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1.
Pharmacol Rep ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34617264

RESUMO

Kidney diseases have become one of the most common health care problems. Due to a growing number of advanced aged patients with concomitant disorders the prevalence of these diseases will increase over the coming decades. Despite available laboratory tests, accurate and rapid diagnosis of renal dysfunction has yet to be realized, and prognosis is uncertain. Moreover, data on diagnostic and prognostic markers in kidney diseases are lacking. The kynurenine (KYN) pathway is one of the routes of tryptophan (Trp) degradation, with biologically active substances presenting ambiguous properties. The KYN pathway is known to be highly dependent on immunological system activity. As the kidneys are one of the main organs involved in the formation, degradation and excretion of Trp end products, pathologies involving the kidneys result in KYN pathway activity disturbances. This review aims to summarize changes in the KYN pathway observed in the most common kidney disease, chronic kidney disease (CKD), with a special focus on diabetic kidney disease, acute kidney injury (AKI), glomerulonephritis and kidney graft function monitoring. Additionally, the importance of KYN pathway activity in kidney cancer pathogenesis is discussed, as are available pharmacological agents affecting KYN pathway activity in the kidney. Despite limited clinical data, the KYN pathway appears to be a promising target in the diagnosis and prognosis of kidney diseases. Modulation of KYN pathway activity by pharmacological agents should be considered in the treatment of kidney diseases.

2.
Nutrients ; 13(10)2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34684638

RESUMO

Chronic kidney disease (CKD) is generally progressive and irreversible, structural or functional renal impairment for 3 or more months affecting multiple metabolic pathways. Recently, the composition, dynamics, and stability of a patient's microbiota has been noted to play a significant role during disease onset or progression. Increasing urea concentration during CKD can lead to an acceleration of the process of kidney injury leading to alterations in the intestinal microbiota that can increase the production of gut-derived toxins and alter the intestinal epithelial barrier. A detailed analysis of the relationship between the role of intestinal microbiota and the development of inflammation within the symbiotic and dysbiotic intestinal microbiota showed significant changes in kidney dysfunction. Several recent studies have determined that dietary factors can significantly influence the activation of immune cells and their mediators. Moreover, dietary changes can profoundly affect the balance of gut microbiota. The aim of this review is to present the importance and factors influencing the differentiation of the human microbiota in the progression of kidney diseases, such as CKD, IgA nephropathy, idiopatic nephropathy, and diabetic kidney disease, with particular emphasis on the role of the immune system. Moreover, the effects of nutrients, bioactive compounds on the immune system in development of chronic kidney disease were reviewed.


Assuntos
Microbioma Gastrointestinal/imunologia , Sistema Imunitário/microbiologia , Fenômenos Fisiológicos da Nutrição/imunologia , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/microbiologia , Humanos , Rim/imunologia , Rim/microbiologia
3.
Antioxidants (Basel) ; 10(6)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208703

RESUMO

Confirmation of the biological effectiveness of new ophthalmic preparations introduced in the market is an important element in maintaining the safety of using this type of medications. This study aimed to investigate the activity of Ozodrop® on human corneal and conjunctival epithelial cells, as well as its antibacterial and antifungal activity. Cytotoxicity analyses of ocular surface epithelial cells were performed in vitro by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and Neutral Red uptake assays. The level of nitric oxide released by the cells was assessed by the Griess method. The reduction of the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical by the tested formulation was analyzed. Microbiological tests were also performed. It was found that the Ozodrop® preparation exhibited biological activity, but was less active than the reference antibiotics and the anti-yeast agent. The cytotoxic activity of the Ozodrop® formulation was dependent on the time of cell exposure to it. No toxic effect was observed in the short-term, for up to 3 h. It appeared after 24 h of exposure of the cells to the preparation. The drops showed antioxidant activity in the specified concentration range. They also stimulated the release of nitric oxide, mainly by corneal epithelial cells. The Ozodrop® formulation exhibits biological activity that can be considered useful in the treatment of infections in the front part of the eye.

