Subject(s)
Heart Failure , Myocardial Infarction , Humans , Renal Dialysis/adverse effects , Myocardial Infarction/etiology , LungABSTRACT
The length of telomeres (TLs) that protect chromosome ends may reflect the age of cells as well as the degree of genetic material damage caused by external factors. Since leukocyte telomere length is associated with cardiovascular diseases, the aim of this study was to evaluate whether leukocyte TL reflects femoral artery wall telomeres of patients with atherosclerosis and lower limb ischemia. Samples of femoral artery wall and blood were collected from 32 patients qualified to surgical revascularization. The analysis included blood and artery wall telomere length measurement and biochemical parameters. The study indicated that there was a moderate correlation between artery wall TL and leukocyte TL. Leukocyte TL was, on average, two times shorter than artery wall TL and correlated with the number of white blood cells. In turn, artery TL was impacted by total cholesterol level. The results suggest that the length of leukocyte telomeres may reflect artery wall TL and indirectly reflect the processes taking place in the artery wall in patients with atherosclerosis.
Subject(s)
Atherosclerosis , Femoral Artery , Atherosclerosis/genetics , Humans , Leukocytes , Telomere/geneticsABSTRACT
OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Churg-Strauss Syndrome , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology , Antibodies, Antineutrophil Cytoplasmic , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/epidemiology , Granulomatosis with Polyangiitis/complications , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/epidemiology , Humans , Microscopic Polyangiitis/complications , Microscopic Polyangiitis/epidemiology , Recurrence , Registries , Retrospective StudiesABSTRACT
The over-secretion of monoclonal immunoglobulin light chains by clonal B cells followed by the aggregation and extracellular deposition of fibrillar deposits are responsible forthe clinical course AL amyloidosis. It is well documented that silica significantly increases the number of immunoglobulin-secreting cells. In the present paper, we report on a coal miner with silicosis and fast progressing primary amyloidosis with predominantly heart, kidney, and lung manifestations. Severeheart failure due to myocardial hypertrophy resulted in the patient's death. We conclude that long-term environmental silica exposure and silica deposition may contribute to the development of monoclonal gammopathy and amyloidosis due to chronic stimulus and the dysregulation of the immune system.
Subject(s)
Amyloidosis , Silicosis , Coal , Dust , Humans , Silicon Dioxide , Silicosis/complicationsABSTRACT
PURPOSE: In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a lack of reliable biomarkers of disease activity. The aim of the study was to evaluate soluble urokinase plasminogen activator receptor (suPAR) and anti-endothelin-1 type A receptor (anti-ETAR) antibodies levels in active phase and remission of AAV. PATIENTS AND METHODS: We enrolled 60 patients (median age 63.0 years) with renal AAV into this study. Plasma suPAR, urine suPAR (expressed as urine suPAR/creatinine ratio) and serum anti-ETAR antibodies were assayed by ELISA. Disease activity was assessed using Birmingham Vasculitis Activity Score (BVAS) and patients were divided into 2 subgroups based on their BVAS scores, namely: active AAV subgroup (BVAS≥1) and remission subgroup (BVAS â= â0). Median follow-up was 12 months. RESULTS: Patients with active AAV had higher levels of all candidate biomarkers in comparison to those in remission (p â< â0.05). C-statistics for plasma suPAR, urine suPAR/creatinine ratio and serum anti-ETAR were 0.807, 0.713 and 0.783, respectively. In multivariable analysis, no clear associations were found between serum anti-ETAR and BVAS, while both plasma suPAR and serum anti-ETAR were independently influenced by estimated glomerular filtration rate (eGFR). CONCLUSIONS: Plasma suPAR better discriminated between active AAV and remission in comparison to urine suPAR/creatinine ratio and serum anti-ETAR antibodies.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Receptor, Endothelin A , Receptors, Urokinase Plasminogen Activator , Antibodies, Antineutrophil Cytoplasmic/blood , Biomarkers/blood , Humans , Kidney , Middle Aged , Receptor, Endothelin A/blood , Receptor, Endothelin A/immunology , Receptors, Urokinase Plasminogen Activator/blood , Receptors, Urokinase Plasminogen Activator/immunologyABSTRACT
Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patient-reported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.
