Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

A 47-year-old female with diabetic nephropathy presented with acute onset of severe back pain and progressive weakness in both lower extremities. Neuroimaging revealed a spinal epidural hematoma extending from the T-3 vertebra to the sacrum. Removal of all or every other lamina on levels with epidural hematoma and emergent evacuation of the hematoma were planned. T-9 and T-10 laminectomies were performed, but excessive bleeding during the operation prompted us to abandon the procedure. Plasma and desmopressin administration controlled the bleeding from the drain 8 hours after the operation. Follow-up neuroimaging one month later revealed total resolution of the hematoma with improved neurological status. Acute spinal epidural hematomas extending over more than 15 segments are extremely rare and the surgical treatment is still challenging. Coexisting hemorrhagic diathesis creates more problems. Conservative treatment may be the best option.
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PMID:Multilevel acute spinal epidural hematoma in a patient with chronic renal failure--case report. 1296 10

Bacteremia from central venous catheter (CVC) infection causes morbidity and mortality in patients on hemodialysis (HD). Diagnosis of the infection can be difficult and may require special imaging. A 70-year-old man with diabetic nephropathy was on HD for 11 months through a permanent CVC. Because of symptomatic osteoporosis, he had kyphoplasty in three lumbar vertebrae (L2, L3, L4) 6 months after starting HD. Severe back pain persisted after kyphoplasty. Throughout the HD period, the exit site of the CVC had a clean appearance, there was no fever, and blood leukocyte counts were normal. During the 11th month of HD, he complained of subjective fever at home. Blood count revealed normal leukocyte count with neutrophilic predominance and blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA). Echocardiogram revealed no heart valve vegetations, but irregular thickening of the CVC wall. Fluorodeoxyglucose positron-emission tomography-computed tomography (FDG-PET-CT) revealed severe inflammation of the CVC wall and a picture consistent with osteomyelitis and severe destruction of the body of the 11th thoracic vertebra. He was treated with intravenous vancomycin and removal of the CVC, the wall of which was grossly inflamed and grew in culture MRSA. Three weeks later, he discontinued HD because of persistent severe back pain. CVC infection with bacteremia and remote infectious foci having grave sequelae can develop in HD patients with paucity of clinical manifestations. FDG-PET-CT is a useful imaging tool in establishing the presence and extent of both the CVC infection and remote metastatic infectious foci.
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PMID:Hemodialysis catheter infection with unusual presentation and grave outcome. 2211 28

The burden of chronic kidney disease (CKD) is increasing worldwide. Renal replacement therapy is the lifesaving treatment modality in end-stage renal disease. Among various renal replacement modalities, hemodialysis (HD) is widely preferred one. Intradialytic complications are common and mostly inevitable. This study was conducted to determine pattern of intradialytic complications and its associated factors. This is a cross-sectional study conducted for six months duration among all CKD patients who were undergoing maintenance HD in B. P. Koirala Institute of Health Sciences, Dharan, Nepal. Of 228 patients, most were male 141 (61.8%) with median age 50 years (22-77). In this study, diabetic nephropathy (38.2%) was the most common etiology of CKD. Among 228 patients, complications were noted in 133 (58.3%) patients. Common complications were chills and rigor (44.3%), backache (30.7%), and hypotension (27.2%) in the study patients. Intradialytic complications were significantly associated with increasing age (P <0.001) and irregular HD (P <0.001). The common complications among CKD patient undergoing maintenance HD were chills, backache, and hypotension. Increasing age and irregular HD were significantly associated with intradialytic complications.
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PMID:Spectrum of complications in chronic kidney disease patients undergoing maintenance hemodialysis: An experience of a tertiary care center in Nepal. 3080 83