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.

Leptin receptor gene polymorphisms in kidney transplant patients with post-transplant diabetes mellitus treated with tacrolimus.

Post-transplant diabetes mellitus (PTDM) is a metabolic complication that often occurs after kidney transplantation. Factors that increase the risk of this complication are currently being researched, including polymorphisms in genes affecting carbohydrate-lipid metabolism. Leptin is a hormone that affects appetite and adipose tissue and plays an important role in regulating insulin secretion as well as glucose and lipid metabolism. The aim of this study was to examine the association between leptin receptor gene polymorphisms and the development of post-transplant diabetes mellitus in patients treated with tacrolimus. The study was carried out in a group of 201 patients who underwent kidney transplantation. The follow-up period was 12 months. PTDM was diagnosed in 35 patients. Analysing the LEPR gene rs1137101 polymorphism, we observed in patients with PTDM an increased frequency of GG genotype carriers (GG vs AA, OR 3.36; 95 % CI 0.99-11.46; p = 0.04). There were no statistically significant differences in the distribution of the LEPR rs1137100 and LEPR rs1805094 polymorphisms between patients with and without PTDM. Multivariate regression analysis confirmed that female sex, advanced age, increased BMI and a higher number of LEPR rs1137101 G alleles were independent risk factors for PTDM development. The risk of PTDM development was almost 3.5 times greater in LEPR rs1137101 G allele carriers than in AA homozygotes (GG + AG vs AA; OR 3.48; 95 %CI (1.09-11.18), p = 0.035). The results suggest that patients after kidney transplantation with the LEPR gene rs1137101 G allele may have an increased risk of post-transplant diabetes development.

Renal Microcirculation Injury as the Main Cause of Ischemic Acute Kidney Injury Development.

Acute kidney injury (AKI) can result from multiple factors. The main cause is reduced renal perfusion. Kidneys are susceptible to ischemia due to the anatomy of microcirculation that wraps around the renal tubules-peritubular capillary (PTC) network. Cortical and medullary superficial tubules have a large share in transport and require the supply of oxygen for ATP production, while it is the cortex that receives almost 100% of the blood flowing through the kidneys and the medulla only accounts for 5-10% of it. This difference makes the tubules present in the superficial layer of the medulla very susceptible to ischemia. Impaired blood flow causes damage to the endothelium, with an increase in its prothrombotic and pro-adhesive properties. This causes congestion in the microcirculation of the renal medulla. The next stage is the migration of pericytes with the disintegration of these vessels. The phenomenon of destruction of small vessels is called peritubular rarefaction, attributed as the main cause of further irreversible changes in the damaged kidney leading to the development of chronic kidney disease. In this article, we will present the characteristic structure of renal microcirculation, its regulation, and the mechanism of damage in acute ischemia, and we will try to find methods of prevention with particular emphasis on the inhibition of the renin-angiotensin-aldosterone system.

Intrapatient Variability (IPV) and the Blood Concentration Normalized by the Dose (C/D Ratio) of Tacrolimus-Their Correlations and Effects on Long-Term Renal Allograft Function.

Tacrolimus, in combination with mycophenolate mofetil and glucocorticoids, is the basis of immunosuppressive therapy after renal transplantation. Tacrolimus intrapatient variability (IPV) and the blood concentration normalized by the dose (concentration/dose ratio, C/D ratio) both have an effect on the function of the transplanted kidney. In this study, we examined whether the metabolism rate affected IPV, whether the C/D ratio value was stable in the long-term follow-up, and whether it could be used for IPV measurements. In addition, our study population was examined for the effect of the C/D ratio and IPV on long-term renal function. The C/D ratio and IPV were examined in 170 patients at appointments held at 3, 6, 12 and 24 months after RTx. The average time post renal transplantation was 70 months. Renal function defined as creatinine concentration at the last appointment was examined. Results: the mean C/D ratio in the study group was 1.63. A negative correlation between the C/D ratio and creatinine concentration at the end of the follow-up was observed. Between the C/D ratio < and ≥1.63 groups, significant differences in creatinine concentration at the last appointment were found. No relationship was identified between the mean C/D ratio and IPV. The C/D ratio values increased significantly over a longer post-transplant period (12, 24, 60 and 120 m). We did not find a correlation between the mean IPV and the creatinine concentration from the last appointment. Our study group was divided into terciles according to IPV, while no renal graft function differences were found at the same appointment. Conclusion: the C/D ratio is useful for assessing the effects of the metabolism rate of tacrolimus on the long-term renal graft function. The C/D ratio does not affect the IPV value. IPV calculated from variability of the C/D ratio does not influence transplanted kidney function. The C/D changes over time.

