losartan-potassium and Hypertension--Renal

Heavy chain deposition disease (HCDD) is a comparatively recently described entity characterized by glomerular and tubular basement membrane deposition of monoclonal heavy chains without associated light chains. To our knowledge, review of the literature shows only 24 previously reported cases of HCDD with unequivocal evidence of monoclonal heavy chain deposition in the kidney using immunofluorescence microscopic and electron microscopic studies. The predominant heavy chain subtype was γ. There has been a single case of μ HCDD and 2 previously reported cases of α HCDD. In this report, we describe 3 additional cases of α HCDD, all with a crescentic pattern of injury and one of which was associated with cutis laxa. We compare their clinicopathologic features with all previously reported cases of HCDD.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Cutis Laxa; Dexamethasone; Diabetic Nephropathies; Erythropoietin; Fatal Outcome; Female; Heavy Chain Disease; Hematuria; Humans; Hypertension, Renal; Immunoglobulin alpha-Chains; Immunoglobulin gamma-Chains; Immunoglobulin mu-Chains; Kidney Glomerulus; Male; Multiple Myeloma; Paraproteinemias; Proteinuria; Pyrazines; Thalidomide; Urticaria; Vasculitis, Leukocytoclastic, Cutaneous

Topics: Anemia; Animals; Blood Pressure; Disease Models, Animal; Double-Blind Method; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Hypertension, Renal; Kidney; Kidney Failure, Chronic; Rats; Recombination, Genetic

Topics: Diagnosis, Differential; Erythropoietin; Hemangiopericytoma; Hormones, Ectopic; Humans; Hypertension, Renal; Hyperthyroidism; Kidney Neoplasms; Paraneoplastic Endocrine Syndromes; Renin; Syndrome; Wilms Tumor

In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing.. 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.. Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.. Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Hypertension, Renal; Incidence; Iron; Kidney Failure, Chronic; Male; Middle Aged; Morbidity; Recombinant Proteins; Renal Dialysis; Thromboembolism; Treatment Outcome

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

Recombinant human erythropoietin (rHuEPO) has been reported to induce hypertension. We investigated the effect of a single injection of rHuEPO on blood pressure in patients receiving hemodialysis (HD) and in patients with predialysis chronic renal failure (CRF). Forty-one patients receiving HD and 36 patients with predialysis CRF received an intravenous injection of rHuEPO, and blood pressure and plasma endothelin-1 were measured before and 30 min after the injection. Mean blood pressure was increased significantly in HD patients, but not in CRF patients (HD: 103+/-5 to 105+/-6 mmHg, p<0.05; CRF: 103+/-4 to 103+/-6, NS). The percentage of patients with increased mean blood pressure of more than 10 mmHg after rHuEPO injection was significantly larger in the HD than in the CRF group (27.0% vs. 5.5%, p<0.01). A positive correlation was found between changes in endothelin-1 level and mean blood pressure in the HD (r=0.43, p<0.01) but not in predialysis chronic renal failure. In conclusion, a single injection of rHuEPO increased blood pressure with a positive correlation with endothelin-1 release in hemodialysis patients, but not in predialysis chronic renal failure patients.

Topics: Adult; Aged; Anemia; Blood Pressure; Endothelin-1; Erythropoietin; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Chronic allograft nephropathy and/or calcineurin inhibitor toxicity are common problems after organ transplantation. The aim of this study was to examine the safety and efficacy of switching from a calcineurin inhibitor-based to a calcineurin inhibitor-free immunosuppressive regimen consisting of sirolimus and mycophenolate mofetil (MMF) late after renal transplantation.. Kidney biopsies were performed in renal-transplanted patients with increasing serum creatinine levels at least 6 months after transplantation (mean time +/- SD after renal transplantation: 76.4 +/- 50.4 months). Patients with no signs of acute rejection were switched to MMF (500-2,000 mg/day) in combination with a low dose of sirolimus (1 mg/day). Renal function, serum chemistry, blood trough levels of sirolimus and MMF, and blood pressure were monitored.. 13 patients were investigated. During our observation period (mean observation time +/- SD: 11.2 +/- 5.9 months), an improvement in renal function was observed in 10/13 patients. In 3/13 patients, renal function deteriorated further and hemodialysis was initiated in 2 patients within the next 6 months. However, a serum creatinine concentration above 3.5 mg/dl was measured in 2 of those 3 patients prior to the switch of the immunosuppressive protocol. Administration of a low dosis of sirolimus (1 mg/day) led to relevant sirolimus (4.16 +/- 1.85 ng/ml) and MMF blood trough levels (month 1: 6.8 +/- 3.46; month 3: 4.67 +/- 1.78 mg/l). The following adverse events were observed: borderline acute rejection (1/11 patients), anemia responding to higher dosage of erythropoietin (3/11), hyperlipidemia (1/11), and urinary tract infections (4/11).. Low-dose sirolimus therapy in combination with concentration-adjusted MMF therapy leads to improvement of organ function late after renal transplantation. The follow-up of those patients should include assessments of blood cell counts, serum lipids and urinalysis to recognize the possible side effects.

