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In December 2019 the SARS-CoV-2 virus appeared in the world, mainly presenting as an acute infection of the lower respiratory tract, namely pneumonia. Nearly 10% of all patients show significant pulmonary fibrotic changes after the infection. The aim of this study was to evaluate the effectiveness and safety of potassium canrenoate in the treatment of COVID-19-associated pneumonia and pulmonary fibrosis. We performed a randomized clinical trial (RCT) of potassium canrenoate vs placebo. A total of 55 patients were randomized and 49 were included in the final analysis (24 allocated to the intervention group and 25 allocated to the control group). Patients were assessed by physical examination, lung ultrasound, CT imaging and blood samples that underwent biochemical analysis. This RCT has shown that the administration of potassium canrenoate to patients with COVID-19 induced pneumonia was not associated with shorter mechanical ventilation time, shorter passive oxygenation, shorter length of hospitalization or less fibrotic changes on CT imaging. The overall mortality rate was not significantly different between the two groups. Adverse events recorded in this study were not significantly increased by the administration of potassium canrenoate. The negative outcome of the study may be associated with the relatively small number of patients included. Any possible benefits from the use of potassium canrenoate as an antifibrotic drug in COVID-19 patients require further investigation.
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The aim of our study was to evaluate the influence of asymptomatic infection and the occurrence of symptomatic COVID-19 on specific biochemical, renal, and immune parameters-renalase, neutrophil gelatinase-associated lipocalin (NGAL) cystatin C (CysC), and creatinine-and their weekly fluctuations during a one-month observation period in COVID-19 patients admitted to hospital. The study involved 86 individuals: 30 patients with diagnosed COVID-19, 28 people with asymptomatic infection confirmed with IgG antibodies-the IG(+) group-and 28 individuals without any (IgG, IgE) anti-SARS-CoV-2 antibodies-the IG(-) group. In the COVID-19 group, blood was drawn four times: (1) on day 0/1 after admission to hospital (C1 group), (2) 7 days later (C7 group), (3) 14 days later (C14 group), and (4) 28 days later (C28 group). In the IG(-) and IG(+) groups, blood was drawn once. There were no significant differences in creatinine, Cys C, and uric acid between any of the analyzed groups. NGAL levels were significantly higher in IG(+) and at all time-points in the COVID-19 groups than in controls. A similar observation was made for renalase at the C7, C14, and C28 time-points. Plasma renalase, NGAL, and CysC are unrelated to kidney function in non-critically ill COVID-19 patients and those with asymptomatic infection. Renalase and NGAL are most likely related to the activation of the immune system rather than kidney function. Asymptomatic SARS-CoV-2 infection causes a rise in plasma NGAL levels similar to those observed in symptomatic COVID-19 patients. Therefore, more attention should be paid to tracking and monitoring the health of these people.
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BACKGROUND: Adiponectin (ADPN) is a biologically active cytokine produced by adipose tissue. This protein exhibits anti-inflammatory, antioxidant, antifibrotic, and insulin-sensitizing properties. As ADPN is primarily eliminated by the kidneys, it is a potential biomarker of chronic kidney disease progression. This study aimed to analyze the fluctuations in ADPN levels after kidney transplantation during a one-year follow-up and to compare them to significant renal (eGFR, NGAL) and metabolic (insulin, glucose, lipids, HOMA-IR) markers. METHODS: Insulin, ADPN, NGAL, and basic biochemical parameters were evaluated in 51 healthy controls and 39 patients right before kidney transplantation and at five time points following transplantation (5-7 days, one month, three months, six months, and twelve months). RESULTS: Mean ADPN levels dropped significantly right after transplantation (from 35.449 to 30.920 µg/mL, p = 0.001) and decreased gradually over a year. From the third month after the transplantation, ADPN levels were comparable to healthy individuals. At the pre-transplant time point, ADPN correlated only with insulin (r = -0.60, p < 0.001) and HOMA-IR (r = -0.55, p < 0.001). At the timepoints after transplantation, ADPN correlated only with NGAL at three months (r = -0.70, p = 0.048). The correlation of ADPN with HOMA-IR found at pre-transplant was not significant at any post-transplant time point, but at one and three months after transplant, the correlations reached a borderline significance (p = 0.07 and p = 0.08, respectively). CONCLUSIONS: Successful kidney transplantation is followed by a gradual and significant ADPN decrease. In pre- and post-transplant patients, ADPN is unrelated to kidney function defined by GFR, but to glucose metabolism. Most of the analyzed metabolic and kidney parameters, apart from NGAL, stabilize within three months after transplantation.
