RESUMEN
SUMMARY: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life. The phytoestrogen genistein at a dose of 54 mg daily in osteopenic postmenopausal women after 2 years implies an improvement on quality of life and depression symptoms. INTRODUCTION: Postmenopausal estrogen decline is implicated in several age-related physical and psychological changes in women, including decreases in perceived quality of life (QoL). A number of trials with hormone therapy showed beneficial effects of the intervention on quality of life parameters. However, because of known or suspected serious side effects of conventional hormone therapy, there is a need for alternatives. METHODS: We conducted a double-blind randomized placebo-controlled trial using the isoflavone genistein, 54 mg, or placebo for 2 years. In this trial, we recruited 262 postmenopausal women aged 49 to 67 years. RESULTS: At baseline, after 1 year, and at final visit, participants filled in the Short Form of 36 questions (SF-36) and the Zung Self-rating Depression Scale (ZSDS). For the placebo group, scores on all dimensions of the SF-36 decreased after 1 and 2 years. The genistein group showed increases on all dimensions of the SF-36 at the end of the study. There were, however, statistically significant differences in changes of scores between the two intervention groups. For the ZSDS, similarly, significant differences were found between groups. CONCLUSION: In conclusion, the findings of this randomized trial showed that genistein improves quality of life (health status, life satisfaction, and depression) in osteopenic postmenopausal women.
Asunto(s)
Enfermedades Óseas Metabólicas/psicología , Depresión/tratamiento farmacológico , Genisteína/uso terapéutico , Fitoestrógenos/uso terapéutico , Calidad de Vida , Anciano , Densidad Ósea/efectos de los fármacos , Enfermedades Óseas Metabólicas/sangre , Enfermedades Óseas Metabólicas/fisiopatología , Depresión/sangre , Método Doble Ciego , Terapia de Reemplazo de Estrógeno , Femenino , Cuello Femoral/fisiopatología , Genisteína/sangre , Humanos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Fitoestrógenos/sangre , Posmenopausia/fisiología , Posmenopausia/psicología , Escalas de Valoración Psiquiátrica , PsicometríaRESUMEN
OBJECTIVE: SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection. PATIENTS AND METHODS: We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization. RESULTS: We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001). CONCLUSIONS: The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.
Asunto(s)
Lesión Renal Aguda , COVID-19 , Insuficiencia Renal Crónica , Masculino , Humanos , Persona de Mediana Edad , Anciano , COVID-19/complicaciones , Estudios Transversales , Interleucina-6 , SARS-CoV-2 , Riñón/fisiología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiologíaRESUMEN
OBJECTIVE: Chronic kidney disease (CKD) and ocular disease share several cardiovascular risk factors as well as pathogenetic mechanisms having Renin-Angiotensin-Aldosterone System (RAAS) as main actor. Moreover, kidney and eyes have common genetic and embryonic origin. In this literature review, we present main evidence supporting this association for early identifying diseases affecting both systems and evaluating potential multi-target therapeutic strategies. MATERIALS AND METHODS: We performed a literature review of the current peer-reviewed English-language randomized controlled studies (RCTs), reference lists of nephrology or ophthalmology textbooks, review articles and relevant studies with ocular or eye and kidney or renal diseases as keywords until March 2020. Prospective and retrospective studies as well as meta-analyses and latest systematic reviews were included. RESULTS: We evaluated a total of 683 records, finally selecting 119 articles related to ocular and renal diseases. Records were divided into two areas: chronic and acute kidney disease and ocular or eye diseases. Some of the examined studies were discarded for population biases/intervention or deemed unfit. CONCLUSIONS: Based on our results, we conclude that there is evidence of a clear association between kidney and eye diseases, being this cross-link mainly based on RAAS dysregulation. Our review suggests that it may be useful to screen CKD patients for associated ocular diseases, such as cataract, glaucoma, diabetic retinopathy and age-related macular degeneration. A comprehensive study of CKD and proteinuric patients should include careful eye examination. Renal impairment in young patients should prompt a search for ocular disease, such as TUNA syndrome or oculo-renal syndrome, in particular if family history of concurrent ocular and renal disease is present. Anti-RAAS agents are mostly recommended in patients with renal and ocular impairment.
