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)

The kidney is one of the most important organs that play a crucial role in homeostasis and, therefore, congenital or acquired renal dysfunction causes refractory diseases, i.e., Alport's syndrome, Fabry's disease, diabetic nephropathy, IgA nephropathy, kidney cancer, transplant glomerulopathy. Nucleic acid transfection technology to the kidney is indispensable for the progress of biomedical research and the realization of gene therapy and nucleic acid drug for renal diseases. Control of renal nucleic acid transfection was difficult because of the structural complexity; however, the study of recombinant virus, synthetic carrier and physical force-mediated nucleic acid transfection to the kidney has advanced. Recombinant virus and synthetic carrier-mediated methods require long-term block of the blood or urinary flow for efficient transfection of nucleic acid because of the rich blood flow of the kidney. In contrast, physical force-mediated methods that transfect with nucleic acid via transient membrane permeability do not apprehend ischemia-reperfusion injury and, therefore, may be beneficial for nucleic acid transfection to the kidney. In this article, we collect the information of therapeutic gene, target molecule of the nucleic acid drug and target cells for renal diseases and structural property of the kidney from the point of view of nucleic acid transfection. Additively, current status of nucleic acid transfection technology to the kidney is reviewed.
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PMID:[Development of nucleic acid transfection technology to the kidney]. 1898 92

Azelnidipine has been reported to have antioxidant effects and attenuates tubulointerstitial ischemia. The aim of the present study was to determine whether azelnidipine exerts additional renoprotective effects to angiotensin II receptor blockers (ARBs) in hypertensive patients with diabetic nephropathy and microalbuminuria. 45 hypertensive patients with diabetes mellitus and microalbuminuria who were already being treated with ARBs were enrolled in this study. Azelnidipine was added to the drug treatment of 30 patients (8 mg/day, n = 15, or 16 mg/day, n = 15) whilst the remaining 15 control patients were not treated with azelnidipine. In all patients, urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and urinary liver-type fatty acid-binding protein (L-FABP) levels were significantly correlated (r = 0.587, p = 0.0006). However, urinary albumin excretion (UAE) was not correlated with the levels of urinary 8-OHdG (r = 0.1975, p = 0.2956) or urinary L-FABP (r = 0.2057, p = 0.2759). Azelnidipine significantly reduced UAE, urinary 8-OHdG and urinary L-FABP after 6 (p < 0.05) and 12 months (p < 0.05). Although blood pressure was comparable between the azelnidipine doses of 8 and 16 mg/day, the UAE (p < 0.05 after 12 months), urinary 8-OHdG (p < 0.05 after 6 and 12 months) and urinary L-FABP (p < 0.05 after 6 and 12 months) levels were more significantly reduced in patients receiving the higher dose of 16 mg/day. These data may suggest that the addition of azelnidipine treatment to therapy with ARBs has dose-dependent antioxidant and renoprotective effects beyond blood pressure-lowering effects in hypertensive diabetic nephropathy patients.
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PMID:Additional renoprotective effects of azelnidipine combined with angiotensin receptor blockers in patients with diabetic nephropathy. 1900 May 38

Diabetes is a major epidemic, and diabetic nephropathy is the most common cause of end-stage renal disease. Two critical components of diabetic nephropathy are persistent inflammation and chronic renal ischemia from widespread vasculopathy. Moreover, acute ischemic renal injury is common in diabetes, potentially causing chronic kidney disease or end-stage renal disease. Accordingly, we tested the hypothesis that acute renal ischemia accelerates nephropathy in diabetes by activating proinflammatory pathways. Lean and obese-diabetic ZS rats (F(1) hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were subjected to bilateral renal ischemia or sham surgery before the onset of proteinuria. The postischemic state in rats with obesity-diabetes was characterized by progressive chronic renal failure, increased proteinuria, and renal expression of proinflammatory mediators. Leukocyte number in obese-diabetic rat kidney was markedly increased for months after ischemia. Intrarenal blood flow velocity was decreased after ischemia in lean control and obese-diabetic rats, although it recovered in lean rats. At 2 mo after ischemia, blood flow velocity decreased further in sham-surgery and postischemia obese-diabetic rats, so that RBC flow velocity was only 39% of control in the obese-diabetic rats after ischemia. In addition, microvascular density remained depressed at 2 mo in kidneys of obese-diabetic rats after ischemia. Abnormal microvascular permeability and increases in interstitial fibrosis and apoptotic renal cell death were also more pronounced after ischemia in obese-diabetic rats. These data support the hypothesis that acute renal ischemia in obesity-diabetes severely aggravates chronic inflammation and vasculopathy, creating a self-perpetuating postischemia inflammatory syndrome, which accelerates renal failure.
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PMID:Postischemic inflammatory syndrome: a critical mechanism of progression in diabetic nephropathy. 1965 16