4.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209289

RESUMO

The continually evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in a vast number of either acute or chronic medical impairments of a pathophysiology that is not yet fully understood. SARS-CoV-2 tropism for the organs is associated with bilateral organ cross-talks as well as targeted dysfunctions, among which acute kidney injury (AKI) seems to be highly prevalent in infected patients. The need for efficient management of COVID-related AKI patients is an aspect that is still being investigated by nephrologists; however, another reason for concern is a disturbingly high proportion of various types of kidney dysfunctions in patients who have recovered from COVID-19. Even though the clinical picture of AKI and COVID-related AKI seems to be quite similar, it must be considered that regarding the latter, little is known about both the optimal management and long-term consequences. These discrepancies raise an urgent need for further research aimed at evaluating the molecular mechanisms associated with SARS-CoV-2-induced kidney damage as well as standardized management of COVID-related AKI patients. The following review presents a comprehensive and most-recent insight into the pathophysiology, clinical manifestations, recommended patient management, treatment strategies, and post-mortem findings in patients with COVID-related AKI.


Assuntos
Injúria Renal Aguda/diagnóstico , COVID-19/patologia , Injúria Renal Aguda/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Biomarcadores/metabolismo , COVID-19/complicações , COVID-19/tratamento farmacológico , COVID-19/virologia , Taxa de Filtração Glomerular , Humanos , Interleucina-6/metabolismo , Sistema Renina-Angiotensina , Rabdomiólise/etiologia , SARS-CoV-2/isolamento & purificação
5.
Acta Diabetol ; 58(12): 1595-1602, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34156537

RESUMO

AIMS: Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). METHODS: In this case-control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN- (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR- (independently of the presence of DN). RESULTS: No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16-1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26-2.75, p = 0.001) than DR- patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). CONCLUSIONS: This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.

6.
Life (Basel) ; 11(5)2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34069386

RESUMO

(1) Background: The aim of the study was to test the hypothesis that the antioxidant status in the vitreous body of eyes, which had been vitrectomized due to rhegmatogenous retinal detachment (RRD) with or without proliferative vitreoretinopathy (PVR), is higher than in eyes vitrectomized due to other retinal diseases. (2) Methods: four patient groups were analyzed: 22 eyes of patients with RRD without PVR, 27 eyes with RRD and PVR, 22 eyes with macular hole (MH) and 10 eyes with epiretinal membrane (ERM). Spectrophotometric methods were used to determine the total antioxidant status (TAS) values as well as superoxide dismutase (SOD) and glutathione reductase (GR) activities in the vitreous fluid samples. (3) Results: no significant differences in TAS values and antioxidant enzyme activities were observed among patient with RRD with and without PVR and with MH and ERM. The longer the duration of RRD leading to PVR and better postoperative visual acuity, the higher the TAS level. No significant differences were found between "macula on" and "macula off" subgroups within the RRD group and the RRD combined with PVR group. (4) Conclusions: The preliminary results do not support the thesis that the antioxidant status of vitrectomized eyes is different in patients with RRD with or without PVR in comparison to patients with MH and ERM. In patients with RRD, PVR presence and detached macula do not affect the values of TAS, SOD and GR in the vitreous fluid. The duration of the disease influences TAS in the vitreous in eyes with RRD complicated with PVR.

