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Genetically hypertensive rats of the Lyon strain (LH) associate high blood pressure (BP), exaggerated salt-sensitivity, and a metabolic syndrome made of overweight together with increased plasma lipids and insulin/glucose ratio. A genetic mapping study in a large population of F2 rats derived from a cross between hypertensive (LH) and normotensive rats (LN) showed the existence, on chromosome 17, of two clusters of Quantitative Traits Loci (QTLs). The first one was associated to morphological parameters whereas the second influenced blood pressure and plasma lipids level. In order to determine the functional importance of this QTLs, we generated a consomic strain LH-17BN in which the LH chromosome 17 has been fully substituted by a normotensive Brown Norway (BN) one. These LH-17BN, as well as LH and BN male rats of the parental strain were phenotyped. This included radio telemetric measurement of BP during normal and elevated salt intake (1% and then 2% in the drinking water) as well as the determination of morphological, metabolic (triglycerides, cholesterol) and renal (creatinine clearance, proteinuria) parameters. LH-17BN, compared to LH rats, exhibited significant decreases in body weight and blood pressure. Renal functions are improved (decreased of proteinuria). Finally, plasma triglycerides were reduced and reach the level observed in BN rats. In conclusion, the present work demonstrates that, in our model, chromosome 17 contains genes which influence morphology, blood pressure, renal function, and lipid metabolism. Interestingly, chromosome 17 almost completely explains the spontaneous hypertriglyceridemia observed in Lyon Hypertensive rats.
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PMID:[Importance of chromosome 17 in genetically hypertensive rats of the Lyon strain (LH): study of a consomic strain]. 1792 82

Abnormal glucose metabolism (AGM) is common but underestimated in patients with coronary heart disease (CHD). Here, we reported 898 in-hospital patients with primary hypertension (PH) at the university hospitals in developed regions of China. Oral glucose tolerance test (OGTT) was performed in those without known type-2 diabetes mellitus (2-DM). A total of 158 patients had known 2-DM and 32 were newly diagnosed as 2-DM by fasting blood glucose (FBG). OGTT revealed that 83 had 2-DM and 296 had impaired glucose tolerance (IGT). The proportion of 2-DM and AGM increased from 21.2 to 30.4% and from 57.5 to 68.7% upon OGTT. Prevalence of AGM and 2-DM increased with the increase of age, and incidence of AGM and 2-DM was significant higher in patients with risk factors (including CHD, overweight, hyperlipidaemia, proteinuria) than those without risk factors mentioned above. Glucose was not sufficiently controlled in 55.1% of the patients with 2-DM upon treatment, well controlled in 35.4% and not controlled in 9.5%. So AGM is also prevalent in PH patients especially the elders and those with risk factors, which was underestimated in most cases. Moreover, much lower awareness, treatment and control of 2-DM occurred in some regions of China, thus strengthening health education for patients and heightening consciousness of doctor are very important and eminent. Except for FBG, more attention should be paid to postprandial blood glucose ignored before, and OGTT should be a routine procedure in PH patients, especially in older patients and those with the factors mentioned above.
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PMID:Glucometabolic state of in-hospital patients with primary hypertension in sub-population of partial regions in China. 1820 32

Leptin, one of adipocytokines, plays a wide range of important roles in reproductive biology. We have previously reported that low hypo-adiponectinemia might be involved in the pathophysiology of overweight preeclampsia (PE) patients. Moreover, recent reports have underscored the importance of circulating angiogenic factors in the pathophysiology of PE. Here, we examined whether leptin in conjunction with adiponectin and/or angiogenic factors plays some role in the pathophysiology of PE. We performed a cross-sectional study in 34 PE patients and normal pregnancies matched for gestational age and body mass index as controls. We measured serum concentrations of leptin, adiponectin, the angiogenic factors vascular endothelial growth factor (VEGF), placental growth factor, and the soluble VEGF receptors sFlt-1 and sFlk-1. We observed that leptin levels in PE patients were significantly higher compared with those in controls, but did not observe significant differences between normal- and overweight patients in both groups. We also showed a significant negative correlation between leptin and adiponectin in controls, but not in PE patients. There was a significant correlation between leptin and sFlt-1 in PE patients, while there were significant differences of body mass index, mean blood pressure and proteinuria between high and low leptin/sFlt-1 ratio group in PE patients. Moreover, there was a significant difference of leptin level between IUGR and normal growth group in PE patients. These results suggest that the circulating increased leptin might be derived mainly from the placenta and regulated by the placental hypoxic condition, whereas adiponectin might be derived mainly from adipose tissue; and that leptin might play some role through insulin resistance, autonomic activation, or direct effect on endothelium with other angiogenic factors in pathophysiology of PE compared with the exaggerated release of adiponectin from adipose tissue.
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PMID:Circulating leptin and angiogenic factors in preeclampsia patients. 1849 Aug 35

