losartan-potassium and Hypotension

Carnitine is a metabolic cofactor which is essential for normal fatty acid metabolism. Patients with chronic kidney disease on dialysis have been shown both to suffer from disordered fatty acid metabolism and to have a significant deficiency in plasma and tissue carnitine. Aberrant fatty acid metabolism has been associated with a number of cellular abnormalities such as increased mitochondrial permeability (a promoter of apoptosis), insulin resistance, and enhanced generation of free radicals. These cellular abnormalities have, in turn, been correlated with pathological clinical conditions common in dialysis patients including cardiomyopathy with attendant hypotension and resistance to the therapeutic effect of recombinant human erythropoietin (EPO). In 1999, the Food and Drug Administration approved levocarnitine injection for the prevention and treatment of carnitine deficiency in patients on dialysis based on documentation of free plasma carnitine levels in dialysis patients similar to other serious carnitine deficiency states for which treatment was required. Data analysis performed by expert panels convened by both the American Association of Kidney Patients and, subsequently, the National Kidney Foundation recommended a trial of levocarnitine therapy for specific subsets of dialysis patients including those with EPO resistance, dialysis-related hypotension, cardiomyopathy and muscle weakness. In 2003, the Centers for Medicare and Medicaid services convened a Medical Advisory Committee which established reimbursement on a national level for carnitine-deficient dialysis patients who had either dialysis-related hypotension or EPO resistance. Recently, a correlation between reductions in hospitalization rates of dialysis patients receiving levocarnitine therapy has been demonstrated in a large retrospective study. Despite data-based recommendations and national reimbursement, only a small minority of dialysis patients have been prescribed a therapeutic trial of levocarnitine. Whereas the reasons for the reluctance of nephrologists to prescribe this therapeutic trial are unclear, possible explanations include a lack of appreciation of the pivotal role played by carnitine in cellular metabolism and the strength of evidence for a substantial deficiency of carnitine in dialysis patients, an underestimation of the prognostic import of EPO resistance and dialysis-related hypotension, inadequate dissemination of the clinical trial data supporting the use of le

Topics: Acetylcarnitine; Anemia; Cardiomyopathies; Drug Resistance; Erythropoietin; Humans; Hypotension; Recombinant Proteins; Renal Dialysis; Vitamin B Complex

The database for carnitine supplements in dialysis includes no large-scale randomized trials and no registered trials. Medical practitioners prefer to make treatment decisions based on the outcome of randomized clinical trials, with appropriate controls. Furthermore, registered trials provide a further level of integrity, since trial registration avoids publication bias by ensuring that all outcomes are reported, including trials that are not completed. Positive effects reported from carnitine administration in dialysis patients include decreased erythropoietin dose, increased hematocrit, less intradialytic hypotension, and less fatigue. The evidence for carnitine effectiveness is limited to trials that are mostly open-label and that include no more than a total of 1,000 patients. An analysis of recent carnitine administrations to patients in a large dialysis practice database indicates no overall change in hemoglobin or erythropoietin dose following 6 months of carnitine administration. As outcomes of controlled trials with appropriate power to examine for the benefits of carnitine are not yet available, the dialysis practitioner cannot justify the administration of carnitine.

Topics: Anemia; Carnitine; Drug Resistance; Erythropoietin; Fatigue; Hypotension; Randomized Controlled Trials as Topic; Recombinant Proteins; Renal Dialysis; Treatment Outcome; Vitamin B Complex

Topics: Acute Kidney Injury; Animals; Biomarkers; Contrast Media; Endothelin Receptor Antagonists; Endothelin-1; Endotoxemia; Erythropoietin; Fibrosis; Glycopeptides; Heart Failure; Humans; Hypotension; Kidney Failure, Chronic; Peptides, Cyclic; Peritoneal Dialysis; Peritoneum; Prognosis; Recombinant Proteins; Renal Dialysis

