Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was aimed to show whether the renin-angiotensin system acts on erythropoiesis in chronic renal failure patients with hemodialysis, since captopril leads to the worsening of anemia in such patients. The average dose of captopril in 13 cases studied was 19.3 mg per day and duration of the administration was 48 days. Blood-pressure fall by captopril was accompanied with the worsening of anemia. There were significant decreases in hemoglobin (8.3%), hematocrit (7.3%), red blood cell count (7.6%) and reticulocyte count (43.7%). Angiotensin II was significantly decreased (15.7%) with significant reductions of plasma aldosterone concentration (15.2%) and angiotensin-I converting enzyme (45.7%), and with significant increases in plasma renin activity (158.6%) and in angiotensin I (238.3%). However, plasma erythropoietin concentration remained unchanged. Serum iron concentration was slightly but significantly increased after captopril. Reticulocyte count was significantly correlated with AII either before (r = 0.716, p less than 0.01) or after captopril (r = 0.658, p less than 0.05). There was significant correlation between angiotensin II and red blood cell count before captopril (r = 0.710, p less than 0.01). It is concluded from the present study that the reduction of angiotensin II by captopril might contribute to the worsening of anemia seen in chronic hemodialysis patients.
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PMID:Participation of the renin-angiotensin system in the captopril-induced worsening of anemia in chronic hemodialysis patients. 352 28

Angiotensin II type 1 receptor blockers belong to a novel class of cardiovascular agents that is characterized by excellent tolerance. The overall rate of their side effects is similar to that of placebo. Specific nonproductive cough is much less common during treatment with angiotensin II blockers compared with angiotensin converting enzyme inhibitors. Nevertheless serious side effects very rarely occur with angiotensin II blockers and include cough, angioneurotic edema, anemia, liver damage, renal failure, aggravation of angina and migraine. The data of current literature concerning adverse effects of angiotensin II in different clinical situations are extensively reviewed. Angiotensin II type 1 receptor blockers are not considered to be safe in pregnancy, bilateral renal artery stenosis and severe renal or hepatic impairment.
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PMID:[Adverse effects of angiotensin II type 1 receptor blockers ]. 1249 95

Inactivation of the gene encoding mouse angiotensin I-converting enzyme (ACE), which converts angiotensin I into angiotensin II, results in anemia in adult animals. This anemia is corrected by angiotensin II, demonstrating the involvement of angiotensin II in adult (definitive) erythropoiesis. We investigated the possible role of the renin-angiotensin system (RAS) in primitive erythropoiesis in the yolk sac of the chicken embryo. Enzymatically active ACE was detected in the yolk sac endoderm, concomitantly with the differentiation of blood islands in the adjacent yolk sac mesoderm. The simultaneous presence of all the other components of the RAS (renin, angiotensinogen, angiotensin II receptor) in the vicinity of the blood islands suggests that this system is involved in erythropoiesis. This role was confirmed by in vivo blockade of the RAS with fosinoprilate, a specific inhibitor of chicken ACE, which decreased hematocrit by 15%. A similar decrease in hematocrit was observed following treatment with the angiotensin II receptor antagonist Sar1-Ile8-Angiotensin II, suggesting that this effect was mediated by angiotensin II. Both treatments affected hematocrit by decreasing erythroblast proliferation. Thus, the RAS, and its effector peptide angiotensin II in particular, modulates primitive erythropoiesis.
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PMID:Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo. 1536 38

Angiotensin II converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) are frequently avoided as treatment for hypertension in the early posttransplant period (0 to 90 days) for fear of nephrotoxicity. The following retrospective study was designed to explore the safety of these drugs in the early posttransplant period and determine appropriate clinical criteria for starting these medications. The records of all adult renal transplants performed between January 1997 and December 2000 (N = 290) were reviewed. All patients started on ACE or ARB for treatment of hypertension within 90 days of their transplant were included in the analysis (n = 17). Controls (n = 19) were patients who were treated with a calcium channel blocker (CCB) for hypertension. Cases and controls were matched for gender and type of transplant, living or cadaver. Patients were considered to be enrolled whey they met the following criteria: hypertension, serum creatinine < or =3.0 mg/dL, or falling 1 mg/dL/d and serum potassium < or =5.5 mEq/L. Exclusion criteria were coexistent pancreas transplant, anaphylaxis to ACE, and use of ACE or ARB for treatment of posttransplant erythrocytosis. There were no differences between cases and controls in hemoglobin or serum potassium concentrations or calculated glomerular filtration rate at 3, 6, and 9 months. In renal transplant patients with reasonable allograft function, administration of ACE and ARB to treat hypertension in the early posttransplant period appears to be well tolerated and not associated with excess hyperkalemia, anemia, or acute renal dysfunction.
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PMID:Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers used for the treatment of hypertension appear to be safe in the early posttransplant period. 1562 Nov 21

