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Query: UMLS:C0011881 (diabetic nephropathy)
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Chronic kidney disease (CKD) has become a major health-care problem of global proportions. Progression to end-stage renal disease (ESRD), the need for renal replacement therapy, and the high annual death rate of dialysis patients are the most noticeable outcomes of CKD. Less appreciated, however, is the fact that most patients with CKD actually die mainly from cardiovascular disease, rather than progress to ESRD. Coronary artery calcification (CAC), a surrogate marker of atherosclerosis, is common in dialysis and CKD patients. Coronary artery calcium scores, as measured by ultrafast computed tomography, is an independent predictor of future cardiac events. Using this technique, several studies have documented extensive calcification in dialysis patients, a subject of several exhaustive reviews. Unfortunately, much less attention has been paid to calcification in nondialyzed patients with CKD. In this review, I will emphasize the fact that CVC is common in patients with CKD not yet on dialysis, develops early in the course of CKD, and worsens with the decline in renal function particularly among diabetics who progressed to ESRD. I will also discuss the pathogenesis of CVC in CKD patients and highlight the lack of a major role for abnormalities of mineral metabolism in the pathogenesis of calcification in CKD patients. In addition to the high prevalence of traditional risk factors for CAD, the presence of proteinuria, reduced renal function, diabetic nephropathy, and the rate of progression to ESRD may represent the main uremia-related factors that increase the risk for calcification in CKD. Finally, I will review the protective role of inhibitors of calcification in CKD.
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PMID:Cardiovascular calcification in nondialyzed patients with chronic kidney disease. 1737 87

In the present quantitative overview of outcome trials, we investigated the efficacy of amlodipine or angiotensin receptor blockers in the prevention of stroke and myocardial infarction in patients with hypertension, coronary artery disease, or diabetic nephropathy. The analysis included 12 trials of 94 338 patients. The analysis of trials involving an amlodipine group showed that amlodipine provided more protection against stroke and myocardial infarction than other antihypertensive drugs, including angiotensin receptor blockers (-19%, P<0.0001 and -7%, P=0.03) and placebo (-37%, P=0.06 and -29%, P=0.04). The analysis of trials involving an angiotensin receptor blocker group showed contrasting results between trials versus amlodipine and trials versus other antihypertensive drugs for stroke (+19% versus -25%; P<0.0001) and myocardial infarction (+21% versus +1%; P=0.03). The results of 3 trials comparing an angiotensin receptor blocker with placebo were neutral (P> or =0.14). The within-trial between-group difference in achieved systolic pressure ranged from -1.1 to +4.7 mm Hg for trials involving an amlodipine group and from -2.8 to +4.0 mm Hg for trials involving an angiotensin receptor blocker group. The metaregression analysis correlating odds ratios with blood pressure differences showed a negative relationship (regression coefficients: -3% to -8%), which reached statistical significance (regression coefficient: -6%; P=0.01) for stroke in trials involving an amlodipine group. In conclusion, blood pressure differences largely accounted for cardiovascular outcome.
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PMID:Prevention of stroke and myocardial infarction by amlodipine and Angiotensin receptor blockers: a quantitative overview. 1772 73

Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.
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PMID:Chronic kidney disease: effects on the cardiovascular system. 1760 56

Heart failure (HF) is a major contributor to poor quality of life, a leading cause of hospitalization, and cause of premature death. Both kidney disease and diabetes are major and independent risk factors for the development of heart failure, such that individuals with diabetic nephropathy are at especially high risk. Such patients not only are likely to have coronary artery disease and hypertension but also are likely to have diabetic cardiomyopathy, a distinct pathologic entity that is more closely associated with the microvascular than the macrovascular complications of diabetes. In addition to a better understanding of the epidemiology of HF, advances in noninvasive imaging have highlighted the importance of early cardiac dysfunction in diabetes and the high prevalence of HF with preserved left ventricular systolic function. Although significant renal dysfunction is usually an exclusion criterion in HF trials, diabetes is often a prespecified subgroup so that subanalyses of large multicenter clinical trials do provide some guidance in therapeutic decision-making. However, further therapies for both HF and nephropathy in diabetes clearly are needed, and a number of new therapeutic strategies that target both disorders have already entered the clinical arena.
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PMID:Heart failure and nephropathy: catastrophic and interrelated complications of diabetes. 1769 8

Hypertension, a major cardiovascular disease risk factor, is increasing in India. Though several studies have studied the prevalence and causes of hypertension in India, only few have examined the control of blood pressure (BP) among people with hypertension. The I-Target survey was carried out to assess the extent of BP control among Indian patients with hypertension receiving antihypertension medications. A total of 270 physicians from four zones of India included 3402 patients with hypertension who were undergoing treatment. They collected information on BP levels, current medication and presence of other risk factors, and determined the average systolic and diastolic BP in hypertensive patients. Of the study population, 1435 patients (42.2%) had diabetes and 787 (23.1%) had coronary artery disease (CAD). Overall, 70.5% patients did not reach target systolic BP (SBP) goal and 36.9% patients did not reach diastolic BP (DBP) goal. Only 27.3% patients had both SBP and DBP under control. Among patients with diabetes, 81.1% had uncontrolled SBP and 76.2% had uncontrolled DBP. In patients with CAD, 71.8% of SBP and 38.5% of DBP readings were outside the recommended target BP levels. Regardless of comorbidities-hypercholesterolaemia, myocardial infarct, metabolic syndrome, stroke, diabetic nephropathy or obesity--the average SBP and DBP were higher than target BP levels. Among patients with hypertension, control of BP to recommended targets was very poor, only to the extent of 27.3%. The average BP of hypertensive patients with comorbidities like diabetes and CAD was also higher than the BP goals recommended by international and local guidelines. Thus, there is an urgent need to increase awareness among patients with hypertension and to ensure that BP goals are achieved.
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PMID:Blood pressure control among Indians with hypertension: the I-Target survey. 1817 98

