Dialysis Catheter Insertion with Extended Ultrasound Monitoring.

INTRODUCTION: Dialysis catheter insertion is a routine procedure performed when there is necessity of urgent renal replacement therapy initiation. Due to limited access, higher costs, and long waiting times for fluoroscopy, alternative visualization methods are introduced into clinical practice. One of the most promising is transthoracic echocardiographic monitoring of guide-wire introduction. OBJECTIVE: The feasibility of the technique was verified by nephrologists inserting dialysis catheters. METHODS: A single center prospective trial was performed (NCT03727581). Introduction of guide-wire was monitored with ultrasound to confirm correct position of the wire in the inferior vena cava (IVC) or right atrium (RA). The study group included 30 patients, 19 males and 11 females, 25-83 years old. RESULTS: It was possible to obtain a good picture of IVC in the majority of patients. In 20 (66.7%) cases, IVC view was excellent; in 9 (30%) cases, was fair; and in 1 (3.3%) patient, we failed to visualize IVC. The guide-wire was identified in IVC in 12 (42.8%) patients, in another 9 (32.1%) patients guide-wire was visible in IVC after withdrawing and advancing it, and in RA in 6 (21.4%) patients. Catheters were successfully placed in 29 (96.7%) patients. CONCLUSIONS: Detection of the guide-wire confirms correct course of the procedure and increases the safety of catheter insertion without fluoroscopy.

Polymers with antiviral properties: A brief review.

Viruses that are pathogenic to humans and livestock pose a serious epidemiological threat and challenge the world's population. The SARS-CoV-2/COVID-19 pandemic has made the world aware of the scale of the threat. The surfaces of various materials can be a source of viruses that remain temporarily contagious in the environment. Few polymers have antiviral effects that reduce infectivity or the presence of a virus in the human environment. Some of the effects are due to certain physical properties, e.g., high hydrophobicity. Other materials owe their antiviral activity to a modified physicochemical structure favoring the action on specific virus receptors or on their biochemistry. Current research areas include: gluten, polyvinylidene fluoride, polyimide, polylactic acid, graphene oxide, and polyurethane bound to copper oxide. The future belongs to multi-component mixtures or very thin multilayer systems. The rational direction of research work is the search for materials with a balanced specificity in relation to the most dangerous viruses and universality in relation to other viruses.

Balloon Dilatation for Removal of an Irretrievable Permanent Hemodialysis Catheter: The Safest Approach.

Long-term hemodialysis catheter dwell time in the central vein predisposes to fibrin sheath development, which subsequently causes catheter malfunction or occlusion. In very rare cases, the catheter can be overgrown with fibrin and rigidly connected with the vein or heart structures. This makes its removal almost impossible and dangerous because of the possibility of serious complications, namely vein and heart wall perforation, bleeding, or catheter abruption in deep tissues. We describe two cases in which standard retrieval of long-term catheters was not possible. Balloon dilatation of catheter lumens was successfully used to increase the catheter diameter with simultaneous tearing of the fibrin sheath surrounding it. This allowed the catheter to be set free safely. Based on this experience, we present recent literature and our point of view.

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.

Different mortality predictor pattern in hemodialysis and peritoneal dialysis diabetic patients in 4-year prospective observation.

