The A allele of the rs759853 single nucleotide polymorphism in the AKR1B1 gene confers risk for diabetic kidney disease in patients with type 2 diabetes from a Brazilian population

ABSTRACT Objective: The AKR1B1 gene encodes an enzyme that catalyzes the reduction of glucose into sorbitol. Chronic hyperglycemia in patients with diabetes mellitus (DM) leads to increased AKR1B1 affinity for glucose and, consequently, sorbitol accumulation. Elevated sorbitol increases oxidative stress, which is one of the main pathways related to chronic complications of diabetes, including diabetic kidney disease (DKD). Accordingly, some studies have suggested the rs759853 polymorphism in the AKR1B1 gene is associated with DKD; however, findings are still contradictory. The aim was to investigate the association of the rs759853 polymorphism in the AKR1B1 gene and DKD. Materials and methods: The sample comprised 695 patients with type 2 DM (T2DM) and DKD (cases) and 310 patients with T2DM of more than 10 years' duration, but no DKD (controls). The polymorphism was genotyped by real-time PCR. Results: Allelic and genotype frequencies of this polymorphism did not differ significantly between groups. However, the A/A genotype was associated with risk for DKD after adjustment for gender, triglycerides, BMI, presence of hypertension and diabetic retinopathy, and duration of DM, under both recessive (P = 0.048) and additive (P = 0.037) inheritance models. Conclusion: Our data suggest an association between the AKR1B1 rs759853A/A genotype and risk for DKD in Brazilians T2DM patients.

Searching for mutations in the HNF1B gene in a Brazilian cohort with renal cysts and hyperglycemia

ABSTRACT Objective To verify the presence of variants in HNF1B in a sample of the Brazilian population selected according to the presence of renal cysts associated with hyperglycemia. Subjects and methods We evaluated 28 unrelated patients with clinical suspicion of HNF1B mutation because of the concomitant presence of diabetes mellitus (DM) or prediabetes and renal cysts. Genotyping was accomplished using Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA). In positive cases, available relatives were recruited. Results We found two patients with HNF1B mutations. The first presented the variant p.Pro328Leufs*48(c.983delC) and had DM, renal cysts, and hypomagnesemia. The second presented a heterozygous whole gene deletion in HNF1B, DM, renal cysts, body and tail pancreatic agenesis, and hypomagnesemia; this alteration was also found in his two siblings and his father. Conclusion The recruitment of suspected cases of HNF1B gene mutations in Brazilians due to hyperglycemia and renal cysts presents two positive cases. Our cases contribute to the annotation of clinical and biochemical phenotypes of this rare form of maturity-onset diabetes of the young (MODY).

Variables associated with lung congestion as assessed by chest ultrasound in diabetics undergoing hemodialysis / Variáveis associadas a congestão pulmonar avaliada por ultrassonografia em diabéticos submetidos a hemodiálise

Abstract Introduction: Ultrasound is an emerging method for assessing lung congestion but is still seldom used. Lung congestion is an important risk of cardiac events and death in end-stage renal disease (ESRD) patients on hemodialysis (HD). Objective: We investigated possible variables associated with lung congestion among diabetics with ESRD on HD, using chest ultrasound to detect extracellular lung water. Methods: We studied 73 patients with diabetes as the primary cause of ESRD, undergoing regular HD. Lung congestion was assessed by counting the number of B lines detected by chest ultrasound. Hydration status was assessed by bioimpedance analysis and cardiac function by echocardiography. The collapse index of the inferior vena cava (IVC) was measured by ultrasonography. All patients were classified according to NYHA score. Correlations of the number of B lines with continuous variables and comparisons regarding the number of B lines according to categorical variables were performed. Multivariate linear regression was used to test the variables as independent predictors of the number of B lines. Results: None of the variables related to hydration status and cardiac function were associated with the number of B lines. In the multivariate analysis, only the IVC collapse index (b = 45.038; p < 0.001) and NYHA classes (b = 13.995; p = 0.006) were independent predictors of the number of B lines. Conclusion: Clinical evaluation based on NYHA score and measurement of the collapsed IVC index were found to be more reliable than bioimpedance analysis to predict lung congestion.

