RESUMEN
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.
Asunto(s)
Acidosis Láctica/inducido químicamente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/efectos adversos , Insuficiencia Renal/etiología , Acidosis Láctica/complicaciones , Humanos , Hipoglucemiantes/efectos adversos , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/terapia , Terapia de Reemplazo Renal , Factores de RiesgoRESUMEN
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.
Asunto(s)
Aterosclerosis/metabolismo , Proteínas Morfogenéticas Óseas/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/metabolismo , Fallo Renal Crónico/complicaciones , Diálisis Renal/métodos , Uremia , Proteínas Adaptadoras Transductoras de Señales , Anciano , Aterosclerosis/diagnóstico , Aterosclerosis/etiología , Aterosclerosis/prevención & control , Remodelación Ósea , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/prevención & control , Femenino , Marcadores Genéticos , Humanos , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estadística como Asunto , Uremia/complicaciones , Uremia/etiología , Uremia/metabolismo , Uremia/terapiaAsunto(s)
Linfoma de Células B Grandes Difuso/radioterapia , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía de Emisión de Positrones , Prednisona/uso terapéutico , Rituximab/administración & dosificación , Vincristina/uso terapéuticoRESUMEN
The use of glucose-lowering drugs in advanced stage diabetic nephropathic patients should be done very carefully. Some drugs are contraindicated or not recommended. The same insulin needs a dose reduction to avoid dangerous hypoglycemia. For some years the use of inhibitors of the DDP-4 has been approved in T2DM patients with CKD III and IV stage, proposing the use without limitations even in case of ESRD. We conducted a prospective observational study of a cohort of 60 patients with T2DM and CKD stage IV, selecting a sample of 15 patients taking an inhibitor of DPP-4 and comparing it with those who took therapy "old" drugs, despite having similar characteristics of CKD. In both groups, we found: 1) the effectiveness of therapy, through the assessment of glycated hemoglobin and glycemic profile; 2) the possible occurrence of "hypoglycemia", "side effects", accelerating the progression of CKD. No patients being treated with inhibitors of DPP-4 have experienced hypoglycemia, or adverse events, or adverse effects on the progression of CKD. The glycated hemoglobin, revealed more stability than the comparison group. Hypoglycaemic episodes were present only in the group receiving intensive insulin. Although kidneys and their dose, in case of high degree of CKD, primarily eliminate inhibitors of DPP-4, with some exceptions, should be reduced, in our experience they have proven beneficial drugs in diabetics with kidney disease, being effective and well tolerated in the case of ESRD, where the only treatment option was represented by insulin.
RESUMEN
Cancer anorexia-cachexia syndrome (CACS) is the most frequent paraneoplastic syndrome occurring in half of all oncologic patients and is considered as a poor prognosticator. Patients usually present with weight loss, lipolysis, muscle wasting, anorexia, chronic nausea, inflammation, and asthenia. The etiopathogenesis of CACS is still poorly understood, although several factors and biological pathways are known to be involved. Because of the complexity of this multifactorial condition, a single agent therapy may not be sufficient. Indeed, there is a tendency toward an integrated multiple approach including nonpharmacological and pharmacological treatments. However, despite encouraging preliminary results, currently there is not enough evidence to support a change in clinical practice. This review provides a brief and practical summary of the diagnosis, pathogenesis, and treatment of CACS. Future perspectives will also be discussed.
