Osteoprotegerin and Inflammation in Incident Peritoneal Dialysis Patients.

Objectives: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the majority of chronic kidney disease (CKD) patients and those undergoing renal replacement therapy. The aim of the study was to assess the relation of OPG and chronic inflammation in peritoneal dialysis (PD) patients and to evaluate whether OPG concentrations in plasma and dialysate were related to plasma and dialysate levels of proinflammatory mediators (interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin 33 (IL-33) and interleukin 1 receptor-like 1IL-1RL1 (IL-1RL1, sST2)). Methods: The study included 37 patients of the Peritoneal Dialysis Center, Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland, 4-6 weeks after the onset of peritoneal dialysis therapy. During a peritoneal equilibration test, plasma (at 2 h) and dialysate (at 4 h) OPG, IL-33, 1IL-1RL1 (sST2), IL-6 and hsCRP concentrations were determined. Results: Plasma concentration of OPG did not correlate with dialysate OPG level (Rs = 0.04, p = 0.8). There was a strong positive correlation between plasma OPG concentrations and plasma IL-1RL1 (sST2) (Rs = 0.41; p = 0.01), plasma IL-6 (Rs = 0.38; p = 0.01) and plasma hsCRP (Rs = 0.35; p = 0.02). Dialysate OPG concentrations were positively associated with dialysate IL-1RL1 (sST2) (Rs = 0.37; p = 0.02) and dialysate IL-6 levels (Rs = 0.44; p = 0.005). Multivariate analysis showed that higher IL-1RL1 (sST2) (ß = +0.38, p = 0.006), higher plasma hsCRP (ß = +0.32, p = 0.02) and older age (ß = +0.35, p = 0.01) were independent determinants of higher plasma OPG concentration and that higher concentrations of dialysate IL-6 (ß = +0.37, p = 0.02) were independent determinants of higher dialysate OPG concentration. Conclusions: Both plasma and dialysate OPG levels are associated with the severity of systemic and local inflammation illustrated by the plasma and dialysate concentrations of IL-1RL1 (sST2), hsCRP and IL-6, suggesting that OPG might have a pivotal role in explaining the milieu of systemic and intraperitoneal inflammation.

An Unusual Case of Vulvar Involvement in the Course of Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis is a rare autoimmune disease with the presence of c-ANCA in most cases. It involves necrotizing inflammation in small and medium-sized vessels with multiple granulomas. The disease can affect many systems, but the typical triad of attacked systems are the upper and lower respiratory tracts and kidneys, with varying degrees of severity. Involvement of the respiratory tract may manifest, among other symptoms, as nasal crusting, nosebleeds, and dyspnea. Among patients with granulomatosis with polyangiitis, only less than 1% develop genitourinary system involvement. We present a case study of a 36-year-old woman with an 8-year-long GPA history and a lesion, which, due to its appearance and accompanying symptoms, aroused the suspicion of a neoplasm but was proven to be a granuloma with a nontypical location. The systemic disease was treated with glucocorticosteroids and cyclophosphamide. The lesion on the labium minus was surgically removed. We concluded that the macroscopic picture of GPA of the vulva and vulvar cancer is similar. The patient's medical history may help differentiate GPA and vulvar cancer. Although vulvar GPA is extremely rare, it should be considered in the differential diagnosis of vulvar lesions, especially those suspected to be oncological.

Repeat exit site infection in peritoneal dialysis patient with polycythemia vera - a case report.

BACKGROUND: Infectious complications of peritoneal dialysis (PD) remain a common cause of catheter loss and discontinuation of PD. Exit site infection (ESI) constitutes a significant risk factor for PD-related peritonitis and determination of predisposing states is relevant. We here present a case of repeat ESI due to Pseudomonas aeruginosa in a PD patient with skin changes in the course of polycythemia vera (PV). CASE PRESENTATION: A 73-year-old PD patient with chronic kidney disease secondary to renal amyloidosis and ankylosing spondylitis, presented to the nephrology unit with signs of ESI. In 2006 he was diagnosed with PV and since then has was successfully treated with hydroxyurea; however, he reported recurrent episodes of developing skin nodules in the course of the disease. Exit site swab yielded Pseudomonas aeruginosa and the infection developed in the ulcerated PV nodule that appeared in exit site 2 weeks earlier. Patient was treated with intraperitoneal amikacin and oral ciprofloxacin, however, due to neurological complications, the treatment had to be interrupted and finally catheter was removed. Similar episode of ESI with Pseudomonas aeruginosa developed in the patient two years earlier and also required catheter removal. CONCLUSION: This is the first case report demonstrating the development of ESI on the polycythemia vera skin lesion in this area. Skin manifestations of PV might be a predisposing factor to ESI in PD patients.

Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5.

BACKGROUND: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30-70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. METHODS: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography. RESULTS: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman's rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. CONCLUSIONS: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.

Dialysate copeptin and peritoneal transport in incident peritoneal dialysis patients.

PURPOSE: Systemic and intraperitoneal inflammation are characteristic features of patients with end-stage renal disease undergoing chronic peritoneal dialysis (PD). Arginine vasopressin (AVP) and its surrogate marker copeptin play important roles in many pathophysiological processes in chronic kidney disease. The aim of this study was to assess if copeptin concentrations in plasma and dialysate were related to peritoneal transport parameters and residual renal function (RRF) in incident PD patients. METHODS: In 37 clinically stable incident PD patients (mean age 50 years, 68% women, 32% diabetes), a 4 h peritoneal equilibration test (PET) was performed 4-6 weeks after the onset of PD. Plasma (at 2 h of PET) and dialysate (at 4 h) concentrations of copeptin, high-sensitivity C-reactive protein and interleukin-6 (IL-6) were determined. RESULTS: Plasma (80.7 ± 37.3 pg/mL) and dialysate (33.2 ± 18.0 pg/mL) concentrations of copeptin were correlated (Rs = 0.52, p = 0.001). Plasma and dialysate copeptin concentrations were negatively correlated with renal function as assessed by renal Kt/V (Rs = - 0.38; p = 0.021 and Rs = - 0.33; p = 0.047, respectively). At PET, dialysate copeptin negatively correlated with D/P creatinine (Rs = - 0.35, p = 0.033), and positively with D/D0 glucose (Rs = 0.33, p = 0.045) and ultrafiltration (Rs = 0.37, p = 0.024). Multivariate analysis showed that low dialysate copeptin (ß = -0.30, p = 0.049) and high dialysate IL-6 (ß = + 0.40, p = 0.012) were independent determinants of higher D/P creatinine. CONCLUSIONS: Dialysate copeptin was negatively associated with D/P creatinine in incident PD patients suggesting a potential influence of copeptin or AVP on peritoneal solute transport rate that might involve vasoactive mechanisms.

Current epidemiology and practice patterns in prevention and treatment of PD-related infections in Poland.

BACKGROUND: Peritoneal dialysis (PD) related infections are associated with technique failure and mortality. The aim of this multicentre study was to examine epidemiology, treatment and outcomes of PD-related infections in Poland as well as practice patterns for prevention of these complications in the context of current ISPD recommendations. METHODS: A survey on PD practices in relation to infectious complications was conducted in 11 large Polish PD centres. Epidemiology of peritonitis and exit-site infections (ESI) was examined in all patients treated in these units over a 2 year period. RESULTS: The study included data on 559 PD patients with 62.4% on CAPD. Practice patterns for prevention of infectious complications are presented. The rate of peritonitis was 0.29 episodes per year at risk, with Gram positive microorganisms responsible for more than 50% of infections and 85.8% effectively treated. Diagnosis and treatment followed ISPD guidelines however most units did not provide an anti-fungal prophylaxis. Although neither of the centres reported routine topical mupirocin on catheter exit-site, the rate of ESI was low (0.1 episodes per year at risk), with Staphylococcus aureus as most common pathogen and full recovery in 78.3% of cases. CONCLUSION: The study shows rewarding outcomes in prevention and treatment of PD-associated infections, mainly due to a thorough compliance with the current ISPD guidelines, although some deviations from the recommendations in terms of practice patterns have been observed. More studies are needed in large numbers of patients to differentiate the importance of specific recommendations and further support the guidelines.

The role of eicosanoids in renal diseases - potential therapeutic possibilities.