Short daily hemodialysis (HD) has a protective effect against dialysis-induced hypotension (DIH). We examined whether this effect extends beyond the treatment period.. We analyzed clinical variables in 6 patients (5 with diabetes mellitus) who underwent conventional hemodialysis (CHD) for 4 h three times weekly for 12 weeks; then short daily HD for 2 h six times weekly for 12 weeks, and then 12 more weeks of CHD. All patients had been given vasopressors for severe DIH.. The severe DIH disappeared during the short daily HD. There were significant decreases in body weight (BW), cardiothoracic ratio (CTR), blood pressure (BP), normal saline solution (NSS) amount (62.8 +/- 26.4 vs. 9.8 +/- 7.4 ml/session, p < 0.05), frequency (0.60 +/- 0.26 vs. 0.10 +/- 0.07 infusions/session, p < 0.05) and postdialysis atrial natriuretic peptide (ANP) (176.8 +/- 56.4 vs. 104.8 +/- 42.3 pg/ml, p < 0.05). Weekly ultrafiltration volume (6.3 +/- 0.9 vs. 7.9 +/- 0.7 l, p < 0.05) was significantly higher during the short daily HD period than during the first CHD period. The vasopressor treatment was therefore stopped or reduced in all patients during the short daily HD period. Because DIH recurred in the second CHD period despite a significant increase in BP, the vasopressor treatment was resumed in 5 patients. BW, CTR, NSS infusion amount and frequency, or postdialysis ANP did not differ significantly between the short daily HD and second CHD periods.. The protective effect of short daily HD against DIH lasted more than 12 weeks after the treatment ended. We therefore conclude that temporary short daily HD is useful for preventing DIH.

Topics: Aged; Anemia; Antihypertensive Agents; Appointments and Schedules; Arteriovenous Shunt, Surgical; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Diabetic Nephropathies; Echocardiography; Erythropoietin; Female; Ferritins; Humans; Hypertension, Renal; Hypotension; Iron; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Quality of Life; Recombinant Proteins; Renal Dialysis; Uremia

Intravenous iron supplementation is an integral part of the management of anemia in patients with chronic kidney disease. Traditionally, this has been administered as an infusion over 1 or more hours, which requires the use of intravenous fluids and administration tubing, along with extra demands on patient and nursing time.. We prospectively investigated the safety and practicality of administering iron sucrose, 200 mg, as a bolus injection over 2 minutes in patients with chronic kidney disease. A total of 2,297 injections were administered to 657 patients. Any adverse events were recorded, including acute anaphylactoid reactions to the iron injection, along with the presence or absence of metallic taste and phlebitis, and these were classified as "serious" and "nonserious.". The most common adverse event was a mild and transient metallic taste that occurred during 412 injections (17.9%); in no case was this of significant distress to the patient. Excluding this, 2,240 injections (97.5%) proceeded uneventfully, and no case of phlebitis was recorded. Adverse events other than metallic taste were recorded in association with 57 injections (2.5%). Seven of these were caused by an acute anaphylactoid reaction to the intravenous iron. All 7 acute reactions resolved completely within 30 minutes with no sequelae, and none required hospitalization. The remaining 50 adverse events consisted of pain during the injection (n = 31), pain after the injection with or without some bruising (n = 9), nausea/gastrointestinal symptoms (n = 3), lethargy (n = 4), and lightheadedness (n = 3).. Administration of 200 mg of iron sucrose as an intravenous bolus injection over 2 minutes is a practical dosing regimen in patients with chronic kidney disease, resulting in considerable savings in time and cost.