Asunto(s)
Caquexia/etiología , Síndromes Paraneoplásicos/etiología , Animales , Caquexia/diagnóstico , Caquexia/metabolismo , Caquexia/terapia , Terapia Combinada , Modelos Animales de Enfermedad , Humanos , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/metabolismo , Síndromes Paraneoplásicos/terapia , PronósticoRESUMEN
Apelin regulates angiogenesis, stimulating endothelial cell proliferation and migration. It is upregulated during tumor angiogenesis, and its overexpression was reported to increase tumor growth. Furthermore, apelin controls vasopressin release and body fluid homeostasis. The aim of this study was to examine the correlations between apelin expression and clinical outcomes in oncologic patients, such as cancer disease progression and patient's survival. Apelin levels were evaluated in a cohort of 95 patients affected by different varieties of cancer. Partial remission and stable disease were assigned to the 'no progression' group, comparing it with the progressor group. Patients were followed up for 2 years. Receiver operating characteristics analysis was employed for identifying the progression of the oncologic disease and Kaplan-Meier curves assessed the survival. Adjusted risk estimates for progression endpoint were calculated using Cox proportional hazard regression analysis. Oncologic patients had higher apelin levels compared with healthy subjects, and apelin was closely related to the stages of the disease. In the hyponatremia group, apelin values were significantly higher than patients with eunatremia. After the follow-up of 24 months, 41 patients (43%) reached the endpoint. Progressor subjects presented significantly increased apelin values at baseline compared with non-progressor. Univariate followed by multivariate Cox proportional hazard regression analysis showed that apelin predicted cancer progression independently of other potential confounders. In patients with cancer, apelin closely reflects the stage of the disease and represents a strong and independent risk marker for cancer progression.
Asunto(s)
Biomarcadores de Tumor/genética , Hiponatremia/diagnóstico , Péptidos y Proteínas de Señalización Intercelular/genética , Neoplasias/diagnóstico , Insuficiencia Renal/diagnóstico , Anciano , Apelina , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Expresión Génica , Humanos , Hiponatremia/complicaciones , Hiponatremia/genética , Hiponatremia/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias/complicaciones , Neoplasias/genética , Neoplasias/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Insuficiencia Renal/complicaciones , Insuficiencia Renal/genética , Insuficiencia Renal/mortalidad , Riesgo , Análisis de SupervivenciaRESUMEN
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.
Asunto(s)
Caquexia/sangre , Caquexia/diagnóstico , Ghrelina/sangre , Leptina/sangre , Neoplasias/sangre , Anciano , Área Bajo la Curva , Biomarcadores/sangre , Caquexia/etiología , Caquexia/mortalidad , Estudios de Casos y Controles , Colesterol/sangre , Diabetes Mellitus/sangre , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias/complicaciones , Neoplasias/mortalidad , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Curva ROC , Albúmina Sérica/metabolismo , Tasa de SupervivenciaRESUMEN
Few studies address alteration of sexual function in women with diabetes and chronic kidney disease (CKD). Quality of life surveys suggest that discussion of sexual function and other reproductive issues are of psychosocial assessment and that education on sexual function in the setting of chronic diseases such as diabetes and CKD is widely needed. Pharmacologic therapy with estrogen/progesterone and androgens along with glycemic control, correction of anemia, ensuring adequate dialysis delivery, and treatment of underlying depression are important. Changes in lifestyle such as smoking cessation, strength training, and aerobic exercises may decrease depression, enhance body image, and have positive impacts on sexuality. Many hormonal abnormalities which occur in women with diabetes and CKD who suffer from chronic anovulation and lack of progesterone secretion may be treated with oral progesterone at the end of each menstrual cycle to restore menstrual cycles. Hypoactive sexual desire disorder (HSDD) is the most common sexual problem reported by women with diabetes and CKD. Sexual function can be assessed in women, using the 9-item Female Sexual Function Index, questionnaire, or 19 items. It is important for nephrologists and physicians to incorporate assessment of sexual function into the routine evaluation protocols.