INTRODUCTION: The aim was to identify factors carrying an ominous prognosis in a cohort of diabetic patients (pts) on a hemodialysis (HD) and peritoneal dialysis (PD) program. MATERIALS AND METHODS: We analyzed survival rates of 61 diabetic dialysis pts (35 HD/26 PD). The participants were matched in baseline characteristics, standard indicators of dialysis care and laboratory parameters. The studied group was prospectively observed up to 4 years. RESULTS: 21 pts (34.4%) survived the whole observation period. The annual mortality rate was 23.2%, with no difference between HD and PD. Irrespective of dialysis modality, the only factor associated with mortality in the Cox proportional hazard model was serum albumin lowering. Referring to dialysis modality, the HD survivors were characterized by lower IL-6 level, higher albumin concentration, and increased serum cholesterol values with higher cholesterol left in multivariate analysis; under PD therapy the only factor significantly associated with mortality was older age. In contrast to HD treatment, elevated cholesterol was a universal finding in PD patients, significantly above levels in HD, with a slight tendency to lower values in PD survivors. CONCLUSIONS: 1. A difference in mortality predictor pattern appeared in diabetic patients treated by PD and HD. 2. In the PD group more advanced age had a decisive negative impact on survival whereas in the HD group the outlook was dependent on factors related to nutrition and inflammation. 3. Elevated cholesterol level was associated with survival benefit in HD patients, being a common abnormality in the PD group, without positive prognostic significance.

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.

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.

A rare variant route of the ulnar artery does not contraindicate the creation of a fistula in the wrist of a diabetic patient with end-stage renal disease.

A superficial variant route of the ulnar artery is a rare variation of the arterial system of the wrist. The route of the arteries in that region is extremely important for patients with end-stage renal disease due to the necessity to create an arteriovenous fistula for hemodialysis. It is thought that the vascular access is too often achieved by catheters or vascular prostheses because of that each possibility to create a fistula in the wrist region should be utilized. In our patient a rare variant route of the ulnar artery was observed in the wrist region. Instead of a deep route between the muscles the artery did not only run superficially, but, also untypically, first laterally and then medially. A variation of the ulnar artery's route may evoke a fear of hand ischemia after creation arteriovenous fistula for hemodialysis. The fear may be connected with blood supply throw the palmar arch which is created by radial and ulnar artery. This fear of the doctor may result in avoiding the attempt to create an arteriovenous fistula on the wrist. The authors demonstrate that the variant route of the ulnar artery is not a contraindication to the creation of a fistula on the wrist using the radial artery because of a fear of hand ischemia.

Partial breakage of a tunneled dialysis catheter: An uncommon finding.

Infections and dysfunction are the most common complications related to catheter use. Here we describe a case of catheter rupture on the course of subcutaneous channel. Catheter fractures are relatively rare, but potentially hazardous complications. In case of partial breakage, a catheter exchange should be a simple solution.

Vascular Access Perspectives in Patients After Kidney Transplantation.

Introduction: More attention has been paid to the influence of arteriovenous fistula (AVF) on the cardiovascular system. In renal transplant recipients, some beneficial effect of an elective vascular access (VA) ligation was observed in patients with a high AVF flow. However, this strategy is not widely accepted and is in contradiction to the rule of vasculature preservation for possible future access. The aim of our study is to elucidate the vascular access function and VA perspective in the kidney transplantation (KTx) population. Materials and Methods: KTx patients with a stable graft function were recruited to participate in this single center observational study (NCT04478968). The measurement of VA flow and vessel mapping for future vascular access was performed by a color Doppler ultrasound. The study group included 99 (63%) males and 58 (37%) females; the median age was 57 (IQR 48-64) years. The median time from the transplantation to the baseline visit was 94 (IQR 61-149) months. Median serum creatinine concentration was 1.36 (IQR 1.13-1.67) mg/dl. Results: Functioning VA was found in 83 out of 157 (52.9%) patients. The sites were as follows: snuffbox in six (7.2%), wrist in 41 (49.4%), distal forearm in 18 (21.7%), middle or proximal forearm in eight (9.6%), upper-arm AV graft in one (1.2%), and upper-arm AVFs in nine (10.8%) patients, respectively. Blood flow ranged from 248 to 7,830 ml/min; the median was 1,134 ml/min. From the transplantation to the study visit, 66 (44.6%) patients experienced access loss. Spontaneous thrombosis was the most common, and it occurred in 60 (90.9%) patients. The surgical closure of VA was performed only in six (4%) patients of the study group with a functioning VA at the time of transplantation. Access loss occurred within the 1st year after KTx in 33 (50%) patients. Majority (50 out of 83, 60.2%) of the patients with an active VA had options to create a snuffbox or wrist AVF on the contralateral extremity. In a group of 74 patients without a functioning VA, the creation of a snuffbox or wrist AVF on the non-dominant and dominant extremity was possible in seven (9.2%) and 40 (52.6%) patients, respectively. In 10 (13.1%) patients, the possibilities were limited only to the upper-arm or proximal forearm VA on both sides. Access ligation was considered by 15 out of 83 (18.1%) patients with a patent VA. Conclusions: In the majority of the patients, vascular access blood flow was below the threshold of the negative cardiovascular effect of vascular access. Creation of a distal AVF is a protective measure to avoid a high flow and preserve the vessels for future access. The approach to VA should be individualized and adjusted to the patient's profile.