Topics: Adult; Antihypertensive Agents; Biopsy; Calcineurin Inhibitors; Creatinine; Drug Interactions; Drug Therapy, Combination; Erythropoietin; Female; Hemoglobins; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney; Kidney Transplantation; Leukocyte Count; Male; Middle Aged; Mycophenolic Acid; Platelet Count; Sirolimus

The association of the angiotensinogen (AGT) gene variation at codon 235, the T235 variant, with hypertension induced by erythropoietin (Epo) was investigated in patients with progressive renal disease requiring treatment for renal anemia with Epo. The subjects for the study were patients with renal diseases with serum creatinine concentration exceeding 2 mg/dl and a hematocrit (Ht) of less than 30%. During the run-in period, blood pressure was well controlled with an appropriate salt restricted diet and/or antihypertensive treatment. The patients were then given 6,000 IU of Epo once a week until the Ht rose by 5%. For the overall patient group, AGT gene polymorphism analysis revealed T235T (T/T) in 31 cases (61%), M235T (M/T) in 19 cases (37%), and M235M (M/M) in 1 case (2%). In response to treatment with Epo, hypertension (defined as an increase in mean blood pressure greater than 10 mmHg) was found in 11 cases (22%), all of who carried the homozygous T allele (T/T). On the other hand, the frequency of T/T in patients who did not develop hypertension was 50% (T/T:T/M=20:19 cases), indicating a significant difference (p=0.003 by Chi-square). Variables estimated to be associated with Epo-induced hypertension were the T allele, gender (male), and the degree of increase in Ht, in descending order. Our preliminary research indicates that individuals who carry two copies of the T allele, i.e., who are homozygous for T, are highly susceptible to development of hypertension when subjected to Epo. These results suggest that the AGT T235 variant may be the primary gene responsible for the development of Epo-induced hypertension.

Topics: Adult; Aged; Angiotensinogen; Blood Pressure; Erythropoietin; Female; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Hypertension, Renal; Male; Middle Aged; Pilot Projects; Polymorphism, Genetic

Evidence for the involvement of endothelial cells in the pathogenesis or erythropoietin-induced hypertension, and for endothelial cell damage in patients with chronic renal failure, has emerged and appears to be of major concern. We, therefore, investigated the effect of recombinant human erythropoietin (rHuEPO) therapy on endothelium-derived hormones in predialysis patients with progressive renal anemia. At the entry to the trial, the serum thrombomodulin concentration (Tm) and plasma endothelin-1 concentration (ET-1) in the predialysis patients were significantly higher than those in age- and sex-matched normal subjects. Following a 16 week period of treatment with 6000IU rHuEPO given intravenously once a week, patients' hematocrit increased from 27.1 +/- 2.6% to 34.6 +/- 3.2% (n = 16, P < .001). A positive correlation was found between Tm and serum creatinine concentration (Cr) (r = 0.61, P < .05 (n = 16), but no correlation was found between ET-1 and Cr. Tm and Tm/Cr significantly decreased from 7.9 +/- 2.8 ng/mL to 6.6 +/- 2.4 ng/mL (P < .01, n = 16), and from 2.1 +/- 0.7 (x10(-10) to 1.6 +/- 0.7 (x10(-10), P < .01, n = 16), respectively. However, there was no change in ET-1 as a result of the rHuEPO therapy. Creatinine clearance (Ccr), Cr, total amount of daily Tm excretion, Tm clearance/Ccr, daily urinary protein and albumin excretion, and blood pressure also remained unchanged throughout the trail. The present study indicates that correcting anemia by rHuEPO therapy reduces an abnormally elevated Tm in predialysis patients while blood pressure and renal function remain unchanged, suggesting that rHuEPO has a beneficial effect on endothelial cell dysfunction in chronic renal failure patients. This effect may be mediated via an improved oxygen supply to the endothelial cells due to the amelioration of anemia by rHuEPO.