RESUMEN
Several studies indicate a relationship between hypovitaminosis D, survival, vascular calcification and inflammation. In addition to its central role in the regulation of bone mineral metabolism, vitamin D also contributes to other systems, including the immune, cardiovascular and endocrine systems. Vitamin D analogs reduces proteinuria, in particular through suppression of the renin-angiotensin-aldosterone system (RAAS) and exerts anti-inflammatory and immunomodulatory effects. In particular vitamin D deficiency contribute to an inappropriately activated RAAS, as a mechanism for progression of chronic kidney disease (CKD) and/or cardiovascular disease. Human and sperimental models of CKD showed that vitamin D may interact with B and T lymphocytes and influence the phenotype and function of the antigen presenting cells and dendritic cells, promoting properties that favor the induction of tolerogenic T regulators rather than T effectory. Interstitial fibrosis may be prevented through vitamin D supplementation. Renal myofibroblast, an activated fibroblast with expression of a molecular hallmark α-smooth muscle actin (α-SMA), is generally considered the principal matrix-producing effector cells that are responsible for the excess production of extracellular matrix (ECM) components in the fibrotic tissues. It turns out that calcitriol effectively blocks myofibroblast activation from interstitial fibroblasts, as evidenced by suppression of TGF-ß1-mediated α-SMA expression.
Asunto(s)
Progresión de la Enfermedad , Insuficiencia Renal Crónica/patología , Deficiencia de Vitamina D/sangre , Vitamina D/fisiología , Animales , Humanos , Riñón/metabolismo , Riñón/patología , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Sistema Renina-Angiotensina/fisiología , Vitamina D/administración & dosificación , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiologíaRESUMEN
BACKGROUND: Ultrafiltration failure and peritonitis are the most important limitations of peritoneal dialysis (PD). The aim of our study was to evaluate peritoneum damage through neutrophil gelatinase-associated lipocalin (NGAL), white blood cell (WBC) count and cancer antigen 125 (CA125). PATIENTS AND METHODS: Thirty patients with peritonitis and 30 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were studied for 12 months. In the peritonitis group, blood samples and peritoneal fluid (lp) were collected before the onset of peritonitis, at the onset of peritonitis (T1) and every day until its resolution. CAPD patients were divided into 3 groups according to the treatment received. Long-dwell effluents were collected for NGAL, WBC count and Ca125 assessment. RESULTS: In the peritonitis group, at time T1, NGAL levels were higher compared with baseline values. lpNGAL levels decreased at least 24 hours earlier than peritoneal WBC (lpWBC). At ROC analysis, lpNGAL was characterized by a very good diagnostic profile identifying treatment failure. In CAPD patients, the highest NGAL values were observed in the icodextrin group. An inverse correlation between lpNGAL, pKt/V and peritoneal ultrafiltration volume was also found. CONCLUSION: Mesothelial cells have an active role in the structural and functional alteration of the peritoneum during PD, and NGAL represents a valid biomarker for peritoneum evaluation.
Asunto(s)
Proteínas de Fase Aguda/análisis , Líquido Ascítico/química , Antígeno Ca-125/análisis , Lipocalinas/análisis , Diálisis Peritoneal Ambulatoria Continua , Peritoneo , Peritonitis/metabolismo , Proteínas Proto-Oncogénicas/análisis , Adulto , Anciano , Antibacterianos/uso terapéutico , Área Bajo la Curva , Líquido Ascítico/microbiología , Biomarcadores/análisis , Cefazolina/uso terapéutico , Ceftazidima/uso terapéutico , Femenino , Humanos , Recuento de Leucocitos , Lipocalina 2 , Masculino , Persona de Mediana Edad , Peritoneo/efectos de los fármacos , Peritoneo/patología , Peritonitis/tratamiento farmacológico , Curva ROC , Insuficiencia del TratamientoRESUMEN
PURPOSE: To evaluate the utility of serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) in depicting an event of contrast material-induced nephropathy (CIN) in patients who received iodinated contrast media, gadoterate meglumine, or radiopharmaceutical technetium-99m ((99m)Tc) and to evaluate the protective effect exerted by isotonic saline infusion, sodium bicarbonate administration, or N-acetylcysteine administration. MATERIALS AND METHODS: Institutional ethics committee approval was given, and informed consent was obtained. One hundred twenty patients were enrolled in a prospective study and divided into three groups: iomeprol group, magnetic resonance (MR) imaging group (gadoterate meglumine), and renal scintigraphy group ((99m)Tc). They randomly received N-acetylcysteine, physiologic saline, or sodium bicarbonate. Receiver operating characteristic (ROC) analysis, Kaplan-Meier curves, and Cox proportional hazard regression analysis were used. RESULTS: In the MR imaging and renal scintigraphy groups, there were significant changes in serum creatinine and NGAL levels, and there were no cases of CIN. In the iomeprol group, an early rise in NGAL was found, while serum creatinine level changes occurred 24 hours after contrast material administration. At ROC analysis, NGAL showed high sensitivity and specificity (serum NGAL: area under the curve, 0.995; 95% confidence interval [CI]: 0.868, 0.992; urinary NGAL: area under the curve, 0.992; 95% CI: 0.925, 1.000) in identifying CIN 8 hours after iomeprol administration. Regression analysis showed that NGAL independently predicted CIN. Administration of N-acetylcysteine, sodium bicarbonate, or physiologic saline did not influence NGAL level. CONCLUSION: NGAL depicted CIN in patients who received iodinated contrast material within 8 hours of contrast material administration. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120578/-/DC1.