Asunto(s)
Retinopatía Diabética , Glaucoma , Degeneración Macular , Insuficiencia Renal Crónica , Humanos , Sistema Renina-Angiotensina/fisiologíaRESUMEN
OBJECTIVE: Arterial hypertension (AH) represents a major risk factor for cardiovascular disease and is associated to several complications, such as prolonged corrected QT (QTc) interval and impaired heart rate variability (HRV). Secondary causes of AH include autosomal dominant polycystic kidney disease (ADPKD) and atherosclerotic renal artery stenosis (ARAS), both known to be related to arrhythmic risk and autonomic imbalance. The aim of the study is to evaluate whether global autonomic activity and QTc interval differently affect ADPKD and ARAS hypertensive patients. PATIENTS AND METHODS: An observational study was performed on 59 patients: 16 ADPKD patients and 19 diagnosed with ARAS, compared to 24 healthy controls (HC). All patients underwent clinical evaluation, biochemical lab tests, 24-hour electrocardiogram (ECG) and renal Doppler ultrasound. HRV was assessed through the analysis of 24-hour ECG to detect standard deviation of normal-to-normal RR intervals (SDNN). QTc interval was defined as prolonged when > 440 msec. RESULTS: SDNN was significantly lower in ADPKD and ARAS patients than HC (p < 0.0001) and no significant differences were found between ADPKD and ARAS patients (p > 0.05). QTc was found significantly higher in ARAS patients than HC (p = 0.001) and in ARAS patients than ADPKD patients (p = 0.004). CONCLUSIONS: The pathogenesis of hypertension in ADPKD and ARAS patients is related to the activation of the renin angiotensin aldosterone system (RAAS). In ADPKD, cyst enlargement leads to kidney ischemia and renin release, associated to endothelial dysfunction, low nitric oxide and sympathetic tone activation. Differently, reduction in renal perfusion pressure activates RAAS and renal adrenergic nerves in ARAS patients. We can speculate that prolonged QTc interval is more present in ARAS vs. ADPKD hypertensive patients due to a greater activation of RAAS. We suggest adding 24-hour HRV evaluation in association with traditional risk factors in course of ADPKD and ARAS hypertension to better stratify cardiovascular risk in these groups of patients.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Hipertensión/fisiopatología , Riñón Poliquístico Autosómico Dominante/fisiopatología , Obstrucción de la Arteria Renal/fisiopatología , Adulto , Anciano , Aterosclerosis/patología , Estudios de Casos y Controles , Electrocardiografía , Femenino , Humanos , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Riñón Poliquístico Autosómico Dominante/complicaciones , Obstrucción de la Arteria Renal/complicaciones , Renina/metabolismo , Sistema Renina-Angiotensina/fisiología , Factores de Riesgo , Ultrasonografía DopplerRESUMEN
BACKGROUND AND AIM: Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women. METHODS AND RESULTS: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone (n=71) or placebo (n=67), daily. Both arms received calcium and vitamin D(3) in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group. CONCLUSIONS: After 3-years of treatment, genistein aglycone plus calcium, vitamin D(3) and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Genisteína/farmacología , Homocisteína/sangre , Carbonato de Calcio/administración & dosificación , Colecalciferol/administración & dosificación , Femenino , Estudios de Seguimiento , Genisteína/efectos adversos , Humanos , Resistencia a la Insulina , Lípidos/sangre , Persona de Mediana Edad , Osteoprotegerina/sangre , Posmenopausia , Proyectos de Investigación , Factores de RiesgoRESUMEN
Kidney diseases are associated with many cardiovascular risk factors, such as anaemia, inflammation and chronic volume overload. Changes in the sympathovagal balance are common findings in patients with end-stage renal disease (ESRD). In particular, sympathetic hyperactivity is linked with an increase in resting heart rate leading to myocardial hypertrophy and fibrosis. The latter increases the risk of sudden cardiac death from fatal arrythmias and therefore assessment of both sympathetic and parasympathetic tones could be clinically relevant in ESRD patients. Heart rate variability and other indices are currently used to evaluate the functionality of the autonomic nervous system. Some of these have emerged as potential diagnostic tools that can support clinical decision-making processes and therapeutic strategies in patients with renal disease, including those who are on dialysis replacement therapy. In this review, we summarize the impact and the relationships between sympathovagal disturbances and kidney diseases, replacement therapies and transplantation.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/terapia , Enfermedades Renales/terapia , Frecuencia Cardíaca , Humanos , Diálisis RenalRESUMEN
OBJECTIVE: Non-invasive positive pressure ventilation (NIV) is now an indispensable safeguard in the management of many pathologies. However, sometimes the positive end-expiratory pressure (PEEP) showed harmful effects on renal function, although effects on renal hemodynamic are unclear. We aimed at evaluating the effects of NIV on renal and endothelial function, in patients with chronic or acute respiratory failure. PATIENTS AND METHODS: We performed a longitudinal, prospective, interventional study. We enrolled 17 hospitalized and non-hospitalized patients (11 males) with indication to NIV and stable hemodynamic parameters. Patients were treated with NIV and followed up at T0, at T1 (at the end of the NIV cycle) and at T2 (fifteen days after). RESULTS: 17 patients (11 males) with a mean age of 71.94 ± 14.89 years were enrolled. A significant increase in flow mediated dilation (FMD) was found (p = 0.004). We showed a significant improvement, after NIV, in the values of pH (p = 0.0002), pCO2 (p = 0.0001), pO2 (p = 0.04), lactates (p = 0.04), sO2 (p = 0.02) and in the P/F Ratio (p = 0.004). We also showed a significant reduction of serum glucose (p = 0.01) and a significant increase of serum chlorine (p = 0.047), while we did not report a significant increase of creatinine (p = 0.297) or a significant change in diuresis. CONCLUSIONS: In our study NIV has no significant effects on renal function in patients with respiratory failure. Probably these patients required low PEEP values, which were less harmful to lung parenchyma and not effective on systemic hemodynamic. Furthermore, NIV has improved endothelial function in the short term, likely by reducing oxidative stress, as improvements of the gas-analysis parameters showed. Therefore, NIV could help to reduce cardiovascular risk of patients improving endothelial function.