Topics: Adult; Aged; Anemia; Blood Pressure; Creatinine; Endothelins; Endothelium, Vascular; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Thrombomodulin; Urinalysis

Treatment of hypertension with an angiotensin converting enzyme inhibitor (ACEI) may be associated with a decrease in haemoglobin concentration especially in patients with renal insufficiency. This open study in 19 patients with a variety of renal diseases with complicating hypertension investigated the effects of the ACEI, enalapril, on haemoglobin and plasma erythropoietin (EPO) concentrations. Blood samples were obtained at baseline and 2, 60 and 120 days after starting treatment with enalapril. By day 60 there was a significant decrease in mean haemoglobin concentration (mean decrease 7.4 g/l) that was sustained until day 120. Apart from a small, but significant, reduction by day 2, mean plasma EPO concentration remained constant throughout the study. The magnitude of the decrease in haemoglobin concentration was, however, significantly correlated with the baseline plasma creatinine concentration and creatinine clearance. These results suggested that the degree of renal insufficiency was important in determining the haematological response to ACE inhibition. While the mechanism of these changes remains unclear, our findings suggest that inhibition of the renin-angiotensin system, rather than decreasing EPO production, may reduce the erythropoietic activity of the hormone.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Erythropoietin; Female; Hemoglobins; Humans; Hypertension, Renal; Kidney; Male; Middle Aged; Polycythemia

The effect of recombinant human erythropoietin (r-HuEPO) on ambulatory blood pressure (ABP) was studied in 13 anemic hemodialysis patients. Eight patients were normotensive and five patients had untreated borderline systolic hypertension. Mean hemoglobin increased from 82 +/- 3 g/L to 114 +/- 3 g/L (P < .01) after 3 to 4 months of r-HuEPO therapy (30 to 40 U/kg) administered subcutaneously three times weekly. Mean 24-h systolic and diastolic ABP measurements were significantly increased by 16 +/- 4 mm Hg and 10 +/- 2 mm Hg, respectively (P < .01 for both). Blood pressure was increased in all but one patient. In six patients, the mean 24-h systolic and diastolic ABP measurements were more than 160 mm Hg or 90 mm Hg at the end of the study. The increase in ABP was slightly but not significantly greater during the waking period as compared with the sleeping period and the circadian blood pressure pattern was not modified by r-HuEPO treatment. The blood pressure load (percentage of ABP reading exceeding 140/90 mm Hg during the waking period and 120/90 mm Hg during the sleeping period) was significantly increased (P < .05) after r-HuEPO therapy. Nine of the 13 patients failed to show the expected reduction in blood pressure during the sleeping period and were defined as "nondippers"; the others were defined as "dippers." During r-HuEPO therapy, the increase in ABP was similar in both dippers and nondippers. This suggests that the nondipper condition is not a risk factor for the development of hypertension during r-HuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Anemia; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Erythropoietin; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Renin

Topics: Anemia; Animals; Blood Pressure; Disease Models, Animal; Double-Blind Method; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Hypertension, Renal; Kidney; Kidney Failure, Chronic; Rats; Recombination, Genetic

The Canadian Erythropoietin Study Group conducted a randomized, placebo-controlled trial to examine the effect of human recombinant erythropoietin on the treatment of anemia in 118 hemodialysis patients. The effectiveness of therapy on hemoglobin concentration and quality of life has been reported elsewhere. Herein is reported the effect of erythropoietin therapy on blood pressure. Patients receiving erythropoietin had a significant increase in diastolic blood pressure (DBP; p = 0.001) and required increased antihypertensive medication. There was no difference in the incidence of severe hypertension (DBP greater than 110 mm Hg or hypertension-related seizure) between placebo-treated patients (13%) and those receiving erythropoietin (14%). The development of severe hypertension in erythropoietin-treated patients was associated with a history of receiving antihypertensive medication or having native kidneys in situ. In the first 5 weeks of the study, there was a correlation between the change in hemoglobin concentration and the change in DBP (r = 0.42, p less than 0.001). Although erythropoietin therapy was associated with a significant increase in DBP, there was no difference between placebo- and erythropoietin-treated patients with respect to severe hypertension or hypertension-related seizures.

