Detección de enfermedad renal crónica oculta mediante determinación de albuminuria en pacientes con diabetes mellitus / Detection of Hidden Chronic Kidney Disease by Determining Albumin Estimates in Patients with Diabetes Mellitus

Introducción: La diabetes mellitus constituye la segunda causa de enfermedad renal crónica en Cuba. La estimación de albuminuria facilitaría la identificación precoz de esta. Objetivo: Determinar el valor predictor de enfermedad renal crónica oculta en la albuminuria de pacientes con diabetes mellitus de la Atención Primaria de Salud en Las Tunas. Métodos: Se realizó un estudio analítico de caso-control en 360 pacientes con diabetes mellitus pertenecientes al Policlínico Manuel Fajardo Rivero, en el período de enero de 2019 a febrero de 2020. La población en estudio fue dividida en dos grupos, atendiendo a la presencia (casos) o no (controles) de daño renal. El poder discriminatorio de la albuminuria como predictor de enfermedad renal crónica oculta se determinó mediante el área bajo la curva ROC, además se identificó el punto de corte óptimo. Se utilizó el análisis multivariado para identificar los factores predictores independientes de enfermedad renal. Resultados: La albuminuria mayor de 160 mg/24h fue identificada como predictor de enfermedad renal crónica oculta (OR: 2,278; IC de 95 por ciento: 1,637-2,908) junto a la edad ˃ 65 años, los años de evolución de DM ˃ 8 años y la hipoalbuminemia. El poder discriminatorio fue bueno, índice C: 0,843 (IC de 95 por ciento: 0,762-0,929). El punto de corte identificado de 160 mg/24h alcanzó una sensibilidad y especificidad de 90,00 por ciento y 97,60 por ciento, respectivamente. Conclusiones: La albuminuria pudiese ser un importante predictor independiente de enfermedad renal crónica oculta en pacientes con diabetes mellitus de la Atención Primaria de Salud(AU)

Introduction: Diabetes mellitus is the second cause of chronic kidney disease in Cuba. Albumin estimates would facilitate its early identification. Objective: To determine the predictive value of albuminuria in hidden chronic kidney disease among patients with diabetes mellitus at primary healthcare level in Las Tunas. Methods: An analytical case-control study was carried out in 360 patients with diabetes mellitus belonging to Manuel Fajardo Rivero Polyclinic, in the period from January 2019 to February 2020. The study population was divided into two groups: occurrence (cases) or not (controls) of kidney damage. The discriminatory power of albuminuria as a predictor of hidden chronic kidney disease was determined by the area under the ROC curve, while its optimal cut-off point was also identified. Multivariate analysis was used to identify independent predictors of kidney disease. Results: Albuminuria over 160 mg on 24 hours was identified as a predictor of hidden chronic kidney disease (OR: 2.278; 95 percent CI: 1.637-2.908) together with age over 65 years, evolution of diabetes mellitus over 8 years, and hypoalbuminemia. The discriminatory power was good: The C index was 0.843 (95 percent CI: 0.762-0.929). The identified cut-off point of 160 mg in 24 hours reached a sensitivity and specificity of 90.00 percent and 97.60 percent, respectively. Conclusions: Albuminuria could be an important independent predictor of hidden chronic kidney disease in patients with diabetes mellitus at primary healthcare level(AU)

Guía de práctica clínica para el tamizaje, diagnóstico y manejo de la enfermedad renal crónica en los estadios 1 al 3 / Clinical practice guideline for the screening, diagnosis and management of chronic kidney disease in stages 1 to 3

La enfermedad renal crónica (ERC) consiste en la pérdida progresiva de la función renal a través de cinco estadios (1, 2). Esta condición es un problema de salud pública que ocasiona daños en la calidad de vida y pérdidas socioeconómicas por la mortalidad, discapacidad y costos asociados que genera (3). Se estima que la ERC afecta al 8% a 16% de la población mundial y tanto la incidencia como mortalidad van en aumento (4). La carga de enfermedad de la ERC se ve incrementada por las comorbilidades asociadas a esta enfermedad, de tal manera que la diabetes mellitus e hipertensión arterial son condiciones frecuentemente asociadas (1, 4). En Perú, un estudio realizado en Lima y Tumbes reportó que la prevalencia de ERC fue de 20.7% y 12.9%, respectivamente, en el año 2011 (5). En adición, un estudio realizado con datos del Ministerio de Salud de Perú, evidenció que durante el periodo del 2010 al 2017, se han registrado 188686 casos de ERC, y que en el 2017 se encontró una prevalencia de 1.51%. Una encuesta nacional realizada a los asegurados del seguro social de salud, EsSalud (ENSSA2015), encontró que el 1.7% de asegurados mayores de 60 años reportó padecer de enfermedad renal crónica en el año 2015 (7). En contraste, un estudio realizado con datos del registro nacional de defunciones de Perú reportó que la incidencia de fallecimientos por ERC se incrementó entre el año 2003 y 2015, siendo Puno la región más afectada (4.1% de muertes por ERC). La tendencia creciente tanto en la incidencia como en la mortalidad de la ERC, dan cuenta que a pesar de contar con estrategias terapéuticas para su manejo, los pacientes son captados en estadios avanzados (9). Ante ello, se ha propuesto que la evaluación y el manejo oportuno y adecuado de los casos de ERC, principalmente en estadios tempranos (1 al 3), reducirían la morbimortalidad y las complicaciones de esta condición, evitando que esta enfermedad impacte en la calidad de vida de las personas que la padecen (1, 9, 10). En consecuencia, el Seguro Social de Salud (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) para establecer lineamientos basados en evidencia y gestionar de la mejor manera los procesos y procedimientos asistenciales de la presente condición. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus / Zinco-alfa2-glicoproteina (ZAG) como biomarcador precoce de nefropatia diabética em pacientes com diabetes mellitus tipo 2

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.