Asunto(s)
Ventilación no Invasiva , Insuficiencia Respiratoria/metabolismo , Anciano , Femenino , Humanos , Pruebas de Función Renal , Masculino , Estrés Oxidativo , Insuficiencia Respiratoria/terapia , Función VentricularRESUMEN
OBJECTIVE: Coronary artery disease is one of the first causes of death in the Western world; for this reason, it is essential to identify new, systemic, non-invasive and low-cost cardiovascular risk markers. The acute coronary syndrome includes ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI), based on ECG findings. We aimed to evaluate Renal Resistive Index (RRI) as a marker of cardiovascular risk and assess the associations with other cardiovascular risk factors (metabolic indexes, mineral metabolism disorders and endothelial dysfunction and atherosclerosis markers) in STEMI and NSTEMI patients. PATIENTS AND METHODS: Clinical, laboratory and instrumental examinations as metabolic and inflammation indexes, markers of atherosclerosis and endothelial dysfunction (renal function, mineral metabolism disorders, inflammation indexes, Intima Media Thickness (IMT), Ankle Brachial Pressure Index, Left Ventricular Mass Index, Relative Wall Thickness) were performed. RESULTS: Eighty-one patients with STEMI and NSTEMI were enrolled. We showed a significant positive correlation between RRI and age (p<0.01), intact parathyroid hormone (p<0.01) and IMT (p<0.01), as well as a significant negative correlation between RRI and body surface area (BSA) (p=0.02), estimated Glomerular Filtration Rate (eGFR) (p<0.01), serum calcium (p<0.01) and 25-hydroxy-vitamin D (p=0.03). Moreover, we found a significant correlation between RRI and male patients (p<0.01), coronary artery disease history (CAD) (p=0.049), hypertension (p=0.025) and left ventricular eccentric hypertrophy (LVEH) (p=0.047). CONCLUSIONS: Our study showed an association between RRI and the main traditional and non-traditional cardiovascular risk factors involved in atherosclerosis pathogenesis, such as age, BSA, hypertension, male sex, CAD history, mineral metabolism disorders and LVEH, in patients with preserved renal function. Moreover, we found a significant correlation between RRI and eGFR, suggesting that RRI could be useful in the evaluation of both renal function and progression of renal damage, even in an early stage with a conserved or only slightly reduced kidney function. We also showed a significant correlation with some markers of systemic atherosclerosis such as IMT and LVEH. For a more precise assessment of prognosis and cardiovascular risk in patients with high cardiovascular mortality, we suggest performing a systematic RRI evaluation, considering the non-invasive nature of the procedure, its reproducibility, easy execution, and low costs.
