Characterization of an experimental model of progressive renal disease in rats

ABSTRACT PURPOSE: To characterize an experimental model of progressive renal disease induced by different degrees of nephrectomy in rats. METHODS: Eighty male Wistar rats were divided into four experimental groups (n=20/group): sham surgery (control group), progressive degrees of nephrectomy leading to mild uremia (group 1), moderate uremia (group 2) and severe uremia (group 3). Ten animals of each group were followed for two or four weeks. At the end, blood and 24-hour urine samples were collected to determine renal function parameters. Urine output and water and food intake were daily monitored. RESULTS: In rats of group 1, serum levels of creatinine and urea and microalbuminuria were increased, while reduced creatinine clearance (p<0.05, compared with control group), without changing blood pressure. Animals of group 2 had more accentuated alterations: increases in urinary output, blood pressure, serum concentrations of urea, creatinine, sodium, potassium, and in microalbuminuria, and reduction of creatinine clearance (p<0.05). Group 3 exhibited even more increased serum concentrations of urea, creatinine, sodium and potassium, blood pressure and microalbuminuria, and decreased creatinine clearance (p<0.05) in comparison with control group and unilateral nephrectomy. CONCLUSION: Progressive nephrectomy in rats seems to be useful to study the physiopathology of chronic kidney disease and its mechanisms of progression.

Evaluation of creatinine-based and cystatin C-based equations for estimation of glomerular filtration rate in type 1 diabetic patients

ABSTRACT Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD-EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine-based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease.

Presença de microalbuminúria como fator de risco em pacientes diabéticos portadores de doença arterial coronária estável / Microalbuminuria as a risk factor in diabetic patients with stable coronary artery disease

A microalbuminúria é admitida como o principal marcadorpara o desenvolvimento de nefropatia diabética. Sua presençatambém é preditora independente de morbidade e mortalidadecardiovasculares. A relação da microalbuminúria com fatoresde risco clássicos para a doença multiarterial coronária (DAC)também tem sido mostrada em estudos epidemiológicos. Opresente estudo tem o objetivo de determinar a prevalênciade microalbuminúria em um grupo de pacientes diabéticosportadores de DAC e relacionar a sua presença com os fatoresclássicos de risco cardiovascular. Trata-se de um estudotransversal realizado com pacientes diabéticos portadoresde DAC, que realizam tratamento no Instituto do Coração(InCor-HCFMUSP). Foram avaliados os seguintes parâmetros:idade, presença ou ausência de HAS, tempo de diabetes,tabagismo, perfil lipídico, hemoglobina glicada e presença demicroalbuminúria/proteinúria, a partir da coleta urinária em24 horas. Os pacientes foram estratificados em três grupos,conforme o valor de albuminúria. Foram feitas análisesestatísticas comparando as diferentes variáveis entre os trêsgrupos. Nesta amostra de pacientes portadores de DM e DACmultiarterial estável, observou-se uma relação crescente entreos valores de albuminúria e o tempo de diabetes mellitus, níveisséricos de LDL-colesterol e triglicérides.

Microalbuminuria is accepted as a surrogate marker for thedevelopment of diabetic nephropathy. Its presence is alsoan independent predictor of cardiovascular morbidity andmortality. The relationship of microalbuminuria with classicrisk factors for coronary multivessel disease (CAD) has alsobeen shown in epidemiological studies. The present studyaims to determine the prevalence of microalbuminuria ina group of diabetic patients with CAD and correlate theirpresence with the classic cardiovascular risk factors. This isa cross-sectional study with diabetic patients with CAD whoperform treatment at the Heart Institute (Incor-HCFMUSP).We evaluated the following parameters: age, presence orabsence of hypertension, duration of diabetes, smoking, lipidprofile, glycated hemoglobin and microalbuminuria/proteinuriafrom urine collection in 24 hours. Patients were stratified into3 groups according to the value of albuminuria. Statisticalanalyzes were performed comparing the different variablesamong the three groups. In this sample of patients with diabetesand stable multivessel CAD there was a growing relationshipbetween the values of albuminuria and duration of diabetesmellitus, serum LDL-cholesterol and triglycerides.

