjects- children with urinary tract lithiasis in the course of idiopathic hypercalciuria and the control group - 33 healthy children with no history of urolithiasis. Determinations of osteopontin, calgranulin, uromodulin and bikunin levels in the first morning urine were performed. Results: The study group had a significantly decreased osteopontin excretion and significantly increased bikunin excretion, and increased, however statistically nonsignificant, calgranulin excretion in comparison with the control group. Uromodulin excretion did not differ between groups. In both groups a statistically significant positive correlation was observed between uromodulin and bikunin levels. Conclusion: Children with urinary tract lithiasis in the course of idiopathic hypercalciuria reveal a different distribution of the study proteins than a healthy population. [ABSTRACT FROM AUTHOR]

Except for benefits in survival and quality of life, renal transplantation is considered a method that is cheaper compared to alternative modalities of renal replacement therapy; it is thought that, after the first post-transplant year, costs of care decrease and then remain relatively low. However, over time, health problems accumulate in transplant recipients, which may be connected to increased costs of care. In this study, we attempted to verify whether costs of care actually remain low until the graft loss. This study included 20 renal transplant recipients with grafts functioning at least 5 years post transplant who were managed in our transplant center and who lost their transplants in 2017 or 2018. Costs of post–renal transplant care in consecutive years post transplant were retrospectively assessed in these cases. Direct costs of inpatient as well as outpatient care, from the perspective of a transplant center, were considered. This study included 8 (40%) men and 12 (60%) women. A significant increase in costs of care was observed in the final period of graft function at least in the year of graft loss. It was observed both in those who lost the transplant because of the graft failure and in those who died with a functioning graft. However, despite this increase, mean costs of post-transplant care in the last 6 years of graft function remained lower compared to hemodialysis. Despite the increase in costs of post–renal transplant care observed in the final period of graft function, treatment with renal transplantation remains cheaper compared with hemodialysis. • A significant increase in costs of care is observed in the final period of graft function. • A significant increase in costs of care is observed both in those who lost the transplant because of the graft failure, and in those who died with a functioning graft. • Despite this fact, treatment with renal transplantation remains cheaper compared to hemodialysis. [ABSTRACT FROM AUTHOR]

Introduction: Intense exercise can cause cellular damage, resulting in activation of inflammatory and fibrotic reactions. Aim: The aim of the present study was to investigate how one session of intense exercise affected liver gene expression and concentrations of tumor necrosis factor a (TNF-a) and profibrotic transforming growth factor ß (TGF-ß) in untrained and trained rats. Material and methods: Here we investigated the impact of intense exercise on liver gene expression and concentrations of TNF-a and TGF-ß in untrained and trained healthy rats (n = 30 each). The trained rats underwent 6 weeks of endurance training with increasing load. From each group, liver samples were collected before, immediately after, and 3 h after one session of intense exercise. Gene expression was evaluated with quantitative real-time polymerase chain reaction. Protein content was measured by enzyme immunoassay. Results and discussion: One session of intense exercise did not influence gene expression at any time point. In trained rats TNF-a and TGF-ß was increased immediately after exercise (P = 0.011 and P = 0.009, respectively). The increase in TGF-ß persisted 3 h post exercise (P = 0.045). In untrained rats the concentration of TNF-a did not change in any time point, while TGF-ß was decreased both immediately and 3 h after intense exercise (P = 0.01 and P = 0.03, respectively). Conclusions: Intense exercise led to increased proinflammatory and profibrotic activity in the liver of trained rats. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was assessment of four selected macromolecules level: osteopontin, calgranulin, uromodulin and bikunin in fresh morning urine sample in children with nephrolithiasis in the course of idiopathic hypercalciuria. Materials and Methods: The study included 90 subjects aged from 12 months to 18 years. The study group comprised 57 subjects-children with urinary tract lithiasis in the course of idiopathic hypercalciuria and the control group - 33 healthy children with no history of urolithiasis. Determinations of osteopontin, calgranulin, uromodulin and bikunin levels in the first morning urine were performed. Results: The study group had a significantly decreased osteopontin excretion and significantly increased bikunin excretion, and increased, however statistically nonsignificant, calgranulin excretion in comparison with the control group. Uromodulin excretion did not differ between groups. In both groups a statistically significant positive correlation was observed between uromodulin and bikunin levels. Conclusion: Children with urinary tract lithiasis in the course of idiopathic hypercalciuria reveal a different distribution of the study proteins than a healthy population. [ABSTRACT FROM AUTHOR]

