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)

Patients receiving recombinant human erythropoietin (rHuEPO) therapy show wide variability in their responsiveness to the drug. Variables that affect rHuEPO dose requirements can be broadly divided into modificable and immutable characteristics. Most of the scientific research on rHuEPO hyporesponsiveness has focused on modificable variables (iron status, dialysis adequacy), while immutable variables such as gender, etiology of chronic renal failure (CRF) and age have been insufficiently explored. A cross sectional study was performed in order to evaluate if immutable patient characteristics determine rHuEPO dose requirements among 215 patients (52% males; mean age 66 +/- 14 years) on hemodialysis (HD) for more than twelve months. Data were collected at 10 hemodialysis units in Aragon. Patients were divided into three groups according to their gender, their cause of CRF (diabetic nephropathy, vascular nephropathy, tubulointerstitial nephropathy and primary glomerulonephritis) and their age (younger than 60 years, from 60 to 75 years, older than 75 years). Despite a similar dose of rHuEPO, women had lower mean hemoglobin (11.1 +/- 1.5 versus 11.6 +/- 1.7 g/dl; p = 0.0258) than men. The greater hemoglobin in men than women may be attributed to greater serum albumin in men (3.5 +/- 0.3 versus 3.7 +/- 0.3 mg/dl; p = 0.0001). Requirements of rHuEPO were higher in the patients with etiology of primary glomerulonephritis compared with those with the other etiologies, even those with diabetic nephropathy (p = 0.0374). The rHuE-PO doses required to obtain similar hemoglobin levels were higher in patients younger than 60 years (p = 0.0249). We conclude that women, patients with primary glomerulonephritis as cause of CRF, and patients younger than 60 years showed the highest requirements of rHuEPO doses.
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PMID:[Study of immutable variables determining rHuEPO dose requirements on hemodialysis patients]. 1639 4

Serum creatinine (SCr) had been considered to be an important predictor of mortality in end-stage renal disease (ESRD) patients at the start of renal replacement therapy (RRT). However, the data were limited about initially extreme azotemia (EA), exclusively defined as blood urea nitrogen (BUN) > or = 300 mg/dL, SCr > or = 30 mg/dL, or both. This retrospective study was conducted to clarify the characteristics and outcome in our EA patients. We had 1682 new ESRD patients from July 1988 to December 1996. With frequency match for age, gender, and starting RRT in the same period, 20 EA patients and 60 controls were included. Fifty percent of our EA patients had unknown etiology. The EA patients had significantly lower prevalence of underlying diabetic nephropathy, and comorbid hypertension. All the EA patients had late referral to nephrologists within 4 weeks before the initiation of RRT, and 90% of them had taken Chinese herbals. The EA group had significantly higher BUN, SCr, and iron storage as well as a higher prevalence of severe anemia, hyperkalemia, hypocalcemia, and acidemia. However, the similar prevalence of cardiomegaly and left ventricular hypertrophy as well as the similar early mortality rate and long-term survival were noted. Age over 40 years, comorbid diabetes mellitus, and hypoalbuminemia were independent predictors of poor survival. Our EA patients had different initial presentations from other uremic ones at the start of RRT. However, the short-term and long-term mortality rates were similar. The lower prevalence of underlying diabetic nephropathy and comorbid hypertension among the EA patients might contribute to their fair outcome.
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PMID:Clinical characteristics and outcomes of new uremic patients with extreme azotemia in southern Taiwan. 1680 92

Oxidants derived either from leukocytes in proliferative glomerulonephritis or from resident glomerular cells in nonproliferative glomerulonephritis have been shown to have several biological effects relevant to chronic kidney disease. These include the ability of oxidants to damage the glomerular basement membrane and directly induce proteinuria, effects that would lead to a fall in the glomerular filtration rate and account for the morphologic changes observed in chronic kidney disease. In experimental models, the role of oxidants has been shown in both proliferative glomerulonephritis (eg, antiglomerular basement membrane antibody disease) as well as experimental models of minimal change disease and membranous nephropathy. Oxidants have also been shown to be an important mediator of the various pathways that have been implicated in diabetic nephropathy. Antioxidants and iron chelators have also been shown to retard functional and morphologic changes observed in progressive kidney disease. Taken together, these experimental studies suggest an important role of oxidants in chronic kidney disease.
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PMID:Oxidants and iron in progressive kidney disease. 1682 16