Alteraciones metabólicas en hijos de padres con hipertensión arterial / Metabolic abnormalities in young offsprings of parents with essential hypertension

El antecedente familiar de hipertensión arterial en jóvenes sanos se ha asociado a hiperinsulinemia, que a su vez produciría aumento en el cortisol sérico, confluyendo ambos mecanismos en daño endotelial renal con la presencia de microalbuminuria. El objetivo del estudio consistió en evaluar en jóvenes sanos, hijos de hipertensos, la asociación entre los niveles de insulinemia, cortisol sérico y microalbuminuria, debido a su relación con mayor riesgo cardiovascular. Se realizó un trabajo transeccional y correlacional en la ciudad de Santa Fe, incluyendo 145 jóvenes sanos mayores de 18 años de edad, que se asignaron a dos grupos: aquellos con antecedente de primer grado de hipertensión arterial esencial (grupo de estudio) y sin dicho antecedente (grupo control). Se valoraron las concentraciones séricas en ayunas de insulina, cortisol, y los niveles de microalbuminuria en primera orina matutina. La media de edad fue de 20 ± 2.9 años, siendo el 58% mujeres. El grupo de estudio incluyó el 48% (n = 69). El 4.8% presentó insulino-resistencia, 13.8% microalbuminuria y el 52% hipercortisolinemia, no encontrándose diferencias significativas de los niveles séricos de insulina y cortisol, ni de microalbuminuria entre los grupos, así como tampoco correlación entre estas variables. No se encontró asociación entre el antecedente de 1er grado de hipertensión arterial y alteraciones de la homeostasis de insulina o cortisol así como tampoco evidencia de daño endotelial con presencia de microalbuminuria.

The familiar history of hypertension in healthy young offsprings is associated with hyperinsulinemia, which could lead to increased serum cortisol, resulting in renal endothelial damage and the presence of microalbuminuria. The aim of this study was to evaluate, in healthy young offsprings of hypertensive parents, association between insulin levels, serum cortisol and microalbuminuria attending to its relationship with increased cardiovascular risk. We performed a cross-sectional correlational study in Santa Fe, Argentina, including 145 healthy individuals aged over 18 years, allocated to two groups: those with a history of essential hypertensive parents (study group) and those without such history (control group). We evaluated fasting serum insulin, cortisol, and microalbuminuria levels in the first morning urine. The mean age was 20 ± 2.9 years, and 58% were women. The study group included 48% (n = 69) of the sample. 4.8% had insulin resistance, microalbuminuria 13.8% and 52% hipercortisolinemia, with no significant differences in serum insulin, cortisol, or microalbuminuria between groups. No correlation was found between these variables. In this study there was no association between a history of first degree hypertension and impaired insulin or cortisol homoeostasis.

Avaliação da função diastólica em crianças e adolescentes diabéticos tipo 1 - Existem sinais precoces de miocardiopatia diabética? / Assessment of diastolic function in children and adolescents with type 1 diabetes mellitus - Are there early signs of diabetic cardiomyopathy?

OBJETIVOS: Avaliar a função diastólica (FD) de crianças e adolescentes diabéticos tipo 1 (DM1). SUJEITOS E MÉTODOS: Estudo transversal de 67 DM1, sem comorbidades, e grupo controle (n = 84) da mesma faixa etária. Analisaram-se: idade, sexo, índice de massa corpórea (IMC), Dopplere-cocardiografia e eletrocardiograma de ambos os grupos e, nos portadores de DM1, o tempo de doença, HbA1C, lipidograma e o valor da microalbuminúria. RESULTADOS: Encontraram-se alterações diastólicas [(A e E mitral, relação E/A, tempo de relaxamento isovolumétrico (TRIV) e tempo de desaceleração da onda E (TDE)] nos diabéticos, com maior prevalência nas meninas na faixa 13-17 anos. TRIV e TDE correlacionaram-se positivamente com o IMC (p = 0,028). Idade e tempo de doença foram fatores preditivos para a onda A mitral (p = 0,004 e 0,033, respectivamente). CONCLUSÕES: Alterações de FD foram detectadas nos DM1, com maior prevalência em meninas púberes. Tempo de doença e idade dos pacientes influenciaram parâmetros de FD.

OBJECTIVES: To evaluate diastolic function (DF) of children and adolescents with type 1 diabetes mellitus (DM1). SUBJECTS AND METHODS: Cross-sectional study of 67 otherwise healthy diabetic patients, and a control group (n = 84) in regard to age, sex, body mass index (BMI), Dopplere-chocardiography, and ECG for both groups; and disease duration, HbA1C, microalbuminuria, and serum lipids for DM 1 patients. RESULTS: Diastolic alterations [(A and E mitral waves, E/A ratio, isovolumic relaxation time (IVRT) and E wave deceleration time (EWDT)] were found in diabetic patients, with higher prevalence among pubertal girls (13-17 years old). IVRT and EWDT correlated positively with BMI (p = 0.028). Chronological age and disease duration were predictive factors for mitral A wave (p = 0.004 and 0.033, respectively). CONCLUSIONS: DF alterations were detected in the group of diabetic patients, with greater prevalence among pubertal girls; disease duration and age influenced parameters of DF.

