Mortality Risk and Urinary Proteome Changes in Acute COVID-19 Survivors in the Multinational CRIT-COV-U Study.

BACKGROUND/OBJECTIVES: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection severity; however, this topic has not been studied in detail. Therefore, within this study, the mortality risk post-acute COVID-19 in the CRIT-COV-U cohort was investigated. METHODS: Survival data from 651 patients that survived an acute phase of COVID-19 were retrieved and the association between urinary peptides and future death was assessed. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched COVID-19-negative controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomic datasets. RESULTS: Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than COVID-19-negative controls, particularly evident in younger individuals (<65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease but also beyond for a period of about one year. In our study, we were further able to identify 201 urinary peptides linked to mortality. These peptides are fragments of albumin, alpha-2-HS-glycoprotein, apolipoprotein A-I, beta-2-microglobulin, CD99 antigen, various collagens, fibrinogen alpha, polymeric immunoglobulin receptor, sodium/potassium-transporting ATPase, and uromodulin and were integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death. CONCLUSIONS: The peptide-based classifier demonstrated significant predictive value for mortality in post-acute COVID-19 patients, highlighting the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. By utilizing these defined biomarkers in the clinic, risk stratification, monitoring, and personalized interventions can be significantly improved. Our data also suggest that mortality should be considered as one possible symptom or a consequence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.

Angiotensin II Type 2 Receptor Antibodies in Glomerular Diseases.

We evaluated the concentration of AT2R antibodies in 136 patients with primary and secondary glomerular diseases: membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (n = 25), systemic lupus erythematosus (n = 17), immunoglobulin A (IgA) nephropathy (n = 14), mesangial (non-IgA) proliferative nephropathy (n = 6), c-ANCA vasculitis (n = 40), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and compared it with a healthy control group (22 patients). Serum creatinine levels, proteinuria, serum albumin, and total protein concentrations were prospectively recorded for 2 years. The mean levels of AT2R antibodies in the lupus nephropathy group were significantly higher compared to the control group, 64.12 ± 26.95 units/mL and 9.72 ± 11.88 units/mL, respectively. There was no association between this level and the clinical course of the disease. The AT2R levels in other kinds of glomerular disease were no different from the control group. We found significant correlations between AT1R and AT2R in patients with membranous nephropathy (r = 0.66), IgA nephropathy (r = 0.61), and c-ANCA vasculitis (r = 0.63). Levels of AT2R antibodies in systemic lupus erythematosus are higher compared to other types of glomerulonephritis, vasculitis, and a healthy control group. Levels of AT2R antibodies correlate with AT1R antibodies in the groups of patients with membranous nephropathy, IgA nephropathy, and c-ANCA vasculitis. These kinds of AT2R antibodies have a stimulative effect on AT2R, but we have not found the influence of these antibodies on the clinical course of glomerular diseases.

Subthreshold rejection activity in many kidney transplants currently classified as having no rejection.

Most kidney transplant patients who undergo biopsies are classified as having no rejection based on consensus thresholds. However, we hypothesized that because these patients have normal adaptive immune systems, T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR) may exist as subthreshold activity in some transplants currently classified as no rejection. To examine this question, we studied genome-wide microarray results from 5086 kidney transplant biopsies (from 4170 patients). An updated molecular archetypal analysis designated 56% of biopsies as no rejection. Subthreshold molecular TCMR and/or ABMR activity molecular activity was detectable as elevated classifier scores in many biopsies classified as no rejection, with ABMR activity in many TCMR biopsies and TCMR activity in many ABMR biopsies. In biopsies classified as no rejection histologically and molecularly, molecular TCMR classifier scores correlated with increases in histologic TCMR features and molecular injury, lower estimated glomerular filtration rate, and higher risk of graft loss, and molecular ABMR activity correlated with increased glomerulitis and donor-specific antibody. No rejection biopsies with high subthreshold TCMR or ABMR activity had a higher probability of having TCMR or ABMR, respectively, diagnosed in a future biopsy. We conclude that many kidney transplant recipients have unrecognized subthreshold TCMR or ABMR activity, with significant implications for future problems.

