Enyioma N. Obineche

Morphological changes in the rat kidney following long-term diabetes.

The morphological basis of diabetic nephropathy has been studied using light and electron microscopy. Kidneys of streptozotocin-induced diabetic rats were examined on the light microscope at 4 weeks and 8 months after induction of diabetes mellitus. In addition, the 8-month diabetic kidneys were examined with the electron microscope. Renal hypertrophy was evidenced by the increase in the weight of kidneys of diabetic rats. Whilst the diabetic kidneys were approximately twice as large after 4 weeks they were only 30% larger compared to age-matched controls after 8 months of induction of diabetes. After 4 weeks, light microscopy revealed dilated tubules within the cortex of the diabetic kidneys. Light microscopy showed a significant amount of destruction of the distal convoluted tubules while electron microscopy revealed a spectrum of damage that included basement membrane thickening, loss of podocytic foot processes, disruption of tubular basal infoldings and their related mitochondria and fibrosis of the tubules 8 months after induction of diabetes. It is concluded that renal hypertrophy persists after a prolonged occurrence of diabetes but the extensive damage and loss of renal tissue including the loss of the foot processes of podocytes might be partly responsible for the clinical presentation of diabetic nephropathy.

Prevalence and determinants of microalbuminuria among diabetic patients in the United Arab Emirates

BackgroundMicroalbuminuria (MA) represents the earliest clinical evidence of diabetic nephropathy and is a predictor of increased cardiovascular morbidity and mortality. The aim of this study was to determine the prevalence of MA among diabetic patients in the Al-Ain district of the United Arab Emirates (UAE).MethodsThe study was part of a general cross-sectional survey carried out to assess the prevalence of diabetes mellitus (DM) complications in Al-Ain district, UAE and was the first to assess the prevalence of MA among diabetic patients. A sample of 513 diabetic patients with a mean age of 53 years (SD: ± 13) was randomly selected during 2003/2004. All patients completed an interviewer-administered questionnaire and underwent medical assessment. First morning urine collections were obtained and were tested for clinical proteinuria using urine dipsticks and for MA using the single Micral-Test II strips.ResultsMA was found in 61% (95% CI: 56.7–65.7) of the sample and the rate was significantly higher among males, positively related to body mass index (BMI), type 2 DM and presence of other DM complications such as diabetic retinopathy and neuropathy. Of the total sample population, 12.5% (95% CI: 8.1-14.1) had clinical proteinuria.ConclusionThe prevalence rate of MA was considerably high ( 61%) among diabetic patients in the UAE. Therefore, regular screening for MA is recommended for all diabetic patients, as early treatment is critical for reducing cardiovascular risks and slowing the progression to late stages of diabetic nephropathy (overt proteinuria and end-stage renal disease).

Under- treatment and under diagnosis of hypertension: a serious problem in the United Arab Emirates

BackgroundHypertension, notably untreated or uncontrolled, is a major risk factor for cardiovascular diseases (CVD) morbidity and mortality. In countries in transition, little is known about the epidemiology of hypertension, and its biochemical correlates. This study was carried out in Al Ain, United Arab Emirates, to characterize self-reported (SR) normotensives and hypertensives in terms of actual hypertension status, demographic variables, CVD risk factors, treatment, and sequalae.MethodsA sample, stratified by SR hypertensive status, of 349 SR hypertensives (Mean age ± SD; 50.8 ± 9.2 yrs; Male: 226) and 640 SR normotensives (42.9 ± 9.3 yrs, Male: 444) among nationals and expatriates was used. Hypertensives and normotensive subjects were recruited from various outpatient clinics and government organizations in Al-Ain city, United Arab Emirates (UAE) respectively. Anthropometric and demographic variables were measured by conventional methods.ResultsBoth under-diagnosis of hypertension (33%) and under-treatment (76%) were common. Characteristics of undiagnosed hypertensives were intermediate between normotensives and SR hypertensives. Under-diagnosis of hypertension was more common among foreigners than among nationals. Risk factors for CVD were more prevalent among SR hypertensives. Obesity, lack of exercise and smoking were found as major risk factors for CVD among hypertensives in this population.ConclusionHypertension, even severe, is commonly under-diagnosed and under-treated in the UAE. Preventive strategies, better diagnosis and proper treatment compliance should be emphasized to reduce incidence of CVD in this population.

Plasma BNP in patients on maintenance haemodialysis: a guide to management?