Correlation of brain natriuretic peptide and microalbuminuria in patients with heart failure / Correlación del péptido natriurético cerebral y la microalbuminuria en pacientes con insuficiencia cardíaca

OBJECTIVE: To evaluate the changes of plasma levels of N-terminal probrain natriuretic pepide (NT-proBNP) and microalbuminuria (MAU) in patients with heart failure and the correlation between them. METHODS: Ninety-one patients with heart failure were divided into different groups according to different stages of heart failure. Plasma levels of NT-proBNP were measured by microsome enzyme immuno-assay (MEIA). Plasma levels of MAU were determined by immune scattering turbidimetry (ICTM). Simultaneously, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were measured by Doppler echocardiography for all patients. The correlation of NT-proBNP and MAU was evaluated at different stages of heart failure. RESULTS: The plasma levels of NT-proBNP and MAU increased with the severity of heart failure. There was a high correlation between NT-proBNP and MAU (r = 0.885, p < 0.001). CONCLUSION: Both NT-proBNP and MAU levels were closely associated with the severity of heart failure.

OBJETIVO: Evaluar los cambios en los niveles de plasma de la fracción N-terminal del propéptido natriurético cerebral (NT-proBNP), y la microalbuminuria (MAU) en pacientes con insuficiencia cardíaca y la correlación entre ambas. MÉTODOS: Noventa y un pacientes con insuficiencia cardíaca fueron divididos en diferentes grupos de acuerdo con las diferentes etapas de insuficiencia cardíaca. Los niveles de plasma de NT-proBNP fueron medidos mediante inmunoensayo enzimático microsomal (MEIA). Los niveles plasmáticos de MAU se determinaron mediante turbidimetría inmune de difusión (ICTM). Simultáneamente, a todos los pacientes se les midió la fracción de eyección ventricular izquierda (FEVI) y el diámetro de fin de diástole del ventrículo izquierdo (DFDVI), mediante ecocardiografía Doppler. La correlación de NT-proBNP y MAU fue evaluada en diferentes etapas de la insuficiencia cardíaca. RESULTADOS: Los niveles de plasma de NT-proBNP y MAU aumentaron con la severidad de la insuficiencia cardíaca. Hubo una alta correlación entre NT-proBNP y MAU (r = 0.885, p < 0.001). CONCLUSIÓN: Tanto los niveles de NT-proBNP como los de MAU estuvieron estrechamente asociados con la severidad de la insuficiencia cardíaca.

A pilot study on the effect of telmisartan & ramipril on 24 h blood pressure profile & dipping pattern in type 1 diabetes patients with nephropathy.

Background & objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern. Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria. Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study. Interpretation & conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

Higher mitochondrial DNA copy number is associated with lower prevalence of microalbuminuria

It has been suggested that mitochondrial dysfunction contributes to the initiation and development of atherosclerosis and cardiovascular disease. We examined the association between mitochondrial DNA (mtDNA) copy number and microalbuminuria in a cross-sectional community-based study. We measured peripheral blood mtDNA copy number in 694 adults without chronic kidney disease by a real-time PCR method. The overall prevalence of microalbuminuria (defined as an albumin creatinine ratio of 30 to 299 mg/g) was 4.5%. The prevalence of microalbuminuria decreased progressively from the lower to the upper quartiles of mtDNA copy number (6.9%, 5.7%, 2.9%, and 2.3% in quartiles 1, 2, 3, and 4, respectively, P = 0.017 for trend). Multiple logistic regression models showed that the quartile of mtDNA copy number was independently associated with the prevalence of microalbuminuria (P = 0.01 for trend). Compared with the lowest quartile, the highest quartile had an odds ratio of 0.22 for microalbuminuria (95% confidence interval, 0.05 to 0.87; P = 0.03). Higher mtDNA copy number was associated with the lower prevalence of microalbuminuria in a community-based population.

Prevalence and determinants of albuminuria in a cohort of diabetic patients in Lebanon

Few data are available on the extent of albuminuria in diabetic populations in the Middle East generally and in Lebanon specifically. We conducted this study to determine the prevalence of albuminuria and its major risk factors in a cohort of diabetic patients in Lebanon.Diabetic patients followed in the outpatient department at the American University of Beirut Medical Center [AUBMC] were included in a prospective observational study. AUBMC is a tertiary referral center and the outpatient department typically handles patients of low socioeconomic status with advanced disease. Patients were classified according to their urinary albumin-to-creatinine ratio [ACR] as having normoalbuminuria [ACR<30 mg/g creatinine], microalbuminuria [ACR=30 to <300 mg/g creatinine], or macro-albuminuria [ACR >/= 300 mg/g creatinine]. The three groups were compared to analyze the association between albuminuria and its risk factors. In addition, independent predictors of albuminuria were determined using multivariate logistic regression and presented as an odds ratio. Microalbuminuria and macroalbuminuria were present in 33.3% and 12.7% of 222 patients [mean age 56.4 years, mean deviation of diabetes 8.6 years, 58.7% women, 43.8% obese], respectively. Factors significantly associated with microalbuminuria included glycemic control, insulin use, and total and LDL cholesterol. Those associated with macroalbuminuria included in addition to glycemic control and insulin use, duration of diabetes, hypertension, elevated mean arterial pressure [MAP], and presence of neuropathy, retinopathy and peripheral vascular disease by bivariate analysis. Only glycemic control was an independent risk factor for both in addition to MAP and retinopathy for macroalbuminuria by multivariate analysis. Albuminuria is highly prevalent among this cohort of diabetic patients in Lebanon. Both glyce-mic control and blood pressure need to be better targeted in its management

