Asociación entre el polimorfismo rs2032487 del gen de la cadena pesada de la miosina no muscular tipo IIA (MHY9) y la enfermedad renal crónica secundaria a diabetes tipo 2 en población de las Islas Canarias / Association between polymorphism rs2032487 in the non-muscle myosin heavy chain IIA gene (MHY9) and chronic kidney disease secondary to type 2 diabetes mellitus in a population of the Canary Islands

Introducción: Ciertos polimorfismos de los genes de la miosina no muscular de tipo IIA (MYH9) y de la apolipoproteína L1 (APOL1) se han asociado con la enfermedad renal crónica (ERC) en distintas poblaciones. Este estudio evaluó la asociación entre los polimorfismos rs2032487 de MYH9 y rs73885319 de APOL1 con la ERC avanzada asociada a diabetes tipo 2 en una población de Gran Canaria. Material y métodos: Los polimorfismos se genotiparon en 152 pacientes con ERC avanzada (filtrado glomerular estimado [FGe] < 30 ml/min/1,73 m2) secundaria a diabetes tipo 2, 110 pacientes con diabetes tipo 2 con evolución ≥ 20 años sin ERC avanzada (FGe ≥ 45 ml/min/1,73 m2 y ausencia de proteinuria) y 292 hemodonantes sanos de más de 50 años sin ERC ni diabetes. Resultados: La frecuencia del alelo de riesgo de rs2032487 fue de 10,7% entre pacientes con diabetes y ERC avanzada, 7,1% en aquellos con diabetes sin ERC avanzada y 6,1% en los sujetos sanos, alcanzándose diferencias significativas entre el primer y el tercer grupo (P = 0,015). El 78,5% de los sujetos con ERC avanzada eran homocigotos para el alelo protector, frente al 87,9% en los otros dos grupos (P = 0,015 y P = 0,016, respectivamente). La frecuencia del alelo de riesgo del polimorfismo rs73885319 no superó el 0,5% en ninguno de los tres grupos. Conclusiones: Estos datos sugieren que el polimorfismo rs2032487 se asocia con la ERC avanzada asociada a diabetes tipo 2 en la población de Gran Canaria

Introduction: Certain polymorphisms in the non-muscle myosin IIA (MYH9) and apolipoprotein L1 (APOL1) genes have been associated to chronic kidney disease (CKD) in different populations. This study examined the association between the MHY9 rs2032487 and APOL1 rs73885319 polymorphisms and advanced CKD related to type 2 diabetes mellitus (T2DM) in a population of Gran Canaria (Canary Islands, Spain). Patients and methods: Polymorphisms were genotyped in 152 patients with advanced CKD (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) secondary to T2DM, 110 patients with T2DM onset ≥ 20 years before without advanced CKD (eGFR ≥ 45 mL/min/1.73 m2 and no proteinuria), and 292 healthy blood donors over 50 years of age without CKD or diabetes. Results: The frequency of the risk allele for rs2032487 was 10.7% in patients with diabetes and advanced CKD, 7.1% in those with diabetes but without advanced CKD, and 6.1% in healthy subjects, with significant differences between the first and third groups (P = .015). Among subjects with advanced CKD, 78.5% were homozygous for the protective allele, as compared to 87.9% in the other two groups (P = .015 and P = .016 respectively). The frequency of the risk allele for the rs73885319 polymorphism did not exceed 0.5% in any of the three groups. Conclusions: These data suggest that polymorphism rs2032487 is associated to advanced CKD related to T2DM in the population of Gran Canaria

Association between polymorphism rs2032487 in the non-muscle myosin heavy chain IIA gene (MHY9) and chronic kidney disease secondary to type 2 diabetes mellitus in a population of the Canary Islands. / Asociación entre el polimorfismo rs2032487 del gen de la cadena pesada de la miosina no muscular tipo IIA (MHY9) y la enfermedad renal crónica secundaria a diabetes tipo 2 en población de las Islas Canarias.

