No description available.

MMed (Paediatrics), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Introduction HIV-Associated Nephropathy (HIVAN) is the commonest cause of proteinuria, especially in black HIV seropositive children. This chronic nephropathy is a late complication of untreated HIV that requires earlier intervention to prevent progression of renal disease. Microalbuminuria is an early marker of the presence of subclinical renal disease in systemic diseases such as diabetes mellitus and hypertension. This study assessed the prevalence and clinical significance of a single screening test for microalbuminuria in a cohort of HIV seropositive children without any symptoms of renal disease at Chris Hani Baragwanath hospital situated in Johannesburg, South Africa. Methods A prospective study was undertaken at Chris Hani Baragwanath hospital (a major tertiary facility that serves the people of Soweto and the surrounding areas of southern Gauteng). HIV seropositive and seronegative patients from both an inpatient and outpatient ambulatory setting were screened for qualitative proteinuria and microalbuminuria. Those on antiretroviral therapy, anti tuberculosis treatment, known chronic kidney disease, hypertension, fever, acute illness and urinary tract infection were excluded from the study. Results 180 patients were enrolled into the study, of which 110 were HIV positive and 70 HIV negative. Majority of the patients were black (98%) with 100 (56%) males and 80 (44%) females. Microalbuminuria was present in 27(25%) of HIV positive patients and 1 (1%) HIV negative patient, p=0.00003. The mean age at presentation of microalbuminuric HIV positive patients was 6 ± 3.2 years. With normal renal function and no proteinuria; microalbuminuria was present in 21 (19%) patients, p=0.03. Microalbuminuric patients were moderately immunosuppressed (mean CD4 % of 16.8 ± 8%, mean viral load 8 ± 18 x 105 RNA copies/ml) and had WHO clinical stage 2 and 3 disease. Absolute CD4 counts appear to correlate better with microalbuminuria than CD4 percentage as the mean CD4 absolute count in HIV positive patients with microalbuminuria (493 ± 330 x 106/l) was significantly lower than those without microalbuminuria (780 ± 702 x 106/l), p=0.03. Conclusion Microalbuminuria screening of HIV positive patients is a more sensitive screening test compared to standard urine dipsticks as it is present in patients with normal renal function who have no proteinuria. This may allow for early identification of subclinical renal disease in patients with some evidence of immunosuppression; thus possibly preventing the deterioration of renal function and severity of HIV disease with early initiation of antiretroviral therapy.

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Background: Predictive models allow clinicians to more accurately identify higher- and lower-risk patients and make more targeted treatment decisions, which can help improve efficiency in health systems. Microalbuminuria (MA) is a condition characterized by the presence of albumin in the urine below the threshold detectable by a standard dipstick. Its presence is understood to be an early marker for cardiovascular disease. Therefore, identifying patients at risk for MA and intervening to treat or prevent conditions associated with MA, such as high blood pressure or high blood glucose, may support cost-effective treatment. Methods: The National Health and Nutrition Examination Survey (NHANES) was utilized to create predictive models for MA. This database includes clinical, medical and laboratory data. The dataset was split into thirds; one-third was used to develop the model, while the other two-thirds were utilized to validate the model. Univariate logistic regression was performed to identify variables related with MA. Stepwise multivariate logistic regression was performed to create the models. Model performance was evaluated using three criteria: 1) receiver operator characteristic (ROC) curves; 2) pseudo R-squared; and 3) goodness of fit (Hosmer-Lemeshow). The predictive models were then used to develop risk-scores. Results: Two models were developed using variables that had significant correlations in the univariate analysis (p-value<0.05). For Model A, variables included in the final model were: systolic blood pressure (SBP); fasting glucose; C-reactive protein; blood urea nitrogen (BUN); and alcohol consumption. For Model B, the variables were: SBP; glycohemoglobin; BUN; smoking status; and alcohol consumption. Both models performed well in the creation dataset and no significant difference between the models was found when they were evaluated in the validation set. A 0-18 risk score was developed utilizing Model A, and the predictive probability of developing MA was calculated. Conclusion: The predictive models developed provide new evidence about which variables are related with MA and may be used by clinicians to identify at-risk patients and to tailor treatment. Furthermore, the risk score developed using Model A may allow clinicians to more easily measure patient risk. Both predictive models will require external validation before they can be applied to other populations.

No description available.

No description available.