Topics: Adult; Aged; Anaphylaxis; Anemia, Hypochromic; Chronic Disease; Cohort Studies; Dysgeusia; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Graft Rejection; Humans; Hypotension; Injections, Intravenous; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies

This report describes the response of 18 Diamond-Blackfan anemia (DBA) patients to recombinant human interleukin 3 (rhIL-3). rhIL-3 was administered s.c. once daily on an escalating dose schedule (0.5-10 micrograms/kg/day). The rhIL-3 dose was escalated every 21 days until erythroid response was attained, grade III or IV nonhematologic toxicity was observed, or the maximal rhIL-3 dose was reached. Four patients experienced clinically significant erythroid responses. Two of the responders were steroid-dependent and transfusion-independent, while two were steroid-independent and transfusion-dependent. Baseline clinical or laboratory parameters, in particular in vitro bone marrow erythroid progenitor assays, were not useful in predicting rhIL-3 response. Two of the responding patients remain on maintenance rhIL-3 without diminution of effect at 490 and 855+ days. rhIL-3 was discontinued in the other two responders because of the development of deep venous thrombi.

Topics: Animals; Blood Cell Count; Child; Eosinophilia; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Fanconi Anemia; Female; Hematopoietic Cell Growth Factors; Humans; Hypotension; Immunologic Factors; Interleukin-3; Male; Mice; Recombinant Proteins; Stem Cell Factor; Thrombophlebitis; Treatment Outcome

Erythrocyte mass contributes to maintaining systemic oxygen delivery and blood viscosity, with the latter being one of the determinants of blood pressure. However, the physiological response to blood pressure changes under anaemic conditions remain unknown.. We show that anaemia decreases blood pressure in human patients and mouse models. Analyses of pathways related to blood pressure regulation demonstrate that anaemia enhances the expression of the gene encoding the vasopressor substance renin in kidneys. Although kidney juxtaglomerular cells are known to continuously produce renin, renal interstitial fibroblasts are identified in the present study as a novel site of renin induction under anaemic hypotensive conditions in mice and rats. Notably, some renal interstitial fibroblasts are found to simultaneously express renin and the erythroid growth factor erythropoietin in the anaemic mouse kidney. Antihypertensive agents but not hypoxic stimuli induced interstitial renin expression, suggesting that blood pressure reduction triggers interstitial renin induction in anaemic mice. The interstitial renin expression was also detected in injured fibrotic kidneys of the mouse and human, and the renin-expressing interstitial cells in murine fibrotic kidneys were identified as myofibroblasts originating from renal interstitial fibroblasts. Since the elevated expression levels of renin in fibrotic kidneys along with progression of renal fibrosis were well correlated to the systemic blood pressure increase, the renal interstitial renin production seemed to affect systemic blood pressure.. Renal interstitial fibroblasts function as central controllers of systemic oxygen delivery by producing both renin and erythropoietin.. Grants-in-Aid from Japan Society for the Promotion of Science (JSPS) KAKENHI (17K19680, 15H04691, and 26111002) and the Takeda Science Foundation.

Topics: Aged; Anemia; Animals; Biomarkers; Blood Pressure; Chronic Disease; Disease Models, Animal; Erythropoietin; Female; Fibroblasts; Fibrosis; Gene Expression; Humans; Hypotension; Hypoxia; Kidney; Kidney Diseases; Male; Mice; Mice, Knockout; Mice, Transgenic; Middle Aged; Renin; Signal Transduction

The objective of this study was to investigate the effects of erythropoietin (EPO) on systemic and renal hemodynamics in a rat model of renal ischemic/reperfusion (I/R) injury. We used 30 male Sprague-Dawley rats distributed among the following 3 groups (10 rats per group): (i) the sham-operated group, (ii) the control group (I/R injury only), and (iii) the EPO-treated group (I/R injury with 1500 U EPO·(kg body mass)⁻¹ on day 0, and 500 U·kg⁻¹ on days 2 and 4 after ischemia). Renal function, arterial blood pressure (ABP), renal plasma flow (RPF), renal blood flow (RBF), and renal vascular resistance (RVR) were measured on days 1, 2, and 7 after ischemia. The expression of endothelial NO synthase (eNOS) and histopathology of kidney were evaluated on day 7. The contractility of aortic strips was recorded from the different groups. The results show that renal function and histopathology were significantly improved after treatment with EPO. Compared with the control group, the EPO-treated group showed a significant increase in RPF, RBF, haematocrite, ABP, eNOS expression, and a decrease in RVR (p < 0.05).The response of aortic strips to the relaxant effect of acetylcholine was improved in the EPO-treated group. In conclusion, treatment with EPO improves renal function and renal haemodynamics in renal I/R injury, and causes significant rise of ABP and haematocrite value.