Resumo Introdução: A ultrassonografia é um método emergente e ainda raramente utilizado na avaliação da congestão pulmonar. A congestão pulmonar é um importante fator de risco para eventos cardíacos e óbito entre pacientes com doença renal terminal (DRT) em hemodiálise (HD). Objetivo: Foram investigadas as possíveis variáveis associadas a congestão pulmonar em indivíduos diabéticos com DRT em HD, utilizando a ultrassonografia torácica para detectar água extracelular nos pulmões. Métodos: Foram estudados 73 pacientes com diabetes como causa primária de DRT submetidos a HD regular. A congestão pulmonar foi avaliada pela contagem do número de linhas B detectadas por ultrassonografia torácica. O estado de hidratação foi avaliado por análise de bioimpedância e a função cardíaca por ecocardiografia. O índice de colabamento da veia cava inferior (VCI) foi medido por ultrassonografia. Todos os pacientes foram classificados segundo a escore da NYHA. Foram analisadas as correlações entre o número de linhas B e variáveis contínuas e as comparações entre o número de linhas B em relação às variáveis categóricas. Regressão linear multivariada foi utilizada para testar as variáveis enquanto preditores independentes do número de linhas B. Resultados: Nenhuma das variáveis relacionadas a estado de hidratação e função cardíaca apresentou associação com o número de linhas B. Na análise multivariada, apenas o índice de colabamento da VCI (b = 45,038; p < 0,001) e as classes da NYHA (b = 13,995; p = 0,006) foram preditores independentes do número de linhas B. Conclusão: A avaliação clínica baseada na classificação da NYHA e na medição do índice de colabamento da VCI foram mais confiáveis do que a análise de bioimpedância para predizer congestão pulmonar.

Fisiopatología de la nefropatía diabética: una revisión de la literatura / Pathophysiology of diabetic nephropathy: a literature review

La enfermedad renal crónica es una complicación frecuente en la diabetes mellitus. Su importancia radica en la alta prevalencia y la proyección a futuro que ésta tiene. Se asocia a altos gastos en salud y además a deterioro cardiovascular global. La fisiopatología del desarrollo de esta enfermedad está siendo estudiada y se sabe que en ella participan una serie de vías moleculares complejas que determinan una enfermedad microvascular. En esta revisión se intenta abordar las vías conocidas en el desarrollo de nefropatía diabética, con el fin de comprender mejor posibles blancos terapéuticos que se podrían desarrollar.

Chronic kidney disease is a common complication of diabetes. Its importance lies in its high prevalence and future projection. It is associated with high health costs and global cardiovascular deterioration as well. The development of this disease pathophysiology is being studied and it is known that a series of complex molecular pathways determining a microvascular disease are involved. This review addresses the known pathways in the development of diabetic nephropathy aiming to improve the understanding of potential therapeutic targets that could be developed in the future.

Nodular glomerulosclerosis in a non-diabetic hypertensive, dyslipidemic, smoker patient: a case report / Glomeruloesclerose nodular em paciente fumante não diabético, hipertenso e dislipidêmico: relato de caso

Abstract Introduction: This is a case report of a patient with idiopathic nodular glomerulosclerosis whose pathogenesis and morphology are similar to diabetic nephropathy. Case presentation: A 64-year-old Brazilian man, leukoderma, dyslipidemic, obese with chronic obstructive pulmonary disease secondary to tobacco smoking, known to be hypertensive for five years and he had no history of diabetes. He was admitted with sudden anasarca, rapid loss of renal function and needed to start hemodialysis immediately. Renal biopsy was performed, and the sections were examined by light microscopy, immunofluorescence and electron microscopy. Morphological and ultrastructural findings showed that the profile of the disease studied herein strongly resembles diabetic nephropathy. However, the absence of diabetes mellitus, the presence of arteriolar hyalinosis in renal arterioles, tobacco smoking, and other clinical factors observed can play a significant role in nodular formation. Conclusion: The clinical features of the patient, and most importantly, the fact that he is a smoker, favor the diagnosis of "nodular glomerulosclerosis associated with smoking", a nomenclature proposed by some authors as an alternative to the term idiopathic nodular glomerulosclerosis. This clinical case report highlights idiopathic nodular glomerulosclerosis as a rare disease of little known etiopathogenesis; thus, further studies are necessary in order to elucidate the causes of this disease.

Resumo Introdução: Este é um relato de caso de um paciente com glomeruloesclerose nodular idiopática, cuja patogênese e morfologia são semelhantes à nefropatia diabética. Apresentação do caso: Homem, 64 anos de idade, leucodermo, com dislipidemia, obesidade, doença pulmonar obstrutiva crônica secundária ao tabagismo, hipertenso há cinco anos e sem história de diabetes mellitus. Ele foi internado com anasarca súbita, perda rápida da função renal com necessidade de hemodiálise imediata. A biópsia renal foi realizada, e as seções foram examinadas por microscopia luz, imunofluorescência e microscopia eletrônica. Achados morfológicos e ultraestruturais mostraram que o perfil da doença estudado fortemente se assemelha à nefropatia diabética. No entanto, a ausência de diabetes mellitus, a presença de hialinose arteriolar em arteríolas renais, o fumo do tabaco, e outros fatores clínicos observados podem desempenhar um papel significativo na formação nodular. Conclusão: As características clínicas do paciente e, o mais importante, o fato de que ele é fumante favorecem o diagnóstico de "glomeruloesclerose nodular associada ao tabagismo", uma nomenclatura proposta por alguns autores como uma alternativa para o termo glomeruloesclerose nodular idiopática. Este relato de caso clínico realça glomeruloesclerose nodular idiopática como uma doença rara, de etiopatogenia pouco conhecida. Desse modo, mais estudos são necessários para elucidar as causas desta doença.

