Background: The management of patent dialysis fistulas in patients after kidney transplantation (KTx) is controversial—the options that are usually considered are the fistula’s closure or ...observation. Many complications of dialysis fistulas occur in patients after KTx, and immunosuppression increases the risk of fistula aneurysms and hyperkinetic flow. This study aimed to evaluate the results of dialysis fistula aneurysm treatment in patients after KTx and to compare them to procedures performed in an end-stage renal disease (ESRD) dialyzed population. Methods: We enrolled 83 renal transplant recipients and 123 ESRD patients with dialysis fistula aneurysms qualified for surgical revision to this single-center, prospective study. The results of the surgical treatment of dialysis fistula aneurysms were analyzed, and the primary, assisted primary and secondary patency rate, percentage and type of complications were also assessed. Results: For the treatment of dialysis fistula aneurysms in transplant patients, we performed dialysis fistula excisions with fistula closure in 50 patients (60.2%), excision with primary fistula reconstruction (n = 10, 12.0%) or excision with PTFE bypasses (n = 23, 27.7%). Postoperative complications occurred in 11 patients (13.3%) during a follow-up (median follow-up, 36 months), mostly in distant periods (median time after correction procedure, 11.7 months). The most common complication was outflow stenosis, followed by hematoma, dialysis fistula thrombosis and the formation of a new aneurysm and postoperative bleeding, infection and lymphocele. The 12-month primary, primary assisted and secondary patency rates of fistulas corrected by aneurysm excision and primary reconstruction in the KTx group were all 100%; in the control ESRD group, the 12-month primary rate was 70%, and the primary assisted and secondary patency rates were 100%. The 12-month primary, primarily assisted and secondary patency rates after dialysis fistula aneurysm excision combined with PTFE bypass were better in the KTx group than in the control ESRD group (85% vs. 71.8%, 90% vs. 84.5% and 95% vs. 91.7%, respectively). Kaplan–Meier analysis showed a significant difference in primary patency (p = 0.018) and assisted primary (p = 0.018) rates and a strong tendency in secondary patency rates (p = 0.053) between the KTx and ESRD groups after dialysis fistula excisions combined with PTFE bypass. No statistically significant differences in patency rates between fistulas treated by primary reconstruction and reconstructed with PTFE bypass were observed in KTx patients. Conclusions: Reconstructions of dialysis fistula aneurysms give good long-term results, with a low risk of complications. The reconstruction of dialysis fistulas can be an effective treatment method. Thus, this is an attractive option in addition to fistula ligation or observation in patients after KTx. Reconstructions of dialysis fistula aneurysms enable the preservation of the dialysis fistula while reducing various complications.
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.
Lupus erythematosus is an autoimmune disease characterized by complex immune disturbances concerning humoral and cell-mediated immune responses. Despite intensive research, many pathological ...processes regarding this disorder remain unexplained. During interdisciplinary investigations on the etiology of lupus and its complications special interest has recently been referred to heat-shock proteins, antibodies directed against such proteins and galectin-3. These issues are extensively studied not only by dermatologists and rheumatologists, but also by cardiologists (in terms of cardiovascular complications) and nephrologists (in terms of lupus nephritis). This study presents the current state of dermatological, nephrological and cardiological knowledge on this topic.
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.
Objective. Presence of anti-HLA antibodies has a well-known impact on kidney grafts survival; however their role in liver transplantation has not been fully elucidated. We conducted a 7-year ...prospective study to show correlation between presence of anti-HLA and anti-MICA antibodies and liver graft survival. Methods. Blood samples from 123 liver transplant recipients were collected during patients routine visits. Time from transplantation to blood sample collection was different for each patient. Blood samples were tested for anti-HLA (separately class I and II) and MICA antibodies using Luminex assays. Results. There were 32 (26%) patients with positive anti-HLA and 37 (30%) with positive anti-MICA antibodies. Graft loss occurred in 7 cases (23%) in anti-HLA positive group compared to 20 (22%) in anti-HLA negative group (P=ns) and in 8 cases (22%) in anti-MICA positive group but 19 (23%) in anti-MICA negative group (P=ns). No correlations were detected between presence of antibodies and acute graft rejection (AGR). Presence of any antibodies (anti-HLA or anti-MICA antibodies) correlated with late graft rejection (P=0.04). Conclusion. Presence of anti-HLA or anti-MICA had no impact on long-term liver graft survival; however, detection of any antibodies was correlated with episodes of late graft rejection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Background and Aims
Oxidative stress (OS) is known as a disturbance between pro- and antioxidant factors, that may lead to DNA or protein oxidation, resulting in cellular damage. ...Peroxiredoxins (PRDXs) are enzymes with an antioxidant properties. They play dominant role in regulation of cellular peroxide levels, which is crucial in maintaining organisms’ oxidative balance. PRDXs types 1-5 are involved in the pathophysiology of various diseases (e.g. cancer, inflammatory, or renal). We aim to study their role as a prognostic marker of eGFR changes in IgA nephropathy (IgAN), lupus nephritis (LN) and membranous nephropathy (MN) patients.