Topics: Animals; Aorta, Thoracic; Drug Resistance; Enzyme Induction; Epoetin Alfa; Erythropoietin; Hematinics; Hemodynamics; Hypotension; Ischemia; Kidney; Male; Nitric Oxide Donors; Nitric Oxide Synthase Type III; Protective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Renal Circulation; Reperfusion Injury; Vascular Resistance; Vasodilation; Vasodilator Agents

In contrast to other sympathetic outflow tracts, renal sympathetic nerve activity (RSNA) decreases in response to hypotensive hemorrhage. The functional significance of this "paradox" is not known. We tested the hypothesis that RSNA modulates renal perfusion and thus erythropoietin (EPO) release after transient hypotensive hemorrhage in anesthetized rats. Plasma EPO was measured before and after 30 min of transient hypotensive hemorrhage (i.e., -40 mmHg from mean baseline blood pressure, followed by reinfusion of shed blood) and 120 min thereafter in sham-denervated rats, and after renal denervation (DNX) or bilateral cervical vagotomy (VX) to abolish/blunt the RSNA decrease mediated by a cardiopulmonary reflex. RSNA, renal Doppler flow, renal vascular resistance (RVR), resistance index, and oxygen delivery/uptake (Do(2)/Vo(2)) were measured. RSNA decreased in intact animals (-40 +/- 5% from baseline, P < 0.05). This was blunted by VX. With intact nerves, EPO level did not increase. In DNX rats, EPO was increased at minute 120 (49 +/- 3 vs. 74 +/- 2 mU/ml; P < 0.05), in VX rats this (47 +/- 2 vs. 62 +/- 4 mU/ml; P < 0.05) was less pronounced. Do(2) in DNX rats was lower compared with intact and VX rats (0.25 +/- 0.04 vs. 0.51 +/- 0.06 and 0.54 +/- 0.05 ml O(2)/min; P < 0.05) due to lower Doppler flow and increased RVR. RVR and Do(2) were similar in intact and VX rats, but resistance index differed between all groups (0.70 +/- 0.02 vs. 0.78 +/- 0.02 vs. 0.85 +/- 0.02; P < 0.05, intact vs. VX vs. DNX), indicating differential reactivity of renal vasculature. Vo(2) was unaffected by VX and DNX. Renal sympathoinhibition during hypotensive hemorrhage might help to preserve sufficient oxygenation of renal tissue by modulation of hemodynamic mechanisms that act to adapt renal oxygen availability to demand.

Topics: Animals; Blood Pressure; Erythropoietin; Hemorrhage; Hypotension; Kidney; Kidney Diseases; Lactic Acid; Male; Oxygen; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Sympathetic Nervous System; Vascular Resistance

We hypothesized that intravenous iron will improve hemoglobin (Hgb) concentrations in anemic patients with chronic kidney disease (CKD), and the response would be greater if the underlying erythropoietin deficiency also was treated.. Charts of 58 CKD veterans (glomerular filtration rate < 80 mL/min) administered at least 125 mg of sodium ferric gluconate complex in sucrose (SFGC) during a period of 1 year for the primary outcome of an increase in Hgb level by at least 0.5 g/dL were reviewed.. Mean Hgb level at baseline was 10.5 +/- 1.4 (SD) g/dL (105 +/- 14 g/L) in the 30 patients administered recombinant human erythropoietin (rHuEPO) plus SFGC and 10.1 +/- 1.3 g/dL (101 +/- 13 g/L) in the 28 patients administered SFGC alone (P = not significant). The primary event occurred in 83% of the rHuEPO-plus-SFGC group at 31 days compared with 60% at 62 days in the group administered SFGC alone (P = 0.037, Cox F test). In patients administered SFGC alone, mean maximal Hgb level was 11.4 +/- 0.9 g/dL (114 +/- 9 g/L) in contrast to 12.4 +/- 1.7 g/dL (124 +/- 17 g/L) in the combination group, which remained significantly different even after adjustment for biologically important covariates (P = 0.01, analysis of covariance). Of the 240 doses of SFGC administered for which infusion records were available, 237 doses were well tolerated; three hypotensive episodes occurred in 2 patients, which did not result in discontinuation of the drug in either case.. Correction of anemia with parenteral iron alone suggests a high prevalence of iron deficiency in patients with CKD. Treatment of concomitant iron deficiency with SFGC was well tolerated in patients with CKD and appears to optimize management of anemia.