Forty five (24 male & 21 female) moderate to severe degree of predialysis CRF patients were prospectively studied over a period of 6 months (July- December, 2004) to see the effect of Recombinant Human Erythropoietin (rHuEpo/EPO) therapy on renal anaemia, progression of renal excretory function & quality of life at 3 and 6 months intervals from the starting of EPO therapy. Mean +/- SD age of the patients was 56 +/- 12 (30-77 yrs) and causes of CRF were Diabetic Nephropathy (DN)=15 (33%), Chronic Glomerulonephritis (CGN) =14(31%), Hypertension (HTN)=11(21%), Chronic Pyelonephritis (CPN)=03 (6.5%) and Obstructive Uropathy (OU)=02 (4.5%). Doses of rHuEpo was 80-100 IU/k week subcutaneously (SC) until the target Hb 11gm% & Hct 30% were achieved; there after the dose was titrated as appropriate. Serum Iron & Ferritin levels were also kept within normal reference level by iron therapy during the study period. Mean +/- SD base line (before starting EPO therapy) level of haemoblobin were 8.4 +/- 0.81(gm%), Hct 27.86 +/- 1.6 (%), blood urea 21.72 +/- 10.5 (mmol/L), S. creatinine 431.93 +/- 228.79 (mmol/L) & Ccr. 21.25 +/- 10 mum respectively. The results showed that significant improvement of haemoglobin level occurred (gm%) from 8.4 +/- 0.81 (gm%) to 9.51 +/- 1.02 (p<0.001) at 3 months and 8.4 +/- 0.81 to 11.10 +/- 1.4, (p<0.001) at 6 months interval. Haematocrit (Hct%) value also significantly increased from 27.86 +/- 1.5 to 30.57 +/- 3.62, (p<0.001) at 3 months and 27.86 +/- 1.5 to 32.81 +/- 3.92 (p<0.001) at 6 months of EPO therapy. Mean blood urea and S. creatinine levels decreased from base line level during the study period but did not show any statistical significance. There was no significant side-effects like uncontrolled hypertension, seizure or hyperviscosity syndrome in any of the study population. The quality of life in terms of improvement of physical ability and sense of well being were also improved in all the study patients. In conclusion, this study showed that the effect of rHuEpo therapy is beneficial for the correction of renal anaemia, can delay the progression of renal failure and improvement of overall quality of life in predialysis CRF patients.
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PMID:Effect rHuEpo on predialysis CRF patients: study of 45 cases. 1696 14

To verify the hypothesis of an early impairment of erythropoietin (Epo) production and to assess the adequacy of its circulating levels in diabetic nephropathy, we investigated Epo values in 18 microalbuminuric type 2 diabetic patients with normal renal function (7 anaemic and 11 nonanaemic), 24 subjects with uncomplicated iron-deficiency anaemia, and 15 healthy controls comparable for sex and age. Mean+/-S.D. plasma Epo level was 56.4+/-12.7 mU/mL in iron-deficient patients and 9.3+/-2.6 mU/mL in controls. In diabetic groups, mean+/-S.D. Epo level was 11.38+/-3.65 mU/mL in nonanaemic and 49.12+/-6.44 mU/mL in anaemic subjects. No significant difference (P>.05) in Epo values was found between controls and nonanaemic diabetic patients. Anaemic diabetics and iron-deficient subjects had significantly higher values than the nonanaemic groups (P>.001). An inverse significant relation between Epo levels and Hb concentration resulted in both anaemic diabetics (r=-.44, P>.05) and iron-deficient patients (r=-.61, P=.001). Analysis of covariance (P>.05) and comparison of the two regression lines (t=0.4, df=29, P>.05) did not show any significant difference between diabetic patients with anaemia and iron-deficient patients. These results suggest that normochromic anaemia observed in microalbuminuric diabetic patients with normal renal function is not due to Epo deficiency, and circulating levels of this hormone are suitably increased with regard to Hb concentration.
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PMID:Circulating erythropoietin in microalbuminuric type 2 diabetic patients with normal renal function: a pilot study. 1707 Apr 42

We conducted this study to determine the achievements of the current practice guidelines in the management of anemia in the Arabian Gulf Countries. The survey was designed as a retrospective, one day screening of adult patients with end-stage renal disease in six Arabian Gulf countries including Saudi Arabia, Kuwait, Bahrain, Oman, United Arab Emirates and Qatar. Data were collected on patients undergoing chronic dialysis. For random patient sampling, each participating center drew up an alphabetical list of all hemodialysis (HD) or peritoneal dialysis (PD) patients which were 18 years or older and selected every fourth patient on the list. A total of 563 patients from 18 centers were included in the survey. The most common cause of end-stage renal failure was diabetic nephropathy, closely followed by chronic glomerulonephritis. The majority of patients were treated by HD, with only 20% receiving PD. The mean (+/-SD) hemoglobin (Hgb) concentration was 115 +/- 15 g/L (median, 115 g/L; range, 61-159 g/L). The Hgb concentration was > or = 110 g/L in 28%, > or = 120 g/L in 38% and < 100 g/L in 16%. Information on their iron status was available for 97% of patients, ferritin levels were available for 97% and TSAT values for 67% were available. The mean serum ferritin concentration for the study patients was 503 +/- 406 ng/ml (median, 390 ng/ml; range, 20.0-2960 ng/ml); 90.5% had a serum ferritin concentration > 100 ng/ml. We conclude that the results of our study demonstrate anemia management in the Gulf countries which is comparable to the European Survey on Anemia Management 2003 (ESAM 2003). However, many patients still have not reached the current recommendation of anemia management.
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PMID:The Gulf Survey on Anemia Management (GSAM 2005). 1749 96