Is Uric Acid elevation a random finding or a causative agent of diabetic nephropathy?

SUMMARY OBJECTIVE In this study, we aimed to analyze the relationship between serum uric acid (UA) and microalbuminuria as a marker of renal injury in type 2 diabetes mellitus. METHODS A total of 100 patients with type 2 diabetes mellitus were enrolled in the study. Participants were divided into two groups according to the urinary microalbumin/creatinine ratio: diabetic nephropathy and non-nephropathy group. UA and microalbuminuria were compared between the study groups. RESULTS Serum UA levels of diabetic nephropathy patients were significantly higher than those in the non-nephropathy group (UA in patients with diabetic nephropathy groups: 6.3 (1.82) mg/dl, UA in patients of the non-nephropathic group: 4.85 (1.92) mg/dl) (p<0.001). There was a correlation between microalbuminuria and UA (r=0.238). This correlation was statistically significant (p=0.017). CONCLUSION UA levels may be an important predictor of nephropathy in diabetic patients.

RESUMO OBJETIVO O objetivo deste estudo foi analisar a relação entre o ácido úrico sérico e a microalbuminúria como marcador de lesão renal no diabetes mellitus tipo 2. MÉTODOS Um total de 100 pacientes com diabetes mellitus tipo 2 foram inscritos no estudo. Os grupos de estudo foram divididos em dois, de acordo com a relação microalbumina/creatinina na urina: nefropatia diabética e grupo não nefropático. UA e microalbuminúria foram comparados entre os grupos de estudo. RESULTADOS Os níveis séricos de AU de pacientes com nefropatia diabética foram significativamente maiores do que o grupo sem nefropatia (AU em pacientes com grupos de nefropatia diabética: 6,3 (1,82) mg/dl, AU em pacientes com grupos não nefropáticos: 4,85 (1,92) mg/dl ) (p<0,001). Houve correlação entre microalbuminúria e AU (r=0,238). Essa correlação foi estatisticamente significativa (p=0,017). CONCLUSÃO Os níveis de AU podem ser um importante preditor de nefropatia em pacientes diabéticos.

Prescripción de fármacos bloqueadores del sistema renina angiotensina en pacientes con enfermedad renal crónica etapa 3 en atención primaria de salud / Prescription of renin-angiotensin-aldosterone system blockers in patients with stage 3 chronic kidney disease

Background: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. Aim: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. Material and Methods: Review of clinical records of patients with CKD in an urban primary care clinic. Results: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. Conclusions: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.

Microalbuminuria como factor pronóstico de mortalidad en pacientes con estado de choque / Microalbuminuria as a prognostic factor for mortality in patients with shock

La detección de micro albuminuria permite el rápido diagnóstico de nefropatía incipiente, predecir desarrollo de proteinuria y aumento de mortalidad; siendo la medición en orina de 24 horas Gold standard para su diagnóstico. En sepsis el aumento de permeabilidad vascular favorece paso de sustancias como albúmina y con ello producir micro albuminuria, cuya medición es pronostica de mortalidad en unidad de terapia intensiva. Diseño: estudio descriptivo transversal donde se evaluaron 27 pacientes ingresados en unidad de terapia intensiva de adultos del hospital general de enfermedades debiendo cumplir con: antecedentes de hipertensión arterial y/o diabetes mellitus, tener diagnóstico de choque hipovolémico o séptico, medición de escalas pronosticas de mortalidad y tener examen de orina de 24 horas para evaluar presencia de micro albuminuria, posteriormente se evaluó la condición de egreso como vivo o muerto. Métodos: Se realizó cálculo de Chi2 de homogeneidad o Test Exacto de Fisher para variables categóricas. La normalidad de variables numéricas se determinó con Shaphiro Wilk; si era normal se realizó t de Student de Muestras independientes y de lo contrario U de Mann Whitney. Resultados: Edad media de 50.29 años, principalmente hombres con antecedente de diabetes y diagnóstico de choque séptico. Obteniéndose una media para micro albuminuria en 31.93 mg/dl en pacientes vivos y para fallecidos 58.69 mg/dl. Las escalas pronosticas de mortalidad fueron estadísticamente significativas (p =0.03) para SOFA y (p =0.010) para escala APACHE, así también se obtuvo (p =0.03) para presencia de Micro albuminuria. Conclusiones: La cuantificación de Micro albuminuria en orina de 24 horas en pacientes con estado de choque en unidadde terapia intensiva es un factor pronóstico de mortalidad al ingreso del paciente.(AU)

Prevalence of chronic kidney disease in a population in southern Brazil (Pro-Renal Study) / Prevalência da doença renal crônica em uma população do Sul do Brasil (estudo Pro-Renal)