Diabetic nephropathy is found to be significantly associated with diabetic retinopathy and coronary artery disease. Few studies have also shown an association between diabetic nephropathy and neuropathy, and peripheral vascular disease. A cross sectional study was done among consecutive type 2 diabetics presenting to Christian Medical College and Hospital, Ludhiana from June 2004 to May 2005. Patients were subjected to the clinical and laboratory investigations 174 patients were studied over a period of one year. Diabetic nephropathy was found to be associated with proliferative diabetic retinopathy, neuropathy and cardiovascular disease by univariate analysis. In multivariate analysis, diabetic nephropathy was again significantly associated with proliferative diabetic retinopathy and coronary artery disease. We conclude that close association between diabetic nephropathy and other micro and macrovascular complications exists in our Indian patients also.
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PMID:Association between diabetic nephropathy and other diabetic microvascular and macrovascular complications. 1897 77

The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study provides an extensive evidence base for the efficacy and tolerability of fenofibrate treatment in patients with type 2 diabetes mellitus, predominantly in a primary prevention setting. The FIELD study did not show a significant effect with fenofibrate on the primary end point, coronary artery disease death or nonfatal myocardial infarction (p = 0.16). Treatment with fenofibrate did reduce all cardiovascular disease (CVD) events, the secondary end point (by 11%, p = 0.035). The primary end point was reduced by the same percentage. The modest percent reduction in the primary and secondary end points is probably a result of a number of study confounders, notably an excess of statin drop-in therapy and disproportionate treatment with other drugs for CVD prevention in the placebo arm. Estimates of relative risk reduction used by the FIELD investigators to equalize the use of statins in the fenofibrate and placebo groups suggest a true benefit of treatment on reduction of CVD events of 17%-21%. There was no excess of elevated serum liver enzymes and no cases of rhabdomyolysis in patients receiving both fenofibrate and a statin. Prevention of microvascular disease, specifically, reduction in the rate of laser treatment for retinopathy (by 30%, p = 0.0003), progression of albuminuria (p = 0.002), and nontraumatic amputations (by 38%, p = 0.011), may well be the most innovative finding of the FIELD study, especially in view of the current lack of effective preventative treatments for diabetic retinopathy and the need for additional treatments that slow the progression of diabetic nephropathy. These findings also give impetus to investigate mechanisms by which fenofibrate and peroxisome proliferator-activated receptor-alpha activation may protect the endothelium of small blood vessels in patients with type 2 diabetes.
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PMID:After the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: implications for fenofibrate. 1908 88

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

Cardiovascular disease is a frequent complication of renal failure and is the most common cause of death in patients with chronic kidney disease (CKD). Accelerated atherogenesis has been widely documented in CKD and diabetic nephropathy is the leading cause of renal failure worldwide. Furthermore, CKD promotes hypertension and dyslipidemia, which in turn may contribute to the progression of renal failure. All together, hypertension, dyslipidemia and diabetes are considered major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Elevated inflammatory mediators and activation of the renin-angiotensin system contribute through enhanced production of reactive oxygen species, to atherogenesis in CKD. Vascular calcification is also important. Calcification of arteries occurs in the intima in association with atherosclerosis, where it may contribute to plaque formation, and in the media, where it causes stiffening. Increased serum levels of calcification promoters, such as hyperphosphatemia, and a decrease in circulating and local inhibitors of calcification, favor vascular calcification. On the other hand, transdifferentiation of vascular smooth muscle cells to osteblast-like cells would be the pivotal event in calcification. Bone morphogenetic protein agonists and antagonists are playing a role in this osteogenic differentiation. Accelerated atherosclerosis and media calcification will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with CKD.
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PMID:[Vascular damage in chronic kidney disease]. 1930 81

With the arrival of a new class of drugs for the management of hypertension comes the need to define its role. Aliskiren, an orally administered direct renin inhibitor, has been approved by the US Food and Drug Administration for the treatment of hypertension. Currently, the recommendation for choice of agent in the treatment of uncomplicated hypertension is a thiazide diuretic, and for patients with diabetic nephropathy, heart failure, or coronary artery disease, an angiotensin-converting enzyme inhibitor. Patients for whom an angiotensin-converting enzyme inhibitor is indicated who are intolerant as a result of side effects should take an angiotensin receptor blocker. A new class of medicines that specifically inhibits renin is an exciting addition to the armamentarium in the treatment of hypertension. This article explores the role of aliskiren in treating hypertension as well as its side effects and appropriate dosing.
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PMID:Renin inhibition for hypertension: selecting the right role for a new class of drug. 1943 72


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