Asunto(s)
Síndrome Coronario Agudo/metabolismo , Pruebas de Función Renal , Enfermedades Metabólicas/metabolismo , Síndrome Coronario Agudo/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Femenino , Humanos , Masculino , Enfermedades Metabólicas/patología , Persona de Mediana EdadRESUMEN
UNLABELLED: This study aimed at evaluating the effects of genistein (54 mg/die) on calcaneus and phalanges ultrasound (QUS) parameters and bone mineral density in osteopenic postmenopausal women. We concluded that genistein prevented bone loss in the osteopenic postmenopausal women and improves QUS parameters at the calcaneus and phalanges. INTRODUCTION: The purpose of the study was to evaluate the effects of genistein (54 mg/die) on quantitative ultrasound (QUS) parameters of the calcaneus and hand phalange and on bone mineral density (BMD) in osteopenic postmenopausal women. METHODS: One hundred thirty-eight women (age 49-67 years) were assigned to receive genistein or placebo. Bone status was assessed by measuring the anteroposterior lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry and by ultrasound of the calcaneus (Achilles Plus, GE, Lunar) and of the phalanges (Bone Profiler. IGEA) at baseline and after a 1- and 2-year treatment. RESULTS: At the end of the experimental period, genistein had significantly increased BMD in the femur and lumbar spine (p < 0.001). The stiffness index, amplitude-dependent speed of sound, and bone transmission time in the genistein group had increased significantly at the end of study (+5.3, p < 0.001; +3.6%, p < 0.001; +4.6, p < 0.001, respectively). CONCLUSIONS: This study confirms that genistein prevented bone loss in the osteopenic postmenopausal women and it improves the QUS parameters.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Genisteína/uso terapéutico , Osteoporosis Posmenopáusica/tratamiento farmacológico , Absorciometría de Fotón , Anciano , Conservadores de la Densidad Ósea/sangre , Calcáneo/diagnóstico por imagen , Calcáneo/fisiopatología , Femenino , Cuello Femoral/fisiopatología , Falanges de los Dedos de la Mano/diagnóstico por imagen , Falanges de los Dedos de la Mano/fisiopatología , Genisteína/sangre , Humanos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/sangre , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/fisiopatología , UltrasonografíaRESUMEN
Secondary hyperparathyroidism is a complex metabolic alteration secondary to chronic kidney disease (CKD). Reduction of 1,25(OH)2D3 synthesis is the first derangement, followed by an increase in PTH, and, lastly, calcium and phosphate modifications. Vitamin D is a hormone whose actions take place through a specific receptor, the vitamin D receptor (VDR), which is ubiquitous. Accordingly, heterogeneous biological effects can be added to the classical effects on mineral bone metabolism. In the pathophysiology of secondary hyperparathyroidism, an important role is also played by alterations of calcium transport, which is under the control of two receptors: VDR and CaSR (calcium-sensing receptor). The expression of these receptors is reduced during CKD. Recent findings have allowed to identify a new hormonal system, the FGF23-Klotho axis, that integrates the old and simple, but now inadequate, PTH-Vit D axis. FGF23 is a circulating factor produced by osteocytes that inhibits renal phosphate reabsorption and 1-alpha-hydroxylase activity. As such, FGF23 is involved in phosphate homeostasis and its serum levels increase along with the progression of CKD. Interestingly, FGF23 has very low affinity for its receptor and requires the activity of Klotho, an anti-aging gene, to become active. These new actors allow us to identify a bone-kidney axis, whose real physiological importance is still under evaluation.
Asunto(s)
Factores de Crecimiento de Fibroblastos/sangre , Glucuronidasa/sangre , Hiperparatiroidismo Secundario/fisiopatología , Biomarcadores/sangre , Calcio/sangre , Enfermedad Crónica , Factor-23 de Crecimiento de Fibroblastos , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/enzimología , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/metabolismo , Enfermedades Renales/complicaciones , Proteínas Klotho , Hormona Paratiroidea/sangre , Fosfatos/sangre , Receptores de Calcitriol/sangre , Receptores Sensibles al Calcio/sangreRESUMEN
Exposure of the skin to sunlight is now considered the most important source of vitamin D in Western countries. It is presumed to contribute approximately two thirds of the total requirement, leaving the remaining one third to the few foods naturally rich in this vitamin. In the skin, vitamin D is synthesized as a cholesterol chain which undergoes structural modifications following exposure to UVB rays. Once produced in the skin or absorbed in the gut as cholecalciferol, vitamin D enters the blood to be transported by a specific vitamin D binding protein, which is synthesized in the liver and has a powerful buffering capacity. The transport system carries the metabolites to the sites of further activation (25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney), ultimately resulting in the production of calcitriol. This last compound, now regarded as a hormone, circulates freely in minimal amounts and, compared with the other metabolites, shows the highest affinity for the vitamin D receptor (VDR). The mechanism of VDR activation is rather complex, resulting in either stimulation or inhibition of protein synthesis. Importantly, besides its presence in parathyroid, bone, kidney and intestine, this receptor has been demonstrated in several tissues, where its stimulation results in a reduced proliferation rate and increased differentiation. Accordingly, vitamin D is now regarded as a complex hormonal system, involved not only in the regulation of divalent ions and bone, but also in the proliferation and differentiation of numerous cell types with potential involvement in several diseases like cancer, immune diseases, diabetes, hypertension and heart failure.