Subject(s)
Cardiovascular Diseases , Kidney Failure, Chronic , Cardiovascular Diseases/diagnostic imaging , Heart Disease Risk Factors , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Lung/diagnostic imaging , Quality of Life , Renal Dialysis/adverse effects , Risk Factors , Ultrasonography, InterventionalABSTRACT
INTRODUCTION: The majority of the end-stage renal disease patients begin hemodialysis with the central tunneled catheter as a permanent or bridge vascular access. The procedure of central tunneled catheter insertion can be complicated by exit site bleeding, prolonged tunnel healing, and infection. The study aimed at evaluating whether the catheter exit site wound closing with a single-suture method is equally effective as the double suture method, which is most frequently applied. The assumption was that the single-suture method, which is less traumatizing for the skin, could offer an advantage for the patients with "paper" skin, that is, elderly, after long-term immunosuppressive treatment. METHODS: Insertion of central tunneled catheter with antegrade tunnel formation was performed in 140 patients divided randomly into two groups of 70 patients using either single-suture method or double suture method. RESULTS: Follow-up observations revealed a comparable number of early complications, that is, bleeding or exit site infection, in about 26% of the patients from both groups. No difference appeared in the catheter displacement, either. The percentage of patients with a prolonged central tunneled catheter exit site wound healing was not significantly lower in the single-suture method group: 5.8% versus 11.3%, p = 0.367. There was no impact of single-suture method versus double suture method on the central tunneled catheter long-term function and survival. CONCLUSION: The single-suture method of the central tunneled catheter exit closure is equal in efficacy to the double suture method. Its potential benefit for the patients with an increased risk of poor wound healing should be tested in further study.
ABSTRACT
Central tunneled catheter (CTC)-related infections are a leading cause of a catheter loss, thus being the source of significant morbidity and mortality. The study aims at evaluating the impact of the implementation of the innovative redness, edema, discharge and tenderness, symptoms (REDS) scale (devised by the authors) for the description of the tunnel condition on the frequency of infection in long-term catheter users. The same cohort of the 40 patients was observed for 4 years altogether: 2 years before and 2 years after REDS application. The results, as well as follow-up evaluation of participants, were compared. The 2-year cumulative incidence of the CTC exit site infection (ESI) dropped significantly (log-rank p < 0.001) from 0.89 episode/1,000 catheter days (53.5%, 95% CI [35.9%; 66.2%]) in the period before REDS was used-to 0.26 episode/1,000 catheter days (18.6%, 95% CI [6.1%; 29.4%]) in the time of REDS application. There were also significantly fewer episodes of ESI complicated with catheter-related blood stream infection (CRBSI) requiring the CTC removal (0.6 episode/1,000 catheter days; 18.6%, 95% CI [6.1%; 29.4%] vs. 0.3 episode/1,000 catheter days; 4.7%, 95% CI [0.0; 10.7%]; log-rank p = 0.04, in pre-REDS and REDS time, respectively). The REDS scale appears to be a simple, cost-effective tool reducing the frequency of the tunneled CTC exit site infection and associated bloodstream infections.
ABSTRACT
OBJECTIVES: ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV. METHODS: In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry. RESULTS: LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. CONCLUSIONS: Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , Granulomatosis with Polyangiitis , Microscopic Polyangiitis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Antibodies, Antineutrophil Cytoplasmic , Granulomatosis with Polyangiitis/diagnosis , Humans , Latent Class Analysis , Microscopic Polyangiitis/diagnosis , Peroxidase , PolandABSTRACT
The proteasome to immunoproteasome (iPS) switch consists of ß1, ß2 and ß5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VALIGA) study the relationships between iPS switch and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous long follow-up (6.4 years in median) that allowed an accurate calculation of their slope of renal function decline. We also evaluated the effects of the PSMB8/PSMB9 locus (rs9357155) associated with IgAN in genome-wide association studies and the expression of messenger RNAs (mRNAs) encoding for TLRs and CD46, a C3 convertase inhibitor, acting also on T-regulatory cell promotion, found to have reduced expression in progressive IgAN. We detected an upregulation of LMP7/ß5 and LMP2/ß1 switches. We observed no genetic effect of rs9357155. TLR4 and TLR2 mRNAs were found to be significantly associated with iPS switches, particularly TLR4 and LMP7/ß5 (P < 0.0001). The LMP7/ß5 switch was significantly associated with the rate of eGFR loss (P = 0.026), but not with eGFR at biopsy. Fast progressors (defined as the loss of eGFR >75th centile, i.e. -1.91 mL/min/1.73 m2/year) were characterized by significantly elevated LMP7/ß5 mRNA (P = 0.04) and low CD46 mRNA expression (P < 0.01). A multivariate logistic regression model, categorizing patients by different levels of kidney disease progression, showed a high prediction value for the combination of high LMP7/ß5 and low CD46 expression.