Eicosanoids are biologically active molecules that are created in the process of oxidation of arachidonic acid (AA) which is a constituent of the cell membrane phospholipids. Throughout the years it was evidenced by experiments that the lipid and lipid-derived metabolites play an important role in physiological and pathological processes in the kidneys. They are being considered as biomarkers in detecting acute kidney injury, nephrotoxicity, glomerulonephritis and early stages of diabetic nephropathy because of their participation in inflammatory processes and in oxidative stress. They might be also considered as potential novel targets of therapy. However, the role of eicosanoids is still not fully clear and needs to be explored in future studies. In this brief review, studies on the role of eicosanoids in physiological and pathological conditions, e.g. acute kidney injury (AKI) and chronic kidney disease (CKD), and in different renal replacement therapies, including kidney transplantation, are being discussed.

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes.

Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients. Inflammatory biomarkers, such as high sensitivity C-reactive protein and interleukin-6, independently predict mortality in these patients. The causes of inflammation in CKD are multifactorial and include imbalance between increased production (due to multiple sources of inflammatory stimuli such as oxidative stress, acidosis, volume overload, co-morbidities, especially infections, genetic and epigenetic influences, and the dialysis procedure) and inadequate removal (due to decreased glomerular filtration rate or in ESRD patients, inadequate dialytic clearance) of pro-inflammatory cytokines. Though there are currently no established guidelines for the treatment of low-grade inflammation in ESRD patients, several strategies have been proposed, such as lifestyle modifications, pharmacological treatment, and optimization of dialysis. Further studies on pathways involved in pathogenic processes of inflammation in ESRD, and long-term effects of anti-inflammatory interventions targeting production or removal of cytokines or both on premature CVD and clinical outcomes in this patient group are warranted.

Prognostic Value of Copeptin in Chronic Kidney Disease: From General Population to End-Stage Renal Disease.

Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), is released in response to osmotic and non-osmotic stimuli and plays a key role in many physiologic and pathologic processes. The main function of AVP is the control of fluid homeostasis by inducing water conservation by the kidney, but it also stimulates arteriolar vasoconstriction and the release of adrenocorticotropic hormone (ACTH). These actions are mediated by different AVP receptors located on various target cells. Produced in hypothalamus from a larger precursor, pre-proAVP, AVP is produced in equimolar amounts to copeptin, a glycopeptide with yet unknown biologic function. Copeptin remains stable in plasma and its circulating concentrations correlate directly with those of AVP. Because AVP is unstable in isolated plasma or serum and its half-life is short, copeptin has become an easily measured surrogate marker reflecting vasopressin concentration. Recently, associations between high circulating copeptin and decline in glomerular filtration rate as well as greater risk of new-onset chronic kidney disease (CKD) have been reported. In addition, copeptin has been shown to be associated with increased risk of complications such as myocardial infarction, heart failure, diabetes mellitus and metabolic syndrome. In this brief review, studies on the prognostic value of copeptin measurement in the general population and in CKD are presented and discussed.

Bioactive lipids derived from arachidonic acid metabolism in different types of renal replacement therapy.

INTRODUCTION: Metabolism and plasma concentration of lipids and lipid-derived compounds play an important role in kidney physiology and pathological processes. The component of membrane phospholipids - arachidonic acid (AA) and its active derivatives - eicosanoids are involved in the development of hypertension, diabetes, inflammation and may contribute to progression of chronic kidney disease (CKD). The purpose of the study was to determine, whether the type of renal replacement therapy has an effect on eicosanoids metabolism. MATERIALS AND METHODS: The study included 145 patients with CKD: on conservative treatment (n=68), on peritoneal dialysis (PD) (n=23) and undergoing chronic haemodialysis (HD) (n=54). The concentrations of TXB2, 20-HETE, 8-epi-PGF2α in platelet poor plasma (PPP) were determined using the ELISA method and 5-HETE, 12-HETE, 15-HETE were measured using the RP-HPLC. RESULTS: The concentrations of TXB2 in HD group, both before (2.28±0.72ng/mL) and after (1.49±0.63ng/mL) haemodialysis treatment differed significantly from PD group (57.76±6.13ng/mL). Haemodialysis session led to the significant decrease in TXB2 plasma concentration (p=0.046). 20-HETE concentrations in HD group (113.55±107.54pg/mL and 199.54±142.98pg/mL before and after haemodialysis, respectively) were significantly higher than in CKD 3-5 group (8.96±12.66pg/mL) and PD group (47.78±34.07pg/mL). The highest concentration of 12-HETE was obtained in PD patients (3.58±3.99ng/mL) and differed significantly from HD group after haemodialysis (0.97±0.28ng/mL) and CKD3-5 group (1.06±0.52ng/mL). The concentrations of 5-HETE, 15-HETE and 8-epi-PGF2α-III did not differ significantly among examined groups. CONCLUSIONS: The concentrations of active AA metabolites depend on the mode of renal replacement therapy and are associated with intensity of oxidative stress. They might be considered as potential indicators of kidney damage.

