IgA nephropathy (IgAN), membranous nephropathy (MN), and lupus nephritis (LN) represent important causes of chronic kidney disease. They belong to the immune-mediated glomerulonephritis (GNs), and ...have distinct pathogenesis, distinct clinical courses, and variable responses to treatment. Therefore, specific diagnostic procedures are necessary for more effective patient management. Recently, a role for oxidative stress has been proposed in various renal disorders. Thus, molecules related to oxidative stress, such as 2-Cys-peroxiredoxins (PRDXs), may represent plausible candidates for biomarkers in renal pathologies. The aim of this study was to assess whether there are differences between individual GNs and healthy controls in the context of PRDXs serum concentration. We enrolled 108 patients with biopsy-proven IgAN (47), MN (26), LN (35) and 30 healthy age- and sex-matched controls. The serum concentrations of PRDX 1–5 were measured with ELISA assays and correlated with demographic and clinical data. The PRDXs’ concentration varied depending on the GN type. We also observed an association of PRDXs with lower estimated glomerular filtration rates, complement, hemoglobin, and body mass index. Our study indicates that individual PRDX can play roles in pathophysiology of selected GNs and that their serum concentrations may become useful as a new supplementary diagnostic markers in IgAN, MN as well as LN. The results of this study open a new avenue for prospective research on PRDXs in renal diseases.
Polysaccharides isolated from
are bioactive compounds with immunomodulatory properties. In our previous studies from
mycelium, we have isolated a selenium(Se)-enriched fraction (named Se-Le-30), a ...mixture of linear 1,4-α-glucan and linear 1,3-β- and 1,6-β-glucans. In this study, we analyzed the effects of Se-Le-30 on the activation and proliferation of human T lymphocytes stimulated by anti-CD3 and anti-CD3/CD28 antibodies (Abs) and on the production of cytokines by peripheral blood mononuclear cells (PBMCs). Se-Le-30 had effects on T cell proliferation induced by Abs against CD3 and CD28. It significantly inhibited the proliferation of CD3-stimulated CD4
and CD8
T cells and enhanced the proliferation of CD4
T cells stimulated with anti-CD3/CD28 Ab. Moreover, Se-Le-30 downregulated the number of CD3-stimulated CD4
CD69
cells, CD4
CD25
cells, as well as CD8
CD25
cells, and upregulated the expression of CD25 marker on CD4+ and CD8+ T cells activated with anti-CD3/CD28 Abs. Furthermore, Se-Le-30 enhanced the synthesis of IFN-γ by the unstimulated and anti-CD3/CD28-stimulated PBMCs, inhibited synthesis of IL-2 and IL-4 by CD3-stimulated cells, and augmented the synthesis of IL-6 and IL-10 by unstimulated, CD3-stimulated, and CD3/CD28-stimulated PBMCs. Together, we demonstrated that Se-Le-30 exerts immunomodulatory effects on human T lymphocytes. These observations are of importance for the prospective use of Se-Le-30 in research or as a therapeutic compound.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are the most commonly used drugs worldwide and their availability over-the-counter is increasing. The aim of this study was to examine the ...frequency of their use as well as the awareness of the associated risk of side effects in patients with chronic kidney disease (CKD) compared to the patients at general practice (GP) offices. We found that 88.5% of the CKD and 97.1% of the GP group used NSAIDs and/or analgesics (p < 0.0001). Paracetamol was chosen the most often by both study groups, but the proportion of patients taking paracetamol was significantly higher in the CKD group (p < 0.006). On the contrary, the proportion of patients taking ibuprofen was significantly higher in GP group (p < 0.0001). Furthermore, almost 37% of CKD and 60% of GP patients never consult with their doctor before taking NSAIDs or analgesics. The influence of advertisements on the decision to take these drugs was found to be marginal in both groups. In conclusion, the NSAIDs and/or analgesics use is very common. The differences between the studied cohorts in self-decision making and the type of drugs used between the studied cohorts warrant tailored educational approaches.
Immunization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly limited the spread of coronavirus disease 2019 (COVID-19) and reduced the associated complications, ...especially mortality. To prolong immunity, an immune booster was implemented. We evaluated the role of SARS-CoV-2 infection history in the vaccination schedules of kidney and liver transplant recipients and patients with chronic kidney disease (CKD). To this end, we retrospectively analyzed the data of 78 solid organ transplantation (SOT) recipients and 40 patients with immunoglobulin A (IgA) nephropathy as representatives of the CKD group. Patients received two or three doses of the BNT162b2 vaccine. At the follow-up, antibody (Ab) titer, graft function, COVID-19 history, and patients’ clinical condition were assessed. Ab level was higher after two doses in patients with a COVID-19 history over three doses in patients with no COVID-19 history. Compared to three doses, subjects who were administered two doses had a longer median time to infection. Positive antibodies, in response to the third dose, were not observed in up to 8.4% of SOT patients. The results show that the vaccination schedule should take into account the vaccine response rate and COVID-19 history. So-called hybrid immunity appears to be most efficient at providing humoral responses against SARS-CoV-2 infection in immunocompromised patients.
