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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of streptozotocin (STZ) diabetes in hypertensive rats transgenic for the mouse ren-2 gene (TGR) has been described as a model of progressive diabetic nephropathy. We investigated the long-term course of STZ diabetes in TGR and appropriate Sprague-Dawley control rats (SD) and tested the role of angiotensin-dependent hypertension by treating rats with the angiotensin II type 1 receptor blocker losartan (1 mg.kg(-1).day(-1)) via osmotic minipumps. Five weeks after STZ injection, diabetes developed in TGR and SD. Urinary albumin excretion was increased by diabetes and, to a much higher degree, by hypertension. The effects of hypertension and diabetes were not additive, and only the effects of hypertension were ameliorated by losartan. A similar pattern was observed for cell proliferation and macrophage infiltration in the kidney. In contrast, the effects of hypertension and diabetes on glomerular collagen IV accumulation were additive 5 wk after STZ injection. In a long-term study for 20 wk after STZ, survival was better in STZ-treated TGR than in normoglycemic TGR, whereas all SD survived. Impaired creatinine clearance and increased macrophage infiltration as well as glomerular and interstitial matrix deposition were prominent in TGR compared with SD, regardless of the presence or absence of diabetes. In conclusion, STZ diabetes in TGR may be useful to study glomerular and interstitial matrix deposition early in the course of diabetes. However, the long-term course of this animal model resembles severe hypertensive nephrosclerosis, rather than progressive diabetic nephropathy.
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PMID:Renal injury in streptozotocin-diabetic Ren2-transgenic rats is mainly dependent on hypertension, not on diabetes. 1747

The aim of this study was to describe the clinical spectrum of chronic renal failure (CRF) in the elderly. The diagnosis of CRF was made using standard clinical criteria. The elderly was defined as person with over 60 years of age. In total, 200 elderly patients with CRF were evaluated between July 2002 and February 2004. Their age (male: 146; female: 54) ranged between 60 and 90 (mean 64.31+/-4.18) years. Diabetic nephropathy was the most common (46%) cause of CRF. Hypertensive nephrosclerosis, chronic interstitial nephritis and obstructive uropathy were responsible for CRF in 18%, 14% and 13% of patients, respectively. We observed chronic glomerulonephritis in 7% of elderly CRF. Urinary tract infection (55.5%), hypovolemia (22.2%), accelerated hypertension (11.1%) and sepsis (11.1%) were responsible for acute exacerbation of renal failure in 36 (18%) patients. Associated co-morbid conditions were noted in 93 (46.5%) patients. They included; coronary artery disease 46 (49.46%), cerebrovascular disease 20 (21.50%), osteoarthritis 13 (13.97%), chronic obstructive pulmonary disease 6 (6.45%), dilated cardiomyopathy 5 (5.37%), and malignancy in 3 (3.22%) patients. Acute dialytic support was required in 164 (82%) cases and remaining 36 (18%) patients received conservative management. Mortality was noted in 25 (12.5%) cases. The coronary artery disease (48%), acute pulmonary edema (20%) and hyperkalemia (12%) were the main causes of death. Subsequent evaluation revealed that 102 (51%) patients had ESRD of which only 3 (2.94%) patients could afford CAPD. A total of 11 (10.7%) patients underwent chronic maintenance hemodialysis for 3-4 months and then discontinue dialysis mainly because of financial constraints. Remaining 88 (86.27 %) patients with ESRD were discharged from hospital after symptomatic improvement with acute dialysis. Thus, diabetic nephropathy related to type-2 diabetes was the commonest cause of CRF in our elderly patients. Chronic renal failure in elderly was associated with a number of co-morbid conditions, which contributed significantly to morbidity and mortality. Acute on chronic renal failure with severe uremic complications were an important cause of hospitalization. The financial constraint was the major limiting factor for the management of elderly ESRD patients.
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PMID:Clinical spectrum of chronic renal failure in the elderly: a hospital based study from eastern India. 1709 77