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Adiponectina , Transplante de Rim , Biomarcadores , Feminino , Seguimentos , Humanos , Insulina , Rim , Lipocalina-2 , MasculinoRESUMO
BACKGROUND: Renalase is an enzyme and a cytokine involved in cell survival. Since its discovery, associations between it and both cardiovascular and kidney disease have been noted. Recognizing this, we conducted a study in which we followed patients with chronic kidney disease. MATERIAL AND METHODS: The study involved 90 CKD patients with varying stages of the disease and 30 healthy controls. Renalase was measured with an ELISA kit, and patients were followed-up after a median of 18 months. During the follow-up, we asked about the occurrence of MACE, all-cause mortality and the need for dialysis initiation. RESULTS: In CKD subgroups, RNSL correlated with all-cause death only in the HD group (Rs = 0.49, p < 0.01). In the whole CKD population, we found a positive correlation of RNSL concentration and both MACE occurrence (Rs = 0.38, p < 0.001) and all-cause death (Rs = 0.34, p < 0.005). There was a significant increase in MACE occurrence probability in patients with elevated renalase levels (>25 µg/mL). CONCLUSIONS: Elevated renalase levels can be used as a risk factor of MACE in patients with CKD, but its long-term utility needs further research. High renalase levels are a risk factor of death among CKD patients. In HD patients, all deaths were observed among patients with >30 µg/mL; this level could be used as a "red flag" marker in future studies.
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Doenças Cardiovasculares/sangue , Monoaminoxidase/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/patologia , Causas de Morte , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/patologiaRESUMO
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.
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Catecolaminas , Hipertensão , Pressão Sanguínea , Humanos , Monoaminoxidase , Nefrectomia , Diálise RenalRESUMO
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.
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Função Retardada do Enxerto/genética , Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Polimorfismo Genético , Proteínas Proto-Oncogênicas c-vav/genética , Adulto , Alelos , Aloenxertos/metabolismo , Feminino , Genótipo , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Transplante HomólogoRESUMO
The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic and a burden to global health at the turn of 2019 and 2020. No targeted treatment for COVID-19 infection has been identified so far, thus supportive treatment, invasive and non-invasive oxygen support, and corticosteroids remain a common therapy. High-flow nasal cannula (HFNC), a non-invasive oxygen support method, has become a prominent treatment option for respiratory failure during the SARS-CoV-2 pandemic. HFNC reduces the anatomic dead space and increases positive end-expiratory pressure (PEEP), allowing higher concentrations and higher flow of oxygen. Some studies suggest positive effects of HFNC on mortality and avoidance of intubation. Spontaneous pneumothorax has been observed in patients suffering from SARS-CoV-2 pneumonia. Although the viral infection itself contributes to its development, higher PEEP generated by both HFNC and mechanical ventilation is another risk factor for increased alveoli damage and air-leak. Herein, we present three cases of patients with no previous history of lung diseases who were diagnosed with COVID-19 viral pneumonia. All of them were supported with HFNC, and all of them presented spontaneous pneumothorax.
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COVID-19 , Oxigenoterapia/efeitos adversos , Pneumotórax , Insuficiência Respiratória , Idoso de 80 Anos ou mais , Cânula , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Pneumotórax/terapia , Insuficiência Respiratória/terapiaRESUMO
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.