Topics: Anemia; Blood Pressure; Erythropoietin; Humans; Hypertension, Renal; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Recombinant human erythropoietin (rh-EPO) has been shown to be effective in the treatment of renal anemia. Additionally, rh-EPO improves the hemostatic defect of uremia. On the other hand, a hypertensinogen effect and an increased risk for thrombosis have been reported in hemodialysis (HD) patients with rh-EPO. 20 HD patients in Homburg were recruited for a multicenter, placebo-controlled study (MF 3981), aiming to assess the risk of rh-EPO. Initially, 10 patients received rh-EPO at a dose of 3 x 80 U/kg body weight and week which was subsequently adjusted according to the hematocrit. After 6 months, the patients receiving placebo were changed to rh-EPO therapy. Clinical and laboratory data were obtained before, as well as 1, 3, 6 and 12 months after beginning of the study. Erythrocyte counts increased significantly in the rh-EPO group. Also, an increase of platelet count, fibrinogen and plasma viscosity was observed during rh-EPO. Tissue type plasminogen activator and plasminogen activator inhibitor as well as von-Willebrand-factor remained unchanged, although a shortening of the bleeding time was observed. Blood pressure and arterial blood flow were not influenced by rh-EPO.

Topics: Blood Viscosity; Erythrocyte Count; Erythropoietin; Hematocrit; Humans; Hypertension, Renal; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Risk Factors; Thrombosis

Several polymorphisms of vasoactive hormones have been implicated in hypertension. Erythropoietin (EPO) interacts with vasoactive substances, such as angiotensin II. Previously detected single nucleotide polymorphisms in the hypoxia-responsive element of EPO might be associated with hypertension and hypertensive end organ damages.. 400 hypertensive patients and 200 age- and gender-matched normotensive controls were genotyped for an EPO polymorphism [cytosine (C)/thymine (T) single nucleotide polymorphism] at position 3434. Patients were grouped according to their genotype into the CC group (CC genotype) and the CT/TT group (CT and TT genotype). BP was measured by ambulatory BP monitoring.. The CC genotype was present in 87% of hypertensive patients and in 78.5% of controls (p = 0.007). In addition, patients with the CC genotype had higher BP levels compared with CT/TT genotypes (BPsys 143.7 ± 20.4 vs. 136.1 ± 13.5 mm Hg, p = 0.01, and BPdias 85.8 ± 11.6 vs. 82.4 ± 8.9, p = 0.043) despite a nearly identical number of antihypertensive drugs (2.3 ± 1.5 vs. 2.3 ± 1.6; p = 0.257). 100% of the small number of patients with end-stage renal disease (n = 15) had the CC genotype.. The CC genotype of the EPO gene at position 3434 is more frequently found in patients with hypertension and is associated with higher BP levels.

Topics: Adult; Aged; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Erythropoietin; Female; Genotype; Homozygote; Humans; Hypertension, Renal; Hypoxia; Male; Middle Aged; Myocardial Infarction; Polymorphism, Genetic; Stroke; Vascular Diseases

The hematopoietic cytokine erythropoietin has cytoprotective effects in endothelial cells in vitro that are mediated through direct activation of the pro-survival Akt tyrosine kinase signaling pathway. We tested the hypothesis that low-dose therapy with the long-acting recombinant human erythropoietin analogue darbepoetin alpha protects vascular endothelium in vivo in a classic remnant kidney rat model characterized by severe endothelial damage, progressive vascular sclerosis, and ischemia-induced tissue fibrosis.. Using a parallel group study design, we randomly assigned animals after 5/6 nephrectomy to treatment with either saline (n=36) or 0.1 microg/kg body wt darbepoetin (n=24) subcutaneously once weekly. We monitored hematocrit, blood pressure, and serum creatinine regularly and obtained renal tissue 6 weeks after nephrectomy for morphological and immunohistochemical analysis. Darbepoetin-treated animals had significantly improved survival compared with saline-treated controls (63% versus 33%; P<0.05), although hematocrit levels were similar in both groups. Darbepoetin treatment ameliorated endothelial damage; attenuated the composite tissue injury score (saline 1.9+/-0.4; darbepoetin 0.4+/-0.2; P<0.001), which included vascular sclerosis, glomerulosclerosis, and tubulointerstitial damage; and preserved renal function. We found persistent activation of the pro-survival Akt signaling pathway in endothelial and epithelial glomerular cells in darbepoetin-treated animals, accompanied by a significant reduction of apoptotic cell death in renal tissue.. Low-dose darbepoetin treatment confers vascular and tissue protection that is associated with persistent stimulation of the pro-survival Akt signaling pathway. The use of recombinant human erythropoietin or analogues may have utility in preventing ischemia-related progressive vascular injury and organ failure.

