RESUMO
Background and Objectives: Several studies revealed a relation between abnormal cardiac remodeling and glomerular filtration rate (GFR) decline, but there are limited data regarding echocardiographic changes in chronic kidney disease (CKD). This study evaluated the abnormal cardiac structures characterizing patients with CKD, assessing the independent association between echocardiographic parameters and the risk of decline in renal function. Materials and Methods: In total, 160 patients with CKD were studied. All patients underwent an echocardiographic exam and 99mTc-DTPA renal scintigraphy to measure the GFR. After the baseline assessments, patients were followed prospectively for 12 months, or until the endpoint achievement, defined as a worsening in renal function (doubling of baseline serum creatinine, GFR decline ≥25%, the start of dialysis). Results: Patients with GFR values of 34.8 ± 15 mL/min, identifying stages III-IV of CKD, were associated with high levels of left ventricular mass index (LVMi) (101.9 ± 12.2 g/m2), which was related to proteinuria, systolic blood pressure, and pulmonary artery systolic pressure in a multiple regression model. During the observational period, 26% of patients reached the endpoint. Regression analysis revealed LVMi as a predictor of change in renal function after adjusting for kidney and cardiac risk factors. Multiple Cox regression indicated that an increase in LVMi was associated with a 12% increased risk of kidney disease progression (HR: 1.12; 95% CI: 1.04-1.16; p = 0.001). Conclusions: In patients with CKD, high LVMi represents an independent predictor of the progressive decline of the renal function, until the start of renal replacement therapy. Echocardiography can help identify patients at high risk for renal disease worsening in patients with CKD independently of clinical cardiac involvement.
Assuntos
Diálise Renal , Insuficiência Renal Crônica , Humanos , Ecocardiografia , Taxa de Filtração Glomerular , Rim/diagnóstico por imagem , Insuficiência Renal Crônica/complicaçõesRESUMO
Background and Objectives: Iron deficiency and anemia characterize patients on chronic hemodialysis (HD). Available intravenous iron agents, such as ferric gluconate (FG) and ferric carboxymaltose (FCM), vary in dosing regimens and safety profiles. The aim of the present study was to analyze the modification of the iron status, the correction of anemia, and the economic implications after the shift from FG to FCM therapy in chronic HD patients. We evaluated, during the study, the variations in iron metabolism, assessing ferritin and transferrin saturation, erythropoietin-stimulating agent (ESA) doses and the number of administrations, the effects on anemic status, and consequent costs. Materials and Methods: A retrospective study was performed with a follow-up period of 24 months, enrolling forty-two HD patients. The enrolment phase started in January 2015, when patients were treated with iv FG, and continued until December 2015, when FG was discontinued, and, after a wash-out period, the same patients were treated with FCM. Results: The iron switch reduced the administered dose of ESA by 1610.500 UI (31% of reduction; p < 0.001) during the entire study period and reduced the erythropoietin resistance index (ERI) (10.1 ± 0.4 vs. 14.8 ± 0.5; p < 0.0001). The FCM group had the highest percentage of patients who did not require ESA treatment during the study period. The FCM patients were characterized by higher levels of iron (p = 0.04), ferritin (p < 0.001), and TSAT levels (p < 0.001) compared to the FG patients. The annual cost during FG infusion was estimated at EUR 105,390.2, while one year of treatment with FCM had a total cost of EUR 84,180.7 (a difference of EUR 21,209.51 (20%), saving EUR 42.1 per patient/month (p < 0.0001). Conclusions: FCM was a more effective treatment option than FG, reducing ESA dose requirements, increasing Hb levels, and improving iron status. The reduced ESA doses and the decreased number of patients needing ESA were the main factors for reducing overall costs.