End-stage renal disease (ESRD), due to its high morbidity and mortality as well as social and financial implications, is a major public health problem. Outcome depends not only on different modalities of treatment like hemodialysis and peritoneal dialysis, but also on existing co-morbidities, age, duration on dialysis, supportive therapies and infection control strategies. Thus, a detailed study becomes necessary to improve health care delivery, provide medical care and to establish a geographical reference. The present study was undertaken to characterize the ESRD patients by their demographic and co-morbid conditions and relate this to the morbidity and mortality trends. The medical records of 110 ESRD patients seen over a five-year period (June 1995 to December 1999) in two tertiary-care hospitals in Riyadh, Saudi Arabia were studied retrospectively. There were 79 (64.5%) males and 31 (35.5%) females; their age ranged from 17 to 92 years (mean age 53.8 +/- 17.8 years). Diabetes was the commonest cause of ESRD seen in 26 (26.6%) followed by nephrosclerosis, unknown etiology, lupus nephritis, pyelonephritis and primary glomerulonephritis. Diabetes mellitus was the most prevalent co-morbidity seen during the study period and occurred in 65 patients (59%) followed by heart disease in 36 (32.7%), liver disease in 30 (27.3%), cerebrovascular accidents in 13 (11.8%) and neoplasm in 11 (10%). Seven (6.3%) patients only were smokers. Hemodialysis was the most frequent treatment choice as renal replacement therapy. Among the causes of hospitalization, cardiovascular conditions were the leading single cause (19.1%), followed by access related reasons and infections (11.5% each). The overall hospitalization rate was 11.2 days/year. The overall mortality rate was 8.07 deaths/year. The leading cause of death was cardiovascular in 15 (51.7%) followed by unknown/sudden death in eight (27.5%). Other causes of death included fluid overload, gastrointestinal hemorrhage, septicemia, liver disease and pulmonary embolism. Diabetes was the commonest co-morbid cause among the deceased. Old age, diabetes mellitus, prolonged duration on dialysis and cardiac diseases were the common causes of mortality. Our findings are consistent with worldwide reports. The study provides a reference data and will hopefully be helpful in improving the medical care.
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PMID:Morbidity and mortality in ESRD patients on dialysis. 1766 Jun 70

There are racial differences in primary renal diseases for end-stage renal disease (ESRD) and the incidence and prevalence of cardiovascular disease (CVD). To reduce the number of patients with both ESRD and CVD, an effective screening method for CKD should be established. In Japan, screening with the urine dip-stick test for proteinuria has been used since 1972 targeting every child and worker and since 1983 for every resident over 40 years old. There are several reasons for continuing this screening program. First, the positive rate of proteinuria is high in the Japanese general population, especially subjects with neither hypertension nor diabetes. Most of these subjects have no symptoms, and the only sign of renal disease is asymptomatic urinary abnormalities. Second, the prevalence and incidence of glomerulonephritis, especially IgA nephropathy, are high in the Japanese and Asian races, and urinalysis is the only method for early detection of chronic glomerulonephritis. Third, 10-year survival of the ESRD patients due to glomerulonephritis was approximately twice that of ESRD patients due to diabetes and nephrosclerosis. Consequently, reducing the incidence of ESRD due to glomerulonephritis is one of the best ways to reduce the prevalence of ESRD. Furthermore, higher incidence of ESRD in Asian races than in Caucasians was reported. Proteinuria is known to be the best predictor for reducing renal function, and the urine dip-stick test for proteinuria is less expensive and is cost-effective. For an effective screening strategy to reduce the ESRD population in Japanese and Asians, universal screening with the urine dip-stick test for proteinuria could be one solution.
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PMID:Chronic kidney disease perspectives in Japan and the importance of urinalysis screening. 1817 65