Subject(s)
Glomerulonephritis, IGA , Proteasome Endopeptidase Complex , Genome-Wide Association Study , Glomerulonephritis, IGA/genetics , Humans , Membrane Cofactor Protein , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , RNA, Messenger , Up-RegulationABSTRACT
Telomeres are repetitive nucleoprotein structures located at the ends of chromosomes. Reduction in the number of repetitions causes cell senescence. Cells with high proliferative potential age with each replication cycle. Post-mitotic cells (e.g. cardiovascular cells) have a different aging mechanism. During the aging of cardiovascular system cells, permanent DNA damage occurs in the telomeric regions caused by mitochondrial dysfunction, which is a phenomenon independent of cell proliferation and telomere length. Mitochondrial dysfunction is accompanied by increased production of reactive oxygen species and development of inflammation. This phenomenon in the cells of blood vessels can lead to atherosclerosis development. Telomere damage in cardiomyocytes leads to the activation of the DNA damage response system, histone H2A.X phosphorylation, p53 activation and p21 and p16 protein synthesis, resulting in the SASP phenotype (senescence-associated secretory phenotype), increased inflammation and cardiac dysfunction. Cardiovascular cells show the activity of the TERT subunit of telomerase, an enzyme that prevents telomere shortening. It turns out that disrupting the activity of this enzyme can also contribute to the formation of cardiovascular diseases. Measurements of telomere length according to the "blood-muscle" model may help in the future to assess the risk of cardiovascular complications in people undergoing cardiological procedures, as well as to assess the effectiveness of some drugs.
Subject(s)
Cardiovascular Diseases/pathology , Cellular Senescence , DNA Damage , Telomerase/metabolism , Telomere Shortening , Animals , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Humans , Telomerase/geneticsABSTRACT
BACKGROUND: Optimal care of patients treated with a central tunneled catheter (CTC) as vascular access for hemodialysis requires a number of procedures. One of them is CTC removal, usually carried out using mostly the cut-down method (CDM) and the traction method (TM). The procedure seems to be simple and safe; however, occasionally, serious complications may occur. To eliminate the risk of such events, we have introduced a modified cut-down method (MCDM). METHODS: The study included the analysis of retrospective results of 143 CTC removal procedures, 76 of which were performed using the standard cut-down method (CDM), and in 67 cases, the modified cut-down method (MCDM) was applied. RESULTS: As minor side effects occurred in patients treated with both methods with comparable frequency, serious complications were observed only in the CDM patients group. CONCLUSIONS: In our opinion, the new MCDM procedure is the simplest and safest method of CTC removal.
Subject(s)
Catheterization, Central Venous , Catheters, Indwelling , Device Removal , Aged , Aged, 80 and over , Device Removal/adverse effects , Device Removal/methods , Female , Humans , Male , Middle Aged , Renal Dialysis , Retrospective Studies , Treatment OutcomeABSTRACT
Despite all efforts, still many end-stage kidney disease (ESKD) patients are dialysed using a central tunnelled catheter (CTC) as vascular access. When the CTC blood flow becomes ineffective, a number of protocols are advised. However, all of them are time- and cost-consuming. The manoeuvre of a non-invasive tunnelled catheter reposition (NTCR) was introduced to restore the CTC function. NTCR was based on gentle movements of the CTC, with or without a simultaneous flushing of the CTC lines, which resulted in a quick reposition of the CTC tip. This study comprises the analysis of a total of 297 NTCRs, which were performed in 114 patients, thus enabling an effective blood flow after 133 procedures (44.7%).Partially effective blood flow followed 123 procedures (41.4%), and it failed altogether in 41 cases (13.9%). Overall, 86% of conducted NTCRs improved the CTC patency to perform a haemodialysis session. The procedure could be successfully repeated, with a similar result after the first and the second attempt. Complications were observed only after 3.4% of all interventions. The novel NTCR manoeuvre was safe and effective in the majority of the CTC dysfunction episodes. It seemed to reduce fibrinolytic usage, allowed an immediate haemodialysis session commencement, therefore, it might save both the costs and the nursing staff time.