Compelling evidence is accumulating indicating a pathophysiological role of the serum-and-glucocorticoid-inducible-kinase-1 (SGK1) in the development and complications of diabetes. SGK1 is ubiquitously expressed with exquisitely high transcriptional volatility. Stimulators of SGK1 expression include hyperglycemia, cell shrinkage, ischemia, glucocorticoids and mineralocorticoids. SGK1 is activated by insulin and growth factors via PI3K, 3-phosphoinositide dependent kinase PDK1 and mTOR. SGK1 activates ion channels (including ENaC, TRPV5, ROMK, KCNE1/KCNQ1 and CLCKa/Barttin), carriers (including NCC, NKCC, NHE3, SGLT1 and EAAT3), and the Na(+)/K(+)-ATPase. It regulates the activity of several enzymes (e.g., glycogen-synthase-kinase-3, ubiquitin-ligase Nedd4-2, phosphomannose-mutase-2), and transcription factors (e.g., forkhead-transcription-factor FOXO3a, beta-catenin and NF-kappaB). A common SGK1 gene variant ( approximately 3 - 5% prevalence in Caucasians, approximately 10% in Africans) is associated with increased blood pressure, obesity and type 2 diabetes. In patients suffering from type 2 diabetes, SGK1 presumably contributes to fluid retention and hypertension, enhanced coagulation and increased deposition of matrix proteins leading to tissue fibrosis such as diabetic nephropathy. Accordingly, targeting SGK1 may favourably influence occurrence and course of type 2 diabetes.
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PMID:Targeting SGK1 in diabetes. 1976 91

The ultrasensitive energy sensor AMP-activated protein kinase (AMPK) orchestrates the regulation of energy-generating and energy-consuming pathways. AMPK is highly expressed in the kidney where it is reported to be involved in a variety of physiological and pathological processes including ion transport, podocyte function, and diabetic renal hypertrophy. Sodium transport is the major energy-consuming process in the kidney, and AMPK has been proposed to contribute to the coupling of ion transport with cellular energy metabolism. Specifically, AMPK has been identified as a regulator of several ion transporters of significance in renal physiology, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), the Na(+)-K(+)-2Cl(-) cotransporter (NKCC), and the vacuolar H(+)-ATPase (V-ATPase). Identified regulators of AMPK in the kidney include dietary salt, diabetes, adiponectin, and ischemia. Activation of AMPK in response to adiponectin is described in podocytes, where it reduces albuminuria, and in tubular cells, where it reduces glycogen accumulation. Reduced AMPK activity in the diabetic kidney is associated with renal accumulation of triglyceride and glycogen and the pathogenesis of diabetic renal hypertrophy. Acute renal ischemia causes a rapid and powerful activation of AMPK, but the functional significance of this observation remains unclear. Despite the recent advances, there remain significant gaps in the present understanding of both the upstream regulating pathways and the downstream substrates for AMPK in the kidney. A more complete understanding of the AMPK pathway in the kidney offers potential for improved therapies for several renal diseases including diabetic nephropathy, polycystic kidney disease, and ischemia-reperfusion injury.
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PMID:Role of the energy sensor AMP-activated protein kinase in renal physiology and disease. 2018 68

Hydrogen sulfide (H(2)S) is enzymatically generated in mammalian tissues from either L-cysteine or L-homocysteine. H(2)S possesses multiple biological activities, including regulation of vascular tone and blood pressure. Hydrogen sulfide produced in endothelial cells, vascular smooth muscle cells, and perivascular adipose tissue dilates blood vessels by activating ATP-sensitive potassium channels. In addition, H(2)S produced locally within the kidney stimulates natriuresis and diuresis by increasing glomerular filtration and inhibiting tubular sodium reabsorption. Because H(2)S is oxidized in mitochondria in pO(2)-dependent manner and ambient pO(2) is physiologically low in the renal medulla, it is expected that the activity of H(2)S is higher in the medullary region than the cortical region. H(2)S, accumulating in increased amounts in the renal medulla under hypoxic conditions, may function as an oxygen sensor that restores O(2) balance by increasing medullary blood flow, reducing energy requirements for tubular transport, and directly inhibiting mitochondrial respiration. Hypoxia is an important pathogenic factor in many renal diseases, such as ischemia/reperfusion- or nephrotoxin-induced acute renal failure, progression of chronic nephropathies, diabetic nephropathy, and arterial hypertension. Deficiency of endogenous H(2)S may contribute to the pathogenesis of these pathologies by compromising medullary oxygenation, and administration of H(2)S donors may be of therapeutic value in these disorders.
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PMID:Hypoxia in the renal medulla: implications for hydrogen sulfide signaling. 2042 75