SARS-CoV-2 mRNA Vaccine-Induced Cellular and Humoral Immunity in Hemodialysis Patients.

BACKGROUND/AIMS: Chronic kidney disease CKD patients on intermittent hemodialysis IHD are exposed to SARS-CoV-2 infection and carry a risk of developing severe symptoms. The aim of this study was to evaluate the humoral and cellular immunity induced by two doses of mRNA vaccines, the Pfizer-BioNTech (Comirnaty) COVID-19 Vaccine and the Moderna (mRNA-1273) COVID-19 vaccine. PATIENTS AND METHODS: The study included 281 patients from five dialysis centers in northern Poland. Within 2 weeks prior to the first dose of the vaccine, a blood sample was collected for an evaluation of SARS-CoV-2 antibodies. Thirty to forty-five days after the second dose of the vaccine, a blood sample was taken to evaluate humoral and cellular response. RESULTS: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate. The strongest factors influencing the antibodies AB level after vaccination were a pre-vaccination history of SARS-CoV-2 infection, age, the neutrophil-to-lymphocyte ratio NLR, neutrophil absolute count, and the hemoglobin level. Cellular immunity was higher in patients with a pre-vaccination history of SARS-CoV-2 infection. Cellular immunity depended on the albumin level. Positive cellular response to vaccination was a positive factor reducing all-cause mortality, except for COVID-19 mortality (no such deaths were reported during our follow-up). Cellular immunity and humoral immunity were positively mutually dependent. High levels of albumin and hemoglobin, low neutrophil count, and a reduced NLR, translated into better response to vaccination. CONCLUSIONS: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate and a good rate of cellular immunity. The factors that change with exacerbating inflammation and malnutrition (albumin, hemoglobin, neutrophil count, the NLR) affected the efficacy of the vaccination.

Role of Endothelial Glucocorticoid Receptor in the Pathogenesis of Kidney Diseases.

Glucocorticoids, as multifunctional hormones, are widely used in the treatment of various diseases including nephrological disorders. They are known to affect immunological cells, effectively treating many autoimmune and inflammatory processes. Furthermore, there is a growing body of evidence demonstrating the potent role of glucocorticoids in non-immune cells such as podocytes. Moreover, novel data show additional pathways and processes affected by glucocorticoids, such as the Wnt pathway or autophagy. The endothelium is currently considered as a key organ in the regulation of numerous kidney functions such as glomerular filtration, vascular tone and the regulation of inflammation and coagulation. In this review, we analyse the literature concerning the effects of endothelial glucocorticoid receptor signalling on kidney function in health and disease, with special focus on hypertension, diabetic kidney disease, glomerulopathies and chronic kidney disease. Recent studies demonstrate the potential role of endothelial GR in the prevention of fibrosis of kidney tissue and cell metabolism through Wnt pathways, which could have a protective effect against disease progression. Another important aspect covered in this review is blood pressure regulation though GR and eNOS. We also briefly cover potential therapies that might affect the endothelial glucocorticoid receptor and its possible clinical implications, with special interest in selective or local GR stimulation and potential mitigation of GC treatment side effects.

The Mechanism of Drug Nephrotoxicity and the Methods for Preventing Kidney Damage.

Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19-26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and the secretion of drugs from the basolateral surface into the tubular lumen; (2) tubular obstruction by crystals or casts containing drugs and their metabolites (a dose-dependent mechanism); (3) interstitial nephritis induced by drugs and their metabolites (a dose-independent mechanism). In this article, the mechanisms of the individual types of injury will be described. Specific groups of drugs will be linked to specific injuries. Additionally, the risk factors for the development of AKI and the methods for preventing and/or treating the condition will be discussed.

The Effect of Bilateral Nephrectomy on Renalase and Catecholamines in Hemodialysis Patients.

BACKGROUND/AIMS: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients. METHODS: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit. RESULTS: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01). CONCLUSIONS: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.

VAV1 Gene Polymorphism is Associated With Kidney Allograft Rejection.