Method
This is a retrospective 5-year-follow-up study of 108 IgAN, MN and LN patients, in whom PRDX 1-5 serum levels were assessed with ELISA in 2017. In 2022, we were able to collect the data out of 80 patients: IgAN (n=36); MN (n=22) and LN (n=22). The remaining 28 were considered as lost-to-follow-up, namely: lack of any medical results within last 2 years (n=23); on dialysis (n=2); after renal transplantation (n=2); deceased (n=1). We classified patients depending on the changes of eGFR (decline/stable/increase; Fig. 1) between baseline and after 5 year follow-up and the PRDX levels (high/medium/low; Table 1). The Mann Whitney-U, Kruskal-Wallis and Chi-Square Test were used for statistical analysis, the p-values <0.05 were considered significant.
Results
Baseline PRDX measurements indicated, that the mean concentrations of serum PRDX 1-5 differ between the glomerulonephropathies (GN). In 2022, we observed significantly different (P = .012) change of eGFR depending on the GN type. 16/80 individuals had eGFR decline and 75% of them were diagnosed with IgAN. The MN and LN groups had increase of eGFR in the last 5 years in most cases, probably as a result of the treatment. We verified if follow-up eGFR was associated with baseline PRDX levels. The 2022 eGFR differed significantly between the GNs depending on the level of serum PRDX 2, 4 and 5 at baseline (P = .002; P = .009; P = .006, respectively, Table 1).
Conclusion
Our results showed the link between serum PRDXs concentration and IgAN, MN and LN follow-up. Importantly, selected PRDXs’ might be used to predict eGFR decline, particularly in IgAN and LN.
Abstract
Background and Aims
The use of vaccination against severe acute respiratory syndrome coronavirus (SARS-CoV-2) significantly limited the spread of the coronavirus disease 2019 (COVID-19) ...pandemic. However, it was reported that after 6 months of vaccination (including the BNT162b2 vaccine) immunity decreases in general population. The results for chronic kidney disease (CKD) patients and solid-organ transplant (SOT) recipients appeared similar. Therefore, it was proposed to use an immune booster with the next, third or fourth vaccination dose to prolong immunity. We aimed to find the most effective immunization schedules in CKD patients in comparison to kidney (KTRs) and liver transplant recipients (LTRs).
Method
We retrospectively analyzed the data of randomly selected 40 patients with IgA nephropathy (IgAN) as representatives of the CKD group and 78 SOT recipients (37 KTRs and 41 LTRs). They received two or three 30 μg doses of BNT162b2 vaccine. The follow up was performed in five time points (TP1-5): 4-6 weeks after the 1st dose (TP1), 4-8 weeks after 2nd dose (TP2), 9-20 weeks after 2nd dose (TP3), 21-32 weeks after 2nd dose and 1-12 weeks after 3rd dose (TP4), 33-48 weeks after 2nd dose, at the same time 4-20 weeks after 3rd dose (TP5). We assessed the anti-SARS-CoV-2 spike 1 protein IgG antibody (anti-S1 Ab) titer as well as graft function, COVID-19 history and patients’ clinical condition.