Recent studies emphasize the role of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal failure. When advanced, tubulointerstitial damage is associated with the loss of peritubular capillaries. Associated interstitial fibrosis impairs oxygen diffusion and supply to tubular and interstitial cells. Hypoxia of tubular cells leads to apoptosis or epithelial-mesenchymal transdifferentiation. This in turn exacerbates fibrosis of the kidney and subsequent chronic hypoxia, setting in train a vicious cycle whose end point is ESRD. A number of mechanisms that induce tubulointerstitial hypoxia at an early stage have been identified. Glomerular injury and vasoconstriction of efferent arterioles as a result of imbalances in vasoactive substances decrease postglomerular peritubular capillary blood flow. Angiotensin II not only constricts efferent arterioles but, via its induction of oxidative stress, also hampers the efficient utilization of oxygen in tubular cells. Relative hypoxia in the kidney also results from increased metabolic demand in tubular cells. Furthermore, renal anemia hinders oxygen delivery. These factors can affect the kidney before the appearance of significant pathologic changes in the vasculature and predispose the kidney to tubulointerstitial injury. Therapeutic approaches that target the chronic hypoxia should prove effective against a broad range of renal diseases. Current modalities include the improvement of anemia with erythropoietin, the preservation of peritubular capillary blood flow by blockade of the renin-angiotensin system, and the use of antioxidants. Recent studies have elucidated the mechanism of hypoxia-induced transcription, namely that prolyl hydroxylase regulates hypoxia-inducible factor. This has given hope for the development of novel therapeutic approaches against this final common pathway.
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PMID:Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure. 1629 37

Analysis of the biologic effects of erythropoietin and pathophysiology of chronic kidney diseases (CKD) suggests that treatment with erythropoiesis-stimulating agents (ESA) could slow the progression of CKD. By decreasing hypoxia and oxidative stress, it could prevent the development of interstitial fibrosis and the destruction of tubular cells. It could have direct protective effects on tubular cells through its antiapoptotic properties. It could help maintain the integrity of the interstitial capillary network through its effects on endothelial cells. Thus, suggesting that correcting anemia with ESA could slow the progression of CKD is biologically plausible. In patients with CKD, three small prospective studies and a retrospective study have suggested that treatment with ESA may have protective effects. Post-hoc analysis of the Reduction in Endpoints in Noninsulin-dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan study has also shown that anemia was an independent risk factor for progression of nephropathy in patients with type 2 diabetes. In addition, a large clinical trial, which had to be stopped prematurely because of labeling change for subcutaneous administration of epoetin alfa, suggests that complete normalization of hemoglobin levels is safe in CKD patients not on dialysis and without severe cardiovascular disease. Thus, it seems reasonable to advocate starting a large randomized, prospective study to determine if normalization of hemoglobin concentration can effectively slow the progression of CKD.
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PMID:Anemia management and chronic renal failure progression. 1633 82

Anemia is a well-known consequence of chronic kidney disease (CKD), and its prevalence progressively increases when the estimated glomerular filtration rate decreases to less than 60 mL/min/1.73 m2. However, analyses of the consequences of anemia and of the mechanisms of progression of CKD suggest that anemia also could contribute to the deterioration of kidney function. This hypothesis is based mostly on experimental data that imply that hypoxia of tubular cells plays an important role in tubulointerstitial damage associated with CKD and, thus, in the progression of renal failure. It also is supported by the fact that red blood cells represent a major antioxidant component of blood and that oxidative stress appears to contribute to glomerulosclerosis and tubulointerstitial damage. In humans, post hoc analysis of the Reduction of End points in non insulin-dependent diabetes mellitus (NIDDM) with the Angiotensin II Antagonist Losartan study and analyses of smaller prospective cohorts of CKD patients have shown that anemia is an independent risk factor for progression of CKD. In addition, 3 small randomized studies have suggested that anemia correction could slow the progression of CKD. Thus, the existence of a relationship between anemia and progression of CKD is not only plausible biologically, but also is supported by observational studies and by small intervention studies. However, only a large, randomized, prospective trial will be able to establish if anemia correction can slow the progression of CKD effectively.
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PMID:Role of anemia in progression of chronic kidney disease. 1694 66