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In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin-angiotensin-aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.
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BACKGROUND: Platelet activation is an important side effect of dialysis, resulted in a subsequent release of arachidonic acid (AA) from activated platelets. AA is involved in many pathologic conditions, such as inflammation, asthma, cancer, diabetes, hypertension, and the pathogenesis of kidney disease. The aim of this study was to define whether the dialysis type affects the concentration of AA derivatives in patients with chronic kidney disease. METHODS: 117 patients were qualified to the study group. Based on the type of renal replacement therapy, patients were divided into the following groups: hemodialysis (HD A - before/HD B - after hemodialysis), peritoneal dialysis (PD), kidney transplant patients (TE - before/TE A - after transplantation) and conservative treatment (CT) (30; 30; 27; 30 patients, respectively). The control group consisted of 30 healthy volunteers (NK). The ELISA methods were used to measure the concentrations of TXB2, 5-HETE, 12-HETE, and 15-HETE in the blood serum. RESULTS: Renal replacement therapy significantly influences the concentration of TXB2 (mean ± SD [ng/mL]: HD A- 34.6 ± 9; HD B- 28.3 ± 15.2; PD- 28.3 ± 15.2; CT- 34.2 ± 8.0; TE- 36.7 ± 42.9; TE A- 27.9 ± 8.8; NK- 19.6 ± 15; p = 0.010), 5-HETE (mean ± SD [ng/mL]: HD A- 284.2 ± 428.4; HD B- 304.8 ± 516.2; PD - 530.0 ± 553.3; CT- 318.7 ± 366.0; TE- 525.6 ± 358.0; TE A - 409.8 ± 377.1; NK 838.1 ± 497.8; p < 0.001) and 15-HETE (HD A-18.1 ± 8.7; HD B- 42.2 ± 14; PD - 36.3 ± 13.8; CT- 33.7 ± 14.0; TE- 19.5 ± 10.2; TE A - 34.4 ± 16.3; NK 22.2 ± 17.8; p < 0,001). There was a significant relationship between the type of renal replacement therapy and the duration of dialysis, and the concentration of TXB2, 12-HETE acid, and 15-HETE. CONCLUSIONS: The type of renal replacement therapy significantly affects the concentration of AA derivatives. Peritoneal dialysis is the best method of dialysis, taking into account the concentration of arachidonic acid derivatives.
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Ácido Araquidônico/sangue , Ácidos Hidroxieicosatetraenoicos/sangue , Falência Renal Crônica/sangue , Terapia de Substituição Renal/métodos , Tromboxano B2/sangue , Ácido 12-Hidroxi-5,8,10,14-Eicosatetraenoico/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Tratamento Conservador/métodos , Feminino , Humanos , Falência Renal Crônica/terapia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Diálise Renal/métodosRESUMO
BACKGROUND: Renalase is a flavoprotein that plays a protective role in chronic kidney disease (CKD) and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and CKD patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR). METHODS: Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase. RESULTS: Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p = 0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration. CONCLUSIONS: The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to the glomerular filtration rate and not associated with blood pressure.