INTRODUCTION: Certain polymorphisms in the non-muscle myosin IIA (MYH9) and apolipoprotein L1 (APOL1) genes have been associated to chronic kidney disease (CKD) in different populations. This study examined the association between the MHY9 rs2032487 and APOL1 rs73885319 polymorphisms and advanced CKD related to type 2 diabetes mellitus (T2DM) in a population of Gran Canaria (Canary Islands, Spain). PATIENTS AND METHODS: Polymorphisms were genotyped in 152 patients with advanced CKD (estimated glomerular filtration rate [eGFR]<30mL/min/1.73 m2) secondary to T2DM, 110 patients with T2DM onset ≥ 20 years before without advanced CKD (eGFR ≥ 45mL/min/1.73 m2 and no proteinuria), and 292 healthy blood donors over 50 years of age without CKD or diabetes. RESULTS: The frequency of the risk allele for rs2032487 was 10.7% in patients with diabetes and advanced CKD, 7.1% in those with diabetes but without advanced CKD, and 6.1% in healthy subjects, with significant differences between the first and third groups (P=.015). Among subjects with advanced CKD, 78.5% were homozygous for the protective allele, as compared to 87.9% in the other two groups (P=.015 and P=.016 respectively). The frequency of the risk allele for the rs73885319 polymorphism did not exceed 0.5% in any of the three groups. CONCLUSIONS: These data suggest that polymorphism rs2032487 is associated to advanced CKD related to T2DM in the population of Gran Canaria.

Relationship between Anemia and Serum Concentrations of Calcium and Phosphorus in Advanced Non-Dialysis-Dependent Chronic Kidney Disease.

BACKGROUND/AIMS: Different biochemical abnormalities of metabolic bone disease have been associated with anemia of chronic kidney disease (CKD), mainly in hemodialysis patients. However, all of these abnormalities are closely inter-related and their individual effect on the development of anemia is uncertain. This study was aimed to assess the relationship between anemia and a set of metabolic bone disease biomarkers in a cohort of adult patients with advanced non-dialysis-dependent CKD. METHODS: The sample consisted of 382 patients submitted to a Nephrology Unit for evaluation of advanced CKD in a tertiary hospital from Gran Canaria during 3 years. Associations between anemia and serum levels of calcium (albumin-corrected), phosphorus, PTH, 25-hydroxivitamin D (25(OH)D3) and alkaline phosphatase were analyzed by using logistic regression models with adjustment for other demographic, clinical and biochemical covariates potentially related to anemia and to bone mineral metabolism. RESULTS: Serum levels of calcium and 25(OH)D3 (negatively) and phosphorus (positively) were significantly associated with anemia in an unadjusted logistic regression model. In a fully adjusted multivariable model, the OR for anemia was 0.29 (95% CI 0.16-0.49; p < 0.0001) for every 1 mg/dl increase in serum calcium and 2.19 (95% CI 1.55-3.15; p < 0.001) for every 1 mg/dl increase in serum phosphorus. Female sex and lower serum albumin levels were also independently associated with anemia. The inclusion of albumin in the adjusted model displaced the significance of 25(OH)D3. CONCLUSIONS: Circulating levels of calcium and phosphorus are strongly linked to anemia in patients with advanced non-dialysis CKD.

Prevalence and determinants of the metabolic syndrome among subjects with advanced nondiabetes-related chronic kidney disease in Gran Canaria, Spain.

BACKGROUND: The relationship between the metabolic syndrome and mild chronic kidney disease (CKD) has been extensively studied. This study was aimed to estimate the prevalence and factors associated with the metabolic syndrome among subjects with advanced stages of nondiabetes-related CKD. METHODS: Study population was composed of incident patients with advanced CKD not related to diabetes in a tertiary hospital from Gran Canaria (Spain) since February 2011 to December 2014. Participants fulfilled a survey questionnaire and underwent physical examination and biochemical evaluation. RESULTS: The sample was composed of 167 subjects (mean age 63.9 ± 13.7 years; estimated glomerular filtration rate 21.9 ± 6.6 mL/min/1.73 m(2)). The prevalence of the metabolic syndrome was 68.9% (65.2% in men and 73.3% in women). Highest rates were observed in groups with chronic interstitial nephropathy (80%), CKD of uncertain etiology (76.7%) and CKD related to vascular causes (76.2%). Subjects with metabolic syndrome were older, had higher values of C-reactive protein and more often reported to have first-degree relatives with diabetes and to be physically inactive. In multivariate analyses, age (OR: 1.034 [CI 95%: 1.004-1.065]; p = 0.024) and family history of diabetes (OR: 2.550 [1.159-5.608]; p = 0.020) were independently associated with the metabolic syndrome. CONCLUSIONS: The prevalence of the metabolic syndrome among subjects with advanced nondiabetes-related CKD is high, and greater than that observed in general Canarian population of similar age groups. Age and family history of diabetes are the two factors more strongly associated with the metabolic syndrome in this population.

