Urine proteomics for prediction of disease progression in patients with IgA nephropathy.

BACKGROUND: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification. METHODS: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models. RESULTS: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81). CONCLUSIONS: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.

The impact of location and patency of the arteriovenous fistula on quality of life of kidney transplant recipients.

BACKGROUND: Arteriovenous fistulae (AVFs) may remain patent after kidney transplantation (KTx), contributing to maladaptive cardiac remodeling. The flow in AVFs is associated with the diameter of its vessels and thus with the AVF location. The main objective of this study is to assess the influence of AVF location and its patency on the self-reported quality of life (QOL) of kidney transplant recipients (KTRs) with past history of hemodialysis. METHODS: To gain clinical data, during a scheduled visit, 353 KTRs were asked to fill out an anonymous questionnaire. From this group, 284 respondents were found eligible for analysis. The outcome was defined as prevalence of symptoms and health status, measured with the Left Ventricular Dysfunction-36 (LVD-36) Questionnaire in symptomatic patients. RESULTS: The hemodialysis patients (n = 243) were divided into two groups according to AVF location, i.e., DAVF - distally located AVF - (n = 174) and PAVF - proximally located AVF - (n = 69). The proportion of patients with heart failure (HF) was higher in PAVF group (24% vs. 12%, p = 0.0482). In the multivariable regression, PAVF, serum creatinine levels, and the presence of HF or coronary artery disease (CAD) remained independent predictors of lower functional capacity. Among patients with heart disease, the presence of active AVF was independently associated with worse functional outcome (higher LVD-36 scores). CONCLUSIONS: The influence of persistent PAVF in KTRs seems to be unfavorable, especially when coexisting with CAD or HF. Abbreviations: AVF arteriovenous fistula; BMI body mass index; CAD coronary artery disease; D-AVF distally-located arteriovenous fistula; EC exercise capacity; HD hemodialysis; HF heart failure; KTx kidney transplantation; KTR kidney transplant recipient; LVD-36 Left Ventricle Disfunction - 36; LVEF left ventricle ejection fraction; LVH left ventricle hypertrophy; NYHA New York Heart Association; P-AVF proximally located arteriovenous fistula; PD peritoneal dialysis; PRO patient-reported outcomes; QOL quality of life.

The Application of Nanoparticles in Diagnosis and Treatment of Kidney Diseases.

Nanomedicine is currently showing great promise for new methods of diagnosing and treating many diseases, particularly in kidney disease and transplantation. The unique properties of nanoparticles arise from the diversity of size effects, used to design targeted nanoparticles for specific cells or tissues, taking renal clearance and tubular secretion mechanisms into account. The design of surface particles on nanoparticles offers a wide range of possibilities, among which antibodies play an important role. Nanoparticles find applications in encapsulated drug delivery systems containing immunosuppressants and other drugs, in imaging, gene therapies and many other branches of medicine. They have the potential to revolutionize kidney transplantation by reducing and preventing ischemia-reperfusion injury, more efficiently delivering drugs to the graft site while avoiding systemic effects, accurately localizing and visualising the diseased site and enabling continuous monitoring of graft function. So far, there are known nanoparticles with no toxic effects on human tissue, although further studies are still needed to confirm their safety.

Intra-arterial computed tomography angiography with ultra-low volume of iodine contrast and stent implantation in transplant renal artery stenosis in terms of contrast-induced kidney injury - a preliminary report.