Assuntos
Anemia Ferropriva , Anemia , Eritropoetina , Hematínicos , Humanos , Anemia/etiologia , Anemia Ferropriva/tratamento farmacológico , Eritropoetina/metabolismo , Compostos Férricos/uso terapêutico , Ferritinas , Hematínicos/uso terapêutico , Ferro/uso terapêutico , Diálise Renal/efeitos adversos , Estudos RetrospectivosRESUMO
The accumulation of globotriaosylceramide (Gb-3) in multiple organs, such as the heart, kidney, and nervous system, due to mutations in the galactosidase alpha (GLA) gene, represents the key point of Fabry disease (FD). The common symptoms appear in childhood or adolescence, including neuropathic pain, angiokeratoma, acroparesthesia, and corneal opacities. A multi-organ involvement induces a significant deterioration in the quality of life with high mortality in adulthood. The accumulation of Gb-3 involves all types of kidney cells beginning at fetal development, many years before clinical manifestations. A decline in the glomerular filtration rate is rare in children, but it can occur during adolescence. Pediatric patients rarely undergo kidney biopsy that could assess the efficacy of enzyme replacement therapy (ERT) behind its diagnostic role. To date, diagnosis is achieved by detecting reduced α-Gal-A activity in leukocytes and plasma, allowing for the early start of ERT. This review focuses on pediatric kidney involvement in FD, analyzing in depth its diagnostic processes and treatment options.
Assuntos
Doença de Fabry , Rim , Criança , Terapia de Reposição de Enzimas , Doença de Fabry/patologia , Previsões , Humanos , Rim/patologiaRESUMO
INTRODUCTION: Impact assessment of new technologies in chronic hemodialysis (HD) is challenging due to HD patient frailty, the complexity of HD clinical trials and practice variability among countries. Among the most recent HD innovations, medium cut-off (MCO) dialyzers present an optimized membrane geometry that provides enhanced clearances for middle and large molecular weight uremic toxins (UT). These toxins are poorly cleared by available HD techniques and largely contribute to patient morbidity and mortality. The aim of this paper is to assess the available clinical evidence about MCO membranes and to identify the next steps needed to generate conclusive data on their use in HD. METHODS: With this purpose, we first reviewed and compared the current HD technologies aimed to improve the clearance of middle and large UT; subsequently, we used a Delphi questionnaire to identify and discuss the consensus about MCO efficacy within a large sample of the Italian Nephrology community. RESULTS AND CONCLUSIONS: Our investigation gathered a significant degree of consensus on the beneficial role of MCO membrane and expanded HD. Finally, we used our results to propose future trial designs and clinical investigations aimed to improve evidence quality about the use of these membranes in the present clinical scenario of dialysis units.
Assuntos
Hemodiafiltração , Toxinas Biológicas , Humanos , Diálise Renal/métodos , Hemodiafiltração/métodos , Inquéritos e QuestionáriosRESUMO
Hemodialysis (HD) is a life-saving therapy for patients with end-stage renal disease. In dialyzed patients, the prevalence of multi-morbidity is rising driven by various factors, such as the population aging, the incomplete correction of uremia, and the side effects of the dialysis therapy itself. Each dialyzed patient has their own specific clinical and biochemical problems. It is therefore unthinkable that the same dialysis procedure can be able to meet the needs of every patient on chronic dialysis. We have very sophisticated dialysis machines and different dialysis techniques and procedures beyond conventional HD, such as hemodiafiltration (HDF) with pre- and post-dilution, acetate-free biofiltration (AFB), hemofiltration (HF), and expanded HD. Each of these techniques has its own specific characteristics. To solve some intradialytic clinical issues, such as arterial hypotension and arrhythmias, we have biofeedback systems with automatic regulation of the blood volume, body temperature, arterial pressure, as well as potassium profiling techniques in the dialysis bath. New technical innovations, such as citrate-containing dialysate or heparin-coated membranes, could reduce the risk of bleeding. To better address to patient needs, the strengths and weaknesses of each of these systems must be well-known, in order to have a personalized dialysis prescription for each patient.