The Effect of Selected Nitric Oxide Synthase Polymorphisms on the Risk of Developing Diabetic Nephropathy.

BACKGROUND: Nitric oxide synthase (NOS) is an enzyme that catalyzes the formation of nitric oxide (NO), the altered production of which is characteristic of diabetic nephropathy. NOS exists in three isoforms: NOS1, NOS2, and NOS3. Moreover, there are reports about the potential role of NOS3 polymorphisms in the development of diabetes complications. The aim of this study was to assess the role of selected NOS polymorphisms-rs3782218 (NOS1), rs1137933 (NOS2), rs1799983, rs2070744, and rs61722009 (NOS3)-in the risk of developing diabetic nephropathy and in the likelihood of renal replacement therapy. METHODS: The studied polymorphisms were analyzed in a group of 232 patients divided into three groups. Four polymorphisms (rs3782218, rs1137933, rs1799983, rs2070744) were genotyped using the PCR-RFLP, while the rs61722009 polymorphism was genotyped using the PCR. RESULTS: The C/C genotype and the C allele of the rs3782218 polymorphism (NOS1) were associated with an increased risk of developing diabetic nephropathy and an increased likelihood of renal replacement therapy. In turn, the G allele of the rs1137933 polymorphism (NOS2) reduces the likelihood of renal replacement therapy. CONCLUSIONS: The specific genotypes or alleles of the rs3782218 (NOS1) and rs1137933 (NOS2) polymorphisms seem to be potential risk factors for diabetic nephropathy and renal replacement therapy.

Interstitial Foci Expression of Indoleamine 2,3-Dioxygenase 1: A Potential Biomarker for Kidney Transplant Rejection.

(1) Background: Kidney transplantation is the best therapy for patients with end-stage renal disease, but the risk of rejection complicates it. Indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme involved in immune response modulation, has been suggested to play a role in transplant immunological injury. The aim of the study was to explore the expression of IDO1 in the interstitial foci of transplanted kidneys and its potential association with rejection episodes. (2) Methods: This retrospective study analysed kidney transplant biopsies from 121 patients, focusing on IDO1 expression in interstitial foci. Immunohistochemistry was used to detect IDO1, and patients were categorised based on IDO1 presence (IDO1-IF positive or negative). The incidence of rejection was compared between these groups. (3) Results: Patients with IDO1 expression in interstitial foci (IDO1-IF(+)) exhibited higher incidences of rejection 46/80 (57.5%) vs. 10/41 (24.34%) patients compared to IDO1-IF(-) patients, which was statistically significant with p = 0.0005. The analysis of antibody-mediated rejection showed that IDO1-IF(+) patients developed AMR at 12/80 (15%), while only 1 IDO1-IF(-) negative patient did (2,44%), with p = 0.035. T-cell-mediated rejection was also more common in IDO1-IF(+) patients 43/80 (53.75%) than in IDO1-IF(-) patients 7/41 (17.07%), with p = 0.0001. (4) Conclusions: IDO1 expression in interstitial foci of renal transplant biopsies is associated with a higher incidence of rejection, suggesting that IDO1 could serve as a potential biomarker for transplant rejection. These findings highlight the importance of IDO1 in immune regulation and its potential utility in improving the management of kidney transplant recipients.

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.

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.

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.

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.

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.

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.

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.

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.

Chronic Active T-Cell Mediated Kidney Rejection as a Clinically Significant Type of Allograft Loss?