The specific relationship between vitamin D deficiency and diabetic nephropathy among patients with advanced chronic kidney disease: a cross-sectional study in Gran Canaria, Spain.

AIMS: Vitamin D deficiency is highly prevalent in subjects with advanced chronic kidney disease (CKD), but diabetes, the most common cause of CKD, has also been linked to low levels of serum 25-hydroxyvitamin D [25(OH)D]. We compare vitamin D status between subjects with type 2 diabetes-related advanced CKD and subjects with either advanced CKD without diabetes or type 2 diabetes without advanced CKD. METHODS: Subjects were patients with advanced CKD (estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2) from February 2011 to November 2013 (113 with diabetes-related CKD and 80 without diabetes) and 61 patients with long-lasting type 2 diabetes without advanced CKD, simultaneously enrolled from our center. Participants fulfilled a survey questionnaire and underwent physical examination, blood samples, and 24-h urine collection. Kidney disease was assessed using eGFR and 24-h urinary protein excretion. Serum 25(OH)D was measured by chemiluminescence immunoassay. RESULTS: The prevalence of vitamin D deficiency (25(OH)D < 20 ng/mL) was 70.8% in subjects with diabetes-related CKD, 38.8% in subjects with non-diabetic CKD and 41% in subjects with diabetes without advanced CKD. Adjusted means (95% confidence interval (CI)) of 25(OH)D in participants with diabetes-related CKD, in nondiabetic participants with CKD, and in participants with diabetes without advanced CKD were, respectively, 17.5 (14.2 - 20.7), 23.6 (19.4 - 27.8), and 23.5 (16.8 - 30.3) ng/mL (p = 0.023). CONCLUSIONS: Low vitamin D status is characteristically associated with advanced diabetic nephropathy. This relationship is not entirely attributable to the individual effects of CKD or long-lasting diabetes.

Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis.

RATIONALE: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. OBJECTIVES: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. METHODS: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21-45 Hz) was investigated (n = 13 pairs + 4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n = 15). RESULTS: In the resting state, there was a significant condition × frequency interaction (p = 0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21-27 Hz] and increased low gamma [27-45 Hz]). There was also a condition × frequency × location interaction (p = 0.006), such that the reduction in 21-27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27-45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r = 0.429, p = 0.042). In the motor task, there was a main effect of THC to increase 65-130-Hz ERS (p = 0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85-130-Hz band (p = 0.02) and not the 65-85-Hz band. CONCLUSIONS: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state.

Factores clínicos y farmacológicos relacionados con los requerimientos de fotocoagulación láser en pacientes con nefropatía diabética secundaria a diabetes mellitus tipo 2 / Clinical and pharmacological factors related to the requirements of laser photocoagulation in patients with diabetic nephropathy due to type 2 diabetes mellitus

Fundamento y objetivo: La retinopatía diabética es una complicación microvascular de la diabetes mellitus cuya prevalencia está estrechamente relacionada con la presencia de nefropatía y la hipertensión. Los objetivos fueron estudiar qué factores clínicos y farmacológicos se relacionan con una mayor necesidad de fotocoagulación láser en pacientes con nefropatía y retinopatía diabética y, en segundo lugar, determinar las características diferenciales entre ambos subgrupos de pacientes diabéticos tipo 2 según si/no hubieran recibido fotocoagulación láser. Pacientes y métodos: Estudio descriptivo transversal de 63 pacientes seguidos en consulta de Nefropatía Diabética. A los pacientes se les dividió en 2 grupos según hubiesen recibido o no previamente fotocoagulación. En cada subgrupo se estudiaron variables de tipo demográfico, antropométrico, analítico, factores de riesgo cardiovascular y tratamiento que recibían los pacientes para el control de la hipertensión arterial, diabetes u otras enfermedades asociadas. Resultados: Se observó que el grupo que había recibido fotocoagulación tenía más años de evolución de la diabetes, más antecedentes de enfermedad cardiovascular y un aclaramiento de creatinina inferior. Asimismo, el porcentaje de pacientes tratados con carvedilol era significativamente superior en el subgrupo que no había recibido fotocoagulación, mientras que el porcentaje de pacientes tratados con betabloqueantes era significativamente superior en el subgrupo que sí la había recibido, no observándose diferencias en el grado de control de la tensión arterial. Conclusiones: Los factores clínicos y farmacológicos relacionados con una mayor necesidad de fotocoagulación fueron el tiempo de evolución de la diabetes, la historia previa de enfermedad cardiovascular, el grado de insuficiencia renal y el tratamiento con betabloqueantes (AU)