PURPOSE: Traditional digital subtraction angiography is still regarded as the gold standard in the diagnostics of transplant renal artery stenosis (TRAS). However, this procedure requires a high volume of iodine contrast medium for optimal visualisation of the renal artery. The aim of this study was to analyse both the usefulness and the safety of intra-arterial computed tomography angiography (IA-CTA) with ultra-low-volume iodine contrast administration in the diagnostic and therapeutic management of TRAS in patients with impaired renal transplant function. MATERIAL AND METHODS: Thirty-three patients with a suspicion of TRAS based on Doppler-ultrasound and clinical setting underwent IA-CTA with ultra-low iodine contrast volume. A special, author-elaborated CTA protocol was used. The volume of 8-18 ml of diluted iodine contrast medium was administered through a catheter with the tip placed 2 cm below the aortic bifurcation. RESULTS: In six patients the CTA examinations revealed TRAS in three configurations: in the anastomosis, in the trunk (critical and high-grade), or in both sections. Stenoses were treated with primary stenting obtaining favourable anatomical outcome. No intervention-related complications were observed. No contrast-induced acute kidney injury was diagnosed in this study. Mean serum creatinine concentration was 2.93 ± 0.89 mg/dl at the baseline and 2.89 ± 1.73 mg/dl and 2.17 ± 0.51 mg/dl after three and seven days from IA-CTA, respectively. CONCLUSIONS: Intra-arterial CTA with ultra-low volume of iodine contrast seems to be a safe and reliable diagnostic tool to detect and assess TRAS in the aspect of stent implantation. Application of this imaging modality eliminates the need for a high volume of iodine contrast and thus does not adversely influence renal transplant function.

Immune activation- and regulation-related patterns in stable hand transplant recipients.

We assessed cell subsets and expression of a set of genes related to the T-cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). The study was conducted on five HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGF-B, and TNF-A genes on a custom-designed low-density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations. HTx presented significantly increased expression of immunomodulatory genes (TNF, IL10, GITR, and PDCD1) compared to KTx and controls. HTx revealed a proinflammatory molecular pattern with higher expression of NOTCH and CD8 compared to KTx and controls. KTx showed a reduced level of regulatory T cells compared to controls and HTx. Both HTx and KTx presented an increased number of CD8+ and CD8+ CD28- T cells compared to controls. Stable hand transplant recipients exhibit persistent immune activation with rejection-related gene expression pattern counterbalanced by secondary induction of regulatory mechanisms.

Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function.

Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan). Results. Immediate posttransplant graft function (14-day GFR) was influenced negatively by TGFB1 (P = 0.039) and positively by IL-2 gene expression (P = 0.040). Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18) and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P = 0.027, FAS: P = 0.021, and IFNG: P = 0.029) and long-term graft function (24-month GFR CASP3: P = 0.003, FAS: P = 0.033, IL-18: P = 0.044, and IFNG: P = 0.04). Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes' expression in the recipients' peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function.

Intraarterial CT Angiography Using Ultra Low Volume of Iodine Contrast - Own Experiences.

BACKGROUND: High volume of intravenous contrast in CT-angiography may result in contrast-induced nephropathy. Intraarterial ultra-low volume of contrast medium results in its satisfactory blood concentration with potentially good image quality. The first main purpose was to assess the influence of the method on function of transplanted kidney in patients with impaired graft function. The second main purpose of the study was to evaluate the usefulness of this method for detection of gastrointestinal and head-and-neck haemorrhages. MATERIAL/METHODS: Between 2010 and 2013 intraarterial CT-angiography was performed in 56 patients, including 28 with chronic kidney disease (CKD). There were three main subgroups: 18 patients after kidney transplantation, 10 patients with gastrointestinal hemorrhage, 8 patients with head-and-neck hemorrhage. Contralateral or ipsilateral inguinal arterial approach was performed. The 4-French vascular sheaths and 4F-catheters were introduced under fluoroscopy. Intraarterial CT was performed using 64-slice scanner. The scanning protocol was as follows: slice thickness 0.625 mm, pitch 1.3, gantry rotation 0.6 sec., scanning delay 1-2 sec. The extent of the study was established on the basis of scout image. In patients with CKD 6-8 mL of Iodixanol (320 mg/mL) diluted with saline to 18-24 mL was administered at a speed of 4-5 mL/s. RESULTS: Vasculature was properly visualized in all patients. In patients with impaired renal function creatinine/eGFR levels remained stable in all but one case. Traditional arteriography failed and CT-angiography demonstrated the site of bleeding in 3 of 10 patients with symptoms of gastrointestinal bleeding (30%). In 8 patients with head-and-neck bleeding CT-angiography did not prove beneficial when compared to traditional arteriography. CONCLUSIONS: 1. Ultra-low contrast intraarterial CT-angiography does not deteriorate the function of transplanted kidneys in patients with impaired graft function. 2. 3D reconstructions allow for excellent visualization of vascular anatomy of renal transplants. 3. Intraarterial CT-angiography is useful for detection of the bleeding site.