Asunto(s)
Vitamina D/fisiología , HumanosRESUMEN
OBJECTIVE: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a heterogeneous inherited disease characterized by renal and extrarenal manifestations with progressive fluid-filled cyst development leading to end-stage renal disease. Our aim was to evaluate the prevalence of obstructive urological disease in ADPKD patients and possible associations with endothelial dysfunction, nutritional, metabolic and inflammatory markers. PATIENTS AND METHODS: The study included ADPKD patients and control group, who carried out uroflowmetry, an assessment of renal function, metabolic and nutritional parameters and an evaluation of endothelial dysfunction and atherosclerotic markers, such as Renal Resistive Index (RRI), Intima-Media Thickness (IMT) and Flow-Mediated Dilation (FMD). RESULTS: We enrolled 37 ADPKD patients (20 males with 51.0 ± 14.3 years) and 34 control group (18 males with 60.7 ± 14.4 years). We showed a significant reduction in Max Flow Rate (Qmax) (p ≤ 0.001), age (p = 0.006), FMD (p = 0.023) and Voiding Volume (p = 0.053), in addition to a significant increase in Voiding Time and Diastolic Blood Pressure (p ≤ 0.001, p = 0.049; respectively) in ADPKD patients with respect to control group. Moreover, we found a negative correlation between Qmax and creatinine (r= -0.44, p = 0.007), RRI (r= -0.49, p ≤0.001) and intact Parathyroid Hormone (r = -0.329, p = 0.046), while we found a positive correlation between Qmax and MDRD (r = 0.327, p = 0.048) and between Voiding Time and serum uric acid (r= 0.34, p = 0.039) in ADPKD patients with respect to control group. CONCLUSIONS: In our study, we showed an elevated prevalence of urological functional diseases in ADPKD patients; therefore, we suggest to include uroflowmetry in the assessment of these patients, considering the non-invasiveness, repeatability and low cost of the exam. An early intervention could slow down the progression of renal damage and an early screening of the main cardiovascular risk factors could reduce the high morbidity and mortality in ADPKD patients.
Asunto(s)
Fallo Renal Crónico/etiología , Riñón Poliquístico Autosómico Dominante/fisiopatología , Reología/métodos , Enfermedades Urológicas/fisiopatología , Adulto , Anciano , Aterosclerosis/metabolismo , Biomarcadores/sangre , Enfermedades Cardiovasculares/prevención & control , Grosor Intima-Media Carotídeo/estadística & datos numéricos , Estudios de Casos y Controles , Estudios Transversales , Progresión de la Enfermedad , Diagnóstico Precoz , Endotelio/fisiopatología , Femenino , Humanos , Riñón/fisiopatología , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Riñón Poliquístico Autosómico Dominante/sangre , Riñón Poliquístico Autosómico Dominante/complicaciones , Prevalencia , Reología/economía , Ácido Úrico/sangre , Enfermedades Urológicas/diagnóstico , Enfermedades Urológicas/epidemiologíaRESUMEN
Advanced glycation end products (AGE) increase as a consequence of diabetic hyperglycemia and, in nephropathic patients, following renal function loss. Protein-bound AGE behave as immunogens, inducing formation of specific antibodies (Ab-AGE). In this work AGE immunogenicity was studied in 42 diabetic patients, 26 nephropathic patients on hemodialysis and 26 patients with end-stage renal disease who underwent kidney transplantation and in 20 normal subjects. Non-oxidation-derived AGE (nox-AGE), oxidation-derived AGE (ox-AGE) and Ab-AGE were measured by competitive or direct enzyme-linked immunosorbent assay (ELISA) and circulating immune complexes (CIC) by C1q ELISA. Nox- AGE increased significantly in all patient groups (p < or = 0.05 to < or = 0.0001) except in patients on hemodialysis for less than 6 yr. Ox-AGE were only significantly increased in patients transplanted more than 3 yr previously (p < 0.05). Ab-AGE were significantly lower than controls in both diabetic groups and in patients on hemodialysis for more than 6 yr (p < 0.005 to < 0.0001) and not unlike controls in the other groups. These results demonstrate that hemodialysis or renal transplantation can, initially, reduce either nox- or ox-AGE levels, which however go back to being high in time. Renal transplantation fails to normalize nox-AGE. More importantly, plasma Ab-AGE levels are reduced or unchanged in all patient groups in comparison with controls, despite higher circulating AGE levels. This suggests the importance of tissue-bound AGE as Ab-AGE targets. Additional interventions are needed to control AGE levels in treated nephropathic patients. The search and quantification of specific Ab-AGE would give more meaningful results if performed over specific tissue specimens.