7.
Front Pharmacol ; 12: 656774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995079

RESUMO

Purpose: To evaluate the effect of repeated intravitreal bevacizumab injections on blood-aqueous barrier permeability in eyes with neovascular age-related macular degeneration (AMD). Patients and Methods: Forty-eight consecutive patients with neovascular AMD received 3 intravitreal bevacizumab injections (1 mg) every 30-40 days. Subjects were followed for a period of 4 months and were examined at baseline, 1 day and 1 month after each injection. A control group comprised of 19 neovascular AMD patients waiting to begin anti-vascular endothelial growth factor (VEGF) therapy. Anterior chamber (AC) inflammation was evaluated with biomicroscopy and laser flare photometry. Results: None of the subjects treated with bevacizumab had detectable ocular inflammation during follow-up. An analysis for variance (ANOVA) of the mixed-effects model has shown neither an effect between treatment and control group (p = 0.921), nor over the time course of the follow-up (p = 0.773). Before treatment, median AC inflammation was 6.7 photons/ms (range: 3.5-18.2 photons/ms). One month after the first, second, and third injections, median laser flare was 6.4, 6.8, and 6.6 photons/ms, respectively, none of which were significantly different from baseline (all p > 0.05). Blood-aqueous barrier permeability did not change between injections and was not different from the control group. Conclusion: Inflammation induced by intravitreal bevacizumab was not detected by examination or flare photometry. This suggests that monthly bevacizumab dosing seems to be safe. The absence of AC inflammation could also reflect the known anti-inflammatory properties of anti-VEGF agents.

8.
BMC Nephrol ; 22(1): 201, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051741

RESUMO

BACKGROUND: Iron overload is inevitably related to chronic kidney disease (CKD) treatment. Haemochromatosis leads to multiorgan damage and is associated with increased mortality. Primary haemochromatosis is the most common autosomal recessive disease in white populations. In most cases, the classic form of hereditary haemochromatosis is caused by mutations, mainly C282Y and H63D, in the haemochromatosis gene (HFE). Secondary haemochromatosis can be triggered by iron administration and blood transfusions. Haemochromatosis is rarely reported in kidney transplant recipients. Atypical factors may evoke haemochromatosis in patients without HFE mutations or other standard risk factors. CASE PRESENTATION: In the current study, we present a patient who started to have haemochromatosis symptoms after kidney transplantation. A 37-year-old man after kidney transplantation from a deceased donor was admitted to the hospital due to high serum ferritin levels and impaired graft function. The patient's past medical history included arterial hypertension, embolization of both renal arteries and necrosis of the left femoral head. Glomerulonephritis was suspected as a cause of CKD; however, severe kidney failure was diagnosed, kidney biopsy was not performed, and the patient started intermittent haemodialysis. While on dialysis to treat anaemia, the patient had received erythropoietin and iron intravenously, and the maximal serum ferritin level was 2115 ng/ml. After kidney transplantation, ferritin levels started to increase rapidly, with a maximum level of 9468 ng/ml one and a half years after surgery. His genetic study showed HFE C282Y heterozygosity. Symptoms of haemochromatosis, such as skin hyperpigmentation, elevated activity of aminotransferases, impaired glucose tolerance and heart failure, were observed. Therapeutic phlebotomy was started, and 36 procedures were performed. After treatment, graft function significantly improved, most haemochromatosis symptoms resolved, and the serum ferritin level significantly decreased. CONCLUSIONS: Haemochromatosis can occur in heterozygotic HFE patients after kidney transplantation. Iron administration, infections, type of immunosuppression and liver dysfunction should be considered potential triggers of haemochromatosis in this group of patients.

9.
Cells ; 10(3)2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808831

RESUMO

Contrast-induced acute kidney injury (CI-AKI) is a serious complication associated with considerable morbidity and mortality. Heat-shock protein 27 (HSP27) plays a role in the defense of the kidney tissue against various forms of cellular stress, including hypoxia and oxydative stress, both features associated with CI-AKI. The aim of our study was to evaluate a potential predictive value of HSP27 for CI-AKI in patients subjected to percutaneous coronary interventions (PCI). Included were 343 selected patients subjected to PCI. Exclusion criteria were conditions that potentially might influence HSP27 levels. HSP27 serum levels were evaluated prior to PCI, together with serum creatinine, the concentration of which was also evaluated twice at 48 and 72 h post PCI. CI-AKI was diagnosed in 9.3% of patients. Patients in whom CI-AKI was diagnosed were older (p < 0.001), were more often females (p = 0.021), had higher prevalence of diabetes (p = 0.011), hypotension during PCI (p < 0.001), albuminuria (p = 0.004) as well as multivessel disease (p = 0.002), received higher contrast volume (p = 0.006), more often received contrast volume (CV) above the maximum allowed contrast dose (MACD) (p < 0.001), and had lower HSP27 level (p < 0.001). On multivariate analysis, CV > MACD (OR 1.23, p = 0.001), number of diseased vessels (OR 1.27, p = 0.006), and HSP27 (OR 0.81, p = 0.001) remained independent predictors of CI-AKI. Low concentration of HSP27 is an emerging, strong and independent predictor of CI-AKI in patients subjected to PCI.