BACKGROUND: VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells. Several studies suggest that VAV1 signaling plays significant roles in allograft rejection. The aim of this study was to examine the association between VAV1 gene polymorphisms and renal allograft function. METHODS: The study included 270 patients after allograft renal transplantation. We examined the associations between VAV1 gene polymorphisms and complications after transplantation, such as delayed graft function, acute rejection, and chronic allograft dysfunction. RESULTS: There were no statistically significant associations between VAV1 genotypes and delayed graft function and chronic allograft dysfunction. Among patients with acute allograft rejection, we observed decreased frequencies of VAV1 rs2546133 TT and CT genotypes (P = .03) and T allele (P = .02), as well as VAV1 rs2617822 GG and AG genotypes (P = .05) and G allele (P = 0.04). In the multivariate regression analysis, the higher number of VAV1 rs2546133 T alleles showed a protective effect against the acute rejection in kidney allograft recipients. CONCLUSIONS: The results of our study suggest that polymorphisms in the VAV1 gene are associated with kidney allograft rejection.

Renalase in Haemodialysis Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is an inflammatory disease leading to kidney insufficiency and uremia. Renalase is a novel flavoprotein with enzymatic activities. Previous studies have shown that chronic kidney disease may influence renalase serum levels. Renalase metabolises catecholamines and therefore may be involved in the pathogenesis of hypertension and other diseases of the circulatory system. In this study, we examined renalase levels in serum, erythrocytes and urine from haemodialysis CKD patients. The study enrolled 77 haemodialysis CKD patients and 30 healthy subjects with normal kidney function as the control group. Renalase serum and urine concentrations in CKD patients were significantly increased when compared with control subjects (185.5 ± 64.3 vs. 19.6 ± 5.0 ng/mL; p < 0.00001 and 207.1 ± 60.5 vs. 141.6 ± 41.3 ng/mL; p = 0.00040, respectively). In contrast, renalase levels in erythrocytes were significantly lower in CKD patients when compared with control subjects (176.5 ± 60.9 vs. 233.2 ± 83.1 ng/mL; p = 0.00096). Plasma levels of dopamine, adrenaline and noradrenaline were also significantly lower in CKD patients when compared with controls. Conclusions: Increased serum and urine concentrations of renalase in haemodialysis CKD patients are likely related to compensatory production in extrarenal organs as a result of changes in the cardiovascular system and hypertension. The decreased plasma concentrations of catecholamines may be due to their increased degradation by plasma renalase. Decreased renalase levels in erythrocytes may be probably due to lower renalase synthesis by the kidneys in CKD. The results indicate the presence of renalase in erythrocytes.

Adiponectin in Chronic Kidney Disease.

Adiponectin is the adipokine associated with insulin sensitization, reducing liver gluconeogenesis, and increasing fatty acid oxidation and glucose uptake. Adiponectin is present in the kidneys, mainly in the arterial endothelium and smooth muscle cells, as well as in the capillary endothelium, and might be considered as a marker of many negative factors in chronic kidney disease. The last few years have brought a rising body of evidence that adiponectin is a multipotential protein with anti-inflammatory, metabolic, anti-atherogenic, and reactive oxygen species (ROS) protective actions. Similarly, adiponectin has shown many positive and direct actions in kidney diseases, and among many kidney cells. Data from large cross-sectional and cohort studies showed a positive correlation between serum adiponectin and mortality in chronic kidney disease. This suggests a complex interaction between local adiponectin action, comorbidities, and uremic milieu. In this review we discuss the role of adiponectin in chronic kidney disease.

Paraplegia Caused by Spontaneous Spinal Hemorrhage in a Patient Undergoing Rivaroxaban Therapy.

BACKGROUND Spinal hematomas can be post-traumatic, iatrogenic, or spontaneous. A spontaneous spinal hematoma is a rare finding, but one with very serious clinical implications. There are some risk factors linked to its occurrence, e.g. arteriovenous malformations, lumbar puncture, coagulopathy, neoplasms, or therapeutic anticoagulation. At present, only a few cases of spontaneous spinal hematoma (SSH) associated with new oral anticoagulants (NOACs) have been described, three of which were linked with rivaroxaban. CASE REPORT We report the case of an 82-year-old Caucasian woman with persistent atrial fibrillation treated with rivaroxaban, who presented to the Urology Department with acute-onset back pain which was thought to be due to urolithiasis. No kidney stones were found, but her creatinine serum level was elevated, so she was transferred to our clinic for further treatment. During hospitalization she quickly developed paraplegia with urine and stool retention. MRI was performed, and demonstrated an acute epidural hemorrhage in her thoracic and lumbar spine. The neurosurgeons disqualified this patient from surgical intervention due to the extent of the hematoma and its location. The patient was referred to the Neurology Department for treatment and rehabilitation, but, to the best of our knowledge, she did not recover her motor function. CONCLUSIONS Although rivaroxaban has been shown to be more effective than warfarin in stroke prevention in patients with atrial fibrillation, physicians must remember that its use also carries the risk of major bleeding. SSH occurrence should be taken into account in a patient taking NOACs who develops paraplegia, even if there is no history of trauma prior to admission.