Topics: Animals; Apoptosis; Darbepoetin alfa; Disease Models, Animal; Disease Progression; Drug Evaluation, Preclinical; Endothelium, Vascular; Erythropoietin; Glomerulosclerosis, Focal Segmental; Hematocrit; Hematopoietic Stem Cell Mobilization; Hypertension, Renal; Ischemia; Kidney; Life Tables; Male; Multiple Organ Failure; Nephrectomy; Nephritis, Interstitial; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Random Allocation; Rats; Rats, Sprague-Dawley; Signal Transduction

Progressive renal failure occurs in a large number of patients even in the absence of the original cause of injury. It is suggested that the initial reduction in nephron number progressively damages the remaining ones. Various mechanisms underlie the pathogenesis of progressive glomerular injury. Several studies have extensively shown that both dietary protein restriction and pharmacologic intervention with ACE-inhibitiors and angiotensin receptor antagonists effectively slow the progression of chronic renal diseases. This article will present treatment recommendations designed to delay the progression of chronic renal disease, to optimize its medical management and to reduce complications induced by renal insufficiency including hypertension, renal osteodystrophy and anemia. Ten steps in the management of patients with chronic renal failure recommended by an international panel of experts based on existing guidelines are presented.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Calcitriol; Calcium Channel Agonists; Chronic Kidney Disease-Mineral and Bone Disorder; Diuretics; Erythropoietin; Glomerular Filtration Rate; Humans; Hypertension, Renal; Kidney Failure, Chronic; Kidney Function Tests; Proteinuria; Renal Replacement Therapy

The anemia associated with chronic renal failure is one of the best target diseases for erythropoietin (Epo) gene transfer. We previously reported a short-term (1 month) study of continuous rat Epo delivery by muscle-targeted gene transfer of plasmid DNA expressing rat Epo (pCAGGS-Epo) using in vivo electroporation in normal rats. Here, we performed a long-term pharmacokinetic study of continuous Epo delivery by this method in normal rats and uremic five-sixths nephrectomized rats. In normal rats, Epo gene expression and sufficient erythropoiesis occurred with Epo gene transfer in a dose-dependent manner, and persisted for at least 11 weeks. Repeated administration of the plasmid DNA effectively produced erythropoiesis. Similar erythropoiesis was observed in the uremic rats, and persisted for more than 15 weeks. Both normal and uremic rats showed a significant decrease in platelet count. Moreover, the uremic rats showed Epo-induced hypertension, which is the major side-effect of recombinant human Epo. These results demonstrate that muscle-targeted pCAGGS-Epo transfer by in vivo electroporation is a useful procedure for the long-term continuous delivery of Epo in both normal and uremic rats.

Topics: Animals; DNA; Electroporation; Erythrocytes; Erythropoietin; Genetic Therapy; Hypertension, Renal; Kidney Failure, Chronic; Linear Models; Models, Animal; Muscle, Skeletal; Rats; Uremia

Topics: Blood Donors; Blood Transfusion, Autologous; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Fees, Pharmaceutical; Hematinics; HIV Infections; Hypertension, Renal; Neoplasms; Premedication; Preoperative Care; Recombinant Proteins; Renal Insufficiency