Pleural effusion with arm, breast, and face edema as a complication of subclavian vein catheterization and arteriovenous fistula in a patient after renal transplantation: A therapeutic approach.

A 52-year-old woman after renal transplantation developed unilateral pleural effusion as well as a massive edema of the upper limb, breast, and face as a complication of the subclavian vein catheterization and arteriovenous fistula for hemodialysis. We revealed that impaired venous drainage due to extensive vein occlusion after temporary catheter insertion, together with high venous flow from the arteriovenous fistula, were the explanation. Because of moderately impaired renal graft function and limited availability of vascular access in the patient, fistula ligation as a therapeutic method described in literature, was not an option in our case. The patient underwent an unsuccessful attempt of venous angioplasty, and eventually banding of the fistula and blood flow reduction resolved pleural effusions and edema. This is a reasonable approach to the problem of massive upper torso edema due to central vein occlusion with ipsilateral arteriovenous fistula.

Endothelin A Receptors Expressed in Glomeruli of Renal Transplant Patients May Be Associated with Antibody-Mediated Rejection.

BACKGROUND: Non-human leukocyte antigen (HLA) anti-endothelin A receptor antibodies are presented as being potentially important, but the expression of the endothelin A receptor in glomeruli (ETA receptor (g+)) has not yet been described. We decided to evaluate the presence and relevance of the ETA receptor in for-cause renal transplant biopsies. The aim of our study was to evaluate the immunoreactivity of the ETA receptor and its significance in patients who underwent a renal transplant biopsy due to the deterioration of transplant function, with detailed characterization of staining in glomeruli. METHODS: The immunohistochemical expression of ETA receptor (ETAR) was analyzed in renal transplant biopsies. Microscopic evaluation was performed on paraffin sections in glomeruli. The analysis was performed using a two-step scale (0: lack of ETAR expression; 1: the presence of ETAR expression-mild to moderate immunoreactivity). RESULTS: We analyzed 149 patients who underwent renal allograft biopsy after renal transplantation. Positive staining of ETA receptors in glomeruli (ETA receptor (g+)) was noticed in 13/149 (8.7%) patients. Five of these 13 (38.5%) patients with ETA receptor (g+) developed antibody-mediated rejection (AMR), while 13 of the remaining 136 (9.5%) ETA receptor (g-) patients developed AMR (p = 0.0022). Graft loss was noticed in all but one ETA receptor (g+) patient with AMR (4/5; 80%), but only in 2/13 (15%) ETA receptor (g-) patients with AMR (p = 0.009) during the first year after biopsy. CONCLUSIONS: The expression of endothelin A receptors in glomeruli seems to be a potentially important feature in the diagnosis of damage during antibody-mediated rejection. It may help to identify patients at a higher risk of allograft rejection and injury.

The Summarized Assessment of Endothelin A Receptor Expression in Renal Transplant Compartments Associated with Antibody-Mediated Rejection.