The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes.

Non-HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti-angiotensin II type 1-receptor-activating antibodies (anti-AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti-AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti-AT1R antibodies in 117 consecutive renal transplant recipients in pre- and post-transplant screening. Anti-AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti-AT1R(+) group. The patients with anti-AT1R Abs >9 U/ml lost their graft more often. Biopsy-proven AR was described in 4/27 (15%) pts in the anti-AT1R(+) group and 13/90 (14.4%) in the anti-AT1R(-) group, but more severe cases of Banff IIB or antibody-mediated rejection (AMR) were more often observed in anti-AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti-AT1R(+) (P = 0.009). Patients with anti-AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti-AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti-AT1R-positive ones lost the graft. Our study suggests monitoring of anti-AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.

The Role of Angiotensin-Converting Enzyme (ACE) Polymorphisms in the Risk of Development and Treatment of Diabetic Nephropathy.

BACKGROUND: Angiotensin-converting enzyme (ACE) is responsible for the production of angiotensin II, and increased production of angiotensin II is observed in diabetes. What is more, ACE polymorphisms may play a role in the development of diabetic nephropathy. The aim of this study was to assess the role of selected ACE polymorphisms (rs4343 and rs4646994) in the risk of development of diabetic nephropathy and in the likelihood of renal replacement therapy. METHODS: ACE polymorphisms were analyzed in a group of 225 patients who were divided into three subgroups. The rs4343 polymorphism was determined using the PCR-RFLP, and the rs4646994 polymorphism was determined using the PCR. Molecular docking between domains of ACE and its ligands was performed by using AutoDock Vina. RESULTS: The G/G genotype of rs4343 polymorphism is associated with increased odds of developing diabetic nephropathy. The G allele is also associated with a higher risk of this disease. Similar results were obtained in patients who had already had a kidney transplant as a result of diabetic nephropathy. CONCLUSIONS: The presence of G/G and G/A genotypes, and the G allele increases the likelihood of developing diabetic nephropathy. This may also be a risk factor for renal replacement therapy.

Therapy in the Course of Kidney Graft Rejection-Implications for the Cardiovascular System-A Systematic Review.

Kidney graft failure is not a homogenous disease and the Banff classification distinguishes several types of graft rejection. The maintenance of a transplant and the treatment of its failure require specific medications and differ due to the underlying molecular mechanism. As a consequence, patients suffering from different rejection types will experience distinct side-effects upon therapy. The review is focused on comparing treatment regimens as well as presenting the latest insights into innovative therapeutic approaches in patients with an ongoing active ABMR, chronic active ABMR, chronic ABMR, acute TCMR, chronic active TCMR, borderline and mixed rejection. Furthermore, the profile of cardiovascular adverse effects in relation to the applied therapy was subjected to scrutiny. Lastly, a detailed assessment and comparison of different approaches were conducted in order to identify those that are the most and least detrimental for patients suffering from kidney graft failure.

Toll-Like Receptor 3 mRNA Expression of Peripheral Blood Mononuclear Cells Identifies Kidney Recipients with Potential for Improved Graft Performance.