Assuntos
Injúria Renal Aguda/complicações , Creatinina/sangue , Proteínas de Choque Térmico HSP27/metabolismo , Intervenção Coronária Percutânea/efeitos adversos , Injúria Renal Aguda/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Feminino , Proteínas de Choque Térmico HSP27/sangue , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Intervenção Coronária Percutânea/mortalidade , Fatores de Risco
10.
Artigo em Inglês | MEDLINE | ID: mdl-33809199

RESUMO

The coronavirus SARS-CoV-2 responsible for the current human COVID-19 pandemic has shown tropism toward different organs with variable efficiency, eyes included. The purpose of this study has been to investigate the presence of detectable SARS-CoV-2 infection in ocular swabs in patients affected by COVID-19. A consecutive series of 74 COVID-19-positive patients (age 21-89) were enrolled at two Polish COVID-19 hospitals for 4 months and were characterized by PCR for the presence of the SARS-CoV-2 genetic material in nasopharyngeal (NP) and ocular swabs, while their respiratory and ocular symptoms were noted. Almost 50% of them presented with severe/critical respiratory involvement, and some degree of eye disease. No tight correlation was observed between the presence of ocular and respiratory symptoms. Three male patients presenting with severe/critical lung disease tested positive in ocular swab, however with mild/moderate ocular symptoms. In conclusion, our study lends further support to the view that overt ocular infection by the SARS-CoV-2 virus is not such a frequent occurrence.


Assuntos
COVID-19 , Infecções por Coronavirus , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Polônia , SARS-CoV-2 , Adulto Jovem
11.
J Hum Hypertens ; 35(1): 49-54, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32042072

RESUMO

Oxidative stress plays an important role in hypertension associated vascular damage. It is mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The C242T polymorphism in the p22PHOX gene encoding essential subunit of NADPH oxidase was associated with CVD, hypertension, and endothelial function. The aim of this study was to assess a potential association of C242T polymorphism with hypertension in end-stage kidney disease (ESKD) patients. DNA samples from 495 patients were genotyped by polymerase chain reaction (PCR) with subsequent cleavage with Rsa I restriction endonuclease. There were no significant differences in genotype and allele distribution between ESKD patients and healthy controls. When patients were stratified into male and female subgroups, there were no differences in the frequency of the T allele (0.35 and 0.34, respectively). Genotype and allele frequencies were also comparable between HY+ and HY- subgroups. We analyzed whether there were any differences between genders in the effect of C242T polymorphism on the presence of hypertension by comparing HY+ males with normotensive males and HY+ females with normotensive females. No difference in polymorphism distribution was found in female subgroup. The significant differences were observed in males. In HY+ subgroup, the frequencies of T allele and TT genotype were higher than in HY- males, with OR 1.91 (1.31-2.8), p = 0.0008 and OR 4.2 (1.67-10.6), p = 0.002, respectively. In conclusion, this is the first study to demonstrate significant association of the p22PHOX gene polymorphism with hypertension in male ESKD patients, with T allele as a risk factor for hypertension.