A case study is presented of a 44-year-old woman presented with autosomal dominant polycystic kidney disease, further abdominal ultrasound revealed a cystic mass in the small pelvis, computed tomography showed spinal meningeal cysts; further magnetic resonance imaging was also performed.

Introduction: The advantages of a minimally invasive nephrectomy are a faster recovery and better quality of life for the donors. Until recently, the majority of donor nephrectomies in Poland were done by open surgery. Aim: To present a single centre experience in hand-assisted laparoscopic donor nephrectomy (HALDN). Material and methods: The first videoscopic left donor nephrectomy in Poland was performed in our department in 2003 using a hand-assisted retroperitoneal approach. From 2011, we changed the method to a transperitoneal approach and started to harvest also right kidneys. Since then, it has become the method of choice for donor nephrectomy and has been performed in 59 cases. Preoperatively, kidneys were assessed by scintigraphy and by angio-computed tomography. We harvested 32 left and 27 right kidneys. There were double renal arteries in 2 cases and triple renal arteries in 1 case. The warm ischaemia time (WIT) was 80-420 s (average 176.13 s); operative time was 85-210 min (average 140 min). Results: All procedures were uncomplicated, and all donors were discharged after 2-8 days with normal creatinine levels. The average follow-up period lasted 23 months (1-51 months). Out of all of the cases, 1 case had two minor complications, while all others were uneventful. None of the donors were lost to follow-up. All of the kidneys were transplanted. There were 2 cases of delayed graft function (DGF) and 2 cases of ureter necrosis. One of those kidneys was lost in the third postoperative week. Conclusions: Our limited experience shows that HALDN is a safe method and should be used routinely instead of open surgery. [ABSTRACT FROM AUTHOR]

Objectives To investigate the effects of propofol and isoflurane on urethral pressure profilometry of female dogs and goats, and to identify the method of anesthesia that least influences urethral pressure profilometry and to assess its reproducibility. Methods The effects of premedication with midazolam, propofol sedation and isoflurane anesthesia were assessed in five female dogs. The effects of propofol and isoflurane were compared in seven goats, whereas in another group of 19 goats, the state of deep propofol sedation was compared with the state of recovery from propofol sedation. The coefficient of reproducibility and within-subject coefficient of variation were calculated to evaluate test-retest reproducibility. Results In conscious female dogs, maximal urethral closure pressure and functional area were significantly higher than under propofol or isoflurane ( P = 0.04), but not different from the recovery state. In six of seven goats, maximal urethral closure pressure and functional area were higher when measured under propofol sedation than under isoflurane (median maximal urethral closure pressure, 69 vs 47 cmH2O; P = 0.03). Maximal urethral closure pressure was lower under propofol than during recovery from propofol in 17 of 19 goats (median maximal urethral closure pressure, 54 vs 66 cmH2O; P < 0.001). The test-retest coefficient of reproducibility for goats was 28 cmH2O, and the within-subject coefficient of variation was 16%. Conclusions In dogs, urethral pressure profilometry should be measured in conscious animals whenever possible. In goats, urethral pressure profilometry is least affected during recovery from propofol sedation, and it shows acceptable reproducibility under this condition. [ABSTRACT FROM AUTHOR]