Reno-vascular disease, along with diabetes mellitus, is the leading cause of dialysis in the elderly population, accounting for 50-66% of cases in patients above 65 years of age. Reno-vascular disease is a broad term, which includes renal artery stenosis, ischemic nephropathy, such as atherosclerotic obstruction, thrombo-embolic phenomenon, nephrosclerosis secondary to hypertension and acute occlusion of renal arteries (either bilateral or unilateral in singlekidney patients). Renal artery stenosis, defined as a 50% or greater occlusion of a renal artery (unilateral or bilateral), is an important cause of secondary hypertension. It often presents as drug refractory hypertension or renal insufficiency. Atherosclerotic renal artery stenosis accounts for 90% of such cases, the remaining 10% being caused by fibro-muscular dysplasia. The incidence of atherosclerotic renal artery stenosis is increasing among the aging population, who are at an increased risk due to cardiovascular complications. This is a review of the emerging trends in the diagnosis and management of renal artery stenosis.
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PMID:Renal artery stenosis: an update on diagnosis and management. 1905 47

Heterocyclic indazole derivatives are claimed in patent WO2008138448 as inhibitors of the serum- and glucocorticoid-inducible-kinase 1 (SGK1) and drugs for the pharmacological treatment of SGK1-related diseases, such as diabetes, obesity, metabolic syndrome, systemic and pulmonary hypertension, cardiac fibrosis, hypertrophy and insufficiency, arteriosclerosis, glomerulosclerosis, nephrosclerosis, nephritis, nephropathy, deranged electrolyte excretion, fibrosing and inflammatory disease (e.g., liver cirrhosis, lung fibrosis, rheumatism, arthrosis, Crohn s disease, chronic bronchitis, radiation fibrosis, sclerodermia, cystic fibrosis, scar formation and Alzheimer' disease), tumor growth, peptic ulcers and some disorders hitherto not conclusively shown to involve SGK1. Most of the claims are supported by the literature. SGK1 is ubiquitously expressed and its expression is stimulated by hyperglycemia, cell shrinkage, ischemia, glucocorticoids, mineralocorticoids and several inflammatory mediators including TGF-ss. SGK1 is activated by insulin and growth factors via the phosphatidylinositol-3-kinase pathway. SGK1 regulates ion channels (including ENaC, KCNE1/KCNQ1), carriers (including NCC, NHE3, SGLT1), Na(+)/K(+)-ATPase, enzymes (including glycogen-synthase-kinase-3) and transcription factors (including FOXO3a, ss-catenin, NF-kappaB). A gain-of-function SGK1 gene variant, carried by approximately 3 - 5% of Caucasians and approximately 10% of Africans, is associated with increased blood pressure, obesity and type 2 diabetes. In vitro and in vivo experiments suggested a critical role of SGK1 in renal fluid retention and hypertension, glucose-induced obesity, coagulation and increased matrix protein formation.
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PMID:Heterocyclic indazole derivatives as SGK1 inhibitors, WO2008138448. 2002 Dec 89

The proportion of the population that is elderly (age>or=65 years) is growing across the world. The increasing longevity of humans results in a higher number of elderly patients' presenting with multiple chronic diseases such as hypertension, diabetes, and chronic kidney disease (CKD). These problems increase morbidity and mortality in the elderly. Overactivity of the renin-angiotensin-aldosterone system (RAAS) is associated with the development of hypertension, cardiovascular events, and CKD, so targeting the RAAS is a logical therapeutic approach. Elderly patients present special concerns regarding the benefits versus risks of using RAAS blockers. Plasma renin activity declines with age, which has been attributed to the effect of age-associated nephrosclerosis. Plasma aldosterone is also reduced with age, resulting in a greater risk for hyperkalemia in older individuals, especially when coupled with the age-associated decline in GFR. Moreover, the elderly have a higher frequency of concurrent conditions and are on many medications, which may further increase the risk for adverse effects of RAAS blocking agents. Unfortunately, there is a paucity of literature that is specifically aimed at studying elderly using the RAAS blockers. We present in our in-depth review data regarding benefits and limitations of the use of the RAAS blockades on the various sites along the RAAS pathway for elderly patients. Specific attention was given to the role of combination RAAS blockade therapy and higher monotherapy dosing in the treatment of hypertension in the elderly.
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PMID:Renin-angiotensin-aldosterone system blockade effects on the kidney in the elderly: benefits and limitations. 2049 47