Asunto(s)
Diabetes Mellitus/inmunología , Glomerulonefritis Membranosa/inmunología , Productos Finales de Glicación Avanzada/inmunología , Trasplante de Riñón/inmunología , Diálisis Renal , Adulto , Anciano , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Femenino , Glomerulonefritis Membranosa/genética , Glomerulonefritis Membranosa/terapia , Productos Finales de Glicación Avanzada/genética , Humanos , Fallo Renal Crónico/genética , Fallo Renal Crónico/inmunología , Trasplante de Riñón/tendencias , Masculino , Persona de Mediana Edad , Diálisis Renal/tendencias , Factores de TiempoRESUMEN
BACKGROUND: Recent guidelines for the management of hypertension by the European Societies of Hypertension and Cardiology (ESH-ESC), consider, besides normal and normal high blood pressure, also early renal failure as a significant factor scoring the individual cardiovascular (CV) risk in each patient. Considering that the nephrologists have not yet adopted a similar system to score CV risk in renal failure, we believed reasonable to evaluate whether the ESH-ESC guidelines were applicable to renal patients and to what extent useful to estimate the CV risk in chronic renal disease. PATIENTS AND METHODS: According to the above-mentioned guidelines, CV risk score was evaluated in 386 ambulatory patients (212 M/174 F; aged 53 +/- 15 years) with the following clinical diagnosis: hypertension (n=48), lithiasis (n=49), chronic renal failure (n=182), transplantation (n=61) and dialysis (n=46). RESULTS: We obtained a "no score" group and five progressive risk classes graded from 1 to 5. Infact thirthyfour cases were not scored because of "optimal" blood pressure control, whilst the remaining 352 averaged a score of 3.9 +/- 1.1 ("high" CV risk condition). In these, all the scores were present and the distribution of cases evidenced a prevailing of score 4 and 5 in chronic renal failure (19 and 52% of the cases, respectively) and in transplantation (26% and 39%), but not in hypertension and lithiasis. In dialysis, only score 4 and 5 (35% and 59% respectively) occurred, while 4 cases (6%) were not scored due to "optimal" blood pressure values. Target organ damage, acquired clinical conditions, modifiable and non-modifiable risk factors had all a positive correlation with the risk score. CONCLUSIONS: Our study suggests that ESH-ESC guidelines for the management of hypertension can be used to obtain a global CV risk score also in chronic kidney diseases, with the exception of dialysis. In chronic renal failure, the risk of underestimating the real incidence of future CV events might be overcome, at least partially, by the possibility of highlighting in individual patients the concomitance of risk factors requiring a very early preventive and aggressive therapy.
Asunto(s)
Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Adhesión a Directriz , Hipertensión/complicaciones , Hipertensión/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Sensitivity and specificity of the most widely employed techniques of parathyroid glands localization, namely echography and scintigraphy, are mostly obtained with short-term follow-up data and do not underline the existence of a methodological problem. As a matter of fact, both methods identify only pathological glands, with no "normal" results; therefore "true negatives" cannot be obtained. Aim of our study was to compare, by means of a statistically appropriate approach, the results of echography, scintigraphy and surgery with the data obtained after a mid term follow-up period, enabling us to discover all parathyroid glands. METHODS: Twenty six consecutive dialysis patients (14M/12F; age 50+/-12 years) underwent echography and scintigraphy immediately before a total parathyroidectomy with autotransplantation and were followed-up for 6 months to recognize all the existing glands (PTH levels and scintigraphy). RESULTS: Total identified glands were: 73 by scintigraphy, 86 by echography, 99 by surgery and 103 by follow-up data. The concordance indexes (K0) between the number of glands effectively present in the individual patient (follow-up data) and those identified with each method were rather low with scintigraphy (0.071) and echography (0.218), and acceptable (0.578) with surgery. The number of patients correctly classified was: 9/26 (34,6%) with scintigraphy, 13/26 (50%) with echography and 22/26 (85%) with surgery. Finally, the number of wrongly identified glands (from zero to three) in each patient was similar with scintigraphy (65,4%) and echography (50%) and significantly better with surgery (15,6%; p<0.01). CONCLUSIONS: The most reliable technique to identify parathyroid glands in uremic subjects is surgery, nonetheless a meticulous clinical follow-up is necessary to recognize all of them.