Assuntos
Hipertensão , Falência Renal Crônica , Feminino , Frequência do Gene , Genótipo , Humanos , Hipertensão/genética , Falência Renal Crônica/genética , Masculino , NADPH Oxidases/genética , Polimorfismo Genético
12.
Diagnostics (Basel) ; 10(11)2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171856

RESUMO

BACKGROUND: We aimed to identify diagnosed cases of ocular cystinosis and describe clinical, epidemiological and therapeutic characteristics. METHODS: This is a descriptive and retrospective case series. All patients underwent a full check-up examination every 4-6 months by ophthalmologists, nephrologists and other required specialists. RESULTS: Of the seven cases, six (85.7%) were females and one (14.2%) was male. The infantile nephropathic form of cystinosis was observed in five patients and the juvenile nephropathic form in two patients. No patients with the ocular form of cystinosis were identified. Corneal cystine crystals (CCC) were found in all analyzed patients. Severe ocular and general complications of the disease that had been standing for years, connected to the infantile nephropathic form, delayed diagnosis or inappropriate treatment, were observed only in two patients. All patients received topical therapy. No adverse events related to the therapy were observed. CONCLUSIONS: Cystinosis is a rare, progressive disease. Early diagnosis and treatment prevent serious complications from numerous systemic organs. Patients require constant systematic monitoring by various specialists.

13.
Int J Mol Sci ; 21(21)2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33121190

RESUMO

Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) on T and B lymphocytes in patients with PGN and nonproliferative glomerulonephritis (NPGN). A cohort of 45 newly-diagnosed patients (23 with PGN and 22 with NPGN) and 20 healthy volunteers was enrolled. The percentage of peripheral blood mononuclear cells expressing PD-1 and PD-L1 antigens was determined by flow cytometry. We found PD-1 and PD-L1 expression on T and B lymphocytes was higher in PGN patients than in NPGN patients and controls. We also found that reactivation of the Epstein-Barr virus (EBV) correlated with the expression of PD-1/PD-L1 antigens in patients with PGN. Further receiver operating characteristic analysis indicated that PD-1 expression could distinguish EBV-positive PGN patients from those with NPGN or healthy controls. The use of PD-1 expression as a non-invasive marker of PGN should be further investigated.


Assuntos
Linfócitos B/metabolismo , Antígeno B7-H1/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Glomerulonefrite/virologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Glomerulonefrite/imunologia , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Regulação para Cima , Adulto Jovem
14.
BMC Nephrol ; 21(1): 434, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054714

RESUMO

BACKGROUND: Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy affecting the peripheral nervous system. This neurological disorder has been previously reported in bone marrow transplant recipients but is uncommon after kidney transplantation. Viral infections and calcineurin inhibitors are the main triggers of GBS in renal transplant recipients. CASE PRESENTATION: In this report, we present a case of a 47-year-old male patient 12 years after his second kidney transplantation who developed GBS due to papillary renal cell carcinoma. Infectious and drug-related origins of GBS were excluded. Despite intensive treatment, graftectomy was performed, after which neurological symptoms resolved. CONCLUSIONS: In kidney transplant recipients, paraneoplastic aetiology should be considered in the differential diagnosis of GBS.


Assuntos
Aloenxertos , Carcinoma de Células Renais/complicações , Síndrome de Guillain-Barré/etiologia , Neoplasias Renais/complicações , Síndromes Paraneoplásicas/etiologia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Transplante de Rim/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
15.
Int J Mol Sci ; 21(18)2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32933213

RESUMO

One of the major challenges faced by modern nephrology is the identification of biomarkers associated with histopathological patterns or defined pathogenic mechanisms that may assist in the non-invasive diagnosis of kidney disease, particularly glomerulopathy. The identification of such molecules may allow prognostic subgroups to be established based on the type of disease, thereby predicting response to treatment or disease relapse. Advances in understanding the pathogenesis of diseases, such as membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, IgA (immunoglobulin A) nephropathy, and diabetic nephropathy, along with the progressive development and standardization of plasma and urine proteomics techniques, have facilitated the identification of an increasing number of molecules that may be useful for these purposes. The growing number of studies on the role of TLR (toll-like receptor) receptors in the pathogenesis of kidney disease forces contemporary researchers to reflect on these molecules, which may soon join the group of renal biomarkers and become a helpful tool in the diagnosis of glomerulopathy. In this article, we conducted a thorough review of the literature on the role of TLRs in the pathogenesis of glomerulopathy. The role of TLR receptors as potential marker molecules for the development of neoplastic diseases is emphasized more and more often, as prognostic factors in diseases on several epidemiological backgrounds.