Clinical outcomes of kidney transplants on patients with end-stage renal disease secondary to lupus nephritis, polycystic kidney disease and diabetic nephropathy / Resultados clínicos de trasplantes de riñón en pacientes con enfermedad renal en etapa terminal secundaria anefritis lupus, enfermedad poliquística renal y nefropatía diabética

Background: Patients with lupus nephritis could progress to endstage renal disease (10-22%); hence, kidney transplants should be considered as the treatment of choice for these patients. Objective: To evaluate the clinical outcomes after kidney transplants in patients with chronic kidney diseases secondary to lupus nephritis, polycystic kidney disease and diabetes nephropathy at Pablo Tobon Uribe Hospital. Methods: A descriptive and retrospective study performed at one kidney transplant center between 2005 and 2013. Results: A total of 136 patients, 27 with lupus nephritis (19.9%), 31 with polycystic kidney disease (22.8%) and 78 with diabetes nephropathy (57.4%), were included in the study. The graft survivals after one, three and five years were 96.3%, 82.5% and 82.5% for lupus nephritis; 90%, 86% and 76.5% for polycystic kidney disease and 91.7%, 80.3% and 67.9% for diabetes nephropathy, respectively, with no significant differences (p= 0.488); the rate of lupus nephritis recurrence was 0.94%/person-year. The etiology of lupus vs diabetes vs polycystic disease was not a risk factor for a decreased time of graft survival (Hazard ratio: 1.43; 95% CI: 0.52-3.93). Conclusion: Kidney transplant patients with end stage renal disease secondary to lupus nephritis has similar graft and patient survival success rates to patients with other kidney diseases. The complication rate and risk of recurrence for lupus nephritis are low. Kidney transplants should be considered as the treatment of choice for patients with end stage renal disease secondary to lupus nephritis.

Antecedentes: Pacientes con nefritis lúpica pueden progresar a enfermedad renal crónica terminal (10-22%); en estos pacientes el trasplante renal debe ser considerado como la terapia de elección. Objetivo: Evaluar los desenlaces clínicos de un grupo de pacientes con enfermedad renal crónica terminal por nefropatía lúpica, enfermedad renal poliquística y nefropatía diabética que fueron sometidos a trasplante renal en el Hospital Pablo Tobón Uribe. Métodos: Estudio retrospectivo, descriptivo, realizado en un solo centro de trasplante renal, durante el período 2005-2013. Resultados: Se evaluaron 136 pacientes: 27 con nefritis lúpica (19.9%), 31 con enfermedad renal poliquística (22.8%) y 78 con nefropatía diabética (57.4%). La supervivencia del injerto a uno, tres y cinco años fue de de 96.3%, 82.5% y 82.5% en nefropatía lúpica, 90%, 86% y 76.5% en enfermedad renal poliquística y 91.7%, 80.3% y 67.9% en nefropatía diabética respectivamente, sin diferencias estadísticas significativas (Long Rank test= 0.488). La tasa de recurrencia de nefritis lúpica posterior al trasplante renal fue de 0.94%/persona-año. Tener lupus vs diabetes o enfermedad renal poliquística no fue un factor de riesgo para disminución del tiempo de supervivencia del injerto (Hazard ratio= 1.43; 95% IC= 0.52-3.93). Conclusiones: Los pacientes enfermedad renal crónica terminal secundaria a nefritis lúpica, que son llevados a trasplante renal tienen tasas de éxito similar en cuanto a supervivencia del injerto y del paciente, al compararlos con otras enfermedades renales. La tasa de complicaciones y el riesgo de recurrencia de la nefropatía lúpica son bajos. El trasplante renal debe ser considerado como la terapia de elección para los pacientes con enfermedad renal crónica estadio terminal secundaria a nefritis lúpica.

Protective Effects of Curcumin on Renal Oxidative Stress and Lipid Metabolism in a Rat Model of Type 2 Diabetic Nephropathy

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.

Mecanismos de inducción de la matriz extracelular en la nefropatía diabética / Mechanisms of induction of the extracellular matrix in diabetic nephropathy