Asunto(s)
Hiperparatiroidismo Secundario/cirugía , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Paratiroidectomía , Uremia/complicaciones , Adulto , Interpretación Estadística de Datos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Cintigrafía , Pertecnetato de Sodio Tc 99m , Tecnecio Tc 99m Sestamibi , Factores de Tiempo , UltrasonografíaRESUMEN
The existence of proteins with bone morphogenetic properties has been suggested for many years to explain the calcifying effect observed, with bone extracts, in ectopic tissues in vivo. Subsequently, at least thirty different proteins (identified as Bone Morphogenetic Proteins, BMPs) with this capacity have been discovered. The osteogenic activity of these substances is evident from the early phases of embryogenesis. However, besides bone, these proteins have been shown to affect other tissues too, where they affect cellular functions like proliferation, differentiation and apoptosis. They act through a specific receptor system partly shared with TGF-beta; in fact, they have been shown to inhibit TGF-beta actions. BMP-7 in particular is of vital importance in embryogenesis through its actions on bone, kidney and eyes, while in adulthood it is mainly expressed in the kidney, where specific receptors have been localized. BMP-7 has been successfully employed, for therapeutic purposes, in several animal models of nephropathies, where the most striking result is the constant reduction of fibrosis. Moreover, BMP-7 has been used successfully in experimental models of renal osteodystrophy and of vascular calcification. To date the only available human data are those obtained in orthopedy where BMP-7 has been successfully employed to induce the healing of pathologic fractures. Clinical data in nephropathic patients are therefore warranted to rule out the true value of this, very interesting, new molecule.
Asunto(s)
Proteínas Morfogenéticas Óseas/fisiología , Enfermedades Renales/etiología , Proteína Morfogenética Ósea 7 , HumanosRESUMEN
The aim of this study was to evaluate in a 24-weeks the effect of anti-TNF-alpha, infliximab, on cytogenetic biomarkers in peripheral lymphocytes of patients with rheumatoid arthritis (RA). A total of 40 patients with RA met the criteria to be treated with methotrexate (15 mg/week) were evaluated. Twenty patients, randomly selected, were treated with infliximab in addition to methotrexate (group I), whereas the other 20 patients continued with only methotrexate treatment (group M). Twenty healthy volunteers matched for age, gender and smoking habits served as control group (group C). At baseline, sister chromatid exchange rate was 7.20 ± 2.21 in group I, 7.40 ± 1.60 in group M and 4.97 ± 1.32 in group C (P < 0.01 vs group I and M). After 24-weeks, sister chromatid exchange rate was 7.87 ± 2.54 in group I and 7.81 ± 1.95 in group M (P = ns). High frequency cells count was 4.9 % and 4.7 % in the groups I and M, respectively, at the end of the study (P = ns). The basal chromosomal aberration frequency was 4.90 % in group I and 5.20 % in groups M; after 24-weeks, this was 5.10 % in group I and 5.10 % in groups M (P = ns). Infliximab treatment, for 24 weeks, did not increase the cytogenetic biomarkers in patients with RA. Our data show that the use of infliximab has not a genotoxic effect in patients with RA.
RESUMEN
Alkaline phosphatase (ALP) activity was used as a novel histomorphometric index of osteoblastic surfaces involved in mineralization. The enzyme cytochemical reaction was done on sections of low temperature processed, glycol methacrylate (GMA) embedded bone biopsies from 39 patients with various types of renal osteodystrophy (age 48 +/- 12 yrs; 19 males, 20 females) who had received tetracycline labelling. Sets of three serial sections were obtained from each tissue block: the 1st section (2 microns thick) was stained with Methylene blue Azure 11 for morphology; the 2nd section (2 microns thick) was used for ALP cytochemistry; the 3rd section was left unstained for UV microscopy. ALP positive osteogenic cells on bone surfaces displayed either of two distinct morphologies: a) typical plump, 'active' osteoblasts, and b) flat, elongated cells otherwise indistinguishable from 'bonelining cells'. These ALP+ flat cells were in contact with sites of active osteoid and mineral deposition and also codistributed with tetracycline labels outside of, and in continuity with, osteoid seams. Flat lining cells which were ALP negative were never associated with labels. Therefore, ALP activity also provided an objective criterion for differentiating two different 'phenotypes' among flat bone lining cells (ALP+ and ALP-), associated or not associated with matrix mineralization, respectively. The following histomorphometric variables were measured: Ob.S/BS, OS/BS, MS/BS and ALP.S/BS. Ob.S/BS, OS/BS and MS/BS were different in different types of ROD. However, OS/BS always exceeded MS/BS which, in