We investigated to see whether an altered role of nitric oxide (NO) system is involved in erythropoietin (EPO)-induced hypertension in chronic renal failure (CRF). Male Sprague-Dawley rats were five-sixths nephrectomized to induce CRF. Six weeks after the operation, EPO or vehicle was injected for another 6 weeks. Plasma and urine nitrite/nitrate (NOx) levels were determined. Expression of NO synthase (NOS) proteins in the aortae and kidneys were also determined. In addition, the isometric tension of isolated aorta in response to acetylcholine and nitroprusside was examined. Blood pressure progressively rose in CRF groups, the degree of which was augmented by EPO treatment. Plasma NOx levels did not differ among the groups, while urine NOx levels were lower in CRF groups. Endothelial NOS expression was lower in the kidney and aorta in CRF rats, which was not further affected by EPO-treatment. The inducible NOS expression in the kidney and aorta was not different among the groups. Acetylcholine and sodium nitroprusside caused dose-dependent relaxations of aortic rings, the degree of which was not altered by EPO-treatment. Taken together, EPO-treatment aggravates hypertension in CRF, but altered role of NO system may not be involved.

Topics: Acetylcholine; Anemia; Animals; Aorta, Thoracic; Body Weight; Erythropoietin; Hypertension, Renal; Isometric Contraction; Kidney; Kidney Failure, Chronic; Male; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Nitroprusside; Rats; Rats, Sprague-Dawley; Vasoconstriction; Vasoconstrictor Agents; Vasodilator Agents

Accurate information on prevalence and status of blood pressure (BP) control in hemodialysis patients is lacking. Our Hemodialysis Quality Improvement Program, sought to determine: 1) The extent and control of hypertension (HTN), 2) whether Erythropoietin (EPO) dose or intradialytic fluid loss had any effect on BP and 3) a means to follow the severity of HTN.. The pre/post mid-week dialysis BP readings of 190 patients (64+/-14.1 years, 53% males, 77% whites) were evaluated over a 3 month period. HTN was defined as BP >150/90. Hypertension was further characterized according to whether the patients had normal or elevated pre-dialysis systolic, pre-dialysis diastolic, post-dialysis systolic or post-diastolic BP readings on more than 6 of the possible 13 recordings. The average EPO dose and weight loss during dialysis was correlated with BP. To better understand the extent of HTN, systolic and diastolic pressures were separately graded from 0 to 3 and a number designated as hypertension sensitivity index (HSI) was assigned to each patient.. Of the 190 patients, 146 (76.8%) were hypertensive. 117 out of 146 hypertensive patients (80.1%) had persistent elevation of BP despite being on one or more antihypertensive medications. Most patients were on calcium channel blockers (39%) with 27% being on beta-blockers and 14% on Angiotensin converting enzyme inhibitors. There was no correlation between the number of medications used and the control of HTN. The dose of EPO also had no effect on the degree of HTN. 69.8% of all HTN was systolic. Of this, 64.7% was pre-dialysis and 35.3% post-dialysis. Multiple regression analysis demonstrated a significant correlation with loss of weight during dialysis and lowering of systolic BP (r = 0.33, p = 0.0001). The mean HSI for this population was 2.3+/-1.8.. HTN was a frequent finding in our hemodialysis population and it was controlled in only 19.9% of hypertensive patients. Most of this HTN was pre-dialysis systolic. There was a significant correlation between fluid loss during dialysis and lowering of blood pressure. The use of the HSI has proven to be helpful in differentiating type and severity of HTN.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Erythropoietin; Female; Humans; Hypertension, Renal; Male; Middle Aged; Prevalence; Renal Dialysis; Retrospective Studies; Weight Loss

Recombinant human erythropoietin (rHuEPO) is used extensively in anemic patients on dialysis and other patients and is regarded as very safe and effective in the management of anemia in these patients. To date, there is no report on the development of antibodies to rHuEPO in the patients treated with this drug. We report here a patient who developed antibodies to rHuEPO and as a result developed pure red cell aplasia. A 63-year-old black male with end-stage renal disease secondary to hypertension was placed on chronic dialytic therapy and tolerated rHuEPO treatment well for two years. A rapidly progressive anemia was then noted which was unresponsive to maximal doses of rHuEPO and the patient soon became transfusion-dependent. Bone marrow examination revealed paucity of red cell precursors. A detailed search for the cause of this pure red cell aplasia was unrevealing. Serological tests for Parvovirus B19 infection were negative. Antibodies for rHuEPO were tested by radioimmuno-precipitation assay and were found positive. In the course of several months, the antibody titer declined spontaneously to negligible levels with simultaneous improvement in the anemia and reappearance of red cell precursors in the bone marrow. This is the first patient to be reported who formed antibodies to rHuEPO and as a consequence developed pure red cell aplasia. Thus we conclude that although very rare, antibody production to rHuEPO should be considered in evaluating patients with EPO-resistant anemia with no obvious etiology.