Idiopathic nodular glomerulosclerosis is an enigmatic condition closely resembling diabetic nodular glomerulosclerosis without evidence of diabetic mellitus or other specific disease. Idiopathic nodular glomerulosclerosis remains a rare disease entity with an unclear pathogenesis. Clinicopathologic features of 15 patients with idiopathic nodular glomerulosclerosis were evaluated in a retrospective review of renal biopsies between 1998 and 2007. Our study cohort consisted predominantly of older (mean age, 64.2 years) white (73%) women (67%). Fourteen patients (93%) had a history of hypertension, and 10 (67%) were active smokers at the time of biopsy. Nine patients (60%) were obese (body mass index, >30 kg/m(2)) and 4 (27%) were overweight (body mass index, 25-29.9 kg/m(2)). Fourteen patients (93%) presented with renal insufficiency with mean serum creatinine level of 2.8 mg/dL. All 15 patients presented with proteinuria (mean urinary protein excretion, 5.6 g/24 h). Eleven patients (73%) presented with nephrotic-range proteinuria and 8 (53%) with nephrotic syndrome. Histopathologic findings showed nodular glomerulosclerosis (100%), moderate to severe arterio-arteriolosclerosis (100%), and glomerular basement membrane thickening (100%). Immunofluorescence and electron microscopy studies had no other specific findings. Our results confirm previous studies of a close association of hypertension and smoking with idiopathic nodular glomerulosclerosis. A significantly higher incidence of obesity and overweight in patients with idiopathic nodular glomerulosclerosis suggests that increased body mass index may also contribute to the development and progression of idiopathic nodular glomerulosclerosis.
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PMID:Idiopathic nodular glomerulosclerosis: a clinicopathologic study of 15 cases. 1870 Nov 35

TREATMENT OF ARTERIAL HYPERTENSION - Blood pressure (BP) should be regularly measured in all patients with CKD (Strength of Recommendation C). - BP control and proteinuria reduction delay progression of CKD (Strength of Recommendation A) and reduce cardiovascular risk (Strength of Recommendation C). Thus, control of both factors should be the treatment objective. - The BP target in patients with CKD should be < 130/80 mmHg, and 125/75 mmHg if proteinuria is > 1 g/24 hours (Strength of Recommendation A). - Lifestyle changes should be made: low-sodium diet (less than 100 mEq/day of sodium or 2.4 g/day of salt); weight reduction if patient is overweight (body mass index 20-25 kg/m2); regular aerobic physical exercise and moderate alcohol intake for BP control and prevention of cardiovascular risk (Strength of Recommendation A). - The choice of the antihypertensive drug in patients with CKD depends on the etiology of CKD, cardiovascular risk, or presence of clinical or subclinical cardiovascular disease (Strength of Recommendation A). - Two or more antihypertensive drugs are usually required to control blood pressure in patients with CKD (Strength of Recommendation B), and will frequently include a diuretic, which in stages 4-5 should be a loop diuretic (Strength of Recommendation B). - Renin-angiotensin-aldosterone system (RAAS) inhibitors are first choice drugs in patients with diabetic nephropathy, patients with non-diabetic nephropathy with a protein/creatinine ratio higher than 200 mg/g, and patients with heart failure (Strength of Recommendation A). The combination of ACEIs and ARBs is indicated for reducing proteinuria that remains high despite treatment with a RAAS inhibitor, provided potassium levels do not exceed 5.5 mEq/L (Strength of Recommendation B). - When RAAS blockers are started or their dose is changed in patients with advanced CKD, kidney function and serum potassium levels should be monitored at least after 1-2 weeks. DIAGNOSIS AND TREATMENT OF DYSLIPIDEMIA - A complete evaluation of the lipid profile including total cholesterol, LDL-C, HDL-C, and triglycerides should be performed in any patient with CKD at baseline and at least annually (Strength of Recommendation B). - In patients with stage 4-5 CKD and LDL-C >or= 100 mg/dL, treatment to decrease levels to < 100 mg/dL should be considered because of their high CV risk. This reduction is recommended in secondary prevention and in primary prevention in diabetic patients. Lipid-lowering treatment is recommended in all other patients, although no evidence showing its benefits is available yet (Strength of Recommendation C). - In patients with stage 4-5 CKD and triglyceride levels >or= 500 mg/dL which are not corrected by treating the underlying cases, treatment with triglyceride-lowering drugs may be considered to reduce the risk of pancreatitis. However, treatment with fibrates should be used with caution, and these drugs should not be associated to statins due to the risk of rhabdomyolysis (Strength of Recommendation C). There is little experience on the efficacy and safety of omega-3 fatty acids for the treatment of hypertriglyceridemia in patients with grade 4-5 CRF, but they may be considered a possibly safer alternative to fibrates (Strength of Recommendation C). SMOKING - Smoking is a cardiovascular risk factor and a risk factor for progression of kidney disease in patients with CRF (Strength of Recommendation B). - Use of active measures to achieve smoking cessation is recommended in patients with CRF (Strength of Recommendation C). HOMOCYSTEINE - Hyperhomocysteinemia has been postulated as a cardiovascular risk factor in the general population and in kidney patients, but the available evidence is not consistent. - There is no evidence that vitamin therapy decreases cardiovascular risk in patients with CRF, and recommendation of routine vitamin measurement and start of vitamin therapy to reduce cardiovascular risk in these patients is therefore questionable (Strength of Recommendation B). LEFT VENTRICULAR HYPERTROPHY - Left ventricular hypertrophy (LVH) is a cardiovascular risk factor in patients with CRF (Strength of Recommendation B). - It is advisable to perform an echocardiogram at baseline and every 12-24 months and to consider treatments allowing for LVH regression (Strength of Recommendation C). The approach to LVH should be early and multifactorial because its reversibility is limited once established (Strength of Recommendation C). - RAAS blockade with ACEIs or ARBs partially reverts LVH in patients with CRF (Strength of Recommendation B). ANTI-PLATELET AGGREGATION - Because of the high cardiovascular risk in patients with CKD, anti-platelet aggregant therapy, especially low-dose aspirin, would be indicated in patients with type 2 diabetes as primary prevention, and in all patients with CKD as secondary prevention. There is however no evidence of the benefits of anti-platelet aggregant therapy in primary prevention in patients with CKD, particularly in stages 4-5; indication for treatment in this situation should therefore be individualised because of its greater risk of bleeding. - Adequate good blood pressure control should previously be achieved to minimise the risk of haemorrhagic stroke (Strength of Recommendation C).
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PMID:[Arterial hypertension and dyslipidemia in patients with chronic kidney disease (CKD). Anti-platelet aggregation. Goal oriented treatment]. 1901 37