La nefropatía diabética es una complicación grave en la diabetes mellitus. Sus principales cambios morfológicos típicos se deben al aumento de la cantidad de proteínas de la matriz extracelular. Los productos finales de glicación avanzada, resultado de la hiperglucemia, estimulan la producción de proteínas de la matriz extracelular en las células mesangiales, lo que resulta en la glomeruloesclerosis. Se revisan las alteraciones de las vías metabólicas que inducen la producción de factores que aumentan la síntesis de proteínas de la matriz extracelular y su acumulación durante el desarrollo de la nefropatía diabética. La glucosa intracelular elevada induce un aumento de angiotensina II y activación de proteína cinasa C, que a su vez, aumentan varios factores de crecimiento, como el transformante 1, el endotelial vascular, el de tejido conectivo, el epidérmico y el derivado de plaquetas, que llevan al incremento en la síntesis de proteínas de la matriz extracelular renal, como el colágeno, la fibronectina, la entactina y la laminina, lo que engrosará las membranas basales y expandirá progresivamente la matriz mesangial glomerular. Las metaloproteinasas de la matriz, que modulan la cantidad de proteínas de la matriz extracelular, son, a su vez, reguladas por los inhibidores tisulares de las metaloproteinasas(AU)

Diabetic nephropathy is a serious complication in diabetes mellitus. Its main and typical morphological changes are caused by the rise of the amount of the extracellulary matrix proteins. The final products of advanced glycation resulting from hyperglycemia stimulate the production of the extracellulary matrix proteins in the mesangial cells which leads to glomerulosclerosis. This article reviewed the alterations in the metabolic pathways that induce the production of factors capable of increasing the extracellulary matrix protein synthesis and their accumulation during the development of diabetic nephropathy. Elevated intracellular glucose leads to increased angiotensin II and C-kinase protein activation which, in turn, increase the number of several growth factors such as B1 transforming, vascular endothelial, connective tissue, epidermal and platelet-derived factors. All the above-mentioned causes more synthesis of renal extracellulary matrix proteins such as collagen, fibronectin, entactin and laminin which will thicken the basal membranes and will progresively extend the glomerular mesangial matrix. The matrix metalloproteins in charge of modulating the amount of proteins in the said matrix are then regulated by the tisular inhibitors of the metalloproteinases(AU)

Attributable causes of chronic kidney disease in adults: a five-year retrospective study in a tertiary-care hospital in the northeast of the Malaysian Peninsula / Causas imputáveis da doença renal crônica em adultos: um estudo retrospectivo de cinco anos de um Hospital de Assistência Terciária no nordeste do Península da Malásia

ABSTRACT CONTEXT AND OBJECTIVE: Chronic kidney disease (CKD) is an escalating medical and socioeconomic problem worldwide. Information concerning the causes of CKD, which is a prerequisite for reducing the disease burden, is sparse in Malaysia. Therefore, this study aimed to evaluate the attributable causes of CKD in an adult population at a tertiary referral hospital. DESIGN AND SETTING: Retrospective study at Hospital Universiti Sains Malaysia (HUSM). METHODS: This was an analysis based on medical records of adult patients at HUSM. Data regarding demographics, laboratory investigations, attributable causes and CKD stage were gathered. RESULTS: A total of 851 eligible cases were included. The patients' mean age was 61.18 ± 13.37 years. CKD stage V was found in 333 cases (39.1%) whereas stages IV, IIIb, IIIa, and II were seen in 240 (28.2%), 186 (21.9%), 74 (8.7%) and 18 (2.1%), respectively. The percentage of CKD stage V patients receiving renal replacement therapy was 15.6%. The foremost attributable causes of CKD were diabetic nephropathy (DN) (44.9%), hypertension (HPT) (24.2%) and obstructive uropathy (9.2%). The difference in the prevalence of CKD due to DN, HPT and glomerulonephritis between patients ≤ 50 and > 50 years old was statistically significant. CONCLUSION: Our results suggest that DN and HPT are the major attributable causes of CKD among patients at a Malaysian tertiary-care hospital. Furthermore, the results draw attention to the possibility that greater emphasis on primary prevention of diabetes and hypertension will have a great impact on reduction of hospital admissions due to CKD in Malaysia.

RESUMO CONTEXTO E OBJETIVO: Doença renal crônica (DRC) é um problema médico e socioeconômico crescente. As informações relativas às causas da DRC são pré-requisito para reduzir a carga da doença, e são escassas na Malásia. Este estudo tem como objetivo avaliar as causas atribuíveis à DRC na população adulta de um hospital de referência terciária. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo realizado no Hospital Universiti Sains Malaysia (HUSM). MÉTODOS: Análise de prontuários de pacientes adultos de HUSM. Foram obtidos dados demográficos, exames laboratoriais, causas atribuíveis e estágio da DRC. RESULTADOS: Um total de 851 casos elegíveis foi incluído. A idade média dos pacientes foi de 61,18 ± 13,37 anos. DRC fase V foi contabilizada em 333 casos (39,1%), enquanto casos de estágio IV, IIIb, IIIa e II foram 240 (28,2%), 186 (21,9%), 74 (8,7%) e 18 (2,1%), respectivamente. A porcentagem de pacientes com DRC estágio V recebendo a terapia de substituição renal foi 15,6%. As causas atribuíveis mais importantes da DRC foram nefropatia diabética (ND) (44,9%), hipertensão (24,2%) e uropatia obstrutiva (9,2%). A diferença na prevalência da DRC devido à ND, hipertensão e glomerulonefrite entre pacientes ≤ 50 anos e > 50 anos de idade foi estatisticamente significativa. CONCLUSÃO: Nossos resultados sugerem que a ND e a hipertensão são as principais causas atribuíveis da DRC em pacientes sob cuidados terciários na Malásia. Os resultados apontam para a possibilidade de maior ênfase na prevenção primária da diabetes e hipertensão como impactante na redução das internações hospitalares devidas a DRC na Malásia.