Assuntos
Biomarcadores/metabolismo , Nefropatias/metabolismo , Receptores Toll-Like/metabolismo , Animais , Humanos , Rim/metabolismo , Rim/patologia , Nefropatias/patologia , Prognóstico
16.
J Clin Med ; 9(2)2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32079183

RESUMO

Toll-like receptor (TLR) signaling may be involved in autoimmune kidney disorders and has been implicated in proliferative and non-proliferative glomerulonephritis (PGN and NPGN). In this study, we investigated the expression of TLR2 on T and B lymphocytes in relation to selected clinical parameters in patients with PGN and NPGN. We collected peripheral blood from the ulnar vein of patients with PGN (n = 15) or NPGN (n = 22) and healthy volunteers (n = 20). The percentage of peripheral blood mononuclear cells expressing TLR2 was determined with flow cytometry. TLR2 expression on T and B lymphocytes was increased in PGN patients compared with NPGN patients and controls (p ≤ 0.001). In patients with PGN, TLR2 expression correlated negatively with the serum concentrations of IgG and albumin and positively with urine protein excretion. Receiver operating characteristic (ROC) analysis indicated that TLR2 expression is a highly specific marker to distinguish PGN patients from NPGN patients and controls, especially on CD4+ T lymphocytes. Its use as a non-invasive marker of disease should be further investigated.

18.
Blood Purif ; 49(1-2): 71-78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31726453

RESUMO

BACKGROUND: A significant drop of serum phosphate and calcium removal or loading during hemodialysis induce reactions in mineral and bone remodeling that may inversely affect phosphate and calcium removal during dialysis. OBJECTIVES: We aimed to analyze the interdependencies between biomarkers of mineral and bone metabolism and removal of phosphate and calcium during hemodialysis, as this complex relationship is not fully understood. METHODS: Three subsequent hemodialysis sessions during a 1-week treatment cycle with interdialytic periods of 2-2-3 days were monitored in 25 anuric patients. Calcium and phosphate concentrations were measured in serum before, at 1, 2, and 3 h, at the end, and 45 min after each session and in the outlet dialysate every 30 min. Biomarkers associated with mineral and bone metabolism: parathyroid hormone (PTH 1-34 and PTH 1-84), calcitonin, 25(OH)-vitamin D, fetuin-A, osteopontin, osteocalcin 1-43/49, and intact osteocalcin were assayed once in each patient before the midweek hemodialysis session. RESULTS: Post-dialytic and intra-dialytic serum phosphate of midweek hemodialysis session and phosphate mass removed within 1 week correlated positively with serum PTH (0.40 < rho <0.46, p value <0.05). Higher concentration of serum PTH was associated with an increased level of osteocalcin. Pre-dialytic, post-dialytic, average for treatment time and average weekly concentrations of ionized calcium in serum correlated positively with serum osteocalcin. Serum osteocalcin and osteopontin levels were associated with the masses of total and ionized calcium, respectively, removed during 3 hemodialysis sessions. CONCLUSIONS: During hemodialysis, phosphate removal was associated with serum PTH, whereas calcium kinetics was influenced by serum osteocalcin and osteopontin. These results demonstrate that active processes involving biomarkers of mineral and bone metabolism are affected by the phosphate and calcium kinetics already within 4 h hemodialysis sessions.