Asunto(s)
Diagnóstico por Imagen/efectos adversos , Yopamidol/análogos & derivados , Enfermedades Renales/inducido químicamente , Lipocalinas/sangre , Meglumina/efectos adversos , Compuestos Organometálicos/efectos adversos , Radiofármacos/efectos adversos , Acetilcisteína/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Medios de Contraste/efectos adversos , Creatinina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Gelatinasas/sangre , Tasa de Filtración Glomerular , Humanos , Yopamidol/efectos adversos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Sensibilidad y Especificidad , Bicarbonato de Sodio/administración & dosificación , Cloruro de Sodio/administración & dosificaciónRESUMEN
This study was designed to assess a protective effect of palmitoylethanolamide (PEA) in the development of inflammation after ischemia-reperfusion injury of the kidney. Moreover, to suggest a possible mechanism, renal ischemia-reperfusion was performed in mice with targeted disruption of peroxisome proliferator-activated receptor α (PPAR-α) gene (PPAR-αKO) to explain whether the observed PEA effect was dependent on PPAR-α pathway. Peroxisome proliferator-activated receptor-αKO and littermate wild-type controls (PPAR-αWT) were subjected to bilateral renal artery occlusion (30 min) and reperfusion (6 h) and received PEA (10 mg/kg i.p.) 15 min before release of clamps. Serum and urinary indicators of renal dysfunction and tubular and reperfusion injury were measured, specifically serum urea, creatinine, aspartate aminotransferase and γ-glutamyl transferase, and creatinine clearance. In addition, renal sections were used for histological scoring of renal injury and for immunologic evidence of nitrotyrosine formation, poly[adenosine diphosphate-ribose] (PAR), and adhesion molecules expression. The oxidative stress-sensitive nuclear factor κB signaling pathway was also investigated by Western blot analysis. Kidney myeloperoxidase activity and malondialdehyde levels were measured for assessment of polymorphonuclear leukocyte cell infiltration and lipid peroxidation, respectively. Apoptotic mechanisms were also investigated. Moreover, the infiltration and activation of mast cells were explored. In vivo, PEA administration during ischemia significantly reduced the increase in (i) creatinine, γ-glutamyl transferase, aspartate aminotransferase; (ii) nuclear translocation of nuclear factor κB p65; (iii) kidney myeloperoxidase activity and malondialdehyde levels; (iv) nitrotyrosine, PAR, and adhesion molecules expression; (v) the infiltration and activation of mast cells; and (vi) apoptosis. Our results clearly demonstrate that PEA significantly attenuated the degree of renal dysfunction, injury, and inflammation caused by ischemia-reperfusion injury. Moreover, the positive effects of PEA were at least in part dependent on PPAR-α pathway.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Endocannabinoides/farmacología , Etanolaminas/farmacología , Riñón/lesiones , Riñón/metabolismo , Ácidos Palmíticos/farmacología , Daño por Reperfusión/tratamiento farmacológico , Amidas , Animales , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/genética , Moléculas de Adhesión Celular/biosíntesis , Moléculas de Adhesión Celular/genética , Regulación de la Expresión Génica , Riñón/patología , Leucocitos/metabolismo , Leucocitos/patología , Ratones , Ratones Noqueados , PPAR alfa/genética , PPAR alfa/metabolismo , Poli Adenosina Difosfato Ribosa/genética , Poli Adenosina Difosfato Ribosa/metabolismo , Daño por Reperfusión/sangre , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Tirosina/análogos & derivados , Tirosina/genética , Tirosina/metabolismo , gamma-Glutamiltransferasa/sangre , gamma-Glutamiltransferasa/genéticaRESUMEN