Topics: Antibody Formation; Erythropoietin; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Red-Cell Aplasia, Pure; Renal Dialysis

Topics: Administration, Oral; Animals; Arginine; Blood Pressure; Erythropoietin; Hypertension, Renal; Male; Nephrectomy; Rats; Rats, Wistar; Recombinant Proteins

An 18-year-old renal transplant patient presented with sudden onset of seizures almost 2 years after she received the graft. Diagnostic work-up was unrevealing except for magnetic resonance imaging abnormalities of the brain that resolved spontaneously 4 weeks later. In this brief report, we discuss the etiology of the seizures and neurological abnormalities in renal transplant patients in light of the findings of our patient.

Topics: Adolescent; Brain Diseases; Diagnosis, Differential; Erythropoietin; Female; Humans; Hypertension, Renal; Kidney Function Tests; Kidney Transplantation; Magnetic Resonance Imaging; Recombinant Proteins; Seizures

To assess the effect of recombinant human erythropoietin (EPO) on the factors regulating blood pressure (BP), we determined the hemoglobin level (Hgb), blood viscosity (BV), plasma renin activity (PRA), plasma concentrations of aldosterone (PAC), adrenaline (Ad), noradrenaline (NAd), and atrial natriuretic peptide (ANP), and serum and intracellular concentrations of cations before and after 3 months of EPO treatment (40 units/kg/week of EPO intravenously after each hemodialysis session) in 11 patients undergoing maintenance hemodialysis. Intracellular sodium concentration ([Na+]i) was measured using erythrocytes with flame photometry. EPO treatment was associated with significant increases in Hgb (7.1 +/- 1.4 to 8.4 +/- 1.8 g/dl, p<0.01), mean BP (103 +/- 11.4 to 116 +/- 19.9 mmHg, p<0.01), [Na+]i (4.99 +/- 0.78 to 6.22 +/- 0.96 mmol/l, p<0.01) and BV (1.39 +/- 0.14 to 1.53 +/- 0.18 c.p., p<0.05), but no significant alteration in PRA, PAC, Ad, NAd, ANP, or in the serum concentration of Na+, K+, and Ca2+. The changes in mean BP (deltaMBP) were significantly correlated with delta[Na+]i (R=0.676, p=0.022) and deltaBV (R=0.668, p=0.034), but not with deltaHgb. By multiple regression analysis, delta[Na+]q and deltaBV independently contributed to deltaMBP; deltaMBP=2.27 X delta[Na+]i+32.2 X deltaBV +3.37 (R=0.695). These data suggest that intracellular sodium accumulation as well as increased blood viscosity may be independently involved in the blood pressure elevation after EPO treatment in patients under maintenance hemodialysis. We found no evidence supporting a role of circulating hormonal factors, such as the renin-angiotensin system, adrenaline, or ANP, in the change in blood pressure.

Topics: Aged; Aldosterone; Anemia; Atrial Natriuretic Factor; Blood Pressure; Blood Viscosity; Calcium; Cations; Epinephrine; Erythrocyte Count; Erythrocytes; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Hypertension, Renal; Injections, Intravenous; Kidney Failure, Chronic; Male; Middle Aged; Norepinephrine; Potassium; Regression Analysis; Renal Dialysis; Renin; Sodium

Topics: Animals; Erythropoietin; Female; Humans; Hypertension, Renal; Male; Middle Aged; Oxygen; Rats; Renal Artery Obstruction