La retinopatía diabética es una complicación crónica de la diabetes mellitus tipo 2, consecuencia del daño que produce la hiperglicemia crónica sobre los vasos pequeños de la retina a lo largo del tiempo. Objetivo: Determinar los factores de riesgo asociados a retinopatía diabética en adultos con Diabetes mellitus tipo 2 atendidos en el Hospital San José durante los años 2015 – 2016. Metodología: Es un estudio observacional, analítico de corte longitudinal, tipo caso control, la recolección de datos se hizo a través de ficha de datos; el grupo de casos lo conforman los pacientes diagnosticados de retinopatía diabética y el grupo control conformado por criterios de inclusión y exclusión, quienes fueron seleccionados por tipo de muestreo probabilístico. Resultados: La retinopatía diabética tuvo una prevalencia de 21%. La duración de la diabetes mellitus ≥10 años obtuvo OR = 41,5 (9.8 - 174,7); HbA1c elevada obtuvo OR = 4,7 (2,3 - 9,7); la hipertensión arterial obtuvo OR = 9,3 (4,9 - 17,6); la microalbuminuria obtuvo OR = 9,7 (4,9 - 19,3). Conclusiones: La duración de diabetes mellitus ≥ 10 años, la hemoglobina glicosilada ≥ 6.5%, la hipertensión arterial y la microalbuminuria son factores de riesgo para padecer retinopatía diabética.

Evidências epidemiológicas indicam que a presença de microalbuminúria prediz maior freqüência de eventos cardiovasculares e mortalidade em hipertensos essenciais. A microalbuminúria pode ser decorrente do aumento da permeabilidade glomerular e/ou da diminuição da reabsorção desta macromolécula no túbulo proximal. Todavia não é sabido se os mecanismos que regulam a reabsorção de albumina em túbulo proximal renal encontram-se alterados na hipertensão essencial. Este trabalho teve como objetivo investigar as bases moleculares da microalbuminúria associada à hipertensão arterial essencial, focando na reabsorção tubular de albumina. Para tanto, avaliamos a evolução temporal da excreção urinária de albumina em ratos espontaneamente hipertensos (SHR) com 6 semanas de idade (pressão arterial sistólica, PAS, = 105 ± 4 mmHg), 14 semanas de idade (PAS = 180 ± 2 mmHg) e 21 semanas de idade (PAS = 202 ± 2 mmHg). Ratos normotensos Wistar da mesma idade serviram de controle. Observou-se que a excreção urinária diária de albumina aumentou progressivamente com o aumento da pressão arterial em SHR (10,5 ± 1,9; 92 ± 7,0 e 154 ± 27 g/dia, em SHR com PAS média igual a 105, 180 e 202 mmHg respectivamente). Este aumento progressivo não foi observado em ratos normotensos com idade correspondente, indicando que este fenômeno é decorrente do aumento da pressão arterial e não pode ser atribuído ao aumento da idade dos animais durante o período estudado. A análise das proteínas urinárias por eletroforese em gel de poliacrilamida (SDS-PAGE) mostrou que SHR excretam proteínas do tamanho da albumina ou menores (< 70kDa), padrão típico de proteinúria tubular. Adicionalmente, verificou-se que os níveis de expressão dos receptores endocíticos megalina e cubilina, bem como do canal para cloreto ClC-5 diminuem progressivamente no córtex renal de SHR com o aumento da pressão arterial. Observou-se também uma diminuição significativa na expressão de uma outra macromolécula importante no processo de endocitose mediada por receptor em túbulo proximal renal, a v-H+-ATPase. Entretanto, a diminuição da expressão protéica da subunidade B2 desta ATPase foi estatisticamente significante apenas em SHR com 21 semanas comparado aos com 6 semanas de idade. Não foram encontradas alterações no padrão de expressão de componentes estruturais da barreira glomerular como a nefrina e podocina. Em suma, o nosso estudo demonstra que o aumento da excreção urinária de proteínas, especialmente de albumina, está associado com uma menor expressão de componentes essenciais do aparelho endocítico do túbulo proximal renal. É tentador especular que a disfunção da via endocítica no túbulo proximal renal possa ser o principal mecanismo subjacente ao desenvolvimento de microalbuminúria na hipertensão / Epidemiological evidences indicate that the presence of microalbuminuria predicts a higher frequency of cardiovascular events and mortality in essential hypertensive patients. Microalbuminuria may arise from increased glomerular permeability and/or reduced proximal tubular reabsorption of albumin. However, it remains to be determined whether the mechanisms that regulate the renal proximal tubular reabsorption of albumin are altered in essential hypertension. The purpose of this work was to investigate the molecular basis of microalbuminuria in essential hypertension, focusing on the renal tubular reabsorption of albumin. To this end, we evaluated the temporal evolution of urinary albumin excretion in spontaneously hypertensive rats (SHR) at 6 weeks of age (systolic arterial pressure, SAP, = 105 ± 4 mmHg), 14 weeks of age (SAP = 180 ± 2 mmHg) and 21 weeks of age (SAP = 202 ± 2 mmHg). Age-matched normotensive Wistar rats were used as controls. It was observed that the daily urinary excretion of albumin progressively increased with blood pressure in SHR from 6 to 21 weeks of age (10.5 ± 1.9, 92 ± 7.0 and 154 ± 27 g in SHR with 105, 180 and 202 mmHg of average SAP, respectively). This progressive increase in microalbuminuria has not been observed in age-matched normotensive Wistar rats, indicating that this phenomenon cannot be attributed to age progression over the studied period. SDS-PAGE analysis of urinary proteins showed that microalbuminuric SHR virtually excreted proteins of the size of albumin or smaller (< 70kDa), typical of tubular proteinuria. Additionally, it was verified that the protein expression levels of the endocytic receptors megalin and cubilin as well as of the chloride channel ClC-5 progressively decreased in the renal cortex of SHR from 6 to 21 weeks of age. Moreover, it was observed reduction of expression of another macromolecule that plays an important role in the process of receptor mediated endocytosis in the renal proximal tubule, the v-H+- ATPase, was reduced. However, reduced cortical expression of the B2 subunit of the v- H+-ATPase, was only statistically significant in 21-wk-old vs. 6-wk-old SHR. Expression levels of structural components of the glomerular barrier such as nephrin and podocin were unchanged. To sum up, our study demonstrates that the increase in urinary protein excretion, especially of albumin, is associated with lower expression of key components of the apical endocytic apparatus in the renal proximal tubule. It is tempting to speculate that dysfunction of the apical endocytic pathway in the renal proximal tubule may be the major mechanism underlying development of microalbuminuria in essential hypertension