Results
We found Ab titer in IgAN group higher than in SOT patients (p = 0.05). LTRs achieved higher values than KTRs. 55 patients received 3 doses of vaccination. The protective level after the 3rd dose was not observed only in 8.4% at TP4 and 5% at TP5. We demonstrated the advantage in Ab levels of a 2 doses vaccination scheme with and without COVID-19 history over a 3 doses in a group of patients with no COVID-19 history in TP 1-4 (p = <0,001 - 0,005, respectively, Table1). Subjects in 2 doses schedule had a longer time to infection from the last dose compared to the 3 doses schedule (31.5-39 vs. 9 weeks, MD). No deterioration of renal or graft function was noted and no rejection episodes were diagnosed.
Conclusion
Immunocompromised patients are non-homogeneous with respect to the vaccine response immunity. Therefore, the approach to the vaccination schedule should be individualized based on measurements of vaccination response and medical history including COVID-19 history. Combined post-infectious and post-vaccination immunization appears to be the most effective in producing anti-SARS-CoV-2 responses.
Cell-free DNA (cfDNA) represents a small fraction of total DNA pool that circulates freely in the blood both in normal and pathological conditions. Data indicate that cfDNA plays an important role in ...the pathogenesis of systemic lupus erythematosus (SLE) and hypomethylation may be crucial for its immunogenic properties. Although differences in quantification methodology hinder the comparison of results between the studies, it appears that levels of cfDNA are abnormally elevated in SLE patients and correlate with various antibody titers, but not with disease activity. Increased cfDNA concentration, however, may be associated with active lupus nephritis. Most of the studies confirmed apoptosis as the major cfDNA release mechanism in various conditions, but formation of neutrophil extracellular traps may significantly contribute to the cfDNA generation in SLE patients. In this review, we summarise current knowledge about the role and possible origin of cfDNA in SLE patients, and discuss why cfDNA testing for diagnostic and prognosis of SLE remains questionable.
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and ...European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10
) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10
), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10
) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10
), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10
), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10
and OR = 3.39, P = 5.2 × 10
, respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.
Abstract Background and Aims Post-transplantation lymphoproliferative disorder (PTLD), a potentially fatal complication of transplantation, affects solid organ transplant recipients at different ...rates, depending on organ graft type: the risk greater in lung transplant recipients (LngTRs), lower for liver transplant recipients (LTRs) and lowest for kidney transplant recipients (KTR). In this study we aimed to investigate the factors affecting the development and treatment outcomes of PTLD and compare their effect on KTRs, LTRs and LngTRs. Method In this retrospective cohort study we have included all KTRs, LTRs and LngTRs diagnosed with PTLD at six transplantation centers in Poland. The data collected from medical records included: immunosuppression (IS), viral infections, PTLD type, treatment and outcomes. Chi-squared test was used to assess the differences in group composition. To determine the impact of variables upon PTLD time of onset and patient survival, univariate Cox regression was used. p-values below 0.05 were considered statistically significant. Results We enrolled 50 KTRs, 36 LTRs and 5 LngTRs from 6 transplantation centers in Poland. Based on the data from the most contributing centers in each group, the prevalence of PTLD was 0.82% of KTRs, 2.03% LTRs and 1.51% of LngTRs. Two thirds of the enrolled patients were male, the median age at first transplantation was 40 years for KTRs, 45 for LTRs and 25 for LngTRs (Table 1). The groups significantly differed in IS treatment: steroid (GCS) and cyclosporin (CsA) use was more frequent in KTRs (p<0.001 and p<0.001 and respectively), tacrolimus (TAC) and anti-CD25 induction in LTRs (p ≤ 0.001 and p<0.001 respectively), sirolimus (RAPA) in LngTRs (p<0.001). KTRs were the latest to develop PTLD (126 months after transplantation, p<0.001). In all groups Monomorphic B-cell PTLD was the most frequent. Initial IS treatment reduction was used in 80-86% of patients, R-CHOP chemotherapy was most common in LTRs (p=0.021), other chemotherapy regimens in KTRs (p=0.031). TAC had the opposite effect on PTLD time of onset in KTRs (HR=2.18, p=0.013) and LTRs (HR=0.18, p=0.036). The overall survival at the end of observation period was 26% for KTRs, 58% for LTRs and 80% for LngTRs. Loss to follow up was most frequent in KTRs at 26%. Patient survival was not affected by PTLD treatment. Conclusion KTRs develop PTLD later than LTRs and LngTRs, and time of disease onset is associated with TAC use. Lower survival in KTRs may result from the longer follow-up period compared to other solid organ transplant recipients.
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