Assuntos
Densidade Óssea , Cálcio/sangue , Osteocalcina/sangue , Osteopontina/sangue , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
PLoS One ; 14(8): e0220764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404089

RESUMO

BACKGROUND: Relative blood volume (RBV) changes during hemodialysis (HD) are typically estimated based on online measurements of hematocrit, hemoglobin or total blood protein. The aim of this study was to assess changes in the above parameters during HD in order to compare the potential differences in the RBV changes estimated by individual methods. METHODS: 25 anuric maintenance HD patients were monitored during a 1-week conventional HD treatment. Blood samples were collected from the arterial dialysis blood line at the beginning and at the end of each HD session. The analysis of blood samples was performed using the hematology analyzer Advia 2120 and clinical chemistry analyzer Advia 1800 (Siemens Healthcare). RESULTS: During the analyzed 30 HD sessions with ultrafiltration in the range 0.7-4.0 L (2.5 ± 0.8 L) hematocrit (HCT) increased by 9.1 ± 7.0% (mean ± SD), hemoglobin (HGB) increased by 10.6 ± 6.3%, total plasma protein (TPP) increased by 15.6 ± 9.5%, total blood protein (TBP) increased by 10.4 ± 5.8%, red blood cell count (RBC) increased by 10.8 ± 7.1%, while mean corpuscular red cell volume (MCV) decreased by 1.5 ± 1.1% (all changes statistically significant, p < 0.001). HGB increased on average by 1.5% more than HCT (p < 0.001). The difference between HGB and TBP increase was insignificant (p = 0.16). CONCLUSIONS: Tracking HGB or TBP can be treated as equivalent for the purpose of estimating RBV changes during HD. Due to the reduction of MCV, the HCT-based estimate of RBV changes may underestimate the actual blood volume changes.


Assuntos
Proteínas Sanguíneas/análise , Determinação do Volume Sanguíneo , Hematócrito , Hemoglobinas/análise , Diálise Renal , Adulto , Idoso , Volume Sanguíneo , Determinação do Volume Sanguíneo/métodos , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade
20.
Arch Immunol Ther Exp (Warsz) ; 67(5): 335-349, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31177287

RESUMO

Major causes of chronic kidney disease are primary proliferative and nonproliferative glomerulonephritides (PGN and NPGN). However, the pathogenesis of PGN and NPGN is still not fully understood. Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a T-cell membrane receptor that plays a key role in T-cell inhibition. Despite its role in autoimmunological diseases, little is known about the involvement of CTLA-4 in the pathogenesis of PGN and NPGN. The objective of this study was to determine the role of CTLA-4 in the pathogenesis of PGN and NPGN by evaluating the frequencies of T and B lymphocytes expressing CTLA-4 and the serum concentration of the sCTLA-4 isoform in patients with PGN and NPGN in relation to clinical parameters. The study included peripheral blood (PB) samples from 40 PGN and NPGN patients and 20 healthy age- and sex-matched volunteers (control group). The viable PB lymphocytes were labeled with fluorochrome-conjugated monoclonal anti-CTLA-4 antibodies and analyzed using flow cytometry. The serum concentration of sCTLA-4 was measured using ELISA. The frequencies and absolute counts of CD4+/CTLA-4+ T lymphocytes, CD8+/CTLA-4+ T lymphocytes and CD19+/CTLA-4+ B lymphocytes and the serum sCTLA-4 concentration were lower in PGN and NPGN patients that in the control group. Reduced sCTLA-4 expression was associated with a lower concentration of serum immunoglobulins. Our results indicate that deregulation of CTLA-4 expression may result in continuous activation of T cells and contribute to the pathogenesis of PGN and NPGN.


Assuntos
Antígeno CTLA-4/genética , Regulação da Expressão Gênica , Glomerulonefrite/imunologia , Glomerulonefrite/fisiopatologia , Imunoglobulinas/sangue , Rim/fisiopatologia , Subpopulações de Linfócitos/metabolismo , Adulto , Idoso , Antígenos CD/metabolismo , Antígeno CTLA-4/sangue , Antígeno CTLA-4/metabolismo , Feminino , Humanos , Ativação Linfocitária , Contagem de Linfócitos , Subpopulações de Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Curva ROC , Adulto Jovem
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