Evidências epidemiológicas indicam que a presença de microalbuminúria prediz maior freqüência de eventos cardiovasculares e mortalidade em hipertensos essenciais. A microalbuminúria pode ser decorrente do aumento da permeabilidade glomerular e/ou da diminuição da reabsorção desta macromolécula no túbulo proximal. Todavia não é sabido se os mecanismos que regulam a reabsorção de albumina em túbulo proximal renal encontram-se alterados na hipertensão essencial. Este trabalho teve como objetivo investigar as bases moleculares da microalbuminúria associada à hipertensão arterial essencial, focando na reabsorção tubular de albumina. Para tanto, avaliamos a evolução temporal da excreção urinária de albumina em ratos espontaneamente hipertensos (SHR) com 6 semanas de idade (pressão arterial sistólica, PAS, = 105 ± 4 mmHg), 14 semanas de idade (PAS = 180 ± 2 mmHg) e 21 semanas de idade (PAS = 202 ± 2 mmHg). Ratos normotensos Wistar da mesma idade serviram de controle. Observou-se que a excreção urinária diária de albumina aumentou progressivamente com o aumento da pressão arterial em SHR (10,5 ± 1,9; 92 ± 7,0 e 154 ± 27 g/dia, em SHR com PAS média igual a 105, 180 e 202 mmHg respectivamente). Este aumento progressivo não foi observado em ratos normotensos com idade correspondente, indicando que este fenômeno é decorrente do aumento da pressão arterial e não pode ser atribuído ao aumento da idade dos animais durante o período estudado. A análise das proteínas urinárias por eletroforese em gel de poliacrilamida (SDS-PAGE) mostrou que SHR excretam proteínas do tamanho da albumina ou menores (< 70kDa), padrão típico de proteinúria tubular. Adicionalmente, verificou-se que os níveis de expressão dos receptores endocíticos megalina e cubilina, bem como do canal para cloreto ClC-5 diminuem progressivamente no córtex renal de SHR com o aumento da pressão arterial. Observou-se também uma diminuição significativa na expressão de uma outra macromolécula importante no processo de endocitose mediada por receptor em túbulo proximal renal, a v-H+-ATPase. Entretanto, a diminuição da expressão protéica da subunidade B2 desta ATPase foi estatisticamente significante apenas em SHR com 21 semanas comparado aos com 6 semanas de idade. Não foram encontradas alterações no padrão de expressão de componentes estruturais da barreira glomerular como a nefrina e podocina. Em suma, o nosso estudo demonstra que o aumento da excreção urinária de proteínas, especialmente de albumina, está associado com uma menor expressão de componentes essenciais do aparelho endocítico do túbulo proximal renal. É tentador especular que a disfunção da via endocítica no túbulo proximal renal possa ser o principal mecanismo subjacente ao desenvolvimento de microalbuminúria na hipertensão / Epidemiological evidences indicate that the presence of microalbuminuria predicts a higher frequency of cardiovascular events and mortality in essential hypertensive patients. Microalbuminuria may arise from increased glomerular permeability and/or reduced proximal tubular reabsorption of albumin. However, it remains to be determined whether the mechanisms that regulate the renal proximal tubular reabsorption of albumin are altered in essential hypertension. The purpose of this work was to investigate the molecular basis of microalbuminuria in essential hypertension, focusing on the renal tubular reabsorption of albumin. To this end, we evaluated the temporal evolution of urinary albumin excretion in spontaneously hypertensive rats (SHR) at 6 weeks of age (systolic arterial pressure, SAP, = 105 ± 4 mmHg), 14 weeks of age (SAP = 180 ± 2 mmHg) and 21 weeks of age (SAP = 202 ± 2 mmHg). Age-matched normotensive Wistar rats were used as controls. It was observed that the daily urinary excretion of albumin progressively increased with blood pressure in SHR from 6 to 21 weeks of age (10.5 ± 1.9, 92 ± 7.0 and 154 ± 27 g in SHR with 105, 180 and 202 mmHg of average SAP, respectively). This progressive increase in microalbuminuria has not been observed in age-matched normotensive Wistar rats, indicating that this phenomenon cannot be attributed to age progression over the studied period. SDS-PAGE analysis of urinary proteins showed that microalbuminuric SHR virtually excreted proteins of the size of albumin or smaller (< 70kDa), typical of tubular proteinuria. Additionally, it was verified that the protein expression levels of the endocytic receptors megalin and cubilin as well as of the chloride channel ClC-5 progressively decreased in the renal cortex of SHR from 6 to 21 weeks of age. Moreover, it was observed reduction of expression of another macromolecule that plays an important role in the process of receptor mediated endocytosis in the renal proximal tubule, the v-H+- ATPase, was reduced. However, reduced cortical expression of the B2 subunit of the v- H+-ATPase, was only statistically significant in 21-wk-old vs. 6-wk-old SHR. Expression levels of structural components of the glomerular barrier such as nephrin and podocin were unchanged. To sum up, our study demonstrates that the increase in urinary protein excretion, especially of albumin, is associated with lower expression of key components of the apical endocytic apparatus in the renal proximal tubule. It is tempting to speculate that dysfunction of the apical endocytic pathway in the renal proximal tubule may be the major mechanism underlying development of microalbuminuria in essential hypertension