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can decrease hemoglobin, causing anemia and this may be an independent risk factor for chronic kidney disease progression. We studied the relationship between a decline in hemoglobin and outcome in 1513 patients with type 2 diabetes and kidney disease by a post hoc analysis of the RENAAL Study (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) with an average follow-up of 3.4 years. The relationship between baseline and year-1 hemoglobin and treatment on end-stage renal disease (ESRD) and ESRD or death was evaluated using multivariate Cox models (covariates: baseline hemoglobin, proteinuria, serum albumin, serum creatinine, and year-1 hemoglobin). Compared with placebo, losartan treatment was associated with a significant decrease of hemoglobin, with the largest between-group difference at 1 year. After adjustment, there were significant relative risk reductions for losartan compared with placebo for ESRD and for ESRD or death regardless of the baseline hemoglobin even in those patients with a baseline hemoglobin below 120 g l(-1). Hence, the renoprotective properties of losartan were maintained despite a significant lowering of the hemoglobin concentration.
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PMID:The effect of losartan on hemoglobin concentration and renal outcome in diabetic nephropathy of type 2 diabetes. 1809 75

The renin-angiotensin system is the major regulator of blood pressure by virtue of controlling vascular resistance and plasma volume. Much less recognition exists for the role of the renin-angiotensin system in regulating erythropoiesis, a biological function critical for oxygen delivery to tissues. In this review, we present evidence that angiotensin II (Ang II) is a physiologically important regulator of erythropoiesis with 2 key actions. First, Ang II is a growth factor of erythroid progenitors and, in cooperation with erythropoietin, increases red blood cell mass. Second, Ang II acts as an erythropoietin secretagogue to maintain increased erythropoietin levels despite increments in hematocrit. Among a multitude of physiologic and pathophysiologic implications, these lines of evidence provide an explanation for the effect of angiotensin-converting enzyme inhibitors and Ang II type 1 receptor blockers to decrease hematocrit or cause anemia in various clinical conditions.
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PMID:The role of the renin-angiotensin system in the regulation of erythropoiesis. 2040 Feb 18

The remnant kidney model in C57BL/6 mice does not develop progressive chronic kidney disease (CKD). In this study we modified the model to mimic features of human CKD and to define accelerants of disease progression using three strains of mice. Following the procedure, there was a progressive increase in albuminuria, progressive loss in renal function, severe glomerulosclerosis and interstitial fibrosis, hypertension, cardiac fibrosis, and anemia by 4 weeks in CD-1 mice and by 12 weeks in 129S3 mice. In contrast, even after 16 weeks, the C57BL/6 mice with a remnant kidney had modestly increased albuminuria without increased blood pressure and without developing CKD or cardiac fibrosis. The baseline blood pressure, determined by radiotelemetry in conscious animals, correlated with CKD progression rates in each strain. Administering angiotensin II overcame the resistance of C57BL/6 mice to CKD following renal mass reduction, displaying high blood pressure and albuminuria, severe glomerulosclerosis, and loss of renal function by 4 weeks. Decreasing blood pressure with olmesartan, but not hydralazine, in CD-1 mice with a remnant kidney reduced CKD progression and cardiac fibrosis. C57BL/6 mice with a remnant kidney and DOCA-salt hypertension developed modest CKD. Each strain had similar degrees of interstitial fibrosis in three different normotensive models of renal fibrosis. Thus, reducing renal mass in CD-1 or 129S3 mice mimics many features of human CKD. Angiotensin II can convert the C57BL/6 strain from CKD resistant to susceptible in this disease model.
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PMID:Angiotensin II overcomes strain-dependent resistance of rapid CKD progression in a new remnant kidney mouse model. 2073 88


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