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Monoaminoxidase/sangue , Monoaminoxidase/urina , Insuficiência Renal Crônica/enzimologia , Adulto , Fatores Etários , Pressão Sanguínea , Complicações do Diabetes , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Proteinúria/complicações , Valores de Referência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores SexuaisRESUMO
Insulin resistance (IR) is characterised by increased gluconeogenesis in the liver and the resistance of peripheral receptors to insulin. Several factors, including IR, type 2 diabetes, new-onset diabetes after transplant (NODAT) and secondary parathyroidism, are related to chronic kidney disease (CKD). These factors are associated with higher mortality due to the increased risk of cardiovascular complications. Many factors have been identified as potential markers of IR in CKD. These factors include fibroblast growth factors (FGFs), a subfamily of endocrine polypeptides. In this study, we examined the association of FGF19, FGF21 and FGF23 with selected parameters related to carbohydrate metabolism and insulin resistance in non diabetic patients with predialysis CKD and in non diabetic patients after renal transplantation. The study included 108 non diabetic subjects: 40 patients with predialysis CKD, 45 patients with CKD who had undergone renal transplantation, and 23 healthy subjects (control group). In patients who had undergone renal transplantation, concentrations of FGF23 were increased compared to the control group and patients with predialysis CKD. The highest and lowest FGF19 concentrations were observed in CKD patients and in patients who had undergone kidney transplantation, respectively. This difference was statistically significant. Leptin concentrations were higher in CKD patients compared to the control group and patients who had undergone kidney transplantation. There were no statistically significant differences in adiponectin concentrations, lean body mass or fat tissue mass between the studied groups. HOMA-IR and insulin levels were significantly increased in CKD patients and in patients who had undergone renal transplantation in comparison to the control group. The results of the study suggest the involvement of FGF in carbohydrate metabolism and insulin resistance in patients with predialysis CKD, as well as a correlation with kidney function.
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Metabolismo dos Carboidratos , Fatores de Crescimento de Fibroblastos , Resistência à Insulina , Insuficiência Renal Crônica , Diabetes Mellitus Tipo 2/complicações , Feminino , Fator de Crescimento de Fibroblastos 23/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Insulina/metabolismo , Masculino , Insuficiência Renal Crônica/complicaçõesRESUMO
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.
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Biomarcadores/sangue , Biomarcadores/urina , Eritrócitos/química , Monoaminoxidase/sangue , Monoaminoxidase/urina , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Chronic kidney disease (CKD) is the result of a reduced number of nephrons, in which adipose tissue and its metabolites play a significant role. Fibroblast growth factors, FGF19 and FGF21, are involved in lipid and carbohydrate metabolism. The aim of the study was to examine the concentrations of FGF19 and FGF21 in patients with CKD, as well as the correlation between FGF19 and FGF21 and selected biochemical parameters. MATERIALS AND METHODS: The study included 178 subjects: 52 patients with CKD in stages 2-4, without haemodialysis (CKD), 47 haemodialysed patients with CKD (HD), 56 patients with CKD after a renal transplantation (Tx) and 23 healthy subjects as the control group (C). RESULTS: The highest FGF19 serum concentrations were observed in CKD patients and the lowest were observed in the Tx group. Patients in the CKD group had significantly higher serum FGF21 concentrations. There were negative correlations between FGF19 and glomerular filtration rate (GFR), as well as high-density lipoprotein cholesterol levels in patients after kidney transplantation. Negative correlations were also found between serum FGF21 concentrations and GFR in patients after Tx, while positive correlations were observed between FGF21 concentrations and lean body mass in the CKD group, body mass index and total cholesterol in the HD group. CONCLUSIONS: Our results suggest that increased concentrations of FGF19 and FGF21 in patients with CKD may be associated with the metabolism of lipids and carbohydrates. Our results also indicate that haemodialysis and transplantation results in the reduction of FGF19 and FGF21 concentrations in patients with CKD.