Birth defects in juvenile Wistar rats after exposure to immunosuppressive drugs during pregnancy.

INTRODUCTION: Immunosuppressive drugs and their active metabolites can cross the placental barrier and enter fetal circulation. The adverse effects on the fetus include chromosomal aberrations, structural malformations, organ-specific toxicity and intrauterine growth retardation. The aim of our study was to investigate the impact of "safe" and "contraindicated" immunosuppressive drugs on birth defects in juvenile Wistar rats after exposure of pregnant female rats to these drugs. MATERIAL AND METHODS: The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. RESULTS: Treatment with mycophenolate mofetil and everolimus turned out to be toxic. We have noticed a significantly reduced number of live births in all pregnant rats exposed to these drugs in combination with calcineurin inhibitors and prednisone. Malformations and histological changes of fetal organs were confirmed after mycophenolate mofetil exposure during pregnancy. CONCLUSIONS: Mycophenolate mofetil turned out to be more toxic when used with tacrolimus than with cyclosporin (delivery of live offspring was possible only in the latter group). Everolimus in combination with cyclosporin effectively suppressed the fetal maturation in utero, but did not contribute to the development of malformations.

The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats.

Pregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone). The animals received drugs for 2 weeks before pregnancy and during 3 weeks of pregnancy. In all treated dams lower body weight (but not kidney mass) and alterations in serum sodium and chloride ions were found; serum creatinine concentration was increased in dams treated with cyclosporine A, everolimus and prednisone. All treatment groups of dams showed increased apoptosis in the distal tubules. In histological examination the changed intensity of acidophilic or basophilic cytoplasm of epithelial cells was found in kidneys of rats treated with calcineurin inhibitors, mycophenolate mofetil and prednisone. All immunosuppressive regimens caused abnormalities affecting nephron tubules. Regimens containing calcineurin inhibitors and mycophenolate mofetil caused higher rate of apoptosis and more pronounced histopathological changes. Regimen based on everolimus despite the lower rate of apoptosis in the proximal tubules and lower accumulation of kidney injury markers revealed higher serum creatinine concentration. Thus, interpretation which combination of drugs is better or worse for long-lasting functioning of kidneys in pregnant females requires further studies.

The influence of intrauterine exposure to immunosuppressive treatment on changes in the immune system in juvenile Wistar rats.

BACKGROUND: In our study, we assessed the impact of immunosuppressive drug combinations on changes in the immune system of juvenile Wistar rats exposed to these drugs during pregnancy. We primarily concentrated on changes in two organs of the immune system - the thymus and the spleen. METHODS: The study was conducted on 40 (32+8) female Wistar rats administered full and half dose of drugs, respectively, subjected to regimens commonly used in therapy of human kidney transplant recipients ([1] cyclosporine A, mycophenolate mofetil, and prednisone; [2] tacrolimus, mycophenolate mofetil, and prednisone; [3] cyclosporine A, everolimus, and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. RESULTS: There were no statistically significant differences in the weight of the thymus and spleen, but changes were found in the results of blood hematology, cytometry from the spleen, and a histologic examination of the examined immune organs of juvenile Wistar rats. In the cytokine assay, changes in the level of interleukine 17 (IL-17) after increasing amounts of concanavaline A were dose-dependent; the increase of IL-17 was blocked after administration of higher doses of immunosuppressive drugs. However, after a reduction of doses, its increase resumed. CONCLUSION: Qualitative, quantitative, and morphological changes in the immune system of infant rats born to pharmacologically immunosuppressed females were observed. Thymus structure, spleen composition, and splenocyte IL-17 production were mostly affected in a drug regimen-dependent manner.