Avaliação da microalbuminúria em indivíduos não diabéticos / Evaluation of microalbuminuria in non-diabetic individuals

OBJETIVO: Avaliar a presença de microalbuminúria em indivíduos não diabéticos, associando-a à presença de fatores de risco cardiovasculares como hipertensão arterial, tabagismo, dislipidemia e obesidade. A taxa de excreção urinária de albumina (EUA) foi avaliada em relação aos índices de secreção e resistência insulínica (RI). PACIENTES E MÉTODOS: 105 indivíduos com idade de 33,4 ± 1,4 anos (57,1 por cento mulheres) foram submetidos ao TOTG com 75 g de dextrose, sendo avaliadas as curvas de glicose e insulina: valores basais e em 2h, valores de pico e áreas sob a curva (ASC). Para a avaliação da secreção e RI, utilizamos os índices: insulinogênico, delta, HOMA, QUICKI, relação glicose/insulina e relação entre os índices insulinogênico e HOMA. As amostras para avaliação da albuminúria foram colhidas overnight. Os indivíduos foram divididos em dois grupos: 1) tolerância normal à glicose e 2) alteração do metabolismo glicídico. RESULTADOS: Houve diferença entre os 2 grupos para idade, IMC, PA, cintura, RCQ, colesterol, triglicerídeos (TG), glicemias (GJ e G2h), ASCg, índices HOMA e QUICKI, e relação entre os índices insulinogênico e HOMA. A EUA foi de 4,28 ± 2,73 æg/mL, apresentando correlação com PAD, GJ, G2h, ASCg, VPG, HOMA, I2h, VPI e ASCi. Após regressão em stepwise, apenas ASCg foi preditora de EUA. Na comparação da amostra estratificada em quartis de EUA, o 1° e o 4° quartis foram estatisticamente diferentes para IMC, PAS, PAD, cintura, quadril, G2h, TG, LDL, ASCg, ASCi, VPG e índices HOMA e QUICKI. CONCLUSÃO: Embora não houvesse nenhum indivíduo com microalbuminúria, encontramos diferença entre a EUA em indivíduos com diferentes graus de tolerância à glicose e diferenças entre as variáveis clínicas e laboratoriais entre o 1° e o 4° quartis de EUA. Nossos achados sugerem que em indivíduos não diabéticos o aumento da EUA está relacionado a algumas características da síndrome metabólica, o que pode conferir uma maior suscetibilidade aterogênica.

Albuminuria in rural Thai people: a community-based screening with Combur Test and Micral Test strips.

OBJECTIVES: To identify albuminuria prevalence and examine the association of albuminuria with plasma glucose, blood pressure and body mass index in rural Thai people aged 35 and older. MATERIAL AND METHOD: All volunteer adults aged 35 and older at Ban Nayao, Chachoengsao Province were recruited in this cross-sectional study. Macroalbuminuria and microalbuminuria were tested in first morning urine using Combur and Micral Test strips. Fasting plasma glucose, blood pressure, weight and height were determined. Chi-square and multiple logistic regression analysis were used for analysis. RESULTS: Of the 357 participants, 26.61% had microalbuminuria, 3.08% had macroalbuminuria, and 9.2%, 19%, 7.3% had diabetes, hypertension, and obese, respectively. The prevalence of microalbuminuria and macroalbuminuria in people with diabetes were 30.30% and 15.15%, respectively. In the obese, the prevalence was 50% and 3.8% and was 30.88% and 7.35% in the hypertensive group, respectively. Strong significant associations between plasma glucose (p = 0.013), and body mass index (p = 0.008) with the progression of albuminuria were observed. According to multiple logistic regression analysis, diabetes and obesity were independent risk factors for albuminuria statistically significant (p = 0.036 and p = 0.005, respectively, 95% CI). CONCLUSION: The present study showed increased risk of albuminuria in diabetes and in obese people in a rural area of Thailand. Thus, community-controlled diabetes and weight program should be introduced to the rural community.