The aim of this study was to investigate the effects of apocynin, a NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase inhibitor, in diabetic rats with nephropathy induced by contrast medium (CIN). Diabetes was induced in male Wistar rats by a single dose of streptozotocin (60 mg/kg i.v.). Animals were then divided into the following groups: 1) control group (diabetic rats treated i.v. with saline solution); 2) iomeprol group (iomeprol at 10 ml/kg was injected i.v. 30 min after saline administration); 3) apocynin group (identical to the iomeprol group, except for pre-treatment with apocynin 5mg/kg i.v., 30 min before iomeprol injection) and 4) N-acetylcysteine group (NAC) (same as iomeprol group, except for the treatment with NAC 20 mg/kg i.v. 30 min before iomeprol injection). CIN in animals were assessed 24h after administration of iomeprol. Apocynin significantly attenuates the impaired glomerular function, concentration of Na(+), K(+), alpha glutathione S-transferase levels in urine and neutrophil gelatinase-associated lipocalin levels in plasma caused by iomeprol. In kidney, immunohistochemical analysis of some inflammatory mediators, such as nitrotyrosine, poly-ADP-ribosyl polymerase, tumor necrosis factor-α, interleukin-1ß as well as apoptosis (evaluated as terminal deoxynucleotidyltransferase-mediated UTP end labeling assay) revealed positive staining in tissue obtained from iomeprol group. These parameters were markedly reduced in animals treated with apocynin. Similarly, these parameters were also markedly modified by NAC pre-treatment. Here, we have shown that apocynin attenuates the degree of iomeprol-induced nephropathy in diabetic rats.
Asunto(s)
Acetofenonas/farmacología , Acetilcisteína/farmacología , Medios de Contraste/efectos adversos , Nefropatías Diabéticas/inducido químicamente , Nefropatías Diabéticas/prevención & control , Inhibidores Enzimáticos/farmacología , NADPH Oxidasas/antagonistas & inhibidores , Proteínas de Fase Aguda/orina , Animales , Apoptosis/efectos de los fármacos , Citosina/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Activación Enzimática/efectos de los fármacos , Glutatión Transferasa/orina , Yopamidol/análogos & derivados , Yopamidol/farmacología , Isoenzimas/orina , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/metabolismo , Glomérulos Renales/patología , Lipocalina 2 , Lipocalinas/orina , Masculino , Poli(ADP-Ribosa) Polimerasas/metabolismo , Potasio/sangre , Proteínas Proto-Oncogénicas/orina , Ratas , Ratas Wistar , Sodio/sangre , Factores de Tiempo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
The aim of this study was to investigate the effects of glutamine in an in vivo rat model of renal ischemia/reperfusion (I/R) injury. Male Wistar rats underwent bilateral renal pedicle clamping for 45 min followed by reperfusion for 6 h. Glutamine (1.5 mg/kg) was administered intraperitoneally (i.p.) 15 min prior to reperfusion. Plasma concentrations of urea, creatinine, γ-glutamyl transferase (γ-GT), and aspartate aminotransferase (AST) were measured for the assessment of renal function and reperfusion injury. Markers of oxidative stress, expression of the pro-inflammatory mediators inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), AT-1 expression, and changes in the oxidative stress-sensitive nuclear factor kappa B (NF-κB) signaling pathway were measured to investigate whether glutamine can reduce the renal dysfunction. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear (PMN) cell infiltration and lipid peroxidation, respectively. Renal sections were used for histologic grading of renal injury and for immunohistochemical localization of nitrotyrosine and poly(ADP-ribose) synthetase (PARS). In vivo, glutamine significantly reduced the increase in urea, creatinine, γ-GT, AST, produced by renal ischemia/reperfusion (I/R), suggesting an improvement in both renal function and injury. Glutamine significantly reduced iNOS and NF-κB, kidney MPO activity and MDA levels, indicating a reduction in PMN infiltration and lipid peroxidation, respectively. Glutamine reduced the histological evidence of renal damage associated with I/R and caused a substantial reduction in the staining for nitrotyrosine and PARS, suggesting reduced nitrosative and oxidative stress. Moreover, glutamine attenuated the reduction of COX-2 expression and prevented the increased AT-1 expression after I/R. Our results suggest that glutamine reduces the renal dysfunction and injury associated with I/R of the kidney.