All-Trans Retinoic Acid Has a Potential Therapeutic Role for Diabetic Nephropathy

PURPOSE: The aim of this study was to examine the effects of all-trans retinoic acid (ATRA) on diabetic nephropathy. MATERIALS AND METHODS: We measured amounts of urinary albumin excretion (UAE) after administrating ATRA to Otsuka Long-Evans Tokushima Fatty (OLETF) rats. In order to understand the mechanism of action for ATRA, we administrated ATRA to examine its inhibitory action on the production of transforming growth factor-beta1 (TGF-beta1), protein kinase C (PKC), and reactive oxidative stress (ROS) in cultured rat mesangial cells (RMCs). RESULTS: After 16 weeks of treatment, UAE was lower in the ATRA-treated OLETF rats than in the non-treated OLETF rats (0.07+/-0.03 mg/mgCr vs. 0.17+/-0.15 mg/mgCr, p<0.01). After incubation of RMCs in media containing 30 or 5 mM of glucose, treatment with ATRA showed time- and dose-dependent decreases in TGF-beta1 levels and ROS. Moreover, ATRA treatment showed a dose-dependent decrease in PKC expression. CONCLUSION: ATRA treatment suppressed UAE and TGF-beta1 synthesis, which was mediated by significant reductions in PKC activity and ROS production. Our results suggest that ATRA has a potential therapeutic role for diabetic nephropathy.

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. .

Efeito do exercício resistido intradialítico em pacientes renais crônicos em hemodiálise / Effect of resistance exercise intradialytic in renal patients chronic in hemodialysis

INTRODUÇÃO: Pacientes com doença renal crônica (DRC) quando submetidos ao exercício resistido (ER) apresentam substancial melhorias de muitas funções, em especial os relacionados ao sistema cardiovascular, respiratório, muscular e na qualidade de vida (QV). Não existem avaliações do impacto de exercício simples e factíveis em pacientes com DRC associada ao Diabetes Mellitus (DM) durante o período intradialítico. OBJETIVO: Estudar o papel do exercício resistido no tratamento e na qualidade de vida em pacientes submetidos à hemodiálise crônica (HD). Assim, submetemos pacientes com DRC e DM ao ER durante a hemodiálise. MÉTODOS: Quinze pacientes em cada grupo: 1: DM com DRC submetidos ao ER; 2: DM com DRC sedentários; 3: DRC e ER e, 4: DRC sedentários. Avaliações durante oito semanas, com ER três vezes na semana. Avaliação laboratorial, teste de força muscular (FM) e QV (SF-36). RESULTADOS: O ER induziu melhoria na glicemia e na FM com discretas, mas significantes alterações na uréia e, K (p < 0,0001). Foi de impacto a melhoria na avaliação dos parâmetros de QV (p < 0,001) com o ER, como a Capacidade Funcional, o Aspecto Físico, redução das Dores (de uma maneira geral), Saúde Geral, Vitalidade, a Função Social, Estado Emocional e na Saúde Mental. Conclusão: O programa de ER (simples e factível) no período intradialítico alterou parâmetros clínicos, na FM e uma significante melhoria na avaliação da QV. O impacto na QV foi importante para o paciente, inclusive envolvendo melhoria em nível familiar e de relacionamento social quando submetidos ao ER.

INTRODUCTION: Patients with chronic kidney disease (CKD) when subjected to resistance exercise (RE) show substantial improvements in many functions, especially those related to the cardiovascular system, respiratory, muscular and quality of life (QOL). There are no evaluations of the impact of exercise simple and feasible in patients with CKD associated with Diabetes Mellitus (DM) during the intradialytic period. Thus, patients with CKD and submit to the DM + RE during hemodialysis. OBJECTIVE: To study the role of resistance exercise in the treatment and quality of life in patients undergoing chronic hemodialysis (HD). METHODS: 15 patients in each group: 1: DM with CKD and RE; 2: DM + CKD sedentary; 3: CKD + RE and 4: DRC sedentary. They were evaluated during eight weeks, with RE three times a week. Parameters: Laboratory assessments, muscle strength testing (FM) and QV (SF-36). RESULTS: RE induced improvement in glucose and FM with subtle but significant changes in urea, or even in the K (p < 0.0001). It was an improvement in the impact assessment of QOL parameters (p < 0.001) with the RE, such as Functional Capacity, Physical Aspect, Reduction of Pain (in general), General Health, Vitality, Social Function, Emotional State and Mental Health. CONCLUSION: The RE program (simple and feasible) during intradialytic clinical parameters changed FM and a significant improvement in QOL assessment were observed. The impact on QOL was important for the patient, including those involving improvement in level of family and social relationships when subjected to RE.