Assuntos
Hemodiafiltração , Hemofiltração , Falência Renal Crônica , Soluções para Diálise , Humanos , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversosRESUMO
Acute and chronic kidney injuries represent critical issues after liver transplantation (LTx), but whereas renal dysfunction in adult transplant patients is well documented, little is known about its prevalence in childhood. It is a challenge to accurately evaluate renal function in patients with liver disease, due to several confounding factors. Creatinine-based equations estimating glomerular filtration rate, validated in nephropathic patients without hepatic issues, are frequently inaccurate in end-stage liver disease, underestimating the real impact of renal disease. Moreover, whereas renal issues observed within 1 year from LTx were often related to acute injuries, kidney damage observed after 5-7 years from LTx, is due to chronic, irreversible mechanisms. Most immunosuppression protocols are based on calcineurin inhibitors (CNIs) and corticosteroids, but mycophenolate mofetil or sirolimus could play significant roles, also in children. Early diagnosis and personalized treatment represent the bases of kidney disease management, in order to minimize its close relation with increased mortality. This review analyzed acute and chronic kidney damage after pediatric LTx, also discussing the impact of pre-existent renal disease. The main immunosuppressant strategies have been reviewed, highlighting their impact on kidney function. Different methods assessing renal function were reported, with the potential application of new renal biomarkers.
Assuntos
Transplante de Fígado , Insuficiência Renal Crônica , Inibidores de Calcineurina , Criança , Humanos , Imunossupressores/efeitos adversos , Rim , Transplante de Fígado/efeitos adversos , Ácido Micofenólico , Insuficiência Renal Crônica/etiologiaRESUMO
Erythropoiesis is triggered by hypoxia and is strictly regulated by hormones, growth factors, cytokines, and vitamins to ensure an adequate oxygen delivery to all body cells. Abnormalities in one or more of these factors may induce different kinds of anemia requiring different treatments. A key player in red blood cell production is erythropoietin. It is a glycoprotein hormone, mainly produced by the kidneys, that promotes erythroid progenitor cell survival and differentiation in the bone marrow and regulates iron metabolism. A deficit in erythropoietin synthesis is the main cause of the normochromic normocytic anemia frequently observed in patients with progressive chronic kidney disease. The present review summarizes the most recent findings about each step of the erythropoietic process, going from the renal oxygen sensing system to the cascade of events induced by erythropoietin through its own receptor in the bone marrow. The paper also describes the new class of drugs designed to stabilize the hypoxia-inducible factor by inhibiting prolyl hydroxylase, with a discussion about their metabolism, disposition, efficacy, and safety. According to many trials, these drugs seem able to simulate tissue hypoxia and then stimulate erythropoiesis in patients affected by renal impairment. In conclusion, the in-depth investigation of all events involved in erythropoiesis is crucial to understand anemia pathophysiology and to identify new therapeutic strategies, in an attempt to overcome the potential side effects of the commonly used erythropoiesis-stimulating agents.
Assuntos
Anemia/terapia , Eritropoese , Falência Renal Crônica/terapia , Anemia/complicações , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sobrevivência Celular , Ensaios Clínicos como Assunto , Glicoproteínas/metabolismo , Hematínicos/uso terapêutico , Humanos , Hipóxia , Rim/metabolismo , Falência Renal Crônica/complicações , Camundongos , Oxigênio/metabolismo , Receptores da Eritropoetina/metabolismoRESUMO
The impact of water intake has been studied in several renal diseases. For example, increasing water intake is useful to prevent primary and secondary nephrolithiasis. In autosomal dominant polycystic kidney disease, arginine vasopressin (AVP) is involved in the progression of the disease, and water intake could play a therapeutic role by inhibiting the synthesis of AVP, but its efficacy is still controversial. Conversely, the use of aquaretics, which are antagonists of AVP V2 receptors, results in the reduction of the increase rate of total kidney volume with a slower decline of glomerular filtration rate. In chronic kidney disease, AVP contributes to glomerular hyperfiltration, arterial hypertension, and synthesis of renin, resulting in renal sclerosis. Increased water intake could reduce AVP activation determining a potential protective effect on the kidney, but its efficacy has not yet been clearly demonstrated. On the other side, sodium and potassium play an important role in the control of arterial blood pressure and are involved in the development and progression of chronic kidney disease. Reduction of sodium intake and increase of potassium intake determine a decrease of arterial blood pressure with a beneficial effect on the kidney; however, adherence to sodium restriction is very poor. Regarding this, sodium-hydrogen exchanger isoform 3 inhibitors may reduce sodium absorption in the gut. The most recent sodium-hydrogen exchanger isoform 3 inhibitor, known as tenapanor, reduces extracellular fluid volume, left ventricular hypertrophy, albuminuria, and blood pressure in experimental studies and increases fecal loss of sodium in humans.
Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos , Ingestão de Líquidos , Isoquinolinas , Nefropatias/terapia , Cloreto de Sódio na Dieta , Sulfonamidas , Adulto , Arginina Vasopressina/fisiologia , Feminino , Humanos , Hipertensão , Cálculos Renais , Nefropatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Potássio na Dieta/administração & dosagem , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/terapia , Sódio na Dieta/administração & dosagemAssuntos
Doença de Fabry , Doença de Fabry/complicações , Doença de Fabry/diagnóstico , Humanos , RimRESUMO
Our aim was to evaluate the role of urotensin II, urantide (urotensin II receptor antagonist) and relaxin-2 on the cellular expression of fibronectin as a surrogate marker for renal fibrosis. We employed LLC-PK1 renal tubular epithelial cells and assessed the influence on the fibrotic process of the above-mentioned substances by using anti-fibronectin antibodies in western blot analysis. The addition of urotensin II increased fibronectin expression. Urantide reduced the positivity for fibronectin caused by urotensin II (P<.05). The anti-fibrotic action was more evident for relaxin-2 (P<.01). Also in the model of TGF-ß1-induced fibrosis, urantide and, to a greater extent, relaxin-2 were able to significantly lessen fibronectin expression (respectively, P<.05 and P<.01). In conclusion, relaxin-2 may reduce urotensin II-induced renal fibrosis.
Assuntos
Fibronectinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Relaxina/farmacologia , Urotensinas/farmacologia , Animais , Modelos Animais de Doenças , Fibrose , Humanos , Masculino , SuínosRESUMO
CONTEXT: Available markers are not reliable parameters to early detect kidney injury in transplanted patients. OBJECTIVE: Examine neutrophil gelatinase associated lipocalin (NGAL) in early detection of delayed graft function (DGF) and as a long-term predictor of graft outcome. PATIENTS AND METHODS: NGAL was evaluated in 124 transplanted patients. RESULTS: Urinary NGAL levels were associated to a 10% (HR: 1.10; 95% CI: 1.04-1.25; p < 0.001) and 15% (HR: 1.15; 95% CI: 1.09-1.26; p < 0.001) increased risk of DGF and allograft nephropathy progression, respectively. CONCLUSION: NGAL reflects the entity of renal impairment in transplanted patients, representing a biomarker and an independent risk factor for DGF and chronic allograft nephropathy progression.
Assuntos
Biomarcadores/metabolismo , Função Retardada do Enxerto , Transplante de Rim/efeitos adversos , Lipocalina-2/metabolismo , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Nefropatias , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROCRESUMO
BACKGROUND: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-ß was correlated with peritoneal transport characteristics. METHODS: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum. RESULTS: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64 ± 3.6 and 70 ± 5.3 ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36 ± 2.5; pHMGB1:30.5 ± 7.0 ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5 ± 7.0 versus 6.9 ± 3.6; p < 0.0001). TGF-ß levels were higher in patients with low peritoneal permeability than in medium or high transporter patients (81 ± 15.5 versus 24.3 ± 7.5 pg/mL; p = 0.01). An inverse correlation was found between TGF-ß levels and dialysate/plasmatic creatinine values (r = -0.83; p = 0.03). CONCLUSION: HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-ß could predict the peritoneal transport status and dialysis technique adequacy.