Chronic kidney disease is associated with increased levels of renalase in serum and decreased in erythrocytes.

INTRODUCTION: Renalase is a novel flavin adenine dinucleotide-dependent amine oxidase with catecholamine-degrading activity. The kidneys are the main source of this enzyme. OBJECTIVES: In this study, we examined the concentrations of renalase in the serum, urine, and erythrocytes of patients with chronic kidney disease (CKD). PATIENTS AND METHODS: We enrolled 155 white patients with CKD and 30 healthy controls. Renalase concentrations were measured using an enzyme­linked immunosorbent assay. RESULTS: Serum renalase levels were higher in patients with CKD than in controls: median (Q1-Q3), 103 ng/ml (55.6-166 ng/ml) vs 17.7 ng/ml (16.3-21.8 ng/ml); P <0.001. Renalase levels in erythrocytes were lower in patients with CKD than in controls (median [Q1-Q3], 122 ng/ml [67.2-189 ng/ml] vs 254 ng/ml [166-293 ng/ml]; P <0.001). Urinary renalase levels did not differ between patients with CKD and controls (median [Q1-Q3], 147 ng/ml [102-193 ng/ml] vs 144 ng/ml [116-170 ng/ml]; P = 0.78). Urinary and erythrocyte renalase concentrations were negatively correlated with estimated glomerular filtration rate (eGFR). A multivariate general linear model analysis adjusted for age, sex, and eGFR of CKD patients showed that higher plasma dopamine and total protein concentrations were independent predictors of higher serum renalase levels (ß = 0.32, P <0.001 and ß = 0.25, P <0.001, respectively). CONCLUSIONS: Our results indicate that serum renalase concentrations are elevated in patients with CKD, whereas renalase concentrations in urine and erythrocytes are correlated with impaired kidney function.

IL17A and IL17F genes polymorphisms are associated with histopathological changes in transplanted kidney.

BACKGROUND: Interleukin 17 is a proinflammatory cytokine involved in immune response after allograft transplantation. IL-17 family of proinflammatory cytokines includes IL-17A and IL-17F. Previous studies have demonstrated that the rs2275913 IL17A and the rs11465553 IL17F gene polymorphism are associated with kidney allograft function. Because of the association between these polymorphisms and post-transplant immune response, we assume that these single nucleotide polymorphisms may affect morphological structure of transplanted kidney. The aim of this study was to examine the association of rs2275913 IL17A and rs2397084, rs11465553 and rs763780 IL17F gene polymorphisms with histopathological changes in transplanted kidney biopsies such as: glomerulitis, tubulitis, arteritis, cell infilitration and fibrosis. METHODS: The study enrolled 82 patients after renal graft transplantation in whom a kidney biopsy was performed because of impaired graft function. The rs2397084 T > C (Glu126Gly), rs11465553 G > A (Val155Ile) and rs763780 T > C (His167Arg) polymorphisms within the IL17F gene and the rs2275913 A > G (- 197 A > G) polymorphism within the IL17A gene promoter were genotyped using TaqMan genotyping assays on a 7500 FAST Real-Time PCR System (Applied Biosystems, USA). RESULTS: There was a significant association between the rs2275913 IL17A gene polymorphism and the grade of tubulitis, which was more severe among patients with the A allele, compared to recipients with the GG genotype (GG vs. AG + AA, P = 0.02), and with the grade of arteriolar hyaline thickening and mesangial matrix increase, which were more severe among patients with the G allele compared to recipients with the AA genotype (AA vs. AG + GG, P = 0.01 and P = 0.04, respectively). Tubular atrophy and interstitial fibrosis were more severe among individuals with the C allele at the rs763780 IL17F gene polymorphism (TT vs. TC, P = 0.09 and P = 0.017, respectively). However, it should be taken into account that the statistical significance was achieved without correction for multiple testing, and no significant association would remain significant after such correction. CONCLUSIONS: The results of this study may suggest a possible association between the rs2275913 IL17A and rs2275913 IL17A gene polymorphisms and some histopathological changes in transplanted kidney biopsies.