Curcumin (U1) has a wide spectrum of therapeutic effects such as antitumor and anti-inflammatory effects, including antibacterial, antiviral, antifungal, and antispasmodic activities. By comparison of the structure-activity relationship, tetrahydrocurcumin (THU1), one of the major metabolites, showed the highest antioxidative activity in both in vitro and in vivo systems. U1 has been reported to have the nephroprotective effect to improve creatinine and urea clearance and also protected the chronic renal allograft nephropathy. These beneficial effects have been explained by the protection of oxidative stress and the induction of antioxidative enzymes. The protective effect of THU1 against ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage using male ddY mice was greater than that of U1, by monitoring not only radical scavenging activity measured by ESR, and TBARS, 4-HNE-modified protein and 8-OHdG formation but also induction of anioxidative enzymes and detoxification enzymes. THU1 was also expected to improve redox regulation through glutathione and suppress the oxidative stress in diabetic nephropathy and neuropathy. Earlier studies reported that U1 reduced the iron-induced hepatic damage, aflatoxin- and benzo[a]pyrene- induced mutagenicity and hepatocarcinogenecity and also the formation of the DNA adduct by inhibiting cytochrome P450 in the liver. The hepatoprotective role of U1 has been examined using carbone terachloride-induced liver damage in rats and alcoholic liver disease model rats, but not examined using THU1. Our recent data suggests that THU1 is a more promising hepatprotective agent because of its strong induction activity of antioxidant and phase 2-metabolizing enzymes in liver compared to kidney, although more detaied examinations are required.
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PMID:Nephroprotective and hepatoprotective effects of curcuminoids. 1756 22

Erythropoietin (EPO) is a haematopoietic cytokine, mainly generated in the renal cortex, and its secretion and action is impaired in chronic kidney disease (CKD). Early renal damage in diabetes mellitus (DM) is usually not detected because diabetes-induced nephron hypertrophy maintains glomerular filtration rate (GFR) and an elevated plasma creatinine concentration is a relatively late manifestation of diabetic nephropathy. However, anaemia occurs more frequently in subjects with DM when compared with those with non-DM renal disease. While reduced production and a blunted response to EPO occurs in DM with early renal damage, other factors including chronic inflammation, autonomic neuropathy and iron deficiency are also important. Although recombinant human erythropoietin (rhEPO) has been an effective therapeutic agent in CKD anaemia, it appears to be more effective in patients with DM, even in earlier stages. Nevertheless, patients with DM are also more likely to be iron deficient, a barrier to effective rhEPO therapy. The effect of treatment on the reliability of haemoglobin A(1c) as an index of glycaemic control must be remembered. It is proposed that anaemia and its causes must be important components of care in subjects with early diabetic renal damage.
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PMID:Potential roles of erythropoietin in the management of anaemia and other complications diabetes. 1764 62

Polymorphic loci regulating oxidative stress are potential susceptibility genes for diabetic nephropathy (DN). Haptoglobin (Hp) is an antioxidant protein which serves to protect against oxidative stress induced by extracorpuscular hemoglobin. There are two alleles at the Hp locus, 1 and 2. The Hp 1 protein is a superior antioxidant to the Hp 2 protein. The Hp 2 allele has been associated with increased prevalence of DN and appears to be associated with a more rapid progression to end-stage renal disease. We sought to recapitulate this association between Hp genotype and DN in mice genetically modified at the Hp locus. We assessed morphometric, histologic, and functional parameters involved in the development and progression of DN in mice with diabetes mellitus (DM) with either the Hp 2-2 or Hp 1-1 genotype. Morphometric analysis demonstrated that glomerular and proximal tubular hypertrophy were significantly increased in Hp 2-2 DM mice. Histological analysis demonstrated that Hp 2-2 DM mice had significantly more collagen type IV, smooth muscle actin, and increased renal iron deposition. Studies of renal function demonstrated creatinine clearance time and albuminuria were increased in Hp 2-2 DM mice. Vitamin E provided significant protection against the development of functional and histological features characteristic of DN to Hp 2-2 DM but not to Hp 1-1 DM mice. These studies serve to strengthen the association between the Hp 2-2 genotype and diabetic renal disease and suggest a pharmacogenomic interaction may exist between the Hp genotype and vitamin E.
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PMID:Pharmacogenomic effect of vitamin E on kidney structure and function in transgenic mice with the haptoglobin 2-2 genotype and diabetes mellitus. 1917

Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na(+)/H(+) exchange and HC(3) (-)/Cl(-) anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs) are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia) and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.
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PMID:Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker? 1966 14


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