Abstract Introduction: Chronic kidney disease (CKD) affects 10-12% of the adult population in many countries. In Brazil, there is no reliable information about the actual prevalence of CKD. Objective: To determine the prevalence of CKD by estimated glomerular filtration rate (eGFR) and proteinuria/albuminuria in an urban population randomly selected in Southern Brazil. Patients and Methods: 5,216 individuals were randomly selected out of a pool of 10,000 individuals identified from the database of a local energy company. The screening consisted of collection of demographic data, history of diabetes mellitus, hypertension, kidney/cardiovascular disease in the family and obesity through the body mass index - BMI (CKD risk factors). Blood samples were collected for determination of serum creatinine and subsequent eGFR estimation by the MDRD formula and urine samples for determination of albuminuria by dipstick. Albuminuria was further evaluated by HemoCue© in a selected CKD risk group. Results: The population was predominantly Caucasians (93%), 64% were females and the mean age of participants was 45 years old (18-87). BMI (kg/m2) was 27±5. Albuminuria was found in 5.25% of individuals. 88.6% of this population had no CKD (eGFR > 60 ml/min/1.73m2 & normoalbuminuria) and 11.4% were identified as having CKD, with majority on stages 3A (7.2%) and 3B (1.1%). Hypertension, diabetes, older age and obesity was associated with a higher prevalence of CKD (p < 0.001). Conclusions: The prevalence of CKD in an urban population in southern Brazil mirrors other developed countries and indicates that kidney disease is an important public health problem in Brazil.

Resumo Introdução: A doença renal crônica (DRC) afeta 10-12% da população adulta em muitos países. No Brasil, não há informações confiáveis sobre a prevalência real de DRC. Objetivo: Determinar a prevalência de DRC pela taxa de filtração glomerular estimada (eGFR) e albuminúria em uma população urbana selecionada aleatoriamente no sul do Brasil. Pacientes e Métodos: 5216 indivíduos foram selecionados aleatoriamente de um grupo de 10 mil indivíduos identificados a partir do banco de dados de uma empresa de energia local. O rastreio consistiu na coleta de dados demográficos, história de diabetes mellitus, hipertensão, doença renal/cardiovascular na família e obesidade pelo índice de massa corporal -IMC (fatores de risco da DRC). Foram coletadas amostras de sangue para determinação da creatinina sérica e subsequente estimativa de eGFR pela fórmula MDRD e amostras de urina para determinação da albuminúria por fita. Albuminúria foi confirmada por HemoCue© em um grupo de risco de CKD selecionado. Resultados: A população era predominantemente de caucasianos (93%), 64% eram do sexo feminino e a idade média dos participantes de 45 anos (18-87). O IMC (kg/m2) foi de 27 ± 5. Albuminúria foi encontrada em 5,25 % dos indivíduos. 88,6% dessa população não apresentou CKD (eGFR > 60 ml/min/1,73 m2 e normoalbuminúria) e 11,4% foram identificados como portadores de DRC, com maioria nos estádios 3A (7,2%) e 3B (1,1%). Hipertensão arterial, diabetes, idade avançada e obesidade foram associados a maior prevalência de DRC (p < 0,001). Conclusões: A prevalência de DRC em uma população urbana no sul do Brasil reflete outros países desenvolvidos e indica que a doença renal é um importante problema de saúde pública no Brasil.

Albuminuria: consideraciones preanalíticas y analíticas / Albuminuria: preanalytical and analytical consideration / Albuminúria: considerações pré-analíticas e analíticas

La albuminuria se define como el incremento subclínico y persistente de la excreción urinaria de albúmina. Los valores que definen esta condición son mayores a 30 mg AU/g creatininuria. La AU es un marcador de daño renal, de progresión de enfermedad renal y de riesgo cardiovascular. Este analito tiene una elevada variabilidad biológica y múltiples condiciones pueden afectar su determinación e invalidar la prueba: esto justifica la necesidad de obtener 2 de 3 muestras positivas en un período de 3 a 6 meses para confirmar la presencia de AU. La primera orina de la mañana es el espécimen más adecuado para la pesquisa de AU y su monitorización, expresando los resultados como la relación AU/creatininuria (RAC) (mg/mmol, mg/g). El valor de creatininuria en el denominador de la RAC depende de la masa muscular del individuo y puede subestimar o sobreestimar el valor de albúmina urinaria, por ello este aspecto se encuentra en revisión. La orina recién emitida es la mejor muestra para medir este analito, pero se puede conservar en heladera una semana o a -80 ºC durante más tiempo. Los inmunoensayos son los métodos más utilizados para medir albuminuria, aunque la falta de estandarización, proceso en desarrollo, es hoy una importante fuente de sesgo entre los diferentes métodos. Es imprescindible la mejora analítica y el consenso respecto del error total e imprecisión para optimizar la medición de este analito.

Albuminuria was defined as a persistent and subclinical increase in urinary excretion of albumin. The values that define this condition are higher albuminuria 30 mg/g creatininuria. It is a marker of kidney damage, kidney disease progression and cardiovascular risk. This analyte has a high biological variability and multiple conditions can affect the determination and invalidate the test, which justifies the need to get two positive specimens over a period of 3-6 months to confirm the presence of albuminuria. The first morning urine specimen is best suited for screening and monitoring albuminuria, expressing the results as albuminuria/creatininuria ratio (RAC) (mg/mmol, mg/g). The value of creatininuria in the RAC denominator depends on the individual muscle mass and may underestimate or overestimate the value of urinary albumin, so this aspect is under review. Freshly voided urine is the best example to measure the analyte, but it can be kept in the refrigerator one week or longer, at -80 ºC. Immunoassays are the most commonly used methods to measure albuminuria, but the lack of standardization which is a process under development is today an important source of bias between the different methods. Analytical improvement and consensus on total errors and imprecision are essential to optimize the measurement of this analyte.