Síndrome do eutireoidiano doente em pacientes com diabetes mellitus tipo 2: correlação com marcadores inflamatórios, controle glicêmico e relação com doença cardiovascular / Euthyroid sick syndrome in patients with type 2 diabetes mellitus: correlation between inflammatory markers, glycemic control and relationship with cardiovascular disease

A síndrome do eutireoidiano doente (SED) é uma entidade caracterizada pela queda das concentrações sanguíneas de triiodotironina nas formas total e livre e aumento da forma reversa. Ocorre principalmente em pacientes portadores de doenças graves e agudas, particularmente dentre aqueles internados em unidade de terapia intensiva. Há descrição desta síndrome em portadores de Diabetes Mellitus, particularmente sob controle glicêmico inadequado. Objetivos: Avaliar as alterações dos hormônios tireoidianos em portadores de DM sob cuidado ambulatorial e a correlação entre concentrações de hormônios tireoidianos e controle glicêmico, presença de complicações crônicas (neuropatia, nefropatia, retinopatia) e marcadores de inflamação sistêmica subclínica, bem como sua relação com presença de eventos cardiovasculares. Metodologia: Estudo transversal avaliando 52 pacientes com diabetes tipo 2 e 52 indivíduos sem diabetes, entre 40 e 75 anos de idade, pareados por sexo, idade e índice de massa corporal. Avaliaram-se dados clínicos e antropométricos, concentrações séricas de hormônios tireoidianos e proteína C reativa, bem como exames laboratoriais que refletem o perfil lipídico e controle glicêmico. Resultados: Cerca de 73% dos pacientes com diabetes e 40% dos indivíduos sem DM apresentaram concentrações séricas diminuídas de T3 total; 25% dos pacientes e apenas 2% dos indivíduos sem DM apresentaram concentrações diminuídas de T3 livre. As concentrações séricas de T3 total (p<0,001), T3 livre (p<0,001) e T4 total (p=0,006) estavam diminuídas em comparação aos de indivíduos sem diabetes. As concentrações de T3 reverso não apresentaram diferença entre os dois grupos. Pacientes com diabetes apresentaram T4 livre mais elevado (p=0,033).

The non-thyroidal illness is an entity characterized by reduced serum levels of total and free triiodothyronine and a rise in its reverse form. It occurs mainly in critically ill patients. There are descriptions of this syndrome in patients with Diabetes Mellitus, especially those under inadequate glycemic control. Objectives: Evaluate the abnormalities in thyroid hormone levels in individuals with diabetes under standard outpatient care and the correlation of thyroid hormone levels with glycemic control, presence of chronic complications (neuropathy, nephropathy and retinopathy) and subclinical systemic inflammation, as well as its relation with the presence of previous cardiovascular events. Methodology: Cross sectional study involving 52 patients with type 2 diabetes and 52 individuals without the diabetes, between 40 and 75 years of age paired by age, gender and body mass index. We evaluated clinical and anthropometric data, serum levels of thyroid hormones and Creactive protein, as well as laboratory parameters that reflect the lipid profile and glycemic control. Results: Approximately 73% of the patients with diabetes and 40% of individuals without diabetes presented reduced serum levels of total T3. Nearly 25% of the patients and only 2% of the individuals without diabetes presented reduced levels of free T3. The levels of total T3 (p<0.001), free T3 (p<0.001) and total T4 (p=0.006) were lower in patients with diabetes compared with those without diabetes. The levels of reverse T3 did not present any difference between both groups. Patients with diabetes presented higher levels of free T4 (p=0.033). The levels of reverse T3 were significantly different only when comparing individuals with previous cardiovascular events with those without this characteristic (p=0.002 for patients with diabetes and p=0.037 for individuals without diabetes). The prevalence of cardiovascular disease was 25%.

Tratamiento de la hipertensión arterial en la nefropatía diabética avanzada / Hypertension treatment in advanced diabetic nephropathy