Mannose binding lectin 2 gene polymorphisms in patients after renal transplantation with acute graft rejection.

Mannose binding lectin 2 (MBL2) is one of the pattern-recognition soluble receptors and is responsible for complement activation via the lectin pathway, so it plays an important role in kidney transplantation. The aim of the study was to examine the association between MBL2 gene polymorphisms and acute rejection of the kidney allograft. This study enrolled 266 Caucasian deceased-donor renal transplant recipients - 69 with diagnosed acute graft rejection, 197 with stable graft function. A 969 bp DNA fragment, from chromosome 10, including promoter region and exon 1 of MBL2 gene was sequenced. The DNA fragment obtained contained 122 SNPs accordingly to the NCBI dbSNP database. Of this number only nine showed variation within our population (rs36014597, rs5030737, rs1800450, rs7095891, rs11003123, rs7096206, rs7084554, rs11003124, rs11003125), and only these were subjected to further analysis. Among the studied polymorphisms in the MBL2 gene only rs1800450 polymorphism was statistically significantly associated with kidney allograft rejection. The AA genotype was significantly associated with an increased risk of acute kidney allograft rejection. (AA vs GA+GG: OR=9.29 (95%CI: 1.83-47.17), p=0.005). The results of our study indicate that MBL2 gene rs1800450 polymorphism may be associated with the risk of acute kidney allograft rejection. The AA genotype, associated with lower MBL2 expression, may be associated with an increased risk of acute kidney allograft rejection.

Association Between Plasma Concentration of Klotho Protein, Osteocalcin, Leptin, Adiponectin, and Bone Mineral Density in Patients with Chronic Kidney Disease.

Patients with early-stage chronic kidney disease (CKD) are susceptible to changes in metabolic processes. Partial loss of kidney function leads to homoeostatic disturbances in bone and fatty tissue. The aim of this study was to investigate the association between plasma concentrations of Klotho protein, FGF23, leptin, adiponectin, osteocalcin, and bone mineral density (BMD) in patients with CKD in the pre-dialysis period. The study involved 52 patients with CKD and 23 patients with no kidney disease. In both groups, BMD, body mass index and serum or plasma concentrations of lipids, glucose, creatinine, calcium, phosphorus, parathormone, leptin, adiponectin, osteocalcin, Klotho, and FGF23 were measured. The group with CKD had statistically significant higher concentrations of leptin (p<0.001), parathormone (p<0.001), and osteocalcin (p<0.001) in comparison with the control group. Patients with CKD also had statistically significant lower BMD in the femoral neck in comparison with the control group. Osteocalcin correlated negatively with BMD. The results of our study suggest that elevated osteocalcin is the most sensitive marker of decreased bone mass in patients with CKD. Osteocalcin correlated negatively with BMD and GFR. The loss of bone mass in CKD patients was greatest in the femoral neck.

Plasma concentration of urokinase plasminogen activator receptor is a marker of kidney allograft function.

BACKGROUND: Urokinase-type plasminogen activator receptor (uPAR) is found in a variety of cell types including monocytes, lymphocytes, macrophages, and endothelial cells and plays an important role in fibrinolysis and in the activation and chemotaxis of neutrophils and lymphocytes. In this study, we examined the correlation between uPAR plasma concentration and kidney allograft function. AIMS: This study enrolled 78 Caucasian deceased-donor renal transplant recipients. METHODS: Plasma concentrations of uPAR were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: We observed elevated with borderline significance (p = 0.095) uPAR plasma concentrations in patients with tubular atrophy. Plasma concentrations of uPAR showed strong statistically significant positive correlations with serum creatinine or urea and strong negative correlation with estimated glomerular filtration rate (eGFR). There was also a borderline positive correlation between uPAR plasma concentration and protein concentration in urine as well as the duration of hemodialysis. CONCLUSIONS: The results of our study indicate that uPAR plasma concentrations in kidney allograft recipients are significantly negatively correlated with graft function and may be elevated in patients with tubular atrophy.