BACKGROUND Toll-like receptor 3 expression is detected both on the cell membrane and in endosomes of peripheral blood mononuclear cells (PBMC). Our goal in this study was to determine to what extent a single, baseline measurement of non-stimulated PBMC TLR3-mRNA can be related to baseline GFR (b-GFR) and post-follow-up-GFR (F-up-GFR) of a kidney transplant (KT) and baseline immunosuppression. MATERIAL AND METHODS In non-stimulated PBMC we investigated averaged mRNA expression of Toll-like receptor 3. A total of 133 patients were enrolled; the median of months after KT surgery was 11.4, with median F-up at 21.3 months. A favorable course (FCF) was determined if F-up-eGFR improved. An unfavorable course (UCF) was determined if F-up-eGFR was lower at the end of the observation. RESULTS The highest TLR3-mRNA expression was at b-GFR grade 3b; it was moderately higher at b-GFR grade 3a, and marginally higher at b-GFR grades 1+2. Most of the FCF group had b-GFR grade 3b, less frequent obesity, more effective immunosuppression, and much higher TLR3-mRNA (59% of cases were in the high-TLR3 area). Both delayed graft function (DGF) and TLR3-mRNA range below the median for the entire KT cohort (low-TLR3 area) had a negative association with b-GFR. The UCF group had more frequent DGFs and obesity, less effective immunosuppression, and lower TLR3-mRNA. CONCLUSIONS In patients with GFR grade 3, high levels of TLR3-mRNA are associated with improved graft efficacy. In patients with impaired graft function, low TLR3- mRNA expression reduces the likelihood of improved renal graft function.

Indoleamine 2,3-Dioxygenase 1 (IDO1) in Kidney Transplantation: A Guardian against Rejection.

Kidney transplantation is a crucial treatment for end-stage kidney disease, with immunosuppressive drugs helping to reduce acute rejection rates. However, kidney graft longevity remains a concern. This study explores the role of indoleamine 2,3-dioxygenase 1 (IDO1) in kidney transplant immunology. IDO1 breaks down tryptophan, affecting immune cell behavior, primarily T-cells. The research focuses on both cellular and antibody-mediated immune responses, often causing graft damage. The study assessed IDO1 expression in renal transplant biopsies from patients with graft function decline, examining its connection to clinical parameters. A total of 121 biopsy samples were evaluated for IDO1 expression using immunohistochemistry. Patients were categorized as IDO1(+) positive or IDO1(-) negative based on immunoreactivity in tubular epithelium. Results showed a significant link between IDO1 expression and rejection incidence. IDO1(+) positive patients had lower rejection rates (32.9%) compared to IDO1(-) negative ones (62.2%) [p = 0.0017], with substantial differences in antibody-mediated rejection (AMR) (5.2% vs. 20%) [p = 0.0085] and T-cell mediated rejection (TCMR) (31.6% vs. 57.8%). These associations suggest that IDO1 may play a protective role in kidney transplant rejection. IDO1 modulation could offer novel therapeutic avenues to enhance graft survival. The study underscores IDO1 as a potential marker for rejection risk assessment, with its potential applications in personalized interventions and improved patient outcomes. Further research is needed to fully comprehend the mechanisms behind IDO1's immunomodulatory functions and its potential clinical translation.

Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study.

Early identification of allograft vasculopathy and the concomitant elimination of adverse risk factors is essential for improving the long-term prognosis of heart transplant (HTx) recipients with underlying cardiovascular disease (CVD). The major aim of this pilot study was to conduct a non-invasive imaging evaluation of the HTx patient microcirculation by employing nailfold video-capillaroscopy (NVC) in a well-characterized patient and control cohort, and to correlate these data with endothelial cell function, accompanied by studies of traditional cardiovascular risk factors and non-HLA antibodies in HTx recipients. Ten patients undergoing HTx (mean age of 38 ± 14 years) were recruited for the study and compared to a control group of 12 well-matched healthy volunteers (mean age 35 ± 5 years) with normal body mass index (BMI). Detailed medical records were collected from all individuals. NVC was performed using CapillaryScope 200 MEDL4N microscope. For functional readout and correlation analysis, endothelial cell network formation in conjunction with measurements of patient serum levels of vascular endothelial growth factor (VEGF) and non-HLA autoantibodies directed against the angiotensin II type-1-receptor (anti-AT1R-Ab), endothelin-1 type-A-receptor (anti-ETAR-Ab), protease-activated receptor-1 (anti-PAR-1-Ab), and VEGF-A (anti-VEGF-A-Ab) were studied. Our NVC analysis found that the average apical loop diameter of nailfold capillaries was significantly increased in HTx recipients (p = 0.001). In addition, HTx patients with more prominent changes in capillaroscopic patterns were characterized by the presence of traditional cardiovascular risk factors, and HTx patients had increased levels of anti-AT1R-ab, anti-ETAR-ab, and anti-VEGF-A-Ab (p = 0.017, p = 0.025, and p = 0.003, respectively). Capillary diameters most strongly correlated with elevated serum levels of troponin T and triglycerides (R = 0.69, p = 0.028 and R = 0.81, p = 0.004, respectively). In conclusion, we found that an abnormal NVC pattern in HTx patients is associated with traditional CVD risk factors and that NVC is a useful non-invasive tool to conveniently monitor changes in the microvasculature of HTx patients.