Topics: Administration, Oral; Aged; Anemia, Iron-Deficiency; Clinical Pharmacy Information Systems; Databases as Topic; Drug Administration Schedule; Erythropoietin; Female; Ferric Compounds; Glomerular Filtration Rate; Humans; Hypotension; Iron; Kidney Failure, Chronic; Male; Medical Records; Recombinant Proteins; Retrospective Studies; Sucrose; Treatment Outcome; Veterans

During hemodialysis, patients whose plasma concentrations of nitric oxide (NO) products increase reportedly experience hypotension. Therefore, whether NO bound to hemoglobin (Hb) could contribute to various clinical and laboratory changes during hemodialysis was explored in patients with end-stage renal disease (ESRD).. Ten patients were studied during 3 hemodialysis treatments with samples of blood analyzed for RBC nitrosyl Hb (HbNO), L-arginine, asymmetric dimethylarginine (ADMA), plasma nitrite+nitrate (NOx), and buffy coat NO synthase (NOS) activities.. HbNO before and during hemodialysis varied considerably. Those with higher predialysis levels had lower HbNO values during dialysis, whereas HbNO levels in those with lower levels before dialysis increased. Plasma NOx did not correlate with HbNO, but change in HbNO in the first hour and change in NOx in the first 2 hours correlated with drop in diastolic and systolic blood pressures (BP), respectively. HbNO concentrations increased in patients with >35% drop in systolic BP, whereas in those with <35% drop, HbNO concentrations decreased. HbNO levels adjusted by the hematocrit showed a drop in HbNO for the <35% group and a >3-fold increase in the >35% group. HbNO levels were higher in men than in women, and levels and changes correlated with the hematocrit, skin temperatures, plasma ADMA, arginine, and buffy coat NOS.. In patients with >35% drop in systolic BP, NO was scavenged by Hb in the circulating RBCs, undoubtedly attenuating the degree of hypotension. These data indicate that the amount of NO that is scavenged or released by Hb in the circulating RBCS during dialysis is highly variable and reversible. Various predialysis factors relate to the concentration of HbNO before and during dialysis, which in turn influence clinical findings that occur during the interdialytic period.

Topics: Anemia; Arginine; Erythropoietin; Hematocrit; Hemoglobins; Humans; Hypotension; Kidney Failure, Chronic; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Renal Dialysis; Skin Temperature

Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim of this study was to estimate whether 1-week treatment with EPO can affect the vascular endothelial function. Rabbits were given with EPO (400 iu kg(-1) s.c.) or saline each other day for 1 week. Hypotensive responses to intravenously given acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside and nitroglycerin) and prostaglandin I2 were tested before and after administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a specific nitric oxide synthase inhibitor, under pentobarbitone anaesthesia. Blood haemoglobin concentration in EPO group was significantly higher than that in control group, whereas baseline values of aortic pressure, heart rate and femoral vascular resistance were similar. The dose of ACh (172 ng kg(-1)) requiring for a 15 mmHg hypotension from the baseline in EPO group was apparently higher than that (55 ng kg(-1)) in control group. On the contrary, hypotensive responses to NOC7, nitroprusside, nitroglycerin and prostaglandin I2 were comparable between two groups. The extent of ACh-induced hypotension did not correlate with haemoglobin concentration. L-NAME significantly inhibited the ACh-induced vasodilating response in control group but did not in EPO group. In another set of rabbits, the same treatment with EPO also decreased vasodilating responses to carbachol, bradykinin and substance P besides ACh as compared with control group. These results indicate that 1-week treatment with EPO selectively attenuates depressor responses to endothelium-dependent vasodilators in anaesthetized rabbits, most likely due to inhibition of endothelial nitric oxide synthase.