Subject(s)
Catheterization, Central Venous/methods , Kidney Failure, Chronic/therapy , Aged , Central Venous Catheters , Female , Humans , Male , Middle Aged , Renal DialysisABSTRACT
INTRODUCTION: Since inflammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifier of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients. OBJECTIVE AND METHODS: We investigated the effect modification by systemic inflammation (serum CRP) on the relationship between a surrogate of the filling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantified by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model. RESULTS: At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r = 0.23, P < 0.001) and serum CRP was a robust modifier of this relationship (P < 0.001). Similarly, in fully adjusted longitudinal analyses US-B lines associated with simultaneous estimates of LAVI (P = 0.002) and again CRP was a strong modifier of this relationship in adjusted analyses (P ≤ 0.01). Overall, at comparable LAVI levels, lung congestion was more pronounced in inflamed than in non-inflamed patients. CONCLUSION: In ESKD systemic inflammation is a modifier of the relationship between LAVI, an integrate measure of LV filling pressure, and lung water. For any given pressure, lung water is increased with higher CRP levels, likely reflecting a higher permeability of the alveolar-capillary barrier.
Subject(s)
Pulmonary Edema , Humans , Inflammation , Longitudinal Studies , Lung/diagnostic imaging , Pulmonary Edema/diagnostic imaging , Pulmonary Edema/etiology , Renal Dialysis/adverse effectsABSTRACT
PURPOSE: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities. RESULTS: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71). CONCLUSIONS: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.
Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Drug-Related Side Effects and Adverse Reactions/diagnosis , Immunosuppressive Agents/adverse effects , Registries/statistics & numerical data , Adult , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Azathioprine/adverse effects , Cyclophosphamide/adverse effects , Drug Therapy, Combination , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Female , Follow-Up Studies , Glucocorticoids/adverse effects , Humans , Male , Methotrexate/adverse effects , Middle Aged , Poland/epidemiology , Prognosis , Retrospective Studies , Rituximab/adverse effects , Survival RateABSTRACT
Post-transplant lymphoproliferative disorder (PTLD) is serious life-threating complication of transplantation. The clinical picture differs from lymphomas observed in the general population, with different manifestation, histopathology, higher aggressiveness with involvement of sites beyond the primary lymph node, and poorer outcome. The objective of the study was to present nine cases of PTLD observed in our centre among the kidney transplant recipient population and discuss the results with up-to-date literature. We performed a retrospective single-centre assessment of PTLD incidence in the cohorts of kidney transplant recipients followed by our centre. We found nine cases of PTLD, five men and four woman, aged from 26 to 67 years at the time of diagnosis (mean [SD] 48 [5] years), transplanted between 1997 and 2013. The disease was diagnosed between 2002 and 2017, from 6 to 440 months after transplantation (mean [SD] 96 [137] months). A diffuse large B-cell lymphoma was found in seven cases early as well as late after transplantation, and two patients presented T-cell lymphoma. Five patients achieved complete remission with no relapses after 6 to 13 months of treatment. In three cases the remission was achieved by switching to mammalian target of rapamycin inhibitors (mTORi) only. Four recipients died from 2 weeks to 15 months after PTLD was diagnosed. Although the diagnostic criteria of different forms of PTLD are commonly known, rapid and correct diagnosis is not easy. PTLD is a relatively a rare disease, so there are too few studies and little consensus on the optimal treatment.
ABSTRACT
The complement system is one of the crucial pathophysiological mechanisms that directly influence the function of a transplanted kidney. Since the complement pathways' activation potential can be easily determined via their functional activity measurement, we focused on fluctuation in the cascade activity in the early post-transplant period. The aim of the study was to relate the kidney transplantation-induced complement system response to allograft outcome. Forty-two kidney recipients (aged: 53.5 [37-52], 17 females/25 males) and 24 healthy controls (aged: 40.5 [34-51], 13 females/11 males) were enrolled in the study. The functional activities of alternative, classical, and lectin pathways were determined before and in the first week after transplantation using Wielisa®-kit. We observed that the baseline functional activity of the alternative pathway (AP) was higher in chronic kidney disease patients awaiting transplantation compared to healthy controls and that its level depended on the type of dialysis. AP-functional activity was decreased following transplantation procedure and its post-transplant level was related to allograft function. The baseline and transplantation-induced functional activities of the classical and lectin pathways were not influenced by dialysis type and were not associated with transplant outcome. Moreover, our study showed that intraoperative graft surface cooling had a protective effect on AP activation. Our study confirms the influence of dialysis modality on persistent AP complement activation and supports the role of AP in an early phase after kidney transplantation and allograft outcome.