The occurrence of anti-endothelin A receptor antibodies may be useful in diagnosis of transplant damage. We noticed that the presence of the endothelin A receptor (ETA receptor) in biopsy compartments is yet to be defined. We decided therefore to analysed the presence and relevance of the ETA receptor in biopsy to define the cause. Our study aims to evaluate the expression of ETA receptors in renal recipients after a biopsy due to the worsening of transplant function. METHODS: The expression of ETA receptors was analyzed in renal transplant biopsies using the immunohistochemical method. The evaluation of ETA receptors was performed on paraffin sections. ETA receptor expression was analyzed in four compartments of renal transplant biopsies: glomeruli; vessels; tubular epithelium; and interstitium. The assessment was presented using a three-step scale (0: lack of expression; 1: mild to moderate immunoreactivity; 2: high expression). The results of each compartment from a single biopsy were summarized and assessed in the context of antibody-mediated rejection (AMR). RESULTS: We analyzed 156 patients who had a renal allograft biopsy after renal transplantation. For each patient, we created a summarized ETA receptor expression score. The summarized ETA receptor expression score analysis showed statistically significant differences in patients with and without AMR. In addition, we noticed that patients with AMR had a significantly higher mean summarized expression of ETA receptor score of 3.28 ± 1.56 compared to patients who had a biopsy for other reasons with a mean summarized ETA receptor expression score of 1.47 ± 1.35 (p < 0.000001). ROC analysis of the ETA receptor expression score for detecting AMR status showed that the most appropriate cut-off for the test of the chosen binary classifier is between 2 and 3 of the summarized ETA receptor expression score. CONCLUSIONS: The expression of endothelin A receptors in renal transplant compartments may be associated with antibody-mediated rejection. The positive ETA receptor staining might be a vital feature in the diagnosis of damage in AMR. The summarized ETA receptor expression score seems to be an exciting diagnostic tool in transplant injury assessment.

Toll-Like 4 Receptor Expression on Peripheral Blood Mononuclear Cells in Renal Transplant Recipients Can Help to Indicate the Risk of Graft Deterioration in Patients Who Experienced an Episode of Symptomatic Cytomegalovirus Infection.

Data binding the expression of Toll-like 4 receptor (TLR4), transplanted kidney (KT) function, and symptomatic CMV infection (CMV+) are scarcely available. OBJECTIVE: To investigate the relationship between TLR4 expression (TLR4ex) in patients who had a relapse of CMV and transplant function. MATERIALS AND METHODS: TLR4ex was measured in peripheral blood mononuclear cells of KT recipients. We compared TLR4ex among 30 CMV+ patients and 87 patients without CMV infection (CMVneg). At the beginning (day 0) TLR4ex, as well as concentrations of cyclosporin A and tacrolimus were determined. All patients, CMV+ and CMVneg patients were divided according to the respective median of TLR4ex into groups of low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex). Estimated glomerular filtration rate (EGFR) was assessed on day 0 and after the follow-up (F-up). The magnitudes of EGFR change (ΔEGFR) were evaluated. Stable treatment along the F-up period (median 11.9 months) was applied. RESULTS: TLR4ex of CMV+ in 67% was below median for all patients. For day 0, in CMV+: no link of TLR4ex with EGFR was found; TLR4ex was lower but day 0 EGFR did not differ from H-TLR4ex. In CMVneg, a GFR-TLR4ex link was present. Post F-up. In CMV+ with L-TLR4ex, EGFR declined, with no change in H-TLR4ex. In CMVneg with H-TLR4ex, EGFR increased, with no change in L-TLR4ex. Both regression and receiver operating characteristic curve analyses points out the impact of CMV+ and TLR4ex on eGFR and ΔEGFR. CONCLUSION: In CMV+, low TLR4ex increases the risk of EGFR deterioration. In CMVneg, high TLR4ex raises the chance of EGFR improvement.

Disability of Dialysis Patients and the Condition of Blood Vessels.

