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)

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

Many possible causes of resistance to human recombinant erythropoietin (rh-EPO) have been reported in patients with renal failure. This case presents an unusual cause of erythropoietin-resistant anemia in a patient with chronic renal failure. A 61-year-old male patient who was on chronic hemodialysis program due to diabetic nephropathy for seven months developed erythropoietin resistant anemia. No iron deficiency was revealed by laboratory data, no megaloblastic anemia were found by biochemical investigation, and no inflammatory states including infection or neoplastic diseases were disclosed by abdominal ultrasonography, chest X-ray, bone marrow aspiration and biopsy, or other methods (normal C-reactive protein levels). This hemodialysis patient had epoetin-resistant anemia with primary autoimmune hyperthyroidism. The anti-thyroid therapy was effective not only against the hyperthyroidism but also against his epoetin resistant anemia.
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PMID:An unusual etiology of erythropoietin resistance: hyperthyroidism. 1776 75

Diabetes as the dominant cause of ESRD is also the major cause of renal anaemia. However, most patients with diabetic kidney disease will succumb to co-morbid vascular disease or heart failure before developing severe renal impairment. In these patients, anaemia is also common finding, with a 2-3 times greater prevalence and earlier onset than in patients with renal impairment from other causes. We have recently shown that at least one in five outpatients with type 1 or type 2 diabetes in tertiary referral clinics have anaemia, in whom it constitutes a significant additional burden. Impaired renal erythropoietin release in response to declining haemoglobin levels appears to be the major contributor to anaemia in diabetes. This may be due to the predominance of damage to cells and vascular architecture of the renal tubulointerstitium associated with diabetic nephropathy that may be apparent, like albuminuria, before demonstrable changes in renal function. In addition, systemic inflammation, autonomic neuropathy and reduce red cell survival may also compound anaemia in diabetes. While anaemia may be considered a marker of diabetic kidney disease, reduced haemoglobin levels, even within the normal range, identify diabetic patients with an increased risk of hospitalisation and mortality. Anaemia may also be significant in determining the outcome of heart failure and hypoxia-induced organ damage in patients with diabetes. Upcoming studies will determine whether correction of anaemia in diabetes will lead to improved outcomes in these patients.
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PMID:Anaemia in diabetes: an emerging complication of microvascular disease. 1822 May 87

Diabetic nephropathy is traditionally considered to be a primarily glomerular disease, although this contention has recently been challenged. Early tubular injury has been reported in patients with diabetes mellitus whose glomerular function is intact. Chronic hypoxia of the tubulointerstitium has been recognized as a mechanism of progression that is common to many renal diseases. The hypoxic milieu in early-stage diabetic nephropathy is aggravated by manifestations of chronic hyperglycemia-abnormalities of red blood cells, oxidative stress, sympathetic denervation of the kidney due to autonomic neuropathy, and diabetes-mellitus-induced tubular apoptosis; as such, tubulointerstitial hypoxia in diabetes mellitus might be an important early event. Chronic hypoxia could have a dominant pathogenic role in diabetic nephropathy, not only in promoting progression but also during initiation of the condition. Early loss of tubular and peritubular cells reduces production of 1,25-dihydroxyvitamin D3 and erythropoietin, which, together with dysfunction of their receptors caused by the diabetic state, diminishes the local trophic effects of the hormones. This diminution could further compromise the functional and structural integrity of the parenchyma and contribute to the gradual decline of renal function.
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PMID:Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. 1826 25

Chronic Kidney Disease (CKD) 5 is defined when glomerular filtration rate (GFR) is <15.0 ml/min/1.73m2. Though nephrology service was started in Nepal as early as in 1970, we do not have data regarding CKD 5 patients till date. So this study is being undertaken to know the epidemiological profile and etiology of CKD 5 patients attending hemodialysis (HD) unit of Nepal Medical College Teaching Hospital. This is a prospective study which was carried out in HD unit over a period of one year. CKD 5 patients having GFR of <15 ml/min/1.73m2 under HD were included in the study. Among 100 patients included in the study 57 were male and mean age of the study population was 46.9+/-17.9 years. Most common cause of CKD 5 in the study was hypertension (54.0%); other causes included diabetic nephropathy (18.0%), idiopathic (13.0%) and glomerulonephritis (6.0%). Fifty percent of patients were from outside Kathmandu Valley. Around 20.0% of the study population is on regular follow up while 45.0% were lost to follow up. Twenty percent of the patient underwent transplantation and 15.0% of the study population died. Majority of patients were anemic (85.0%). Correction of anemia was done with blood transfusion in 88.0% and only 12.0% received erythropoietin. Hypertension was the leading cause of CKD 5; majority of patients (45.0%) discontinued hemodialysis most probably due to economical constrain; blood transfusion was the main modality of treatment of anemia.
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PMID:Chronic kidney disease 5 on hemodialysis in Nepal Medical College Teaching Hospital. 1870 Jun 22