Assuntos
Proteína HMGB1/sangue , Falência Renal Crônica/terapia , Diálise Peritoneal , Peritonite/etiologia , Fator de Crescimento Transformador beta/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/metabolismo , Masculino , Peritonite/sangue , PrognósticoRESUMO
Metformin, belonging to a class of drugs called biguanides, is the recommended first-line treatment for overweight patients with type 2 diabetes mellitus. It has multiple mechanisms of action, such as reduction of gluconeogenesis, increases peripheral uptake of glucose, and decreases fatty acid oxidation. However, a potential serious complication, defined metformin-associated lactic acidosis (MALA), is related to increased plasma lactate levels, linked to an elevated plasma metformin concentrations and/or a coexistent condition altering lactate production or clearance. The mortality rate for MALA approaches 50% and metformin has been contraindicated in moderate and severe renal impairment, to minimize its potential toxic levels. Nevertheless, metformin prescription or administration, despite the presence of contraindications or precipitating factors for MALA, was a common topic highlighted in all reviewed papers. Routine assessment of metformin plasma concentration is not easily available in all laboratories, but plasma metformin concentrations measured in the emergency room could ensure the correct diagnosis, eliminating metformin as the cause of lactic acidosis if low plasma levels occurred. Renal replacement therapies have been successfully employed to achieve the correction of metabolic acidosis and rapidly remove metformin and lactate, but the optimal treatment modality for MALA is still controversial.
Assuntos
Acidose Láctica/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/efeitos adversos , Insuficiência Renal/etiologia , Acidose Láctica/complicações , Humanos , Hipoglicemiantes/efeitos adversos , Insuficiência Renal/diagnóstico , Insuficiência Renal/terapia , Terapia de Substituição Renal , Fatores de RiscoRESUMO
Sclerostin is a marker of low-turnover bone disease in end stage renal disease patients. The aim of this study was to evaluate serum sclerostin in uremic patients, analyzing its behavior during a single hemodialysis session. Twenty-one adult patients on intermittent hemodialysis treatment were enrolled. Acetate Free Bio-filtration (AFB) was the technique employed. Uremic patients were characterized by higher levels of serum sclerostin when compared with values observed in healthy subjects. Sclerostin assessed in pre-dialysis samples was 1.4 ± 1.02 ng/mL, whereas, in post dialysis samples, a reduction of sclerostin values was observed (0.8 ± 0.6 ng/mL; p: 0.008). Sclerostin correlated with parameters of dialysis adequacy, such as creatinine levels and Kt/V values, and it was significantly associated with atherosclerotic disease. Receiver operating characteristics analysis revealed a good diagnostic profile in identifying atherosclerotic disease. Sclerostin, a full dialyzable substance during AFB dialysis, is closely associated with atherosclerotic disease. Its reduction obtained through AFB could represent a defensive mechanism, improving vascular disease and renal osteodystrophy.
Assuntos
Aterosclerose/metabolismo , Proteínas Morfogenéticas Ósseas/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Falência Renal Crônica/complicações , Diálise Renal/métodos , Uremia , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Aterosclerose/diagnóstico , Aterosclerose/etiologia , Aterosclerose/prevenção & controle , Remodelação Óssea , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/prevenção & controle , Feminino , Marcadores Genéticos , Humanos , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estatística como Assunto , Uremia/complicações , Uremia/etiologia , Uremia/metabolismo , Uremia/terapiaRESUMO
High mobility group box -1 (HMGB1) represents a common causal agent for various types of diseases, including infective pathologies. This study aimed to investigate the role of HMGB1 in ß-thalassemia major (TM) by evaluating its diagnostic and prognostic role. Fifty-one TM patients and 30 healthy subjects (HS) were enrolled. Receiver operating characteristics (ROC) analysis was employed to calculate the area under the curve (AUC) for HMGB1 to determine the best cut-off values capable of identifying infectious episodes. Adjusted risk estimates for infective events were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Serum HMGB1 levels were higher in TM patients than in HS (14·6 ± 8·7 vs. 2·08 ± 0·9 ng/ml, P < 0·0001). Patients who underwent splenectomy were characterized by lower levels of HMGB1, when compared with patients with an intact spleen (10·2 ± 8 vs. 19·1 ± 7 ng/ml, P = 0·004). ROC analyses revealed an AUC for serum HMGB1 of 0·801, with a sensitivity and specificity of 92·3% and 68·2% to detect an infectious episode. Low HMGB1 levels predicted high risk of infective events (HR: 0·81; P = 0·006). HMGB1 represents a prognostic marker for TM patients and a predictive factor for infectious events.