Topics: Acetylcholine; Anesthesia; Animals; Blood Pressure; Endothelium, Vascular; Epoprostenol; Erythropoietin; Femur; Heart Rate; Hemoglobins; Hypotension; In Vitro Techniques; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Pentobarbital; Rabbits; Time Factors; Vascular Resistance; Vasodilation; Vasodilator Agents

Topics: Bicarbonates; Erythropoietin; Humans; Hypotension; Middle Aged; Renal Dialysis

Topics: Aged; Amyloidosis; Anticoagulants; Chronic Kidney Disease-Mineral and Bone Disorder; Dialysis Solutions; Erythropoietin; Heart Failure; Humans; Hypotension; Kidney Diseases; Membranes, Artificial; Middle Aged; Renal Dialysis; Survival Rate

The haemodynamic effects of recombinant human erythropoietin (rHuEpo) on anaemic haemodialysis patients suffering from chronic hypotension were examined. rHuEpo increased the haematocrit to around 30% and increased diastolic blood pressure by 12.4%, statistically significant. Correspondingly, the total peripheral resistance index increased 42.3% while the cardiac index decreased 24.4% (P less than 0.05) respectively. Blood volume, plasma renin activity and plasma noradrenaline did not change significantly. The extent of blood pressure elevation and haemodynamic alteration did not differ from our previous report on anaemic haemodialysis patients without hypotension. The incidence of hypotensive episodes and fluid supplementation did not change significantly after rHuEpo treatment. In conclusion, by using rHuEpo, approximately a 10% increase of blood pressure can be expected. However no substantial improvement in hypotensive episodes can be expected in chronic haemodialysis patients suffering from hypotension.

Topics: Adult; Blood Volume; Erythropoietin; Female; Hemodynamics; Humans; Hypotension; Kidney Diseases; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Eighteen patients on chronic hemodialysis with renal anemia were treated with recombinant human erythropoietin (r-HuEPO). Hemodynamic parameters in the resting state were determined before and after successful treatment. Posttreatment cardiac index was decreased (3.3 v 2.8 L/min/m2), whereas diastolic blood pressure (72 v 79 mm Hg) and calculated peripheral resistance (2,230 v 2,860 dyne.cm.s-5) were increased significantly when compared with the pretreatment period. We conclude from our study that the increase of blood pressure as seen in patients on dialysis, who are effectively treated with r-HuEPO, is due to an increase in peripheral resistance. This increase overrules the decrease of cardiac index and might well be a result of peripheral vasoconstriction due to improved oxygen availability.

Topics: Adult; Anemia, Hypochromic; Chronic Disease; Erythropoietin; Female; Hemodynamics; Humans; Hypotension; Male; Recombinant Proteins; Renal Dialysis

Topics: Aged; Agranulocytosis; Anemia, Sideroblastic; Erythropoietin; Humans; Hypotension; Male; Neutropenia; Recombinant Proteins; Renin-Angiotensin System

Topics: Animals; Chlorpromazine; Dogs; Erythropoietin; Female; Glycolysis; Hemorrhage; Hypotension; Hypotension, Controlled; Kidney; Male; Manometry; Regional Blood Flow; Renal Veins; Splenectomy

Topics: Animals; Erythropoietin; Female; Hematocrit; Hemorrhage; Hydronephrosis; Hypotension; Iron Isotopes; Kidney Diseases; Male; Primates; Renal Artery Obstruction; Uremia