Asunto(s)
Glutamina/uso terapéutico , Riñón/irrigación sanguínea , Nefritis/prevención & control , Daño por Reperfusión/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Modelos Animales de Enfermedad , Glutamina/administración & dosificación , Inmunohistoquímica , Riñón/enzimología , Riñón/inmunología , Riñón/patología , Pruebas de Función Renal , Masculino , Nefritis/enzimología , Nefritis/inmunología , Nefritis/patología , Ratas , Ratas Wistar , Daño por Reperfusión/enzimología , Daño por Reperfusión/inmunología , Daño por Reperfusión/patologíaRESUMEN
Glutamine is the most abundant amino acid in the bloodstream. It is important in nucleotide synthesis, is anti-catabolic, has anti-oxidant properties via metabolism to glutathione, may enhance immune responsiveness and possesses immunoregulatory functions. Moreover, it reduces atrophy of intestinal mucosa in animals on total parenteral nutrition and prevents intestinal mucosal injury accompanying small bowel transplantation, chemotherapy and radiation. In the present study, we investigated the effects of glutamine on development of non-septic shock caused by zymosan. Mice received either zymosan (500 mg/kg, administered i.p., as a suspension in saline) or vehicle (saline). Glutamine (1.5 mg/kg i.p.) was administered 1 and 6h after zymosan administration. Organ failure and systemic inflammation in mice were assessed 18 h after administration of zymosan and/or glutamine. Glutamine-treatment reduced the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan-injection and also attenuated the pancreatic and gut injury. Inflammatory and apoptotic parameters were evaluated to better investigate the effects of the glutamine-administration. So, by immunohistochemical analysis and in vitro assays, we have clearly showed that glutamine reduces: 1) the histological damage in pancreas and gut; 2) the inducible nitric oxide synthase expression; 3) nitrotyrosine and poly (ADP-ribose) formation; 4) TNF-α and IL-1ß tissue and plasma levels; 5) FasL localization; and 6) alteration of the balance between Bax and Bcl-2. In addition, at the end of the observation period (7 days), zymosan causes severe illness in the mice characterized by a systemic toxicity, significant loss of body weight and mortality. Glutamine-treatment significantly reduced all these parameters.