Point-of-Care Testing to Differentiate Various Acid-Base Disorders in Chronic Kidney Disease.

BACKGROUND: Normal-anion-gap metabolic acidosis (AGMA) and high-anion-gap metabolic acidosis (HAGMA) are two forms of metabolic acidosis, which is a common complication in patients with chronic kidney disease (CKD). The aim of this study is to identify the prevalence of various acid-base disorders in patients with advanced CKD using point-of-care testing (POCT) and to determine the relationship between POCT parameters. METHODS: In a group of 116 patients with CKD in stages G4 and G5, with a mean age of 62.5 ± 17 years, a sample of arterial blood was taken during the arteriovenous fistula procedure for POCT, which enables an assessment of the most important parameters of acid-base balance, including: pH, base excess (BE), bicarbonate (HCO3-), chloride(Cl-), anion gap (AG), creatinine and urea concentration. Based on this test, patients were categorized according to the type of acidosis-base disorder. RESULTS: Decompensate acidosis with a pH < 7.35 was found in 68 (59%) patients. Metabolic acidosis (MA), defined as the concentration of HCO3- ≤ 22 mmol/L, was found in 92 (79%) patients. In this group, significantly lower pH, BE, HCO3- and Cl- concentrations were found. In group of MA patients, AGMA and HAGMA was observed in 48 (52%) and 44 (48%) of patients, respectively. The mean creatinine was significantly lower in the AGMA group compared to the HAGMA group (4.91 vs. 5.87 mg/dL, p < 0.05). The AG correlated positively with creatinine (r = 0.44, p < 0.01) and urea (r = 0.53, p < 0.01), but there was no correlation between HCO3- and both creatinine (r = -0.015, p > 0.05) and urea (r = -0.07, p > 0.05). The Cl- concentrations correlated negatively with HCO3- (r = -0.8, p < 0.01). CONCLUSIONS: The most common type of acid-base disturbance in CKD patients in stages 4 and 5 is AGMA, which is observed in patients with better kidney function and is associated with compensatory hyperchloremia. The initiation of renal replacement therapy was significantly earlier for patients diagnosed with HAGMA compared to those diagnosed with AGMA. The more advanced the CKD, the higher the AG.

Native Renal Arteries Denervation as a Therapy of Refractory Hypertension in Patient after Heart and Kidney Transplantation-5 Years of Observation.

This case report describes a 59-year-old male patient after heart and kidney transplantation, subsequently diagnosed with refractory hypertension since implemented antihypertensive pharmacotherapy consisting of six agents did not provide a substantial therapeutic response. Elevated blood pressure and its impact on a hypertrophied transplanted heart and impaired renal graft function have led to a significant deterioration in the patient's cardiovascular risk profile. To address this issue, a native renal arteries denervation was performed. It resulted in a noteworthy decrease in both systolic and diastolic pressure values, thus manifesting a positive hypotensive effect. Furthermore, a sustainable reduction of left ventricular mass and stabilization in kidney graft function were noticed. The presented case provides evidence that renal denervation can be an efficacious complementary treatment method in individuals who received kidney and heart grafts as it leads to a decrease in cardiovascular risk.