turn, always exceeded Ob.S/BS. ALP.S/BS exceeded OS/BS in controls, mixed ROD and hyperparathyroidism, whereas the reverse occurred in osteomalacia and aplastic bone, due to the abundance of ALP lining cells over nonmineralizing surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Osteoblastos/ultraestructura , Adulto , Anciano , Fosfatasa Alcalina/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/complicaciones , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/patología , Femenino , Fluorescencia , Histocitoquímica , Humanos , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/patología , Masculino , Persona de Mediana Edad , Osteoblastos/enzimología , Osteomalacia/complicaciones , Osteomalacia/patología , TetraciclinaRESUMEN
Alkaline phosphatase (ALP) activity is a new histomorphometric index of the extent of osteoblastic surfaces involved in mineralization. To assess its validity in the evaluation of bone formation, we carried out a comparative study between histomorphometric values obtained on the basis of the extent of tetracycline labeling and of the length of ALP-positive endosteal surfaces. The following variables were compared (indicated by ALP when based on the extent of ALP positivity): trabecular mineralizing surface (MS/BS vs. ALP.S/BS); osteoid mineralizing surface (MS/OS vs. ALP.S/OS); bone formation rate (BFR/BS vs. ALP.BFR/BS); and adjusted appositional rate (Aj.AR vs. ALP.Aj.AR). Bone biopsies from 39 patients with chronic renal failure and different types of renal osteodystrophy were considered (48 +/- 12 years of age; 19 men and 20 women). Patients were double labeled with tetracycline and biopsies were embedded in glycol-methacrylate at +4 degrees C. Patients showed various types of renal osteodystrophy and were assigned to different groups of pathologies. Although it differed in incidence according to the different groups, ALP activity was found in typical plump osteoblasts bordering osteoid seams and in flat cells, either in contact with osteoid or along the quiescent surfaces of bone in continuity with it. Tetracycline codistributed with all these features to variable extents, according to groups. In all patients, however, ALP.S/BS and ALP.S/OS respectively exceeded MS/BS and MS/OS. In consequence of this, ALP.BFR/BS and ALP.Aj.AR were greater than BFR/BS and Aj.AR, respectively. For each of the variable considered, differences among groups of patients with different types of renal osteodystrophy were highly significant. Good correlations were found between the variables measured with the two methods.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Fosfatasa Alcalina/metabolismo , Desarrollo Óseo/fisiología , Ilion/metabolismo , Osteoblastos/enzimología , Tetraciclina/química , Adulto , Fosfatasa Alcalina/sangre , Biopsia , Calcificación Fisiológica , Calcinosis/fisiopatología , Calcio/sangre , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/fisiopatología , Femenino , Histocitoquímica , Humanos , Hiperparatiroidismo Secundario/fisiopatología , Ilion/fisiología , Procesamiento de Imagen Asistido por Computador , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Osteoblastos/citología , Osteocalcina/sangre , Osteomalacia/fisiopatología , Hormona Paratiroidea/sangre , Fosfatos/sangreRESUMEN
1,24(R)(OH)2D3 is a synthetic analogue of 1,25(OH)2D3 which binds to the same receptors as the physiologic metabolite with a lower affinity. The aim of the present study was to compare the activity of 1,24(R)(OH)2D3 and 1,25(OH)2D3 on several target organs in patients with chronic renal failure. Treatment with 1,24(R)(OH)2D3 at doses of either 1 or 2 micrograms daily was carried out in two groups of 9 patients, with serum creatinine of 4.61 +/- 1.59 and 4.66 +/- 1.46 mg/dl, respectively. Doses of 1,25(OH)2D3 were 0.5 and 1 microgram daily and were administered to 9 and 13 patients, serum creatinine of 4.52 +/- 1.67 and 4.3 +/- 1.16 mg/dl, respectively. Treatment periods were of 2 weeks. Administration of 1,25(OH)2D3, 1 microgram, induced significant increments of intestinal calcium absorption (ICA), ionized calcium, osteocalcin, serum creatinine, urine Ca/GFR, and a decrease in iPTH. 1,25(OH)2D3, 0.5 microgram, induced a significant increase in ICA and osteocalcin and a decrease in iPTH. Similarly 1,24(OH)2D3, 2 micrograms daily, significantly stimulated ICA and raised serum levels of osteocalcin and creatinine while lowering serum iPTH. In addition, 1,24(R)(OH)2D3 administration induced a significant fall of serum 1,25(OH)2D3. Following 1 microgram, only osteocalcin increased. Therefore, the dose of 2 micrograms of 1,24(R)(OH)2D3 has biologic activity similar to 0.5 microgram 1,25(OH)2D3 (4:1). However the activity ratio on osteocalcin production appears to be 2:1. In addition, 1,24(R)(OH)2D3 is able to inhibit renal tubular 1 alpha-hydroxylase. In conclusion 1,24(R)(OH)2D3 may prove to be useful in the treatment of metabolic bone disease.