La diabetes afecta aproximadamente al 10% de la población adulta, por lo que constituye la etiología más frecuente de enfermedad renal entre los pacientes que requieren hemodiálisis. La hipertensión está frecuentemente asociada con la diabetes tipo 2, en la que se presenta como diagnóstico previo, concomitante o posterior, y a la diabetes tipo 1, como consecuencia de la nefropatía. La hipertensión incrementa el riesgo cardiovascular y acelera la progresión de la nefropatía, en tanto que su tratamiento retrasa los eventos cardiovasculares y renales. Los mecanismos principalmente involucrados en la hipertensión y progresión de la nefropatía son la expansión secundaria a la reabsorción incrementada de sodio y la sobreestimulación del sistema renina-angiotensina-aldosterona, y la vasoconstricción por desregulación de los moduladores de la resistencia vascular. Los objetivos generales del tratamiento antihipertensivo en el paciente con diabetes son lograr una presión arterial sistólica < 130 mm Hg y diastólica < 80 mm Hg, y menores en el paciente proteinúrico (< 125/75 mm Hg). Para alcanzar estos objetivos debe restringirse la ingesta de sodio a < 2 000 mg/día, considerándose los inhibidores del sistema renina-angiotensina como las drogas de elección inicial para retrasar la disminución del filtrado glomerular. El algoritmo del tratamiento antihipertensivo sugiere la modificación de los hábitos de vida y asociaciones farmacológicas orientadas fisiopatológicamente para alcanzar los objetivos

Hipertensão arterial no paciente diabético / Arterial hypertension in diabetic patients

A frequente associação entre hipertensão arterial e diabetes tem como consequência um grande aumento no risco cardiovascular e reanl. O tratamento da hipertensão arterial é particularmente importante nos pacientes diabéticos, tanto para a prevenção da doença cardiovascular quanto para minimizar a progressão da doença renal e da retinopatia diabética. A terapêutica inicial inclui métodos não medicamentoso, tais como redução de peso, prática de exercícios físicos, moderação no consumo de sal e álcool e abandono do fumo. A maioria das diretrizes recomenda que os pacientes diabéticos devam manter a pressão arterial abaixo de 130/80 mmHg, embora alguns estudos recentes sugiram que esta concha não é mais vantajosa do que reduzir a pressão apenas a valores inferiores a 140/90 mmHg, a não ser para pacientes com nefropatia. Vários agentes anti-hipertensivos podem se utilizados, sendo que, na maioria das vezes, dois ou três deles precisam ser associados para atingir níveis de controle. Existem vantagens na inclusão de bloqueadores do sistema renina angiotensina (SRA) no esquema terapêutico antihipertensivo, tanto para proteção renal quanto cardiovascular. Na vigência de microalbuminúria ou proteinúria, o bloqueio do SRA é, comprovadamente, a medida mais eficiente para deter a progressão da doença renal.

The frequent association between hypertension and diabetes has resulted in a increase in cardiovascular and renal risk. The treatment of hypertension in particularly important in diabetic patients, both for the prevention of cardiovascular disease as well as to reduce the progression of renal disease and retinopathy. Initial therapy includes non-pharmacological methods such as weight reduction, physical exercise, moderation in salt and alcohol consuption and smoking cessation. Most guidelines recommend that patients with diabetes should keep blood pressure below 130/80 mmHg although some recent studies suggest that this conduct is not more advantageous than just reduce the blood pressure values below 140/90 mmHg, except for patients with nephropathy. All antihypertensive agents can be used and in most cases two or three of them must be associated for blood pressure control. there are advantages in adding renin - angiotensin system (RAS) blocking agents to antihypertensive therapy, both for cardiovascular and renal protection. In the presence of microalbuminuria or proteinuria, RAS blockade is arguably the most effective measure to stop the progression of renal disease.

Hipertensão arterial nos pacientes com doença renal crônica / Hypertension in patients with chronic kidney disease

A hipertensão arterial é o maior fator de risco para doença cardiovascular e renal. Inversamente, a doença renal crônica é a forma mais comum de hipertensão secundária e várias evidências sugerem que é um fator de risco independente para mortalidade e morbidade cardiovascular. Balanço de sal positivo é o fator dominante, mas não único na gênese da hipertensão na doença renal crônica. As evidências experimentais demonstraram , claramente que a hipertensão devido à retenção de sal e água é mantida pelos aumento da resistência periférica.O diagnóstico da hipertensão é criticamente dependente das medidas adequadas da pressão arterial, principalmente em pacientes com doença renal crônica, cujo tratamento anti-hipertensivo precoce é mandatório para a prevenção de eventos cardiovasculares. A monitorização ambulatorial da pressão arterial permitiu identificar pacientes hipertensos de risco elevado. O tratamento da hipertensão em pacientes com doença renal crônica deve levar em consideração a natureza da doença renal subjacente. Pacientes com nefropatia diabética ou doença renal não diabética proteinúrica se beneficiam do tratamento com inibidores da enzima de conversãoda angiotensina ou bloqueadores do receptor de angiotensina II para a meta de pressão arterial < 130/80 mmHG, se tolerado. A meta abaixo de 140/90 mmHg é aceitável para muitos pacientes com outras formas de doença renal. Bloqueio duplo ou triplo do sistema renina angiotensina deve ser evitado.