Assuntos
Proteína HMGB1/sangue , Infecções/sangue , Infecções/diagnóstico , Talassemia beta/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Infecções/etiologia , Masculino , Prognóstico , Fatores de Risco , Esplenectomia , Talassemia beta/diagnóstico , Talassemia beta/cirurgiaRESUMO
INTRODUCTION: Endocrinopathies and metabolic disorders-characterized ß thalassemic (ßT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in ßT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. PATIENTS AND METHODS: Seventy-two ßT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan-Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. RESULTS: High ferritin levels were observed in patients with hypothyroidism [1500 (872.5-2336.5) µg/L], hypogonadism [878 (334-2010) µg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367-1857) µg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = -0.64; P:0.0006) and liver (r = -0.40; P:0.03) values was observed. Patients with ferritin values above 1800 µg/L experienced a significantly faster evolution to hypothyroidism [log-rank (χ(2) ):7.7; P = 0.005], hypogonadism [log-rank (χ(2) ):10.7; P = 0.001], and multiple endocrinopathies [log-rank (χ(2) ):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P < 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. CONCLUSIONS: Ferritin represents a prognostic marker for ßT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility of hypothyroidism.
Assuntos
Ferritinas/sangue , Hipogonadismo/diagnóstico , Hipotireoidismo/diagnóstico , Sobrecarga de Ferro/diagnóstico , Osteoporose/diagnóstico , Talassemia beta/diagnóstico , Adolescente , Adulto , Biomarcadores/sangue , Terapia por Quelação , Comorbidade , Feminino , Humanos , Hipogonadismo/epidemiologia , Hipogonadismo/patologia , Hipogonadismo/terapia , Hipotireoidismo/epidemiologia , Hipotireoidismo/patologia , Hipotireoidismo/terapia , Ferro/sangue , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/terapia , Itália/epidemiologia , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Osteoporose/epidemiologia , Osteoporose/patologia , Osteoporose/terapia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Reação Transfusional , Talassemia beta/epidemiologia , Talassemia beta/patologia , Talassemia beta/terapiaRESUMO
AIM: Semaphorin 3A urinary levels represent an early, predictive biomarker of acute kidney injury and positively correlate with albumin-to-creatinine ratio and serum creatinine in hypertensive patients with chronic kidney disease. Our purpose has been to evaluate semaphorin 3A serum levels in a cohort of haemodialysis (HD) patients, the influence of a single HD session on its concentrations, and the potential correlation with clinical and biochemical parameters. METHODS: We enrolled 18 patients receiving HD with Acetate-Free Biofiltration technique and 16 healthy subjects as controls. Peripheral venous blood samples were obtained from patients at different intervals: start of dialysis (pre-HD), middle, and end of the treatment (post-HD). We also collected dialysate samples by the Quantiscan monitoring system (Hospal, Bologna, Italy). RESULTS: Semaphorin 3A was significantly lower in HD patients at baseline compared to controls (median 19.50 (interquartile range 1.00-65.00) versus 97.50 (23.50-161.00) ng/mL, P = 0.0237). A statistically significant reduction was seen during a single HD session (from 19.50 (1.00-65.00) to 0.86 (0.82-4.21) ng/mL, P < 0.0001), with a reduction ratio of 65.92 ± 33.51%. The median concentration in dialysate was 54.00 (15.00-102.00) ng/mL. Pre-HD values were directly related to serum vitamin D (r = 0.872; P = 0.001) and inversely correlated with calcium levels (r = -0.426; P = 0.012) and calcium × phosphate product (r = -0.422; P = 0.0252). CONCLUSION: Semaphorin 3A removal during HD may be clinically relevant due to its involvement in different aspects of cell physiology and in bone remodelling. Semaphorin 3A both inhibits osteoclastic bone reabsorption and increases osteoblastic new bone formation, thus playing a dual osteoprotective role.