The number of elderly hemodialysis patients is constantly increasing worldwide. This population has a high burden of comorbid conditions, which impair daily activities. The aim of the study was to analyze problems of disability in hemodialysis patients in the context of cardiovascular (CV) complications and vascular condition. In this cross-sectional study, 129 patients (mean age 64.5) were enrolled. The degree of disability in Barthel index (Bi) and 10-year cardiovascular risk (QRISK®3) were assessed. A Mobil-O-Graph monitor was used for measuring hemodynamic parameters. Only 6.2% of patients were professionally active, 19% used a wheelchair for transport, and 16% used crutches. More than half (51%) were independent in everyday activities reaching 80-100 points on Bi. The rest, with Bi < 80, were considered as dependent. The most common causes of disability were CV complications. The independent group (80-100 points) was characterized by significantly lower pulse wave velocity (PWV) and lower QRISK®3 compared to dependent patients. The degree of disability negatively correlated with age, PWV, and QRISK®3. Multivariate logistic regression revealed that disability (Bi < 80) was independently associated with CV events in the past adjusted odds ratio (adj.OR) 4.83 (95% confidence interval (95% CI): 1.74-13.41) and higher PWV adj.OR 1.45 (95% CI: 1.15-1.82). Our results indicate that CV diseases are the most important cause of functional impairment.

Toll-like 4 receptor (TLR4) expression on peripheral blood mononuclear cells in renal transplant recipients with pre-transplant chronic interstitial nephritis indicates patients at risk of graft deterioration.

Data binding the expression of Toll-like 4 receptor (TLR4ex), transplanted kidney function, and the cause of pre-transplant end-stage renal disease are scarcely available. OBJECTIVE: To investigate the relationship between pre-transplant chronic interstitial nephritis (CIN), TLR4ex and transplanted kidney function. MATERIALS AND METHODS: TLR4ex was measured in peripheral blood mononuclear cells of 43 CIN kidney transplant recipients. We compared TLR4ex among 33 patients with pre-transplant chronic non-infectious interstitial nephritis (NIN) and 10 patients with pre-transplant chronic pyelonephritis (Py). At the beginning (Day-0) TLR4ex, as well as concentrations of cyclosporin A (CyA) and tacrolimus (TAC) were determined. Both CIN and NIN patients were divided according to the respective median of TLR4ex into groups of low-TLR4 expression (L-TLR4ex) and high-TLR4 expression (H-TLR4ex). Serum creatinine/glomerular filtration rate (sCr/EGFR) was assessed on Day-0 and after the follow-up (F-up). The magnitudes of sCr/EGFR change (ΔsCr/ΔEGFR) were evaluated. The treatment was maintained stable along the F-up period (median 11.9 months). RESULTS: Day-0: in CIN with L-TLR4ex TAC was lower but sCr/EGFR were not different from H-TLR4ex; in Py TLR4ex and TAC were lower than in NIN with no difference in sCR/eGFR. After F-up: in CIN with L-TLR4ex sCR/EGFR and ΔsCr/ΔEGFR were worse than in H-TLR4ex; in Py sCR/EGFR and ΔsCr/ΔEGFR were worse than in NIN. The regression analysis points out prospective impact of Py and TLR4ex on sCR/eGFR and ΔsCr/ΔeGFR. CONCLUSION: In CIN, both TLR4ex and Tac appear to be a useful positive predictor of the effectiveness of immunosuppression. Chronic pyelonephritis indirectly promotes faster progression of chronic transplanted kidney disease.

The role of toll-like receptors in multifactorial mechanisms of early and late renal allotransplant injury, with a focus on the TLR4 receptor and mononuclear cells.