Assessment of Clinical Indicators Registered on Admission to the Hospital Related to Mortality Risk in Cancer Patients with COVID-19.

BACKGROUND: Oncology patients are a particularly vulnerable group to the severe course of COVID-19 due to, e.g., the suppression of the immune system. The study aimed to find links between parameters registered on admission to the hospital and the risk of later death in cancer patients with COVID-19. METHODS: The study included patients with a reported history of malignant tumor (n = 151) and a control group with no history of cancer (n = 151) hospitalized due to COVID-19 between March 2020 and August 2021. The variables registered on admission were divided into categories for which we calculated the multivariate Cox proportional hazards models. RESULTS: Multivariate Cox proportional hazards models were successfully obtained for the following categories: Patient data, Comorbidities, Signs recorded on admission, Medications used before hospitalization and Laboratory results recorded on admission. With the models developed for oncology patients, we identified the following variables that registered on patients' admission were linked to significantly increased risk of death. They are: male sex, presence of metastases in neoplastic disease, impaired consciousness (somnolence or confusion), wheezes/rhonchi, the levels of white blood cells and neutrophils. CONCLUSION: Early identification of the indicators of a poorer prognosis may serve clinicians in better tailoring surveillance or treatment among cancer patients with COVID-19.

Adherence to Immunosuppressive Therapies after Kidney Transplantation from a Biopsychosocial Perspective: A Cross-Sectional Study.

Kidney transplantation (KT) is the best method for kidney replacement therapy (KRT) because of patient survival rates and quality of life (QoL). Nowadays, the main cause of graft loss is antibody-mediated rejection. The treatment of humoral injury is difficult with uncertain results and still not firmly established. Therefore, appropriate adherence is crucial to prolong graft and patient survival. This study aims to evaluate the association of transplant patients' acceptance of illness, symptoms of anxiety and depression, frailty, and QoL with medication adherence in KT recipients. A total of 210 patients after KT completed the surveys. The instruments were distributed during patients' admission at the clinic by a qualified nurse, who assisted the patients' in completing the questionnaires. A cross-sectional study of KT recipients 9.45 ± 7.26 years after KT was performed. Patient adherence with medications was assessed using the Adherence to Refills and Medications Scale (ARMS). Explanatory variables were examined with validated instruments, such as the World Health Organization Quality of Life (WHOQoL-BREF) questionnaire, The Mini-Mental State Examination (MMSE), the Acceptance of Illness Scale (AIS), the Hospital Anxiety and Depression Scale (HADS), and the Tilburg Frailty Indicator (TFI) scale, respectively. Simple linear and multiple regression analyses demonstrated the positive correlation between acceptance of illness and adherence to immunosuppressive medications in a patient sample of KT recipients. The other important factor facilitating adherence to medications was linked with physical and environmental dimensions. On the other hand, frail kidney transplant patients were more likely to be non-adherent. In conclusion, identifying contributors to better medication adherence in immunosuppressive therapy is crucial in preventing transplant rejection or graft loss. In the kidney transplant population, the acceptance of illness, selected dimensions of QoL, and demographic variables associated with rural living and vocational education favored adherence behaviors.

The Association between Psychosocial and Age-Related Factors with Adherence to Immunosuppressive Therapies after Renal Transplantation.

Renal transplantation (RT) is the optimal renal replacement treatment approach in terms of patient survival and high quality of life. Proper adherence to medication is essential in order to prolong graft life and patient survival. This study aimed to investigate the effects of psychosocial factors and age-related declines on adherence in kidney transplant recipients. Methods: This was a cross-sectional study of kidney transplant recipients, based on regression analysis. Patient adherence was assessed with the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS). Psychosocial and age-related variables were measured with the World Health Organization's quality of life questionnaire (WHOQoL-BREF), the Mini-Mental State Examination (MMSE), the Hospital Anxiety and Depression Scale (HADS), the Acceptance of Illness Scale (AIS), and the Tilburg Frailty Indicator (TFI). Results: A simple linear regression model indicated that the significant predictors of self-reported adherence (p < 0.05) were age, time since transplant, and anxiety and cognitive functions. For problems with implementing immunosuppressive medication, logistic regression models showed that gender, age, retirement status, hypercholesterolemia, and cognitive impairment were the most significant predictors (p < 0.05). However, after controlling for other predictors in the multiple regression models, anxiety and cognitive ability no longer predicted treatment adherence to immunosuppressive medication. Conclusions: Renal transplantation is the most effective therapy in chronic renal failure patients. Proper adherence to immunosuppressive therapy is critical to prolonging graft and person survival. Our study shows that occupational status more significantly influences adherence to the implementation of treatment in kidney transplant recipients.