The number of patients requiring long-term haemodialysis is increasing throughout the world. Cardiovascular disease is much more common in these patients than in the general population and accounts for the majority of deaths. New approaches to management are clearly needed to reduce this excessive cardiovascular burden. We propose that circulating levels of the cardiac natriuretic peptides, B-type natriuretic peptide (BNP) in particular, might provide a useful, objective guide to the management of their hydration status and pharmacotherapy. An overview of the literature shows that plasma levels of the cardiac natriuretic peptides are increased in this patient population and reflect cardiac preload and afterload along with cardiac pathology, thereby providing an index of cardiovascular (especially cardiac) stress and distress. Circulating levels of the cardiac peptides change in parallel with cardiac load, especially across haemodialysis. Furthermore, there is robust evidence that natriuretic peptide levels are predictive of cardiovascular outcome in these patients. Accordingly, we hypothesize that management of their haemodialysis, and pharmacotherapy designed specifically to lower plasma BNP levels to, or close to, the normal range, will reduce the excessive burden on the cardiovascular system and thereby ultimately lower the incidence of cardiovascular disease. We outline, in broad terms, how a trial to test this hypothesis might be designed.

Predicting proteinuria in hypertensive pregnancies with urinary protein-creatinine or calcium-creatinine ratio

Objective:Evaluate the value of random urinary protein-creatinine (PrCr) and calcium-creatinine (CaCr) ratios to predict 24-h proteinuria in hypertensive pregnancies.Study Design:Spot urine samples were collected before routine 24-h urine collections from consecutive pregnant women with hypertension (n=83). Reliability of spot urinary PrCr and CaCr to detect significant proteinuria (⩾300 mg/day) using 24-h urine protein as ‘gold-standard’ was assessed by receiver-operating characteristic (ROC) curve.Results:Fifty-one patients (61.4%) had significant proteinuria (45 pre-eclampsia, 5 superimposed pre-eclampsia, 1 renal hypertension). Area under ROC curve to predict proteinuria was 0.82 (95% confidence interval (CI) 0.73 to 0.92, P<0.001) for PrCr and 0.55 (95% CI 0.43 to 0.68, P=0.2) for CaCr. A cutoff value of >0.19 for PrCr best predicted significant proteinuria with sensitivity, specificity, positive and negative predictive values and likelihood ratios (positive and negative), respectively, of 80.4, 68.8, 80.4, 68.8%, 2.57 and 3.51.Conclusion:Spot urinary PrCr predicts total urinary protein excretion in hypertensive pregnancies.

Alterations in atrial natriuretic peptide and its receptors in streptozotocin-induced diabetic rat kidneys

In this study the effect of diabetes mellitus on atrial natriuretic peptide (ANP) receptors in streptozotocin- (STZ-) induced diabetic rat kidneys was studied. Moreover, plasma ANP concentration was evaluated in diabetic and control rats by using radioimmunoassay. In addition, the expression of ANP in the kidneys of control and diabetic rats was evaluated by immunohistochemistry. Body-weight loss and increased glucose levels were used as indices of diabetes mellitus in the STZ-induced rats. There was a significant loss in the body weight of the diabetic rats compared to controls. The efficacy of STZ administration was confirmed by rising blood glucose levels, which were significantly higher in diabetic rats compared to controls. Plasma ANP concentration was significantly greater in the diabetic rats in comparison with controls. Moreover, our immunohistochemical results show that the expression of ANP in diabetic rats was higher than that in age-matched controls. ANP was observed in the cells lining the proximal convoluted tubules in the cortex. The distribution and levels of ANP receptors in the kidneys of diabetic rats and age-matched controls were investigated using quantitative receptor autoradiography. Our results demonstrate significant decrease in ANP receptors in the kidneys of the diabetic rats compared to controls. The significant decrease was found in the juxtaglomerular medulla, inner medulla, and the papillae. The decrease in ANP receptors observed in the diabetic kidneys could have pathological consequences resulting in renal resistance to ANP in diabetes. (Mol Cell Biochem 261: 3–8, 2004)

Plasma Endothelin-1, Homocysteine, and Nitric Oxide Levels in a Multiethnic Hypertensive Cohort from the United Arab Emirates

Background : Hypertension is a major cause of morbidity and mortality in the United Arab Emirates (UAE). However, little is known regarding vasoactive biomarkers and lipid profiles in hypertensives versus normotensives in this heterogeneous ethnic population. Aims: This study aimed to evaluate plasma endothelin-1 (ET-1), homocysteine (Hcy), nitric oxide (NO), and lipid parameters among hypertensive subjects and normotensives controls in a heterogeneous ethnic population from the UAE. Methods: We collected venous samples from 164 hypertensive and 112 normotensive subjects matched for age, gender and ethnicity to determine their plasma levels of ET-1, Hcy and NO as well as their lipid profile. Results: Hypertensive subjects displayed significantly higher plasma levels of ET-1 (p < 0.001) and NO (p < 0.001) but lower insulin levels (P<0.006) than normotensives. In contrast, there was no statistically significant difference with regard to Hcy concentrations. Very low-density lipoprotein (VLDL) and triglycerides (TG) levels were significantly (p < 0.01) higher in hypertensives than controls. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-esterified fatty acids (NEFA) were significantly lower (p < 0.01) in hypertensives than normotensives. Conclusion: In our heterogeneous ethnic population, levels of ET-1 and NO, but not of Hcy, were found to be associated with hypertension and may possibly contribute to an increased systemic vascular resistance among hypertensives. Whether the elevated ET-1 results are because of overproduction or decreased clearance remains to be ascertained Elevated levels of TG and VLDL, alongside with unaltered TC levels, seem to indicate the presence of type IV hypertriglyceridaemia.