Aims and objectives This study aimed to assess the reasons and the frequency of the use of over-the-counter ( OTC) nonsteroidal anti-inflammatory drugs ( NSAIDs) or analgesics by liver transplant recipients ( LTR). Patient awareness of possible drug-related side-effects was also assessed. Background NSAIDs and analgesics available without prescription belong to the most commonly used class of drugs. However, use of these drugs might be complicated by toxic adverse effects ( AEs). Patients at risk for AEs include the transplant recipients. Design/methods This was a descriptive study. An anonymous survey was carried out in 73 randomly selected LTR, who represented 10% of all LTR at our centre. Results There were 64% of the patients who confirmed taking NSAIDs or analgesics; 16% of these patients took these drugs at least several times a week and 10% took them daily. For 39% of patients, the only way to manage their pain were OTC NSAIDs or analgesics. As many as 36% of patients were unaware of the risks associated with the use of these drugs. Ninety per cent of LTR consider physicians the most trusted source of drugs information. Conclusions Our study shows that two-thirds of LTR take OTC NSAIDs or analgesics and one-third are unaware of the AEs associated with these drugs. Therefore, both transplant nurses and doctors should educate their patients about the use and possible AE of these drugs. Relevance to clinical practice Considering the high NSAIDs consumption rates, the side effects of these drugs should always be suspected. Especially in patients taking these drugs and referring to medical advisors with specific symptoms, such as: abdominal pain, anaemia, elevated serum creatinine concentration or liver enzymes activity. Awareness of the scale of the problem enables health professionals to cooperate in educating patients. Such practices may reduce uncontrolled abuse of these drugs and related health care costs. [ABSTRACT FROM AUTHOR]

Invasive aspergillosis (IA) is a severe infection with a 70% mortality rate. Aspergillus fumigatus is responsible for over 90% of those infections. The diagnosis of invasive aspergillosis is based on clinical sample culture and detection of fungal hyphae in histopathological examination. Additional tests may include the detection of the galactomannan antigen and of fungal genetic material in serum and bronchoalveolar washings. The present study was to assess the use of these two rapid tests in the diagnosis of invasive aspergillosis: serological one - to detect the galactomannan antigen (ELI SA assay), and real-time PCR, and to establish a possible correlation between these two methods. [ABSTRACT FROM AUTHOR]

The strategic location of the liver and its metabolic activity make it a key organ regulating homeostasis. Our purpose was to examine its participation in removal of cytokines: interleukin-6 (Il-6), tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor (HGF), and transforming growth factor-beta (TGF-β) from the portal circulation in human. 20 liver donors and 20 patients with end-stage liver failure were included in the study. Their blood was collected during liver transplantation from the portal, hepatic, and peripheral vein, and the hepatic artery and cytokines’ concentrations were determined. Using the results the mathematical model of cytokine elimination by the liver was developed. In donors significantly lower levels of IL-6, TNF-α, HGF, and TGF-β were detected in portal blood compared to hepatic vein. In patients with cirrhosis there were no significant differences of IL-6, TNF-α, and TGF-β levels between portal and hepatic veins. Significantly higher level of HGF in hepatic compared to portal vein was observed. In healthy liver elimination of the cytokines prevailed over their synthesis, as reflected by the positive values of the elimination ratios. In the cirrhotic liver elimination ratios of Il-6, HGF, and TGF-β were negative indicating the prevalence of intrahepatic synthesis of cytokines over their removal. [ABSTRACT FROM AUTHOR]

Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD) is correlated with an increased frequency of both intracranial aneurysms (ICANs), and arterial hypertension (AH). The aim of our study was to search for the association between blood pressure (BP) and ICANs in ADPKD patients. Methods: Sixty-eight adult, pre-dialysis phase ADPKD patients underwent both screening for ICANs with magnetic resonance angiography of the brain, and ambulatory blood pressure monitoring (ABPM). Results: ICANs were diagnosed in 10 patients (ICAN(+) group), while in 58 were not (ICAN(-) group). The nighttime maximum diastolic blood pressure (DBP), maximum increase in DBP from measurement to measurement (positive delta of DBP) at night, and the standard deviation of the daytime mean arterial pressure were significantly higher in ICAN(+) compared to ICAN(-) patients. Additionally, in a subgroup of patients after 45 years-of-age, ICAN(+) patients had significantly higher maximum 24-hour and daytime systolic blood pressure, maximum 24-hour, daytime, nighttime DBP, maximum daytime and nighttime positive delta of DBP compared to ICAN(-) cases. Conclusions: Development of ICANs in hypertensive ADPKD patients is accompanied with higher values of some BP parameters measured by ABPM. Hypertensive ADPKD patients with substantial fluctuations in BP assessed by ABPM, especially those after 45 years-of-age, should become candidates for screening for ICANs. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article focuses on a study that examine 25-year-old male with stage 2 chronic kidney disease due to the autosomal dominant polycystic kidney disease (ADPKD).

The vast majority of myoblasts transplanted into the skeletalmuscle die within the first week after injection. Inflammatory response to the intramuscular cell transfer was studied in allogeneic but not in autologous model. The aim of this study was to evaluate immune reaction to autotransplantation of myogenic cells and to assess its dynamics within the first week after injection. Musclederived cells or medium alone was injected into the intact skeletal muscles in autologous model. Tissue samples were collected 1, 3, and 7 days after the procedure. Our analysis revealed the peak increase of the gene expression of all evaluated cytokines (Il-1β, Il-1β, Il-6, Tgf-β, and Tnf-β) at day 1. The mRNA level of analyzed cytokines normalized in subsequent time points.The increase of Il-β gene expression was further confirmed at the protein level. Analysis of the tissue sections revealed rapid infiltration of injected cell clusterswith neutrophils andmacrophages.The inflammatory infiltrationwas almost completely resolved at day 7.The survived cells were able to participate in the muscle regeneration process. Presented results demonstrate that autotransplanted muscle-derived cells induce classical early immune reaction in the site of injection which may contribute to cellular graft elimination. [ABSTRACT FROM AUTHOR]

Studies have shown beneficial effects of machine perfusion ( MP) on early kidney function and long-term graft survival. The aim of this study was to investigate whether the type of perfusion device could affect outcome of transplantation of deceased donor kidneys. A total of 50 kidneys retrieved from 25 donors were randomized to machine perfusion using a flow-driven ( FD) device ( RM3; Waters Medical Inc) or a pressure-driven ( PD) device (LifePort; Organ Recovery Systems), 24 of these kidneys ( n = 12 pairs; 48%) were procured from expanded criteria donors ( ECD). The primary endpoints were kidney function after transplantation defined using the incidence of delayed graft function ( DGF), the number of hemodialysis sessions required, graft function at 12 months, and analyses of biopsy. DGF was similar in both groups (32%; 8/25). Patients with DGF in the FD group required a mean of 4.66 hemodialysis sessions versus 2.65 in the PD group ( P = 0.005). Overall, 1-year graft survival was 80% (20/25) vs. 96% (24/25) in the FD and PD groups. One-year graft survival of ECD kidneys was 66% (8/12) in the FD group versus 92% (11/12) in the PD group. Interstitial fibrosis and tubular atrophy were significantly more common in the FD group - 45% (5/11) vs. 0% (0/9) ( P = 0.03) in PD group. There were no differences in creatinine levels between the groups. Machine perfusion using a pressure-driven device generating lower pulse stress is superior to a flow-driven device with higher pulse stress for preserving kidney function. [ABSTRACT FROM AUTHOR]

Highlights: [•] MSCs injected into skeletal muscle are present in the site of transplantation 24h after treatment. [•] Elevation of mRNA for IL-1α, IL-1β and IL-6 and IL-1β after MSCs transplantation. [•] Elevation of IL-1β protein concentration after MSCs transplantation. [•] Injection of MSCs causes infiltration of leukocytes and macrophages. [•] Syngeneic administration of MSC induces the features of inflammatory response. [ABSTRACT FROM AUTHOR]