Effect of Immunosuppressive Therapy on Proteinogram in Rats.

BACKGROUND It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. MATERIAL AND METHODS The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. RESULTS Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. CONCLUSIONS (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively.

The Role of Klotho Protein in Chronic Kidney Disease: Studies in Animals and Humans.

The identification of Klotho gene was a major discovery as the gene encodes a protein regulating multiple functions. A defect in Klotho gene expression in mice results in a phenotype of premature aging including shortened life span, growth retardation, hypogonadism, skin and muscle atrophies, vascular calcification, cognition impairment, motor neuron degeneration and others. This phenotype is associated with phosphate balance disorders and underlines the major function of Klotho in mineral metabolism. As another 2 related paralogs were discovered (beta-Klotho, which is involved in bile acid and energy metabolism, and gamma-Klotho, with a yet to be defined function), this led to the revised naming of Klotho as alpha-Klotho. Two forms of alpha-Klotho protein have been reported: a membrane-bound and a soluble one. Membrane Klotho forms a complex with fibroblast growth factor (FGF) receptors and functions as an obligate co-receptor for the FGF-23 phosphatonin in distal tubules. The soluble form of Klotho seems to function as a humoral factor and regulates glycoproteins on the cell surface including ion channels and growth factors. There is data suggesting that soluble Klotho exerts phosphaturic effects independently of FGF-23. Circulating soluble Klotho is produced either by proteolytic cleavage of the extracellular domain of the transmembrane form by two membrane-anchored proteases (ADAM10 and ADAM17) or by alternative mRNA splicing. In animal models Klotho has been shown to exert pleiotropic actions, including cytoprotection, anti-oxidation, anti-apoptosis, protection of vasculature, promotion of angiogenesis and vascularization, inhibition of fibrogenesis and preservation of stem cells. The exact diagnostic and therapeutic role of Klotho in humans is not fully known yet. The article presents the role of Klotho in physiology and different stages of chronic kidney disease (CKD).

Wegener's granulomatosis and pyoderma gangrenosum--rare causes of facial ulcerations.

BACKGROUND: Pyoderma gangrenosum (PG) is caused by immune system dysfunction, and particularly improper functioning of neutrophils. At least half of all PG patients also suffer from autoimmunological diseases, one of which is Wegener granulomatosis (WG). The purpose of this article was to compare cases of patients with WG and PG in terms of their clinical course, histopathology, and applied treatment. In both, histopathological features are not fully distinct. Data from microbiological and immunological evaluation and clinical presentation are required to establish the diagnosis. We also present the case of a patient with WG and deep facial skin lesions not responding to standard treatment. METHODS: Systematic review of the literature in PubMed using the search terms "Wegener granulomatosis AND Pyoderma gangrenosum" and case report. RESULTS: The finding of 22 reports in the literature (PubMed) suggests that it is a rare phenomenon. This study revealed a similar rate of comorbidity of WG and PG in both genders and an increased incidence of both diseases after the age of 50. Among skin lesions there was a dominance of ulceration, most often deep and painful, covering a large area with the presence of advanced necrosis and destruction of the surrounding tissue. The most common location proved to be the cervical-cephalic area. The most popular treatment included steroids with cyclophosphamide. DISCUSSION: The rarity of the coexistence of these two diseases results in a lack of effective therapy. In such cases sulfone derivatives are still effective and provide an alternative to standard immunosuppression methods. Hyperbaric therapy and plasmapheresis can also play an important complementary role.

Does Immunosuppressive Therapy Affect Markers of Kidney Damage?