Hypertension is a major risk factor for cardiovascular and renal disease. Conversely, chronic kidney disease is the most common form of secondary hypertension and mounting evidence suggest it is independent risk factor for cardiovascular morbidity and mortality. positive salt balance is the dominant but not the sole factor in the genesis of hypertension in chronic kidney disease. The experimental evidences have clearly demonstrated that hypertension due to retention of salt and water is maintained by increased peripheral resistance. The diagnosis of hypertension is critically dependent on accurate blood pressure measurement, especially in patients with chronic kidney disease, in whom early antihypertensive treatment is imperative to prevent cardiovascular events. Ambulatory blood pressure monitoring has successfully identified hypertensive patients at increased risk. The treatment of hypertension in chronic kidney disease patients should take into consideration the nature of the underlying kidney disease. Patients with diabetic nephropathy or proteinuric nondiabetic kidney disease benefit from treatment with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers to a goal blood pressure of < 140/90 mmHg is acceptable for most patients with other forms of chronic kidney disease. Dual or triple blockade of the renin-angiotensin system should generally be avoided.

Clinical features of patients with type 2 diabetes mellitus and hepatitis C infection

The objective of the present cross-sectional study was to assess the prevalence and the clinical and laboratory features of hepatitis C virus (HCV)-positive patients with type 2 diabetes mellitus (DM) attending either an outpatient clinic or hemodialysis units. Serologic-HCV testing was performed in 489 type 2 DM patients (303 outpatients and 186 on dialysis). A structured assessment of clinical, laboratory and DM-related complications was performed and the patients were then compared according to HCV infection status. Mean patient age was 60 years; HCV positivity (HCV+) was observed in 39 of 303 (12.9 percent) outpatients and in 34 of 186 (18.7 percent) dialysis patients. Among HCV+ patients, 32 were men (43.8 percent). HCV+ patients had higher serum levels of aspartate aminotransferase (0.90 ± 0.83 vs 0.35 ± 0.13 µKat/L), alanine aminotransferase (0.88 ± 0.93 vs 0.38 ± 0.19 µKat/L), gamma-glutamyl transferase (1.57 ± 2.52 vs 0.62 ± 0.87 µKat/L; P < 0.001), and serum iron (17.65 ± 6.68 vs 14.96 ± 4.72 µM; P = 0.011), and lower leukocyte and platelet counts (P = 0.010 and P < 0.001, respectively) than HCV-negative (HCV-) patients. HCV+ dialysis patients had higher diastolic blood pressure than HCV- patients (87.5 ± 6.7 vs 81.5 ± 6.0 mmHg; P = 0.005) and a lower prevalence of diabetic retinopathy (75 vs 92.7 percent; P = 0.007). In conclusion, our study showed that HCV is common among subjects with type 2 DM but is not associated with a higher prevalence of chronic diabetic complications.

Prevalencia y clasificación de enfermedad renal crónica en pacientes con diabetes mellitus tipo 2 en el centro comunitario de salud familiar Pantanosa, Frutillar / Frequency of chronic kidney disease among ambulatory patients with type 2 diabetes

Background: Type 2 diabetes mellitus is the main cause of chronic kidney disease in developed countries. Aim: To study the prevalence of chronic kidney disease among adults with diabetes mellitus attended at a public primary health care clinic in southern Chile. Material and Methods: One hundred patients with type 2 diabetes mellitus, aged more than 15 years participated in this cross sectional study. Chronic kidney disease was defined as the presence of a urine albumin/creatinine ratio over 30 mg/g or an estimated glomerular filtration rate of less than 60 mL/min/1,73 m², detected in at least two opportunities, separated at least by three months. Results: Thirty four percent of participants had chronic kidney disease (17% stage 1 or 2 and 17% stage 3). Thirty percent of participants had an abnormal urinary albumin/creatinine ratio. Halfof the patients with an estimated glomerular filtration rate below 60 mL/min/1,73 m², had a normal urinary albumin/creatinine ratio. Conclusions: The rates of chronic kidney disease in this group of diabetic patients are very similar to those reported elsewhere.

Effect of low level laser therapy on neurovascular function of diabetic peripheral neuropathy

Diabetic neuropathy is the most common complication and greatest source of morbidity and mortality in diabetic patients. Thirty male and female patients with painful diabetic neuropathy and abnormal results from nerve conduction studies participated in this study. Their ages ranged from 45 to 60 years with a mean of 52.1 +/- SD 4.7 years. Patients were randomly assigned into two equal groups of 15, an active laser group [laser group] and a placebo laser group [control group]. The laser group received scanning helium neon [He-Ne] infrared laser with wavelength 850 nm and density of 5.7 J/cm[2], applied to the lumbosacral area and the plantar surface of the foot for 15 min each site/session three times per week for four weeks [i.e. 12 sessions]. Pain intensity via visual analogue scale, bilateral peroneal motor nerves, sural sensory nerves conduction velocity and amplitude and foot skin microcirculation, were measured pre- and post-treatment for both groups. Pain was significantly decreased [p