To evaluate the diabetic complications and fate of diabetic nephropathy in Saudi population, we studied 184 diabetic nephropathy (DN) patients who were referred to nephrology clinic of King Khalid University Hospital, Riyadh, Saudi Arabia from January 2003-June 2006. The patients had mean age of 61.9 +/- 13.1 years, included 128 (69.6%) males, and were followed up for a mean period of 10.2 +/- 1.5 years. The mean duration of diabetes mellitus (DM) was 19.5 +/- 5.8 years, and duration of nephropathy was 7.7 +/- 3.3 years. Family history of DN was documented in 52 (28.2%) patients. At initial visit, the mean systolic blood pressure was 164 +/- 14.5 mmHg, the mean diastolic blood pressure was 97.9 +/- 10.4 mmHg. Thirty-seven (20%) patients had normal BMI, 88 (48%) were overweight, while 55 (30%) were obese. Mean creatinine clearance was 51.7 +/- 26.3 mL/min, 24 hrs urinary proteins 1.99 +/- 2.48 gm/day, HbA1C 9.2 +/- 1.8 %, triglyceride 2.1 +/- 1.3 mmol/L, and cholesterol 5.17 +/- 1.54 mmol/L. Diabetic complications included angiography proven coronary artery disease in 106 (57.6 %) patients, stroke in 21 (11.4%), myocardial infarction (MI) in 27(14.6%), angina in 87 (47.2 %), retinopathy in 82 (44.5%), Blindness in 3 (1.6%), peripheral vascular disease in 121 (65.7%), Neuropathy in 123 (66.8%), hypertension in178 (96.7%), diabetic foot in 25 (13.5%), Amputation in 10 (5.4%), and end-stage renal disease in 70 (38%). Total of 13 (7.05%) patients died in the hospital. Thirty-seven percent of patients developed > 6 concomitant complications. 28% developed 5, 17% developed 4, and the rest developed < 3. DN was relatively refractory to therapy and progressive; 123 (66.8%) patients doubled their serum creatinine in 3.59 +/- 2.88 years, 32 (17.3%) maintained stable renal function, 136 (73.6 %) deteriorated, and 12 (6.52%) improved. we conclude that the prevalence of diabetic complications is high among Saudi patients, and many had multiple complications. Baseline creatinine clearance and proteinuria, high systolic blood pressure, advanced age, and longer duration of diabetes were the most significant risk factors for developing complications.
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PMID:Microvascular and macrovascular complications in diabetic nephropathy patients referred to nephrology clinic. 1911 22