Albuminúria é definida como o aumento subclínico e persistente da excreção urinária de albumina. Os valores que definem esta condição são de mais de 30 mg AU/g creatinúria. A AU é um marcador de dano renal, de progressão da doença renal e de risco cardiovascular. Este analito tem uma alta variabilidade biológica e múltiplas condições podem afetar sua determinação e invalidar o teste, o que justifica a necessidade de obter 2 de 3 amostras positivas ao longo de um período de 3-6 meses para confirmar a presença de AU. A primeira urina da manhã é o espécime mais adequado para a pesquisa de AU e seu monitoramento, expressando os resultados como a relação AU/ creatinúria (RAC) (mg/mmol, mg/g). O valor da creatinúria no denominador da RAC depende da massa muscular do indivíduo e pode subestimar ou superestimar o valor de albumina urinária, de modo que este aspecto está em revisão. A urina recém-vertida é a melhor amostra para medir este analito, mas pode ser mantida em geladeira uma semana ou a menos -80 °C durante mais tempo. Os imunoensaios são os métodos mais usados para medir albuminúria, embora a falta de padronização, processo em desenvolvimento, é atualmente uma importante fonte de viés entre os diferentes métodos. É imprescindível a melhora analítica e o consenso a respeito do erro total e imprecisão para maximizar a medição deste analito.

Factores de progresión de disfunción renal en diabéticos ingresados en Medicina Interna / Renal disease´s progression factors in diabetic people admitted in Internal Medicine

Introducción: la nefropatía diabética es un factor de riesgo para desarrollar eventos cardiovasculares. Debido a que si su presencia se establece se reduce el filtrado glomerular y se acelera la aterosclerosis. Existen muchos factores de progresión que comprometen aun más sus aspectos fisiopatológicos y el pronóstico. Objetivo: caracterizar factores de progresión de disfunción renal en diabéticos ingresados en el Servicio de Medicina Interna, período 2012 a 2013. Materiales y Métodos: se realizó un estudio descriptivo, transversal y observacional en diabéticos ingresados en Servicio de Medicina Interna, Hospital Militar de Matanzas, con menos de diez años de evolución, en el período de 2012 a 2013; con consentimiento informado de pacientes y Jefe del Servicio. Se caracterizó la función renal para detectar precozmente factores de progresión de nefropatía diabética, en cada uno, en cuanto a filtrado glomerular y microalbuminuria. Para ello se revisaron historias clínicas. Las variables de afectación renal con factores de riesgo de progresión, tanto clínicos como paraclínicos fueron: edad, microalbuminuria, alteraciones del filtrado glomerular, hiperuricemia, dislipidemia, hiperglucemia, nivel de tensión arterial, sedentarismo, dieta y hábitos tóxicos. Usando la planilla de recolección de datos y la representación mediante tablas, números y por ciento. Resultados: la hipertrigliceridemia, hiperuricemia e hiperglucemia constituyeron los más asociados a descenso del filtrado glomerular y microalbuminuria positiva con 94,44 %, 80,33 % y 48,24 % respectivamente; en tan solo diez años de evolución de la diabetes. Conclusiones: evidente presencia de factores de progresión de enfermedad renal crónica en pacientes diabéticos.

Introduction: Diabetic Nephropathy is a very important risk factor for the development of cardiovascular disorders. It´s related with glomerular filtrate reduction and atherosclerosis. Then also many renal disease´s progression factors affect their physiophatological aspects and the prognosis. Objective: To caracterize renal disease´s progression factors in diabetic people admitted in Internal Medicine period of 2012 to2013. Materials and Methods: A retrospective descriptive longitudinal study was carried out. The sample was formed by 496 patients entered in the Internal Medicine Service, Military Hospital of Matanzas, and they haved less than ten years of evolution of their illness, in the understood period of 2012 at 2013. The used variables of chronic renal disease´s progression factors were: age, microalbuminuria, glomerular filtrate, toxic habits, diet, sedentarism, blood pressure level, serum uric acid and lipid levels. For organizing the obtained indicators authors applied the descriptive statistic method, analyzing the information through distribution tables. The results were represented in numbers and percent. Results: The most associated renal disease´s progression factors were hypertrygliceridemia, hyperuricemia and hyperglucemia. They respectively showed about 94,44 %, 80,33 % and 48,24 %. They were also associated with the worst affectation on glomerular filtrate and microalbuminuria in less than ten years old of diabetes evolution. Conclusions: there is a high presence of chronic renal disease´s progression factors in diabetic people.

The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats

ABSTRACT Objective The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Materials and methods Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Results Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. Conclusion This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.