Several factors are incriminated in the genesis of diabetic nephropathy (DN). To elucidate their interplays, we utilized a diabetic rat model with nephropathy (SHR/NDmcr-cp). This model is characterized by hypertension, obesity with the metabolic syndrome, diabetes with insulin resistance, and intrarenal AGE accumulation. Various therapeutic approaches were used to achieve renoprotection. Caloric restriction corrects metabolic abnormalities and protects the kidney without correcting hypertension. Anti-hypertensive agents, angiotensin II receptor blocker (ARB) and calcium channel blocker, lower blood pressure to the same extent, but only ARBs protect the kidney without changes in metabolic abnormalities. Glycemic control is better with insulin than with pioglitazone. The plasma insulin level is increased by insulin but decreased by pioglitazone which worsens the obesity. Nevertheless, pioglitazone provides renoprotection unlike insulin, perhaps as a result of the up-regulation of TGF-beta by hyperinsulinemia. Cobalt up-regulates the expression of a hypoxia-inducible factor (HIF) and its downstream genes (erythropoietin, VEGF, HO-1). It protects the kidney without correcting hypertension and metabolic abnormalities. Altogether, renoprotection is not necessarily associated with blood pressure or glycemic control. By contrast, it is almost always associated with a decreased AGE formation. AGE reduction may reflect a decreased oxidative stress as it is concomitant with a marked reduction of oxidative stress markers.
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PMID:Inhibition of advanced glycation end products (AGEs): an implicit goal in clinical medicine for the treatment of diabetic nephropathy? 1895 18

Chronic diseases have become a major cause of global morbidity and mortality even in developing countries. The burden of chronic kidney disease (CKD) in India cannot be assessed accurately. The approximate prevalence of CKD is 800 per million population (pmp), and the incidence of end-stage renal disease (ESRD) is 150-200 pmp. The most common cause of CKD in population-based studies is diabetic nephropathy. India currently has 820+ nephrologists, 710+ hemodialysis units with 2,500+ dialysis stations and 4,800+ patients on CAPD. There are 172+ transplant centers, two-thirds of which are in South India and mostly privately run. Nearly 3,500 transplants are done annually, the total number of cadaver donors being approximately 700 till now. Thus, taken together, nearly 18,000-20,000 patients (10% of new ESRD cases) in India get renal replacement therapy. The cost of single hemodialysis varies between USD 15 and 40 with an additional cost of erythropoietin being USD 150-200/month. The cost of CAPD using a 'Y' set with 3 exchanges/week is USD 400/month. The cost of the transplant procedure in a state-run hospital is USD 800-1,000, and the cost of immunosuppression using tacrolimus, steroid and mycophenolate is USD 350-400/month. Until recently, the government did not recognize CKD/ESRD as a significant problem in India. However, some illustrious activities in relation to CKD brought attention of the media and policymakers to this very common but till now deprived group of diseases. On the one side the government has initiated a process by which it is planning to establish stand-alone hemodialysis units in the country to increase the facilities at an affordable cost, and on the transplant side it had launched a National Organ Transplant Program to facilitate transplantation on a national scale. Hemodialysis program is halfway to being implemented. Thus, in India there is still a long way to go with respect to CKD. Until then, in a country like India, screening of high-risk individuals for CKD and the risk factors is the best bet.
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PMID:Chronic kidney disease in India: challenges and solutions. 1919 10