The purpose of this article is to assess the present knowledge about chronic active (CA) T-cell mediated rejection (TCMR) of a kidney. In the research authors review current Banff diagnostic criteria used in kidney rejection, focus on their possible future evolution, and investigate the role of currently available molecular methods that could be implemented into the diagnostic scheme. Research also points out previously and currently available treatment methods applied to CA TCMR and takes into account possible side effects consequent upon the therapy. Moreover, attention is being paid to the CA TCMR coincidence with other kidney rejection types such as antibody-mediated rejection (ABMR) and its influence on the treatment approach. Authors also mark the possibility of non-HLA antibodies coexistence in patients with CA TCMR and describe its possible resonance on kidney allograft function. Nonetheless, it seems that current knowledge about CA TCMR is not sufficient and requires further investigation.

Significance of Indoleamine 2,3-Dioxygenase Expression in the Immunological Response of Kidney Graft Recipients.

Kidney transplantation is unquestionably the most advantageous and preferred treatment when patients with end-stage renal disease are considered. It does have a substantially positive influence on both the quality and expectancy of their lives. Thus, it is quintessential to extend the survival rate of kidney grafts. On account of T-cell-focused treatment, this is being exponentially achieved. The kynurenine pathway, as an immunosuppressive apparatus, and indoleamine 2,3-dioxygenase (IDO1), as its main regulator, are yet to be exhaustively explored. This review presents the recognised role of IDO1 and its influence on the kynurenine pathway, with emphasis on immunosuppression in kidney transplant protection.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study.

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6-77·1%) for mortality (threshold 0·47) and 67·4% (64·4-70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5-95% percentile interval 0·730-1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04). INTERPRETATION: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. FUNDING: German Federal Ministry of Health.

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.

Biomarkers in Primary Focal Segmental Glomerulosclerosis in Optimal Diagnostic-Therapeutic Strategy.

Focal segmental glomerulosclerosis (FSGS) involves podocyte injury. In patients with nephrotic syndrome, progression to end-stage renal disease often occurs over the course of 5 to 10 years. The diagnosis is based on a renal biopsy. It is presumed that primary FSGS is caused by an unknown plasma factor that might be responsible for the recurrence of FSGS after kidney transplantation. The nature of circulating permeability factors is not explained and particular biological molecules responsible for inducing FSGS are still unknown. Several substances have been proposed as potential circulating factors such as soluble urokinase-type plasminogen activator receptor (suPAR) and cardiolipin-like-cytokine 1 (CLC-1). Many studies have also attempted to establish which molecules are related to podocyte injury in the pathogenesis of FSGS such as plasminogen activator inhibitor type-1 (PAI-1), angiotensin II type 1 receptors (AT1R), dystroglycan(DG), microRNAs, metalloproteinases (MMPs), forkheadbox P3 (FOXP3), and poly-ADP-ribose polymerase-1 (PARP1). Some biomarkers have also been studied in the context of kidney tissue damage progression: transforming growth factor-beta (TGF-ß), human neutrophil gelatinase-associated lipocalin (NGAL), malondialdehyde (MDA), and others. This paper describes molecules that could potentially be considered as circulating factors causing primary FSGS.

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.

Prone Position Facilitates Creation of Ulnar-Basilic Arteriovenous Fistula.

BACKGROUND: The distal ulnar-basilic arteriovenous fistula (UBAVF) is a rarely used alternative type of vascular access for haemodialysis. The location of the vein on the back aspect of the forearm forces an extremely uncomfortable external rotation of the upper limb during surgery when the patient is in a supine position. METHODS: We present a new approach towards creating UBAVF, which involves placing the patient in the prone position, thus eliminating the aforementioned inconvenience. The procedure was performed and described in a 46-year-old patient with chronic kidney disease (CKD) due to diabetic nephropathy. In the period from September 2021 to December 2021, we created an additional three UBAVFs with such modifications. RESULTS: All fistulas were patent both immediately after the procedure and 2 weeks after surgery. CONCLUSIONS: The prone position may improve the comfort of both the operator and the patient during the procedure. On top of this, it may have a positive impact on the quality of the arteriovenous anastomosis.