Asunto(s)
Glutamina/farmacología , Insuficiencia Multiorgánica/inducido químicamente , Insuficiencia Multiorgánica/tratamiento farmacológico , Zimosan/administración & dosificación , Zimosan/toxicidad , Animales , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Citocinas/biosíntesis , Activación Enzimática/efectos de los fármacos , Proteína Ligando Fas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Glutamina/administración & dosificación , Glutamina/uso terapéutico , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Insuficiencia Multiorgánica/metabolismo , Insuficiencia Multiorgánica/patología , Infiltración Neutrófila/efectos de los fármacos , Óxido Nítrico/biosíntesis , Cavidad Peritoneal/patología , Poli Adenosina Difosfato Ribosa/biosíntesis , Poli(ADP-Ribosa) Polimerasas/metabolismo , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Tirosina/análogos & derivados , Tirosina/biosíntesis , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: Glutamine is an important substrate for critical cells of the immune system, in particular lymphocytes and macrophages, and it is considered a conditionally essential amino acid. Several studies have indicated that glutamine-enriched total parenteral nutrition improves immunologic status and shortens length of stay of critically ill patients. We investigated the effect of total parenteral nutrition supplemented with glutamine on the immune system in anorectic patients. METHODS: Thirty-six anorectic patients were randomized to receive standard parenteral nutrition or parenteral nutrition supplemented with glutamine 0.18 g kg(-1) d(-1) for 20 d. To evaluate the immune system status, we determined serum levels of neopterin and insulin growth factor-1 and lymphocyte count at baseline and after 10 and 20 d from the beginning of the therapy. RESULTS AND CONCLUSIONS: The results showed a significant increase of the serum levels of neopterin after 10 d of treatment with glutamine (26.44 +/- 3.08 versus 6.75 +/- 1.73 nmol/L, P < 0.001), thus proving a probable stimulating action carried out by glutamine on the immune system, as testified by the increase of lymphocytes.
Asunto(s)
Anorexia/terapia , Glutamina/uso terapéutico , Neopterin/sangre , Nutrición Parenteral , Adolescente , Adulto , Anorexia/sangre , Anorexia/inmunología , Suplementos Dietéticos , Femenino , Glutamina/administración & dosificación , Glutamina/farmacología , Humanos , Recuento de Linfocitos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Adulto JovenRESUMEN
The aim of the present study was to evaluate levels of neutrophil gelatinase-associated lipocalin (NGAL), a stress protein increased after renal and systemic stimuli, in a cohort of 15 patients with severe proteinuria secondary to idiopathic membranous nephropathy and conserved renal function. Neutrophil gelatinase-associated lipocalin levels and the fractional excretion of this protein were higher in patients than in healthy controls. Furthermore, a close correlation was found between serum NGAL and urinary (uNGAL) (r = 0.81; P < 0.01) and between uNGAL and daily proteinuria (r = 0.44; P < 0.03). One hour after infusion of a single high-dose bolus of intravenous immunoglobulin (0.4 g/kg), a new and promising therapy for several kidney diseases, a marked reduction was found in NGAL levels (serum NGAL 194.1 +/- 121 vs 370.1 +/- 180.5 ng/mL, P < 0.05; urinary NGAL 153.3 +/- 108.6 vs 502.2 +/- 293.4 ng/mL, P < 0.03); this was maintained 24 hours after the treatment. The findings made suggest that the NGAL balance is altered in patients with severe proteinuria who have not yet developed overt chronic renal failure, thus confirming the potential use of this protein as an early biomarker of kidney damage preceding the increase in serum creatinine levels. Furthermore, also extra-renal cells (neutrophils, endothelium) may hyper-release NGAL, expressing systemic stress related to severe proteinuria. This would explain the impressive decrease occurring in NGAL values after intravenous immunoglobulin infusion, thus providing further evidence of the antiinflammatory properties of this particular therapeutic approach and indicating the possible value of NGAL measurement in monitoring the efficacy of treatment of renal diseases.