Numerous studies have demonstrated that insulin resistance, impaired glucose tolerance, and diabetes mellitus closely correlate with cardiovascular disease. Diabetic patients frequently have multi-vessel disease, and their coronary arteries show segmental, narrow and complex stenoses with calcified plaques. The features of diabetes mellitus, such as hyperglycemia, insulin resistance and diabetic nephropathy, induce these complicated pathological conditions. In addition, diabetic patients often show silent ischemia due to diabetic neuropathy, which accounts for advanced atherosclerosis in diabetic patients. Therefore, both evaluating cardiovascular disease using non-invasive methods, such as multi-slice CT coronary angiography, and providing an appropriate treatment from an early stage of diabetes mellitus are important to prevent the development of macrovascular disease in diabetic subjects.
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PMID:[Ischemic heart disease]. 2044 92

Diabetic foot is one of the challenging diseases in vascular surgery, especially in patients with end-staged renal disease due to diabetic nephropathy. This disease is based on the neuropathic gangrene due to microangiopathy as well as on the macroangiopathy such as peripheral arterial occlusive disease. Therefore, the strategy for diabetic foot is as follows: the first step is the infection control by minor amputation and/or drainage, the second step is the assessment of the limb ischemia, and the final is the complete vascular reconstruction such as distal bypass to the crural arteries. To salvage the diabetic foot, it is important that doctors, who concern to diabetics, understand these strategies and also that they have a settled opinion for the diabetic foot.
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PMID:[Revascularization in patients with diabetes]. 2044 96

Reduced creatinine clearance is related to an increased risk for diabetic foot ulcer development. Wound healing has been reported to be worse in diabetic patients with impaired kidney functions than general diabetic population. This study aimed to investigate the effect of creatinine clearance on the short-term outcome of neuropathic diabetic foot ulcers. Data from 147 neuropathic diabetic foot ulcer episodes were included in this observational study. Patients were admitted to Dokuz Eylul University Hospital between January 2003 and June 2008. Patients were excluded if they had limb ischemia. Diabetic nephropathy was investigated by 24h urinary albumin excretion and serum creatinine levels. Creatinine clearance was calculated according to Cockcroft-Gault formula. Foot ulcers were followed up for 6 months to determine the outcome. Our short-term follow-up revealed that neuropathic diabetic ulcers healed worse in patients with decreased creatinine clearance than in those who had normal creatinine clearance. Amputation rates were also found to be higher. Our results suggest that creatinine clearance is an important factor affecting wound healing in patients with neuropathic diabetic foot ulcers.
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PMID:The effect of creatinine clearance on the short-term outcome of neuropathic diabetic foot ulcers. 2047 34

The aim of our study was to analyse the foot infections in diabetic patients. We analysed foot ulcerations in 124 diabetics who attended outpatient foot clinic, or were hospitalized in the period from 1996 to 2006. Basic neuropathy screening examination was made with cotton wisp, pin-prick, tuning fork, and monofilament. For evaluation of leg ischemia, besides the evaluation of the presence of pedal pulses, the ankle-brachial pressure index was measured. If the infection of foot ulceration was clinically present, bacteriology examinations was performed. In the case of deep wound infection, x-ray examination was made. If bone destruction was present, osteomyelitis was diagnosed by technecium bone scanning and by technecium-labelled leukocyte scan. Deformation and destruction of the bone without infection was appoited as Charcot neuroarthropathy. Foot ulcer infection was found in 58 % diabetic patients, wounds were more often deep (80 %). Infection was not associated with special location of foot ulcer. Two-third of the total infected wounds were associated with leg ischemia and 30.6 % of infected ulcer ended with leg amputation. More foot ulcer infections were found in the diabetics with HbAlc over 8 %. Infection was coupled with diabetic retinopathy (in 63 % patients) (p=0.023), and also with diabetic nephropathy (in 66 % patients) (p=0.012). Bacteriology examination revealed most often Staphylococci (45.8 %), antibiotic therapy was made most often with chinolones. Osteomyelitis was present in 34.7 % of foot ulcer infections. In 14 diabetics (56 %) after antibiotic therapy it was not necessary to perform a leg amputation. HbAlc seems to be a significant predictor of osteomyelitis (p<0.02; OR=1.76). In conclusion, we confirmed that diabetic foot infections, especially on ischemic leg, in diabetics with poor metabolic control and chronic diabetic microvascular complications, are associated with a higher risk of leg amputations. Further, it is possible to cure osteomyelitis successfully without surgery in more than half the cases (Tab. 1, Ref. 24). Full Text in free PDF www.bmj.sk.
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PMID:Influence of infection on clinical picture of diabetic foot syndrome. 2158 23


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