BACKGROUND: Markers currently used to detect kidney damage are effective in both early (KIM-1, NGAL) and late (MCP-1, MMP, TIMP) stages of renal tubular damage, indicating the progression of chronic kidney disease. Immunosuppressive drugs may damage the transplanted organ through their direct toxic effects and by contributing to the development of chronic fibrosis and tubular atrophy. The aim of this study was to determine if immunosuppressive drugs per se affect the concentration of kidney damage markers, by using concentrations and doses of immunosuppressive within therapeutic, not toxic, levels in rat blood. MATERIAL AND METHODS: The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporin A, rapamycin, and prednisone). The rats were treated with a 3-drug protocol for 6 months. No drugs were administered to the control group. The blood samples were collected to determine the concentration of kidney damage markers by using enzyme-linked immunosorbent assay (ELISA). RESULTS: 1. In the groups receiving regimens based on cyclosporin A (CyA), significantly higher concentrations of KIM-1 in plasma was observed compared to cases not treated with drugs. 2. The use of tacrolimus was associated with increased concentrations of MCP-1 in plasma and rapamycin was associated with decreased concentrations of MCP-1 in plasma. 3. Rapamycin induces an unfavorable, profibrotic imbalance between metalloproteinase-9 and its inhibitor, TIMP-1. CONCLUSIONS: Commonly used immunosuppressive drugs influence the concentration of blood markers of kidney damage. This fact should be taken into account when analyzing the association between the concentration of these markers and pathological processes occurring in the transplanted kidney.

The activity of antioxidant enzymes in blood platelets in different types of renal replacement therapy: a cross-sectional study.

PURPOSE: The changes in redox status characterise physiological platelet activation. Increased oxidative stress in chronic kidney disease (CKD) associated with uremic toxicity and procedures of renal replacement therapy leads to the impairment of antioxidant properties of platelets. It may contribute to thrombosis and cardiovascular complications increasing morbidity and mortality among the CKD patients. The object of the research was to assess the influence of conservative treatment, peritoneal dialysis and haemodialysis on platelet prooxidative-antioxidative balance. METHODS: The examined group consisted of 122 patients: 37 on regular haemodialysis (HD), 23 on peritoneal dialysis (PD) and 62 on conservative treatment with CKD stages 3-5 (CKD3-5). The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione transpherase (GST) in platelets were obtained using kinetic methods. The spectrophotometric method established the concentrations of reduced glutathione (GSH). RESULTS: SOD activity in PD differs significantly from CKD3-5 (4.96 vs 1.66; p < 0.0001). CAT activity assessed in PD and CKD3-5 was significantly different from HD (0.82 and 0.8 vs 0.52 before and 0.35 after HD, respectively). GST activity reached the highest value in PD (1.62), and it was significantly different from CKD3-5 (0.23) and HD before haemodialysis (0.11). During haemodialysis therapy, there was a considerable increase in GST activity (0.11 vs 0.3; p = 0.02) and decrease in SOD activity (from 3.41 to 2.27; p = 0.01). The highest GSH concentrations were obtained in CKD3-5 and differ significantly from HD (4.12 vs 2.01; p = 0.02). CONCLUSIONS: The type of treatment, age and duration of renal replacement therapy determined significant changes in platelet antioxidative enzymes activities and concentration of GSH, which may enhance the thrombotic complications. PD is associated with lower platelet oxidative stress.

Platelet - derived CD154 antigen in patients with chronic kidney disease.

INTRODUCTION: CD154 is a surface glycoprotein present on activated platelets, lymphocytes and mast cells. It mediates the transmission of information between cells and initiates an inflammatory response. The interaction of CD154 with its receptor CD40 leads to increase in concentrations of soluble forms of both molecules (sCD154, sCD40), which has an important prognostic value in cardiovascular complications. The metabolic disorders in chronic kidney disease (CKD), chronic inflammation, increased oxidative stress and type of renal replacement therapy may influence on the balance of sCD154/sCD40 in plasma and blood platelets. The purpose of the reasearch was to analyse the concentrations of sCD154 antigen and sCD40 receptor in platelet pure plasma (PPP) and platelet rich plasma (PRP) of patients with CKD treated conservatively, haemodialysed and on petitoneal dialysis. METHODS: The group examined comprised 141 patients with chronic kidney disease: in pre-dialysis stage (n = 68), haemodialysed (n = 38) and on peritoneal dialysis (n = 35). The concentrations of sCD154 and sCD40 in PRP and PPP were determined with an ELISA method. The biochemical parameters were obtained using colorimetric method. RESULTS: The concentrations of sCD154 and sCD40 in PPP and PRP in examined group were significantly different depending on the method of renal replacement therapy. The haemodialysis procedure caused a significant increase in sCD40 concentration in PRP. The concentrations of sCD40 and sCD154 were correlated with lipid parameters. CONCLUSIONS: The type of renal replacement therapy influences on platelet activation which may be a factor contributing to increased cardiovascular complications in patients suffering from CKD.