Objective: The aim of this study was to determine the prevalence of micro- or macroalbuminuria among type 1 and type 2 diabetic patients and to examine the relationship with diabetes control parameters: haemoglobin A1C (HbA1C), blood pressure (BP) and lipids. Design: Analytical cross-sectional study. Setting and subjects: The study consisted of 754 patients with either type 1 or type 2 diabetes mellitus, attending a diabetic clinic at the Kalafong Hospital in Pretoria, South Africa. Outcome measures: Micro- or macroalbuminuria and estimated glomerular filtration rate (eGFR). Results: Of all patients, 88.9% had HbA1C > 7%, and 81% had low-density lipoprotein (LDL) cholesterol ≥1.8 mmol/l. Overall prevalence of micro- or macroalbuminuria was 33.6%. Logistic regression revealed that HbA1C, duration of diabetes, systolic BP, male sex and triglycerides predicted microalbuminuria. Conclusion: The prevalence of micro- or macroalbuminuria in this study falls within the ranges of what has been previously reported in Africa. In all patients, HbA1C and duration of diabetes were the strongest predictors of microalbuminuria, and age was the strongest predictor of a low eGFR. Diabetes was poorly controlled, making the progression to end-stage renal failure a real concern in these patients. / Dissertation (MPH)--University of Pretoria, 2015. / tm2015 / School of Health Systems and Public Health (SHSPH) / MPH / Unrestricted