Diabetic nephropathy is a leading cause of end-stage renal disease. Statins may exert renoprotective effects independently of lipid-lowering properties. We investigated the pleiotropic effects of rosuvastatin on renal structure and function in streptozotocin diabetic apolipoprotein-E knockout (Apo-E(-/-)) mice, a model of progressive nephropathy in which dyslipidemia is resistant to statin treatment. These effects were compared with those observed with conventional renin-angiotensin system blockade (candesartan) or combined treatment. Nondiabetic and diabetic Apo-E(-/-) mice were randomized to no treatment or treatment with candesartan (2.5 mg/kg), rosuvastatin (5 mg/kg), or their combination per gavage for 20 wk. Urine and blood samples were collected for assessment of albuminuria, creatinine clearance, plasma lipids, glucose, and glycated hemoglobin. Renal sclerosis was analyzed on paraffin-embedded kidney sections stained with periodic acid-Schiff. Renal expression of collagen IV, fibronectin and advanced glycation end products (AGEs), receptor for advanced glycation and products (RAGE), NADPH oxidase 4 (NOX4), and nitrotyrosine was assessed by real-time PCR and/or immunohistochemistry. Diabetes-induced albuminuria was not affected by rosuvastatin and combination treatment but was prevented by candesartan. Diabetes resulted in increased creatinine clearance, which was not modified by the treatments. Rosuvastatin and/or candesartan prevented diabetes-associated renal extracellular matrix accumulation. Rosuvastatin reduced accumulation of AGEs and expression of RAGE, NOX4, and nitrotyrosine. In conclusion, in the diabetic Apo-E(-/-) mouse, rosuvastatin confers renal benefits that are independent of lipid lowering and equivalent or greater to those observed with candesartan. The combination treatment is not superior to monotherapies.
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PMID:The pleiotropic actions of rosuvastatin confer renal benefits in the diabetic Apo-E knockout mouse. 2055 45

Overweightness and obesity are associated with many hemodynamic, structural, and histopathologic alterations in the kidney and with metabolic and biochemical changes that predispose to these abnormalities. Consequent to these disorders, these individuals are more likely to develop chronic kidney disease and end-stage renal failure. Overweight and obese people are more prone to develop albuminuria and, for at least some types of kidney disease, a greater amount of albuminuria and more rapid progression of renal failure. These individuals are more likely to develop diabetes mellitus and hypertension. Diabetic nephropathy, hypertensive nephrosclerosis, focal and segmental glomerulosclerosis, renal cell carcinoma, and urate and calcium oxalate urolithiasis are the more common kidney and urological diseases reported in obese people. Preliminary data indicate that many of the clinical and nephropathologic manifestations associated with obesity can be reversed or ameliorated with reductions in body fat induced by dietary energy restriction or surgical procedures that reduce intake and gastrointestinal absorption of calories.
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PMID:The effect of obesity on chronic kidney disease. 2119 23

In patients with HIV, the use of highly active antiretroviral therapy has improved life expectancy. At the same time, this increase in life expectancy has been associated with a higher frequency of chronic kidney disease due to factors other than HIV infection. Besides HIV-associated nephropathy, a number of different types of immune complex and non-immune complex-mediated processes have been identified on kidney biopsies, including vascular disease (nephrosclerosis), diabetes, and drug-related renal injury. In this setting, renal biopsy needs to be considered in order to obtain the correct diagnosis in individual patients with HIV and kidney impairment. Many issues regarding the optimal treatment of the different pathological processes affecting the kidneys of these patients have remained unresolved. Further research is needed in order to optimize treatment and renal outcomes in patients with HIV and kidney disease.
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PMID:Treatment of HIV-associated nephropathies. 2129 58


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