Background and objetive: Diabetic retinopathy is a microvascular complication of diabetes mellitus whose prevalence is closely related to the presence of nephropathy and hypertension. The aim was to study clinical and pharmacological factors that are associated with an increased need for laser photocoagulation in patients with diabetic nephropathy and retinopathy. Patients and methods: Cross sectional study of 63 patients followed in the Diabetic Nephropathy consultation. Patients were divided into 2 groups according to whether or not previously have received photocoagulation. In each subgroup were studied demographic variables, anthropometric, laboratory, cardiovascular risk factors and treatment received by each patient for the control of hypertension, diabetes and others diseases. Results: We observed that the group had received photocoagulation had more years of diabetes evolution, more history of cardiovascular disease and a lower creatinine clearance. Similary, the percentage of patients treated with carvedilol was significantly higher in the subgroup who had not received photocoagulation while the percentage of patients treated with beta-blockers was significantly higher in the subgroup that received photocoagulation; no significant differences was observed in the degree of control blood pressure. Conclusions: Clinical and pharmacological factors related to the requirements of laser photocoagulation were years of diabetes evolution, history of cardiovascular disease, the stage of kidney disease and the treatment with beta-blokers (AU)

[Clinical and pharmacological factors related to the requirements of laser photocoagulation in patients with diabetic nephropathy due to type 2 diabetes mellitus]. / Factores clínicos y farmacológicos relacionados con los requerimientos de fotocoagulación láser en pacientes con nefropatía diabética secundaria a diabetes mellitus tipo 2.

BACKGROUND AND OBJECTIVE: Diabetic retinopathy is a microvascular complication of diabetes mellitus whose prevalence is closely related to the presence of nephropathy and hypertension. The aim was to study clinical and pharmacological factors that are associated with an increased need for laser photocoagulation in patients with diabetic nephropathy and retinopathy. PATIENTS AND METHODS: Cross sectional study of 63 patients followed in the Diabetic Nephropathy consultation. Patients were divided into 2 groups according to whether or not previously have received photocoagulation. In each subgroup were studied demographic variables, anthropometric, laboratory, cardiovascular risk factors and treatment received by each patient for the control of hypertension, diabetes and others diseases. RESULTS: We observed that the group had received photocoagulation had more years of diabetes evolution, more history of cardiovascular disease and a lower creatinine clearance. Similarly, the percentage of patients treated with carvedilol was significantly higher in the subgroup who had not received photocoagulation while the percentage of patients treated with beta-blockers was significantly higher in the subgroup that received photocoagulation; no significant differences was observed in the degree of control blood pressure. CONCLUSIONS: Clinical and pharmacological factors related to the requirements of laser photocoagulation were years of diabetes evolution, history of cardiovascular disease, the stage of kidney disease and the treatment with beta-blockers.

Hypercalcemia secondary to persistent hyperparathyroidism in kidney transplant patients: analysis after a year with cinacalcet.

INTRODUCTION: The most common cause of hypercalcemia in patients with transplanted kidneys is persistent hyperparathyroidism, which presents in 10%-30% of patients with functioning renal grafts. In these patients, the treatment of vitamin D-resistant hyperparathyroidism traditionally required parathyroidectomy. Calcimimetic agents represent a new therapeutic alternative; they inhibit parathyroid hormone (PTH) secretion, increasing the sensitivity of the calcium-sensitive receptor in the parathyroid gland. The objective of this study is to evaluate the efficacy of cinacalcet in renal transplant patients with persistent hyperparathyroidism. METHODS: Cinacalcet 30 mg/day was prescribed to 17 renal transplant patients (6 women, 11 men) with a mean age of 49 years and hypercalcemia secondary to persistent hyperparathyroidism. The treatment started 58.17 ± 35.16 months posttransplant, with 1 year of follow-up. RESULTS: Calcium in serum fell from 10.5 ± 0.74 to 9.4 ± 0.84 mg/dL (p<0.001), whereas phosphorous levels were not significantly altered. The fall in PTH was from 204.79 ± 78 to 148.55 ± 56 pg/mL (p<0.011). Kidney function remained stable, and immunosuppressant drug levels remained unchanged. The dose of cinacalcet was increased to 60 mg in 2 patients. No significant adverse effects were described, and none of the patients had to suspend the treatment. CONCLUSIONS: Calcimimetic agents represent a therapeutic alternative in transplant patients with persistent hyperparathyroidism, as they correct hypercalcemia and reduce PTH levels with no adverse effects on kidney function. Prospective, controlled studies should be designed to evaluate the long-term effects and evolution after suspension of the treatment.

Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among chronic kidney disease (CKD) patients. Vascular calcification is highly prevalent in this population and is an independent predictor of cardiovascular mortality. Vascular calcification in uraemic patients is known to be an active and regulated process subject to the action of many promoting and inhibitory factors. The role of vitamin D in this process remains controversial. We evaluated the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) and vascular calcification evaluated by plain X-ray images, in predialysis patients with CKD stages 4 and 5. METHODS: We performed a cross-sectional study with 210 CKD patients stages 4 and 5 managed at our predialysis unit. Patients were 63.5 ± 13 years of age, 60.5% males, 64.8% diabetics and 47.1% with a history of CVD. Plain X-ray images of pelvis, hands and lateral lumbar spine from all subjects were studied for calculation of semiquantitative vascular calcification scores as described by Adragao and Kauppila. RESULTS: We found a high prevalence of vascular calcification in our population. Adragao scores revealed only 47 patients (22.4%) without vascular calcification and 120 (57.1%) with scores higher than 3. Kauppila scores revealed only 29 patients (13.8%) without aortic calcifications and 114 patients (54.3%) with scores higher than 7. Higher vascular calcification scores were related to older age, diabetes, history of CVD and lower levels of 25(OH)D. Only 18.5% of patients had adequate levels of 25(OH)D (> 30 ng/mL), 53.7% of them had insufficient levels (15-30 ng/mL) and 27.8% had deficient levels (< 15 ng/mL). Multivariate analysis showed that age, diabetes and CVD were directly associated and 25(OH)D levels were inversely associated with vascular calcifications. CONCLUSIONS: Our results show an independent and negative association between serum levels of 25(OH)D and vascular calcification. Further and larger prospective studies are needed to clarify the possible role of vitamin D deficiency in the development of vascular calcification in CKD patients.

Elevated striatal dopamine function linked to prodromal signs of schizophrenia.

CONTEXT: A major limitation on the development of biomarkers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia. OBJECTIVES: To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment. DESIGN: Case-control study of in vivo striatal dopaminergic function. SETTING: Academic research. Patients Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community. Main Outcome Measure Striatal 6-fluoro-l-dopa F 18-dopa uptake measured using positron emission tomographic (18)F-dopa imaging. RESULTS: Striatal (18)F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal (18)F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms. CONCLUSIONS: These findings indicate that dopamine overactivity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocognitive dysfunction.

CYFRA 21.1 in patients with cervical cancer: comparison with SCC and CEA.

The serum levels of CYFRA 21.1, CEA and SCC were prospectively determined in 156 patients diagnosed with carcinoma of the uterine cervix from 1995 to 2003. Histology revealed squamous cancer in 119 patients, adenocarcinoma in 25 patients and adenosquamous carcinoma in the remaining 12 patients. We considered 3.3 ng/ml, 5 ng/ml and 2 ng/ml as the upper limits of normality for CYFRA 21.1, CEA and SCC, respectively. The sensitivity of CYFRA 21.1, CEA and SCC was 26%, 25% and 43%, respectively, at diagnosis. SCC was clearly related to tumor histology, with significantly higher levels in squamous tumors than in other histological types (p<0.0001). The relationship of CEA with the histological type was poor, but the highest concentrations were found in adenocarcinomas (p=0.034). All the tumor markers were related to well known prognostic factors such as tumor size, tumor stage, parametrial invasion and nodal involvement. Abnormal pretreatment serum levels indicated a high probability (>83%) of parametrial invasion in squamous tumors. Likewise, pretreatment SCC and CYFRA 21.1 serum levels were of prognostic value, with a shorter DFS and OS in patients with abnormal levels. Multivariate analysis indicated that stage, histological grade and parametrial invasion were independent prognostic factors, but not tumor markers. In conclusion, SCC is the tumor marker of choice in squamous tumors and the addition of CEA or CYFRA 21.1 does not significantly increase the sensitivity obtained by using SCC alone.