The aim of the study was to assess specific cardiovascular lesions in patients with type 2 diabetes mellitus and diabetic nephropathy (DN) and search for the methods of their correction. It included 182 overweight or obese (abdominal type) women above 55 yr with arterial hypertension (AH) divided into groups with normal or low (less than 30 ml/day) albuminuria (n = 87), albuminuria (30-300 mg/day, n = 59), proteinuria (above 30 mg/day, n = 21), and stage I-IIa chronic renal insufficiency (CRI, n = 15). It was shown that structural geometric changes in the left ventricle (LV) with the prevalence of myocardial concentric hypertrophy and diastolic dysfunction (DD), enhanced myocardial hardness, and preserved systolic function undergo progression with increasing severity of DN and decreasing glomerular filtration rate combined with poorly controlled DM2, abnormal lipid profile, long history of AH in the absence of adequate AP control, signs of vascular atherosclerosis (thickening of intima and media in carotid arteries), and large number of macrovascular complications. DN-related insulin resistance (IR) was a factor influencing LV remodeling and DD. Long-term combined therapy affecting IR and markers of cardiovascular disorders (AH, chronic hyperglycemia, dyslipidemia) promoted improvement of LV diastolic function, reverse remodeling of LV myocardium, decrease of atherosclerotic lesions and albuminurea in patients presenting with both low albuminuria and DN; in addition, it improved prognosis of the disease.
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PMID:[Cardiovascular disorders and possibilities of their therapy in patients with type 2 diabetes mellitus and diabetic nephropathy]. 2036 9

Chronic kidney disease (CKD) is a worldwide public health problem. Little is known about its burden in Africa. This paper reviews the knowledge of CKD in Kinshasa, summarizing four studies undertaken in the general population and traditional health system of Kinshasa. CKD was defined by either kidney damage (proteinuria> or =300 mg/day) or reduced kidney function (eGFR<60 ml/min/1.73 m(2)). In the general population, the prevalence of CKD all stage is 12.4 %. Our work shows also the high prevalence of proteinuria among subjects who do not have diabetes or hypertension, the lack of early detection and management of CKD risk factors in the traditional health care system leading to late referral or premature deaths, and the limits of renal replacement treatment. CKD affects young people in the DRC, in contrast to the United States, where CKD is more prevalent in older people. Major determinants of CKD in our studies were hypertension, diabetes, overweight, age, lower socioeconomic status, and Human immunodeficiency virus (HIV) infection. Glomerular nephropathy (mainly focal segmental glomerulosclerosis) remains the leading cause of end stage renal disease. An annual screening of the population for proteinuria and CKD risk factors is feasible and will, it is hoped, provide the basis for building a nationwide prevention strategy.
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PMID:[Epidemiology of chronic kidney disease in the Democratic Republic of Congo: review of cross-sectional studies from Kinshasa, the capital]. 2040 70

Preeclampsia is characterized by the onset of high blood pressure and proteinuria during pregnancy, which results in substantial maternal and neonatal morbidity and mortality. Insulin resistance has been observed before the onset of preeclampsia, and is implicated in its pathophysiology. Recently, retinol-binding protein 4 (RBP4), which carries retinol in circulation, has been shown to be a potential regulator of insulin resistance originating from adipose tissue. Here we measured insulin resistance and RBP-4 levels in patients with preeclampsia and in women with normal pregnancies matched for gestational age and body mass index at Okayama University Hospital. Our aim was to examine the potential role of RBP4 in the pathophysiology of this disorder. There were no significant differences in RBP4 levels between all patients with preeclampsia and controls. However, the RBP4 level and homeostasis model assessment as an index of insulin resistance (HOMA-IR) in overweight patients with late-onset preeclampsia were significantly higher than in overweight controls carrying normal pregnancies and in normal weight women with late-onset preeclampsia. In contrast, there were no significant differences between the overweight and normal weight groups among patients with early-onset preeclampsia and in healthy pregnant women. These data suggest that RBP4 might act in the pathophysiology of late-onset preeclampsia via increased insulin resistance in obese women.
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PMID:Retinol-binding protein 4 and insulin resistance in preeclampsia. 2117 8

Obesity is associated with the early onset of glomerulomegaly, hemodynamic changes of a hyperfiltering kidney, and increased albuminuria, which are potentially reversible with weight loss. However, pathologic lesions of focal segmental glomerulosclerosis develop in experimental models of sustained obesity, and are observed in morbidly obese humans presenting with massive proteinuria. In addition, several observational, cross sectional and longitudinal studies document that obesity is as an independent risk factor for the onset, aggravated course, and poor outcomes of chronic kidney disease, even after adjustment for confounding co-morbidities including metabolic syndrome, diabetes and hypertension, the major causes of chronic kidney disease. Early dietary intervention to reduce weight, and where necessary bariatric surgery, should be considered in the management of overweight and obese chronic kidney disease (CKD) patients.
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PMID:Obesity and chronic kidney disease. 2162 93

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