Alterations in Atrial Natriuretic Peptide and Its Receptor Levels in Long-Term, Streptozotocin-Induced, Diabetes in Rats

Abstract:  Diabetes mellitus (DM) shows a markedly increased incidence of cardiovascular pathology that leads to hypertension, endothelial macro‐ and microangiopathy, diabetic nephropathy, and myocardial infarction. Atrial natriuretic peptide (ANP), is a 28 amino acid peptide hormone synthesized mainly by the heart atria and ventricles. It has potent diuretic and natriuretic properties. In this article the effect of long‐term DM on blood plasma, kidney, and heart atrial and ventricular ANP concentrations were evaluated in streptozotocin (STZ)‐induced 8‐month diabetic and control rats by using radioimmunoassay (RIA). Moreover, ANP receptors in STZ‐induced, 8‐month diabetic rat kidneys were studied by receptor autoradiography. In addition, the expression of ANP concentrations in the kidney of diabetic and control rats was evaluated by means of immunohistochemistry. Body weight loss and increased blood glucose levels were used as indices of DM in the STZ‐induced diabetic rats. Our results showed significantly higher ANP concentrations in diabetic plasma ( P < 0.05), kidney ( P < 0.01), heart atria ( P < 0.05), and ventricles ( P < 0.01) compared to controls. We also demonstrated a significant decrease in ANP receptors in the outer cortex ( P < 0.05), juxtaglomerular medulla ( P < 0.05), and papilla ( P < 0.05) of 8‐month diabetic rat kidneys compared to controls. The observed increase in ANP levels in plasma and kidney could play a role in the development of diabetic nephropathy: probably by reducing the levels of ANP receptors in diabetic kidney. Furthermore, the role of ANP in the STZ‐induced diabetic heart merits additional study.

Leptin, lipid and lipid metabolism-related hormones in chronic renal failure in Arabia

SUMMARY: In patients with chronic renal failure (CRF), hyperleptinaemia has been widely reported, but the exact mechanisms leading to elevated leptin levels are unclear. Impaired renal clearance of leptin and the influence of other hormones may be important. In this study, we measured serum leptin levels in 150 patients on haemodialysis, peritoneal dialysis or in the predialysis phase of CRF. Furthermore, we measured plasma levels of insulin, growth hormone (GH) and insulin‐like growth factor 1 (IGF‐1), as well as plasma levels of triacylglycerols and total low density lipoprotein (LDL)‐ and high density lipoprotein (HDL)‐cholesterol. We observed significantly elevated levels of leptin, particularly in female patients, and leptin was shown to correlate significantly with insulin, total and LDL‐cholesterol and log triacylglycerols. Leptin was inversely correlated with GH concentrations, but was not correlated with IGF‐1 levels. Despite the multiple correlations established between leptin levels and other variables, only hyperinsulinaemia in CRF seems to be important as a determinator of leptin levels.

LOSS OF KIDNEY IGF-1 RECEPTORS IN EXPERIMENTAL LONG-TERM DIABETIC RATS

The present study was undertaken to assess the long-term effects of streptozotocin-induced diabetes mellitus on insulin-like growth factor-1 (IGF-1) receptors in rat kidneys. Morphological changes were also evaluated using light and electron microscopy. Using receptor autoradiography the levels of IGF-1 were investigated in rat kidneys diabetic for eight months and controls. Sections from both diabetic and control rats were stained with haematoxylin and eosin for morphological studies. Ultra-thin kidney sections were examined using a transmission electron microscope. IGF-1 receptors were significantly lower in the cortex and the medulla of the diabetic rats compared with controls. Morphological differences between normal and diabetic kidneys were observed in both the cortex and medulla. Glomerular changes and necrosis of the renal cortical and medullary parenchyma were demonstrated in the diabetic rats. Necrosis of cells of the collecting ducts and loops of Henle could explain the loss of IGF-1 receptor concentration in the medulla. Shrinkage of glomeruli and normal proximal convoluted tubules of diabetic kidneys were also observed. Our results also revealed extensive damage to the distal convoluted tubules that have not been reported to possess any insulin-like growth factor-1 receptors. Our results demonstrate a reduction of kidney IGF-1 receptors after long-term diabetes mellitus possibly because of the extensive morphological loss of renal tissue. It could be speculated that early administration of IGF-1 might be useful in longterm diabetes mellitus to prevent the degeneration and/or help regeneration of damaged renal tissue.