Asunto(s)
Proteínas de Fase Aguda/análisis , Inmunoglobulinas Intravenosas/uso terapéutico , Lipocalinas/análisis , Proteinuria/metabolismo , Proteínas Proto-Oncogénicas/análisis , Proteínas de Fase Aguda/orina , Adulto , Anciano , Femenino , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/metabolismo , Humanos , Lipocalina 2 , Lipocalinas/sangre , Lipocalinas/orina , Masculino , Persona de Mediana Edad , Proteinuria/tratamiento farmacológico , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/orinaRESUMEN
The Short Form-36 Health Survey (SF-36) questionnaire is designed to measure the patient's functional capacity and well-being. It was created to reach a compromise between lengthy investigation methods and one dimensional, overly simple tools for measuring quality of life (QoL). In 1987, the psychiatrist Robert Cloninger proposed a psycho-biological model hinged upon three principal and independent dimensions of the human personality: novelty seeking (NS), harm avoidance (HA) and reward dependence (RD), linked with dopaminergic, serotoninergic and noradrenergic activity, respectively. According to Cloninger, each dimension is the expression of the integration of a hereditary condition, characterized by biologic substrates, in response to specific environmental stimuli. We furthermore searched for any interference between the SF-36 scores and plasmatic dopamine, serotonin and noradrenaline concentrations, in an attempt to identify eventual correlations between the condition of the patients, their subjective QoL evaluation and neurohormonal plasmatic equilibrium. We compared results obtained from healthy subjects with populations of patients in different periods of their clinical existence: patients on hemodialysis; with a functioning transplantation; with renal graft function loss; returning to dialysis after graft loss and two years after restarting hemodialysis.
Asunto(s)
Monoaminas Biogénicas/sangre , Modelos Neurológicos , Personalidad , Calidad de Vida , Encuestas y Cuestionarios , Uremia/psicología , Estudios de Casos y Controles , Dopamina/sangre , Rechazo de Injerto/metabolismo , Rechazo de Injerto/psicología , Indicadores de Salud , Humanos , Trasplante de Riñón/psicología , Norepinefrina/sangre , Diálisis Renal/psicología , Serotonina/sangre , Uremia/metabolismo , Uremia/terapiaRESUMEN
Renal damage, which can be caused by gestational anomalies such as pre-eclampsia, carries a risk of gestational complications; the greatest risk being in women who become pregnant while on hemodialysis or peritoneal dialysis. If this rare event occurs, there is a marked increase in the risk of pre-eclampsia, early uterine contractions and hydramnios, hypertensive crisis, preterm delivery and intrauterine growth retard. Furthermore, newborns are almost always of low birthweight. Patients who undergo renal transplantation are another high-risk category. In such cases, the pregnancy itself can compromise the success of the transplant and the immunosuppressive therapy correlated to it can become a threat to the course of the pregnancy and normal fetal growth. Therefore, in view of the lack of appropriate guidelines for the best possible approach to the treatment of women on dialysis or of those with a renal transplantation, it is best to advise these patients against becoming pregnant and/or to provide a valid counselling service illustrating the extreme difficulties and dangers involved in becoming pregnant.
Asunto(s)
Complicaciones del Embarazo/patología , Uremia/patología , Femenino , Humanos , Recién Nacido , Trasplante de Riñón , Diálisis Peritoneal , Embarazo , Complicaciones del Embarazo/terapia , Diálisis Renal , Uremia/terapiaRESUMEN
Hypophosphatemia is an unusual cause of acute respiratory distress syndrome (ARDS). We describe a hypophosphatemia-related ARDS case report of a 50-year-old woman with ACTH dependent Cushing's syndrome secondary to ectopic CRH production. The patient clinically showed hypotension tachypnea and increasing dyspnea. Laboratory data showed carbohydrate intolerance, severe hypokalemia, and hypophosphatemia. Arterial blood gases measurement revealed hypocapnia and elevation in bicarbonate values. Chest X-ray showed diffuse bilateral alveolar infiltrates similar to acute pulmonary edema and Kerley's striae. Chest CT scan evidenced diffuse ground glass opacification, bilateral patchy consolidation, and fibrosis, compatible with the recovery phase of ARDS. Clinical symptoms and laboratory examinations supported the diagnosis of ARDS. The patient was managed with supplemental potassium, octreotide, and oxygen therapy. Hypophosphatemia was managed by treating the underlying disorder. Successive surgical removal of the adrenal gland led to complete resolution of Cushing's syndrome. In conclusion, although rare and associated with specific risk factors, hypophosphatemia should be suspected in patients who develop unexplained ARDS.