The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China

OBJECTIVE: This study investigated the correlation between the albumin-to-creatinine ratio in the urine and 24-hour urine proteinuria and whether the ratio can predict chronic kidney disease progression even more reliably than 24-hour proteinuria can, particularly in primary IgA nephropathy. METHODS: A total of 182 patients with primary IgA nephropathy were evaluated. Their mean urine albumin-to-creatinine ratio and 24-hour proteinuria were determined during hospitalization. Blood samples were also analyzed. Follow-up data were recorded for 44 patients. A cross-sectional study was then conducted to test the correlation between these parameters and their associations with chronic kidney disease complications. Subsequently, a canonical correlation analysis was employed to assess the correlation between baseline proteinuria and parameters of the Oxford classification. Finally, a prospective observational study was performed to evaluate the association between proteinuria and clinical outcomes. Our study is registered in the Chinese Clinical Trial Registry, and the registration number is ChiCTR-OCH-14005137. RESULTS: A strong correlation (r=0.81, p<0.001) was found between the ratio and 24-hour proteinuria except in chronic kidney disease stage 5. First-morning urine albumin-to-creatinine ratios of ≥125.15, 154.44 and 760.31 mg/g reliably predicted equivalent 24-hour proteinuria ‘thresholds’ of ≥0.15, 0.3 and 1.0 g/24 h, respectively. In continuous analyses, the albumin-to-creatinine ratio was significantly associated with anemia, acidosis, hypoalbuminemia, hyperphosphatemia, hyperkalemia, hypercholesterolemia and higher serum cystatin C. However, higher 24-hour proteinuria was only associated with hypoalbuminemia and hypercholesterolemia. Higher tubular atrophy and interstitial fibrosis scores were also associated with a greater albumin-to-creatinine ratio, as observed in the canonical correlation analysis. Finally, the albumin-to-creatinine ratio and 24-hour proteinuria were associated with renal outcomes in univariate analyses. CONCLUSION: This study supports the recommendation of using the albumin-to-creatinine ratio, rather than 24-hour proteinuria, to monitor proteinuria and prognosis in primary IgA nephropathy.

Expression of BAFF and BR3 in patients with systemic lupus erythematosus

The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01). The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01). BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01). The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01). The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

Estrés oxidativo y excreción urinaria de albúmina y en diabéticos tipo 2 / Oxidative stress and urinary albumin excretion in type 2 diabetics

INTRODUCCIÓN: la microalbuminuria se asocia con un incremento en la mortalidad cardiovascular en diabéticos y se comporta como un indicador riesgo vascular en estos pacientes. El estrés oxidativo afecta la función del endotelio y favorece el daño vascular. OBJETIVO: analizar si la microalbuminuria se asocia con indicadores de estrés oxidativo en el paciente diabético tipo 2. MÉTODOS: en 94 pacientes diabéticos tipo 2 que asistieron a Consulta de Endocrinología en el Hospital "Hermanos Ameijeiras" se cuantificó excreción urinaria de albúmina, perfil lipídico, productos reactivos al ácido tiobarbitúrico, oxidación de proteínas y actividad superóxido dismutasa extracelular y catalasa. Se estratificaron los datos de acuerdo a la presencia de microalbuminuria y el control glucémico. RESULTADOS: en pacientes con alta concentración de glucosa en sangre en ayunas, un 48,27 % presentó microalbuminuria. La actividad catalasa resultó mayor en los diabéticos con glucosa en ayunas en el rango de referenciay microalbuminuria. Existe asociación entre la actividad de esta enzima y la microalbuminuria (r= 0,434; p= 0,008. La actividad superóxido dismutasa tiende a ser más baja en los diabéticos con alteración en la glucosa en ayunas y con microalbuminuria. Al tener en cuenta el control glucémico (HbA1c) no se observan diferencias en presencia o no de microalbuminuria, aunque el menor daño oxidativo a biomoléculas se observa en los controlados sin microalbuminuria. CONCLUSIONES: el estudio de la actividad catalasa, puede proporcionar criterios complementarios en relación con la evaluación de la excreción urinaria de albúmina y el riesgo vascular en el paciente diabético tipo 2.

INTRODUCTION: microalbuminuria is associated to an increase of cardiovascular mortality in diabetic patients and acts as a vascular risk indicator in these patients. The oxidative stress affects the function of the endothelium and favors the vascular damage. OBJECTIVE: to analyze whether the microalbuminuria is associated with oxidative stress indicators in type 2 diabetic patient. METHODS: in 94 type 2 diabetic patients, who went to the endocrinology service in "Hermanos Ameijeiras" hospital, their urinary albumin excretion, lipid profile, thiobarbituric acid-reactive products,m protein oxidation and the activity of extracellular dismutase superoxide and catalase were all quantitated. Data on the presence of microalbuminuria and glycemic control were stratified. RESULTS: in patients with high blood glucose concentration on fasting, 48.27 % presented with microalbuminuria. The activity of catalase was greater in diabetics with glucose on fasting in the reference range and microalbuminuria. There was association between the activity of this enzyme and microalbuminuria (r= 0,434; p= 0.008). The activity of dismutase superoxide tends to be lower in diabetics with altered glucose on fasting and with microalbuminuria. As to the glycemic control (HbA1c), there were no differences in presence or absence of microalbuminuria, although the lower oxidative damage to biomolecules is observed in controlled patients without microalbuminuria. CONCLUSIONS: the study of the catalase activity may offer supplementary criteria about the evaluation of urinary albumin excretion and the vascular risk in type 2 diabetic patient.