The BNT162b2 vaccine is reportedly effective in preventing severe disease in more than 90% of the general population, but its efficacy in transplant recipients remains controversial. We aimed to ...determine the immune response to the BNT162b2 vaccine in kidney (KTRs) and liver transplant recipients (LTRs). In this retrospective cohort study, we included randomly 65 KTRs and 65 LTRs, who received two 30 μg doses of BNT162b2 vaccine in 3-to6-week intervals. We analyzed the anti-SARS-CoV-2 spike protein IgG antibody (anti-S1 Ab) titer, biochemical liver and renal tests, immunosuppressive drug trough level, and clinical follow up 4-6 weeks after the first dose and 4-8 weeks after the second dose. The level of protective antibodies was 57.1% in KTRs and 88.9% in LTRs after the second dose. The anti-S1 Ab response was significantly associated with sex, age, and history of COVID-19. A tacrolimus dose at vaccination but not its trough level was significantly correlated with the increase in anti-S1 Ab titer after the second vaccine dose in LTRs. Rejection episodes did not occur after vaccination. Our results showed a higher than previously reported humoral response to the BNT162b2 vaccine in KTRs and LTRs, which was dependent upon age, type of transplanted organ, and immunosuppression.
Many potential biomarkers in nephrology have been studied, but few are currently used in clinical practice. One is osteopontin (OPN). We compared urinary OPN concentrations in 80 participants: 67 ...patients with various biopsy-proven glomerulopathies (GNs)-immunoglobulin A nephropathy (IgAN, 29), membranous nephropathy (MN, 20) and lupus nephritis (LN, 18) and 13 with no GN. Follow-up included 48 participants. Machine learning was used to correlate OPN with other factors to classify patients by GN type. The resulting algorithm had an accuracy of 87% in differentiating IgAN from other GNs using urinary OPN levels only. A lesser effect for discriminating MN and LN was observed. However, the lower number of patients and the phenotypic heterogeneity of MN and LN might have affected those results. OPN was significantly higher in IgAN at baseline than in other GNs and therefore might be useful for identifying patients with IgAN. That observation did not apply to either patients with IgAN at follow-up or to patients with other GNs. OPN seems to be a valuable biomarker and should be validated in future studies. Machine learning is a powerful tool that, compared with traditional statistical methods, can be also applied to smaller datasets.
Glomerular diseases (GNs) are responsible for approximately 20% of chronic kidney diseases. Glucocorticoid receptor gene (
) single nucleotide polymorphisms (SNPs) are implicated in differences in ...predisposition to autoimmunity and steroid sensitivity. The aim of this study was to evaluate the frequency of the
SNPs-rs6198, rs41423247 and rs17209237-in 72 IgA nephropathy (IgAN) and 38 membranous nephropathy (MN) patients compared to 175 healthy controls and to correlate the effectiveness of treatment in IgAN and MN groups defined as a reduction of proteinuria <1 g/24 h after 12 months of treatment. Real-time polymerase chain reactions and SNP array-based typing were used. We found significant rs41423247 association with MN (
= 0.026); a significant association of rs17209237 with eGFR reduction after follow-up period in all patients with GNs (
= 0.021) and with the degree of proteinuria after 1 year of therapy in all patients with a glomerulopathy (
= 0.013) and IgAN (
= 0.021); and in the same groups treated with steroids (
= 0.021;
= 0.012). We also observed the association between rs41423247 and IgAN histopathologic findings (
= 0.012). In conclusion, our results indicate that
polymorphisms may influence treatment susceptibility and clinical outcome in IgAN and MN.
Abstract Background and Aims Multiple factors may contribute to development and progression of glomerulopathies (GN), one of them is oxidative stress (OS). 2-cysteine-peroxiredoxins (PRDXs) possess ...the ability to reduce excessive levels of OS mediators and are crucial for cellular OS regulation. In our pilot study, we found that PRDXs 1-5 are differentially changed in patients with IgA nephropathy (IgAN), lupus nephritis (LN) and membranous nephropathy (MN). Thus, the aim of the current study was to evaluate if PRDXs 1-5 may be a prognostic marker for these 3 types of GN. Method We followed-up (5-year observation) 80 previously recruited patients with: IgAN (n = 36); MN (n = 23) and LN (n = 21). Patients were classified, based on the eGFR change (decline vs. stable and/or increase) and baseline PRDXs 1-5 levels (Table 1). The Mann Whitney-U, Kruskal-Wallis Test and Pearsons’ correlation were used for statistical analysis, the p-values <0.05 were considered significant. Results Baseline measurements indicated that the mean serum PRDXs 1-5 concentrations differ between the GN types. During the follow-up, we observed the significant association of eGFR decline with low baseline PRDX-2 level (p = 0.049) in patients with IgAN (Fig. 1). Conclusion We suggest the possible link between peroxiredoxins and deterioration of kidney function, particularly in IgAN patients.
Exaggerated oxidative stress (OS) is usually considered as a disturbance in regular function of an organism. The excessive levels of OS mediators may lead to major damage within the organism’s cells ...and tissues. Therefore, the OS-associated biomarkers may be considered as new diagnostic tools of various diseases. In nephrology, researchers are looking for alternative methods replacing the renal biopsy in patients with suspicion of chronic kidney disease (CKD). Currently, CKD is a frequent health problem in world population, which can lead to progressive loss of kidney function and eventually to end-stage renal disease. The course of CKD depends on the primary disease. It is assumed that one of the factors influencing the course of CKD might be OS. In the current work, we review whether monitoring the OS-associated biomarkers in nephrology patients can support the decision-making process regarding diagnosis, prognostication and treatment initiation.
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