Assuntos
Nefropatias/terapia , Diálise Renal , Semaforina-3A/sangue , Idoso , Biomarcadores/sangue , Cálcio/sangue , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Tempo , Resultado do Tratamento , Vitamina D/sangueRESUMO
Human relaxin-2 (hereafter simply defined as "relaxin") is a 6-kDa peptidic hormone best known for the physiological role played during pregnancy in the growth and differentiation of the reproductive tract and in the renal and systemic hemodynamic changes. This factor can also be involved in the pathophysiology of arterial hypertension and heart failure, in the molecular pathways of fibrosis and cancer, and in angiogenesis and bone remodeling. It belongs to the relaxin peptide family, whose members comprehensively exert numerous effects through interaction with different types of receptors, classified as relaxin family peptide (RXFP) receptors (RXFP1, RXFP2, RXFP3, RXFP4). Research looks toward the in-depth examination and complete understanding of relaxin in its various pleiotropic actions. The intent is to evaluate the likelihood of employing this substance for therapeutic purposes, for instance in diseases where a deficit could be part of the underlying pathophysiological mechanisms, also avoiding any adverse effect. Relaxin is already being considered as a promising drug, especially in acute heart failure. A careful study of the different RXFPs and their receptors and the comprehension of all biological activities of these hormones will probably provide new drugs with a potential wide range of therapeutic applications in the near future.
Assuntos
Relaxina/farmacologia , Relaxina/fisiologia , Líquidos Corporais/fisiologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Homeostase , Humanos , Hipertensão/fisiopatologia , Rim/fisiologia , Masculino , GravidezRESUMO
Man is water. When life appeared on earth, the primordial cell had a simple structure and could immediately ascertain from the surrounding aquatic environment the substances for nutrition and oxygen, without any need for structural complexity. As part of evolution, during the transition from aquatic to terrestrial life, vertebrates had to fight against dehydration as well as fish in the sea. In this complex mechanism of osmoregulation, the structure and function of some osmoregulatory hormones have been maintained during the evolution of species, from fish to man. Within the homeostatic mechanism, the renin-angiotensin-aldosterone system (RAAS) is crucial in the regulation of renal reasorption of water and sodium. It is also involved in the regulation of renal plasma flux, blood volume and blood pressure. Vasopressin plays a hormonal function in the mechanisms of water homeostasis acting through Aquaporins (AQP), channel-proteins that allow bi-directional water transport across cell membranes.
Assuntos
Aquaporinas/metabolismo , Água/metabolismo , Animais , Homeostase , Humanos , Osmorregulação , Sistema Renina-AngiotensinaRESUMO
BACKGROUND: Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. METHODS: 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at baseline and after a follow-up period of 18 months. RESULTS: Ghrelin levels were significantly higher in cancer patients than in healthy subjects (573.31 ± 130 vs 320.20 ± 66.48 ng/ml, p < 0.0001), while obestatin (17.42 ± 7.12 vs 24.89 ± 5.54 ng/ml, p < 0.0001) and leptin (38.4 ± 21.2 vs 76.28 ± 17.48 ng/ml, p < 0.0001) values were lower. At ROC analyses the diagnostic profile of ghrelin (AUC 0.962; sensitivity 83%; specificity 98%), obestatin (AUC 0.798; sensitivity 74.5%; specificity 81.5%) and leptin (AUC 0.828; sensitivity 79%; specificity 73%) was superior to that of albumin (AUC 0.547; sensitivity 63%, specificity 69.4%) for detecting cachexia among cancer patients. On Cox multivariate analyses ghrelin (HR 1.02; 95% CI 1.01 - 1.03; p < 0.0001) and leptin (HR 0.94; 95% CI 0.92 - 0.96; p < 0.0001) were significant predictors of death even after correction for other known risk factors such as presence of metastasis and chronic kidney disease. CONCLUSION: Ghrelin and leptin are promising biomarkers to diagnose cachexia and to predict survival in cancer patients.