The role of endothelin II type A receptor (ETAR) in transplant injury.

PURPOSE OF REVIEW: Antibody-mediated rejection is the leading cause of deterioration of graft function and graft loss after kidney transplantation. Recent studies have reported an increasing role of non-HLA antibodies in the humoral injury after kidney transplantation. We decided to present the influence of non-HLA antibodies - anti-endothelin II type A receptor (ETAR) on a transplanted kidney and characterize the significance of their receptor. RECENT FINDINGS: The role of non-HLA antibodies is still uncertain. Many studies suggest that the presence of non-HLA antibodies, including anti-ETAR antibodies, is among the risk factors for antibody-mediated rejection, graft injury, and graft loss. The discovery of new antigen targets and antibodies, which participate in the humoral response, has provided a significantly better understanding of the mechanism of antibody-mediated rejection after organ transplantation. SUMMARY: Endothelin and its receptors play an important role in physiology and pathophysiology after solid organ transplantation. ETAR and antibodies against ETAR may participate in humoral rejection and graft damage. The measurement of anti-ETAR antibodies may identify patients with an increased risk of rejection and even loss of a transplanted organ. Expression of ETAR detected in biopsy of transplant could become an additional tool used to better understand humoral activity. More research is needed to address many questions about non-HLA directed rejection and graft damage.

Angiotensin II Type 1 Receptor Antibodies Are Higher in Lupus Nephritis and Vasculitis than Other Glomerulonephritis Patients.

Angiotensin II type 1 receptor (AT1R) antibodies are considered non-HLA (human leukocyte antigen) antibodies connected with humoral rejection after kidney transplantation. The role of AT1R antibodies in the pathogenesis of glomerular diseases and systemic vasculitis is unknown. We assessed the level of AT1R antibodies in 136 patients with different types of glomerulonephritis and systemic vasculitis and we observed kidney function and proteinuria, serum albumin and total protein levels for 2 years. The mean levels of AT1R antibodies were the following: 6.00 ± 1.31 U/ml in patients with membranous nephropathy (n = 18), 5.67 ± 1.31 U/ml with focal and segmental glomerulosclerosis (n = 25), 6.26 ± 2.25 U/ml with lupus nephropathy (n = 17), 10.60 ± 6.72 U/ml with IgA nephropathy (n = 14), 6.69 ± 2.52 U/ml with mesangial proliferative (non IgA) glomerulonephritis (n = 6), 6.63 ± 1.38 U/ml with systemic vasculitis (n = 56), including c-ANCA (anti-neutrophil cytoplasmic antibodies) vasculitis: 11.22 ± 10.78 U/ml (n = 40) and p-ANCA vasculitis: 12.65 ± 14.59 U/ml (n = 16). The mean AT1R antibodies level was higher in patients with lupus nephropathy and systemic vasculitis compared to glomerulonephritis groups. An inverse statistically significant correlation between AT1R antibodies and serum albumin (r = - 0.51) in membranous nephropathy group was also found. Prospective analysis of creatinine levels indicated an increase of creatinine levels during time among patients with higher AT1R antibodies levels in p-ANCA vasculitis. Lupus nephropathy and systemic vasculitis patients may have high levels of AT1R antibodies. AT1R antibodies may be associated with the severity of membranous nephropathy and the course of p-ANCA vasculitis, although influence of concomitant factors is difficult to exclude.