Subject(s)
Complement Pathway, Alternative/immunology , Graft Rejection/immunology , Kidney Failure, Chronic/therapy , Kidney Transplantation/adverse effects , Renal Dialysis/adverse effects , Adult , Aged , Allografts/immunology , Allografts/physiopathology , Female , Glomerular Filtration Rate , Graft Rejection/physiopathology , Humans , Kidney/immunology , Kidney/physiopathology , Kidney Transplantation/methods , Male , Middle Aged , Transplantation, Homologous/adverse effects , Treatment OutcomeABSTRACT
Successful long-term kidney allograft survival with parallel reduction of complications resulting from prolonged immunosuppressive treatment is a goal in kidney transplantation. We studied the immune changes in cell phenotypes and gene expression induced by kidney transplantation. Our goal was to find a phenotypic and/or transcriptional pattern that might be considered prognostic for the kidney transplant outcome. The analysis was performed prospectively on 36 KTx recipients sampled during the first year and followed for five years after transplantation and on 40 long-term KTx recipients (7.9 ± 2.2 y. post-KTx). The research involved flow cytometry assessment of lymphocyte subpopulations (including Tregs and CD3+CD8+CD28- lymphocytes) and gene expression analysis of immune-related genes (CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGFB, and TNFA). The analysis of patterns observed over the first post-KTx year was confronted with control, pretransplant, and long-term transplant results. Treg counts at months one and three post-KTx correlated positively with the current and future allograft function. FOXP3 gene expression at month one post-KTx was also associated with long-term allograft function. The KTx-induced CD3+CD8+CD28- population correlated with GZMB and PRF1 expression and suggested their cytotoxic properties. The size of the Treg population and regulatory FOXP3 gene expression in the early period after transplantation are associated with kidney transplant outcome. The outlined predictive power of the Treg population needs to be investigated further to be confirmed as one of the immune monitoring strategies that may help achieve the best long-term kidney allograft outcomes.
Subject(s)
Gene Expression , Graft Survival/immunology , Immunity, Innate , Kidney Transplantation , T-Lymphocytes, Regulatory/immunology , Adult , Female , Graft Rejection/immunology , Humans , Lymphocytes/immunology , Male , Middle Aged , Monitoring, Immunologic , Outcome and Process Assessment, Health Care , Phenotype , Prospective StudiesABSTRACT
BACKGROUND Being overweight for kidney transplant recipients can cause serious side effects. Weight gain affects two-thirds of kidney transplant recipients and has been attributed to a more liberal diet after transplantation, recovery of appetite due to lack of uremic toxicity, corticosteroid use, and inadequate lifestyle changes. The aim of this study was to assess gender-dependent profile of body mass index (BMI) changes after kidney transplantation (KTx). MATERIAL AND METHODS Sixty-two kidney transplant recipients (38 males and 24 females), aged 46.0±12.8 years at KTx, were observed according to weight gain after KTx. BMI was calculated before transplantation (pre-KTx) and at 6, 12, and 24 months post-KTx. RESULTS During the 24-month observation period, we found an increase in the incidence of kidney transplant recipients being overweight or obese (pre-KTx 43.5% increase and 24-month post-Ktx 61.3% increase, P=0.036). We analyzed a number of factors that could potentially influence a 24-month BMI gain including age at KTx, gender, pre-KTx BMI, time on dialysis, pre-KTx glucose metabolism disorder, and post-KTx diabetes mellitus. For female recipients, there was a significant step-wise post-KTx increase in BMI during the 24-month observation period. The overall pre-KTx to 24-month net increase for female BMI was 2 times greater than that observed for male recipients (1.90±2.20 kg/m² versus 0.89±1.85 kg/m², P<0.001). CONCLUSIONS Weight gain after KTx was observed in both sexes, but the net BMI increase was more than 2 times greater in females than in males at 24-months post-KTx. This indicated the need for diet education and strict weight control in kidney transplant recipients, especially in female patients.