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Fatores de Crescimento de Fibroblastos/sangue , Insuficiência Renal Crônica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Chronic kidney disease (CKD) is a systemic disease affecting many organs. Progression of renal failure aggravates ongoing inflammation and increases oxidative stress. In the final stage of CKD, it is necessary to use renal replacement therapy. A side effect of dialysis therapy is the synthesis of proinflammatory factors and increased oxidative stress, which activates platelets and immune cells. AIM OF THE STUDY: To determine the regenerative potential of platelets in patients with CKD based on the analysis of the relationships between substances with potential regenerative action, as well as analysis of the influence of the type of renal replacement therapy used on regeneration of platelets. MATERIALS AND METHODS: The study group consisted of 117 patients. Based on the type of therapy used, patients were divided into four groups: hemodialysis, peritoneal dialysis, kidney transplant patients, and conservative treatment (30, 30, 27, and 30 patients). The control group consisted of 30 healthy volunteers. The concentrations of IGF-1, TGF-ß, and PDGF-B in the blood serum were measured by ELISA methods. RESULTS: It was shown that renal replacement therapy significantly influences the concentration of platelet growth factors (IGF-1: p = 0.025 and PDGF-B: p = 0.012). There was a relationship between the type of renal replacement therapy and the duration of dialysis, and the concentration of IGF-1, PDGF-B (p < 0.00001, p < 0.001). CONCLUSIONS: The type of renal replacement therapy has a different effect on the concentration of platelet-derived growth factors IGF-1 and PDGF-B. PD patients had the highest concentrations of all growth factors, and this may be due to the presence of inflammation induced by dialysis-related advanced end-products of glycosylation (AGE).
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Plaquetas/fisiologia , Regeneração , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
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Reação Hospedeiro-Enxerto , Interleucina-17/genética , Transplante de Rim/efeitos adversos , Rim/patologia , Adulto , Biópsia/métodos , Feminino , Predisposição Genética para Doença , Reação Hospedeiro-Enxerto/genética , Reação Hospedeiro-Enxerto/imunologia , Humanos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
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Adiponectina/sangue , Glucuronidase/sangue , Leptina/sangue , Osteocalcina/sangue , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Densidade Óssea , Estudos de Casos e Controles , Feminino , Colo do Fêmur/química , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangueRESUMO
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.
Assuntos
Morte Encefálica , Seleção do Doador , Rim/cirurgia , Doadores de Tecidos/provisão & distribuição , Fatores Etários , Aloenxertos , Biomarcadores/sangue , Pressão Sanguínea , Estatura , Creatinina/sangue , Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/fisiopatologia , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Fatores de Risco , Sódio/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION Glomerulonephritis (GN) is a complex disease that affects the function of the whole nephron. There are few data on the serum levels of the most common biomarkers of kidney function and injury in GN, or the studies provide ambiguous results. OBJECTIVES The aim of the study was to evaluate the levels of known kidney-specific and nonspecific markers of renal function or injury in the serum of patients with diagnosed primary or secondary GN, with or without the presence of nephrotic syndrome (NS) and arterial hypertension (AH). PATIENTS AND METHODS The study included 58 patients with diagnosed GN and 6 patients with congenital defects (CD) of the kidney and AH (CD+AH). The serum levels of ß2-microglobulin (ß2M), neutrophilgelatinase associated lipocalin (NGAL), osteopontin, trefoil factor 3 (TFF-3), calbindin, glutathione-Stransferase- π (GST-π), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and monocyte chemoattractant protein 1 (MCP-1) were measured with Kidney Toxicity Panels 1 and 2 using the Bio-Plex method. Renalase levels were measured using an enzyme-linked immunosorbent assay. RESULTS In the whole group and in the subgroups (GN, GN+AH, GN+NS, CD+AH), NGAL, KIM-1, TFF-3, IL-18, ß2M, and calbindin levels correlated with estimated glomerular filtration rate (eGFR). In patients with NS, this correlation for calbindin was reversed. Renalase, MCP-1, GST-π, and osteopontin levels were independent of eGFR. Increase in IL-18 levels in the group with GN was assiociated with lower odds of the kidney disease. When this group was divided according to eGFR into subgroups G1-G5, TFF-3, NGAL, and ß2M levels increased with the stage of the disease. CONCLUSIONS In patients with NS, renalase and MCP-1 might regulate each other's levels. Further studies are needed to investigate associations between renalase, MCP-1, and osteopontin as factors unrelated to eGFR in GN. NS may contribute to the loss of calbindin from serum. NGAL, KIM-1, TFF-3, IL-18, ß2M, and calbindin are good indicators of kidney function loss in patients with GN.