The innate immune system is activated before an adaptive immune response. An expression of a particular toll-like receptor (TLR) in a transplanted kidney depends on the localization of specific cells (e.g., endothelium, elements of the nephron structure), recent pathology and the time passed since transplantation. The TLR4 receptor is expressed on renal tubular epithelial (RTE) and endothelial cells, podocytes, blood and interstitial monocytes/macrophages, and dendritic cells. While circulating in blood, some monocytes are attracted and penetrate the transplanted organ, where they supplement the donor's resident macrophages. The intensity of migration depends on the local activation of inflammation in the graft and on the expression of specific receptors on kidney endothelial cells and monocytes/macrophages. The percentage of cells with shifted TLR4 expression usually increases in circulating monocytes. The TLR4 and the biochemical stimulation cascade derived from it in any type of cell, including monocytes, undergo multi-level regulation with feedback loops with other components of the primary system, and are also dependent on the action of immunosuppression. Toll-like receptor 4 senses stimuli that make monocytes contribute differently both to acute/chronic kidney injuries and to the development of tolerance. After kidney transplantation, TLR4 expression and related cytokine production capacity may vary depending on past diseases and oncoming problems. Since conventional immunosuppression does not prevent chronic allograft injury (CAI), peripheral blood monocytes and TLR4 constitute candidates for diagnostic and therapeutic targets. Considering the mutual communication among various elements of the primary immune system, future therapeutic intervention should be directed toward factors directly or indirectly regulating the expression or post-receptor signaling of the TLR4 receptor.

Can the Toll-like receptors 4 expression in peripheral blood mononuclear cells help assess the effectiveness of immunosuppression and the chance of a future good renal transplant function?

BACKGROUND: A small percentage of peripheral blood mononuclear cells (PBMCs) circulating during the kidney transplantation (KT) period remain in the blood long after transplantation. A part of the PBMCs penetrates the graft. AIM: To examine if the choice of immunosuppression may change TLR4ex and how TLR4ex affects the transplant function in the future. MATERIAL: The study population-143 transplanted patients (pts) (55 females, 88 males), mean age on recruitment day 50.33 ±â€¯12.8 years old, mean BMI 25.04 ±â€¯4.18. 41 pts. experienced delayed graft function (DGF+). 55 pts. were treated with cyclosporine A (CsA) and 88 with tacrolimus (Tac). All were treated with mofetil mycophenolate (MMF). The PBMCs acquisition and starting point of the follow-up (TLR-day) was at least one month after KT. METHOD: We investigated averaged mRNA expression of Toll-like receptors 4 (TLR4ex) in non-stimulated peripheral blood mononuclear cells with the use of real-time polymerase chain reaction. The KT pts. (All, Tac, CsA, DGF+) were divided by the respective median of their TLR4ex (lower: L-TLR4ex, higher: H-TLR4ex). Main clinical parameters and transplant biopsy files (if available) were assessed on TLR-day and post follow-up. RESULTS: We found that TLR4ex was reduced for a long time in patients who experienced delayed graft function. L-TLR4ex had a higher proportion of DGF+ patients, and patients treated with CsA but lower of those treated with Tac than in H-TLR4ex. The amplitude of changes in renal function parameters (ΔEGFR%/ΔsCr/ΔsCr%) was clearly less favorable for L-TLR4ex. Tacrolimus expressed a stabilizing effect. Both the positive vasculitis score and chronic graft nephropathy were more frequent in the L-TLR4ex group. On TLR-day an association of renal function and Tac concentration with TLR4ex was clear only in the tacrolimus population. The TLR4ex was lower in patients with a future deterioration of the graft function. CONCLUSION: In kidney transplant recipients the occurrence of DGF results in a long-term reduction of the averaged TLR4ex in PBMC. Tacrolimus exerts a clear, stabilizing, positive and dose-dependent effect on TLR4ex. An improvement in renal transplant function may be expected in KT patients with high TLR4ex. Evaluation of the averaged TLR4ex can be used to assess the efficacy of immunosuppression in the treatment with tacrolimus and to estimate the likelihood of deterioration in renal function.

Are Females More Prone Than Males to Become Obese After Kidney Transplantation?

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.