Alto rendimiento clínico entre albuminuria semicuantitativa y proteinuria de 24 horas en pacientes con sospecha de síndrome hipertensivo del embarazo / High clinical performance between semiquantitative albuminuria and 24-hour proteinuria in patients with suspected hypertensive syndrome of pregnancy

ANTECEDENTES: La evaluación precisa de la proteinuria constituye un pilar importante para el diagnóstico del síndrome hipertensivo del embarazo (SHE). El estándar dorado para esta medición es la recolección de orina en 24 horas, pero debido a la duración de la toma de la muestra, alternativas como la albuminuria semicuantitativa se utiliza con mayor frecuencia en los servicios de urgencia de nuestro país. OBJETIVO: Evaluar el rendimiento diagnóstico de la albuminuria semicuantitativa y su asociación con proteinuria de 24 horas en pacientes con SHE. MÉTODOS: Estudio retrospectivo de 145 pacientes con sospecha de SHE atendidas en el Hospital Padre Hurtado, Chile. A todas las pacientes se le realizó albuminuria semicuantitativa (categorizada entre 0+ y 4+) y proteinuria de 24 horas (positivo si >0,3 gramos/24 horas). Se realizó análisis por grupos compuestos de albuminuria semicuantitativa y resultado positivo en proteinuria de 24 horas. RESULTADOS: Se evidenció una sensibilidad de 50%, especificidad de 100%, VPP de 100%, VPN de 65,7%, LR+ de 50 y un LR- de 0,5. CONCLUSIÓN: La albuminuria semicuantitativa ≥2+ muestra una fuerte asociación con proteinuria ≥0,3 g/24 horas y es un método rápido para evaluar SHE.

BACKGROUND: One of the basis for the diagnosis of pregnancy induced hypertension syndrome (PIHS), includes the precise evaluation of proteinuria. The gold standard for its evaluation is the collection of a 24-hour urine specimen, but because it is a slow method, other alternatives, such as semi-quantitative albuminuria have been used more frequently on our emergency rooms. OBJECTIVE: To assess the diagnostic performance of semi-quantitative albuminuria and its association with proteinuria measured in a 24-hour urine specimen collection, in patients with PIHS. METHODS: Retrospective study of 145 patients with clinical suspicion of PIHS who assisted to Hospital Padre Hurtado, Chile. Semi-quantitative albuminuria (categorized as 0 to 4+) and proteinuria measured in a 24-hour urine specimen collection was measured on every patient. Abnormal values of proteinuria were considered when values exceeded 0.3 g/24 hours. Composite outcomes analysis was done between albuminuria groups and positive proteinuria in 24 hrs. RESULTS: Sensibility and specificity of semi-quantitative albuminuria was of 50% and 100%, respectively, with a PPV: 100%, NPV: 65.7%, LR+: 50 and a LR-: 0.5. CONCLUSION: semi-quantitative albuminuria ≥2+ shows a strong association with proteinuria ≥0.3 g/24 hours and it could be used as a fast method to assess PIHS.

Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus / Avaliação da N-acetil-beta-D-glucosaminidase urinária como marcador de dano renal precoce em pacientes com diabetes melito tipo 2

Objective To evaluate the clinical usefulness of urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion for the detection of early tubular damage in type 2 diabetes mellitus (T2DM). Subjects and methods Thirty six patients with T2DM were divided into two groups based on urinary albumin to creatinine ratio (ACR): normoalbuminuria (ACR <30 mg/g; n=19) and microalbuminuria (ACR =30‐300 mg/g; n=17). The following parameters were determined in both groups: urinary NAG and albumin, serum and urine creatinine, fasting plasma glucose and glycated hemoglobin (HbA1c). Results Urinary NAG levels [Units/g creatinine; median (range)] were significantly increased in microalbuminuria group [17.0 (5.9 - 23.3)] compared to normoalbuminuria group [4.4 (1.5 - 9.2)] (P<0.001). No differences between groups were observed in fasting glucose, HbA1c, serum creatinine levels and estimated glomerular filtration rates (eGFR). Urinary NAG positively correlated with ACR (r=0.628; p<0.0001), while no significant association was observed between NAG and glycemia, HbA1c, serum creatinine and eGFR. Conclusions The increase of urinary NAG at the microalbuminuria stage of diabetic nephropathy (DN) suggests that tubular dysfunction is already present in this period. The significant positive association between urinary NAG excretion and ACR indicates the possible clinical application of urinary NAG as a complementary marker for early detection of DN in T2DM. .

Objetivo Avaliar a utilidade clínica da excreção urinária da N-acetil-beta-D-glucosaminidase (NAG) para a detecção de dano tubular precoce no diabetes melito tipo 2 (DM2). Sujeitos e métodos Foram estudados trinta e seis pacientes com DM2 que se dividiram em dois grupos com base na excreção urinária de albumina (EUA): normoalbuminúrico (EUA <30 mg/g de creatinina; n=19) e microalbuminúrico (EUA =30‐300 mg/g de creatinina; n=17). Em ambos os grupos foram determinados os seguintes parâmetros: NAG e albumina urinária, creatinina sérica e urinária, glicemia de jejum e hemoglobina glicada (HbA1c). Resultados Os níveis de NAG urinária [unidades/g de creatinina; mediana (intervalo interquartílico)] foram significativamente maiores no grupo microalbuminúrico [17,0 (5,9 - 23,3)] em comparação com o grupo normoalbuminúrico [4,4 (1,5 - 9,2)] (p<0,001). Não se observaram diferenças significativas entre os dois grupos nos níveis de glicemia de jejum, HbA1c, creatinina sérica e taxa de filtração glomerular estimada (TFGe). A NAG urinária se correlacionou positivamente com o EUA (r=0,628, p<0,0001), não sendo observada associação significativa da NAG com glicemia, HbA1c, creatinina sérica e TFGe. Conclusões O aumento da NAG urinária na fase de microalbuminúria da nefropatia diabética (ND) sugere que a disfunção tubular já está presente nesse período. A associação positiva significativa entre a excreção urinária da NAG e EUA indica a possível aplicação clínica da NAG urinária como marcador complementar para a detecção precoce da ND no DM2. .