Anemia is one of the world's most common preventable conditions, yet it is often overlooked, especially in people with diabetes mellitus. Diabetes-related chronic hyperglycemia can lead to a hypoxic environment in the renal interstitium, which results in impaired production of erythropoietin by the peritubular fibroblasts and subsequent anemia. Anemia in patients with diabetes mellitus might contribute to the pathogenesis and progression of cardiovascular disease and aggravate diabetic nephropathy and retinopathy. Anemia occurs earlier in patients with diabetic renal disease than in nondiabetic individuals with chronic kidney disease. Although erythropoietin has been used to treat renal anemia for nearly two decades, debate persists over the optimal target hemoglobin level. Most guidelines recommend that hemoglobin levels be maintained between 105g/l and 125g/l. The suggested role of anemia correction--to prevent the progression of left ventricular hypertrophy in patients with diabetes mellitus--is yet to be established. However, an emphasis on regular screening for anemia, alongside that for other diabetes-related complications, might help to delay the progression of vascular complications in these patients.
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PMID:Erythropoietic stress and anemia in diabetes mellitus. 1935 18

Recombinant human erythropoietin (rHuEPO), which has been used clinically for the management of renal anemia, is reported to exert pleiotropic beneficial properties against acute ischemic/reperfusion injury in various tissues. To investigate the hypothesis that chronic treatment with rHuEPO might ameliorate diabetic nephropathy beyond hematopoiesis, rHuEPO (150 U/kg, subcutaneously) was administered three times per week to the streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, intravenously) significantly increased urinary protein excretion and collagen deposition in glomerular and tubulointerstitial areas in the kidney, which were attenuated by rHuEPO. rHuEPO normalized the levels of creatinine clearance, serum creatinine, and blood urea nitrogen of diabetic rats. RT-PCR analysis revealed that the expressions of mRNA for transforming growth factor-beta, osteopontin and adhesion molecules were enhanced in the diabetic rat kidney and that the overexpression of these molecules was suppressed by rHuEPO. rHuEPO exerted antioxidant properties by inhibiting renal activation and overexpression of NADPH oxidase. We found the activation of the Akt signaling pathway by the increased expression of phosphorylated Akt and GSK-3beta and a reduction of TUNEL-positive apoptotic cell death in renal tissue from rHuEPO-treated diabetic group. We also demonstrated that rHuEPO restored the endothelial nitric oxide synthase (eNOS) content in the diabetic rat kidney. On the other hand, treatment with rHuEPO did not affect blood glucose level, blood pressure, or hematocrit in diabetic rats. These results suggest that chronic treatment with rHuEPO attenuated renal injury beyond hematopoiesis and regulated apoptosis and eNOS expression, which might be due to the activation of Akt pathway.
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PMID:Chronic treatment with recombinant human erythropoietin exerts renoprotective effects beyond hematopoiesis in streptozotocin-induced diabetic rat. 1935 35

Low serum adiponectin is associated with a high incidence of type 2 diabetes or coronary artery disease in the general population. Paradoxically, serum adiponectin is elevated in patients with chronic kidney disease (CKD), such as overt diabetic nephropathy. The current study aimed to investigate whether anemia was independently associated with the serum level of high-molecular-weight (HMW) adiponectin in patients with type 2 diabetes. We studied 207 type 2 diabetic patients (92 women and 115 men). Anemia was defined as a hemoglobin (Hb) <13.0g/dL in men and <12.0g/dL in women according to the guidelines of the World Health Organization (WHO). Overt nephropathy (CKD) was defined as clinical proteinuria and /or estimated glomerular filtration rate (eGFR) lower than 60mL/min for more than 3 months. The diabetic patients were divided into 4 groups according to the presence or absence of anemia and/or CKD. Serum HMW adiponectin levels were measured by a sandwich enzyme-linked immunosorbent assay. In all 207 patients with type 2 diabetes, serum total and HMW adiponectin levels were correlated positively with age, the duration of diabetes, high-density lipoprotein (HDL) cholesterol, urinary albumin, and serum erythropoietin, whereas negative correlations were found with body mass index, triglyceride, eGFR, Hb, hematocrit, and high sensitivity C-reactive protein. A stepwise regression analysis demonstrated that among several significant variables, Hb had the strongest independent influence on HMW adiponectin (beta =-0.487, P < 0.001). Diabetic patients of both sexes with anemia and CKD had the highest serum levels of HMW adiponectin among the 4 groups. In conclusion, anemia is associated with marked elevation of serum HMW adiponectin levels in diabetic patients who have CKD, and this elevation is independent of renal function.
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PMID:Anemia is associated with an elevated serum level of high-molecular-weight adiponectin in patients with type 2 diabetes independently of renal dysfunction. 1976 61


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