Ficolin-2 Gene rs7851696 Polymorphism is Associated with Delayed Graft Function and Acute Rejection in Kidney Allograft Recipients.

Ficolin-2 is an activator of the complement system that acts via the lectin pathway. Complement activation plays a substantial role in the renal injury inherent to kidney transplantation. In this study, we examined the associations between ficolin-2 gene polymorphisms in exon 8 and kidney allograft function. This study comprised 270 Caucasian deceased-donor renal transplant recipients. The following parameters were recorded in each case: delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction. Among patients with DGF, we observed a significantly increased frequency of rs7851696 GT and TT genotypes as well as T allele (TT + GT vs GG OR 1.98, 95% CI 1.12-3.48, p = 0.02; T vs G OR 2.08, 95% CI 1.27-3.41, p = 0.005). There was also an increased frequency of rs4521835 GG and TG genotypes as well as G alleles; however, these differences were on the borderline of statistical significance (GG + TG vs TT, OR 1.75, 95% CI 0.98-3.12, p = 0.07; G vs T OR 1.45, 95% CI 1.00-2.09, p = 0.050). In addition, we observed an increased frequency of acute allograft rejection in carriers of ficolin-2 rs7851696 T alleles on the borderline of statistical significance (TT + GT vs GG OR 1.75, 95% CI 0.97-3.16, p = 0.08), but the frequency of T allele was significantly higher in patients with AR (T vs G OR 1.71, 95% CI 1.02-2.87, p = 0.048). The results of our study suggest that ficolin-2 rs7851696 gene polymorphism influences kidney allograft functions, with T allele increasing the risk of DGF and AR.

Clinical and Biochemical Characteristics of Brain-Dead Donors as Predictors of Early- and Long-Term Renal Function After Transplant.

OBJECTIVES: Organs from brain-dead donors are the main source of allografts for transplant. Comparisons between living-donor and brain-dead donor kidneys show that the latter are more likely to demonstrate delayed graft function and lower long-term survival. This study aimed to assess the effects of various clinical and biochemical factors of donors on early- and long-term renal function after transplant. MATERIALS AND METHODS: We analyzed data from kidney recipients treated between 2006 and 2008 who received organs from brain-dead donors. Data from 54 donors and 89 recipients were analyzed. RESULTS: No relation was observed between donor sodium concentration and the presence of delayed graft function. Donor height was positively correlated with creatinine clearance in recipients in the 1 to 3 months after renal transplant. Donor diastolic blood pressure was negatively correlated with estimated glomerular filtration rate throughout the observation period. Donor age was negatively correlated with the allograft recipient's estimated glomerular filtration rate throughout 4 years of observation. Donor estimated glomerular filtration rate was positively correlated with that of the recipient throughout 3 years of observation. CONCLUSIONS: The results of this study indicate that various factors associated with allograft donors may influence graft function.

Urinary IL-8 is a marker of early and long-term graft function after renal transplantation.

In this study, we examined whether the IL-8 content of urine sampled on day 1 and day 14 after renal transplantation is a marker of early and long-term renal function. Moreover, we assessed whether its concentration is positively correlated with the matrix metalloproteinase-9 (MMP-9) content of urine sampled on day 1 and day 30 and 12 months after renal transplantation. Our analysis covered 87 patients who underwent a kidney transplant. The patients were observed for an average of 30 months (12-60 months). The IL-8 concentration determined on day 1 was significantly negatively correlated with creatinine clearance early after renal transplantation (on days 1, 7, 14 and 30), as well as during long-term observations. IL-8 concentration in urine sampled on day 1 and day 14 was higher in patients demonstrating DGF than in those without DGF. No relationship was found between IL-8 content and cold ischaemia time. MMP-9 activity determined on day 1 and month 3 after renal transplantation was positively correlated with the IL-8 content determined in urine sampled on day 1, Rs = +0.32, p < .05 and Rs = +0.31, p < .05, respectively. The results of this study suggest that a high IL-8 content in urine sampled on day 1 after renal transplantation is an unfavourable marker of early and long-term (years-long) graft function. A high IL-8 content in urine sampled on day 1 after renal transplantation was positively correlated with the activity of metalloproteinase-9 in urine. This proves that both of these chemokines cooperate in ischaemia-reperfusion injuries in transplanted kidneys.