Relevance to Home Blood Pressure Monitoring Protocol of Blood Pressure Measurements Taken Before First- Morning Micturition and in the Afternoon / Relevância das Medidas da Pressão Arterial Pré-Micção Matinal e à Tarde em Protocolo de Monitorização Residencial da Pressão Arterial

Background: The importance of measuring blood pressure before morning micturition and in the afternoon, while working, is yet to be established in relation to the accuracy of home blood pressure monitoring (HBPM). Objective: To compare two HBPM protocols, considering 24-hour ambulatory blood pressure monitoring (wakefulness ABPM) as gold-standard and measurements taken before morning micturition (BM) and in the afternoon (AM), for the best diagnosis of systemic arterial hypertension (SAH), and their association with prognostic markers. Methods: After undergoing 24-hour wakefulness ABPM, 158 participants (84 women) were randomized for 3- or 5-day HBPM. Two variations of the 3-day protocol were considered: with measurements taken before morning micturition and in the afternoon (BM+AM); and with post-morning-micturition and evening measurements (PM+EM). All patients underwent echocardiography (for left ventricular hypertrophy - LVH) and urinary albumin measurement (for microalbuminuria - MAU). Result: Kappa statistic for the diagnosis of SAH between wakefulness-ABPM and standard 3-day HBPM, 3-day HBPM (BM+AM) and (PM+EM), and 5-day HBPM were 0.660, 0.638, 0.348 and 0.387, respectively. The values of sensitivity of (BM+AM) versus (PM+EM) were 82.6% × 71%, respectively, and of specificity, 84.8% × 74%, respectively. The positive and negative predictive values were 69.1% × 40% and 92.2% × 91.2%, respectively. The comparisons of intraclass correlations for the diagnosis of LVH and MAU between (BM+AM) and (PM+EM) were 0.782 × 0.474 and 0.511 × 0.276, respectively. Conclusions: The 3 day-HBPM protocol including measurements taken before morning micturition and during work in the afternoon showed the best agreement with SAH diagnosis and the best association with prognostic markers. .

Fundamentos: A importância das medidas da pressão arterial antes do ato miccional matinal e no período da tarde, durante atividades laborativas, na acurácia da monitoração residencial da pressão arterial (MRPA) não foi estabelecida. Objetivo: Comparar dois protocolos de MRPA, tendo como padrão-ouro a monitoração ambulatorial da pressão arterial de 24 horas (MAPA-vigília) e avaliando-se as medidas antes do ato miccional e à tarde, para o melhor diagnóstico de hipertensão arterial (HAS), e sua associação com marcadores prognósticos. Métodos: Após realizarem MAPA de 24 horas, os 158 participantes (84 mulheres) foram randomizados para realizar MRPA de três ou cinco dias com posterior crossover. Analisou-se o protocolo de três dias nas seguintes situações: aferições antes do ato miccional matinal e à tarde (AM+MT); e aferições após o ato miccional matinal e à noite (PM+MN). Todos os pacientes foram submetidos a ecocardiografia (hipertrofia ventricular esquerda - HVE) e a dosagem de albumina urinária (microalbuminúria - MAU). Resultados: A estatística kappa para diagnóstico de HAS entre MAPA-vigília e MRPA de três dias padrão, MRPA de três dias (AM + MT) e (PM + MN), e MRPA de cinco dias foi de 0,660, 0,638, 0,348 e 0,387, respectivamente. Os valores de sensibilidade de AM+MT versus PM+MN foram 82,6% × 71%, respectivamente, e os de especificidade foram 84,8% × 74%, respectivamente. Os valores preditivos positivos e negativos foram 69,1% × 40% e 92,2% × 91,2%, respectivamente. As comparações das correlações intraclasse para diagnósticos de HVE e MAU, entre AM+MT e PM+MN, foram 0,782 × 0,474 e 0,511 × 0,276, respectivamente. Conclusões: O protocolo de MRPA de três dias ...

The association of vitamin D deficiency with non-alcoholic fatty liver disease

OBJECTIVE: Vitamin D deficiency has been related to diabetes, hypertension, hyperlipidemia and peripheral vascular disease. In this study, we aimed to investigate the role of vitamin D status in non-alcoholic fatty liver disease. METHODS: We included 211 consecutive subjects to examine the presence of non-alcoholic fatty liver disease. Of these subjects, 57 did not have non-alcoholic fatty liver disease and 154 had non-alcoholic fatty liver disease. RESULTS: The non-alcoholic fatty liver disease group had significantly higher fasting blood glucose (p = 0.005), uric acid (p = 0.001), aspartate aminotransferase (p<0.001), alanine aminotransferase (p<0.001), γ-glutamyltransferase (p<0.0001), alkaline phosphatase (p = 0.028), HbA1c (p<0.001), ferritin (p<0.001), insulin (p = 0.016), C-peptide (p = 0.001), HOMA-IR (p = 0.003), total cholesterol (p = 0.001), triglyceride (p = 0.001) and white blood cell (p = 0.04) levels. In contrast, the non-alcoholic fatty liver disease group had significantly lower 25(OH)D levels (12.3±8.9 ng/dl, p<0.001) compared with those of the control group (20±13.6 ng/dl). CONCLUSIONS: In this study, we found lower serum 25(OH)D levels in patients with non-alcoholic fatty liver disease than in subjects without non-alcoholic fatty liver disease. To establish causality between vitamin D and non-alcoholic fatty liver disease, further interventional studies with a long-term follow-up are needed. .

Marcadores de daño vascular y renal en orina en niños y adolescentes obesos / Vascular and renal damage markers observed in urine from obese children and adolescents

INTRODUCCIÓN: la microalbuminuria es considerada un marcador de disfunción endotelial, daño vascular, daño renal y enfermedad cardiovascular, considerada un factor de riesgo independiente de morbilidad y mortalidad. De igual manera, la proteinuria ha sido identificada como un factor de riesgo independiente de enfermedad renal crónica, y un predictor de todas las causas de mortalidad. Ambas, son relativamente frecuentes en los sujetos obesos. OBJETIVO: determinar la frecuencia de marcadores de daño vascular y renal en orina en niños y adolescentes obesos. MÉTODOS: se presenta un estudio observacional, analítico y prospectivo que incluyó a niños y adolescentes obesos atendidos en consulta de referencia "Obesidad y riñón", en el Hospital Pediátrico Docente de Centro Habana. El estudio fue realizado en el periodo comprendido entre enero de 2009 y diciembre de 2012. Se determinaron marcadores de daño vascular y renal en orina (microalbuminuria y proteinuria). El análisis estadístico fue realizado con el programa SPSS versión 13,0. RESULTADOS: solo a un paciente se le identificó proteinuria (0,5 %); sin embargo, al determinar la microalbuminuria, se encontró que más de la mitad (70,8 %) tenía este marcador de daño vascular y renal positivo. En el análisis histopatológico de la biopsia renal del paciente con proteinuria se encontró glomerulomegalia con lesión segmentaria de esclerosis y adherencia a la cápsula de Bowman. CONCLUSIONES: los niños y adolescentes obesos tienen una elevada frecuencia de positividad de marcadores de daño vascular y renal, fundamentalmente microalbuminuria.

INTRODUCTION: microalbuminuria is considered to be a marker of endothelial dysfunction, vascular damage, renal damage and cardiovascular disease in addition to be an independent risk factor for morbidity and mortality. Similarly, proteinuria has been identified as an independent risk factor for chronic renal disease and a predictor of all causes of mortality. Both are relatively frequent in obese subjects. OBJECTIVE: to determine the frequency of vascular and renal markers in the urine from obese children and adolescents. METHODS: prospective, observational and analytical study of obese children and adolescents seen at the reference service called obesity and kidney in the teaching pediatric hospital of Centro Habana. The study was conducted from January 2009 through December 2012. Vascular and renal markers were determined in the urine (microalbuminuria and proteinuria). The statistical analysis was based on SPSS program version 13.0. RESULTS: there was just one patient detected with proteinuria (0.5 %); however, in the microalbuminuria test, it was found that over half of the patients (70.8 %) were positive to this vascular and renal damage marker. In the histopathological analysis of the renal biopsy taken from the patient with proteinuria, segmental glomerulosclerosis and adhesion to Bowman's capsule was discovered. CONCLUSIONS: obese children and adolescents have very frequent positivity to vascular and renal damage markers, mainly microalbuminuria.

Cistatina C, PCR, Log TG/HDLc e Sindrome Metabolica estao Relacionados a Microalbuminuria na Hipertensao / Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

Fundamento: Em pacientes com hipertensão arterial sistêmica, a microalbuminúria é um marcador de lesão endotelial e está associada a um risco aumentado de doença cardiovascular. Objetivo: O objetivo do presente estudo foi determinar os fatores que influenciam a ocorrência de microalbumiúria em pacientes hipertensos com creatinina sérica menor que 1,5 mg/dL. Métodos: Foram incluídos no estudo 133 pacientes brasileiros atendidos em um ambulatório multidisciplinar para hipertensos. Pacientes com creatinina sérica maior do que 1,5 mg/dL e aqueles com diabete mellitus foram excluídos do estudo. A pressão arterial sistólica e diastólica foi aferida. O índice de massa corporal (IMC) e a taxa de filtração glomerular estimada pela fórmula CKD-EPI foram calculados. Em um estudo transversal, creatinina, cistatina C, colesterol total, HDL colesterol, LDL colesterol, triglicerídeos, proteína C-reativa (PCR) e glicose foram mensurados em amostra de sangue. A microalbuminúria foi determinada na urina colhida em 24 horas. Os hipertensos foram classificados pela presença de um ou mais critérios para síndrome metabólica. Resultados: Em análise de regressão múltipla, os níveis séricos de cistatina C, PCR, o índice aterogênico log TG/HDLc e a presença de três ou mais critérios para síndrome metabólica foram positivamente correlacionados com a microalbuminuria (r2: 0,277; p < 0,05). Conclusão: Cistatina C, PCR, log TG/HDLc e presença de três ou mais critérios para síndrome metabólica, independentemente da creatinina sérica, foram associados com a microalbuminúria, um marcador precoce de lesão renal e de risco cardiovascular em pacientes com hipertensão arterial essencial. .

Background: In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. Objective: To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. Methods: This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. Results: In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r2: 0.277, p < 0.05). Conclusion: CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension. .

Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.