In a subset of dialysis patients, erythropoietin (rHuEpo) treatment exacerbates hypertension. The mechanism of this pressor effect is unknown; however, it has been suggested that decreased endogenous nitric oxide (NO) activity may play a role. To explore this hypothesis, Sprague-Dawley rats were given rHuEpo (150 U/kg s.c. three times per week) or corresponding vehicle. Blood pressure, haematocrit, and urinary excretion of the stable NO metabolites, nitrite (NO2) and nitrate (NO3), were determined at baseline and 3 weeks. After 3 weeks of rHuEpo treatment there was a significant increase in blood pressure and haematocrit, while in vehicle-treated rats blood pressure and haematocrit remained at basal levels. Urinary excretion of NO2+NO3 increased compared to basal in rHuEpo, but not vehicle rats. Thus in normal rats rHuEpo does have a significant pressor effect, but this is not associated with decreased activity of the endogenous NO system. Thus decreased endogenous NO activity is not responsible for rHuEpo-associated hypertension. These data further suggest that endogenous NO activity is increased in rHuEpo-treated rats, perhaps as a counter-regulatory mechanism that limits the pressor effect. Whether this mechanism is active in the setting of rHuEpo-treated chronic renal failure in humans is unknown.

Topics: Animals; Blood Pressure; Disease Models, Animal; Erythropoietin; Hematocrit; Hydrogen-Ion Concentration; Hypertension, Renal; Male; Nitrates; Nitric Oxide; Nitrites; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins

Renal endothelin-1 (ET-1) production is diminished in spontaneously hypertensive rats. An increase has been reported of renal ET-1 production associated with progression of renal disease in rats with reduced renal mass. The purpose of the present study was to investigate the evolution over time of the urinary ET-1 excretion in an experimental model of renal mass reduction not caused by renal infarction. Rats were subjected to 2/3 nephrectomy (right nephrectomy and resection of the lower left renal pole) and thereafter randomly assigned to a no-treatment control group or to treatment with recombinant erythropoietin, recombinant erythropoietin plus verapamil, or recombinant erythropoietin plus enalapril. The urinary ET-1 excretion was decreased by week 16 after nephrectomy as compared with healthy animals and with the levels 6 weeks after nephrectomy. The temporal evolution of urinary ET-1 excretion in the various groups of rats showed a trend toward decrease in all groups except the one receiving enalapril. The urinary ET-1 excretion correlated directly with creatinine clearance and inversely with tubulointerstitial damage. We observed an inverse correlation between urinary ET-1 excretion and arterial blood pressure 16 weeks after nephrectomy. These results indicate that renal ET-1 production decreases with the progression of renal disease and in relation with the severity of tubulointerstitial damage. The decrease in renal ET-1 production might contribute to the development and perpetuation of renal disease-associated arterial hypertension; this situation may be favorably modified by the use of enalapril.

Topics: Animals; Enalapril; Endothelins; Erythropoietin; Hypertension, Renal; Kidney; Kidney Diseases; Male; Nephrectomy; Radioimmunoassay; Rats; Rats, Wistar; Recombinant Proteins; Verapamil

Topics: Amputation, Surgical; Bloodletting; Cadaver; Erythropoietin; Glomerulonephritis; Hematocrit; Humans; Hypertension, Renal; Ischemia; Kidney Transplantation; Leg; Male; Middle Aged; Polycythemia; Postoperative Complications; Renal Dialysis

We assessed the influence of hyperoxemia on erythropoietin secretion in patients with various etiological forms of arterial hypertension (essential, n = 15; renoparenchymal, n = 16; renovascular, n = 15) and in 15 healthy subjects. On the first day of the study, blood was withdrawn at 1-hour intervals for the estimation of erythropoietin during a total of 6 hours and at 2-hour intervals for the assessment of PO2. Three days later the same parameters were assessed again at identical time intervals, but the subjects were breathing pure oxygen during the first 2 hours. Breathing with pure oxygen resulted in a significant increase of blood PO2 (184.85 +/- 4.47 versus 85.92 +/- 2.28 in essential, 185.21 +/- 5.52 versus 84.55 +/- 3.04 in renoparenchymal, and 181.7 +/- 3.14 versus 87.49 +/- 2.25 in renovascular hypertension groups and 189.84 +/- 5.2 versus 85.89 +/- 1.73 mm Hg in healthy subjects; P < .001 in all groups). Baseline plasma erythropoietin was not different among the groups (29.33 +/- 4.14 in essential, 24.56 +/- 3.09 in renoparenchymal, and 27.77 +/- 3.29 in renovascular hypertension groups and 24.23 +/- 2.70 mU/mL in the control group). The pattern of erythropoietin decline was different in the groups of hypertensive patients. In patients with essential hypertension, unlike in healthy subjects and patients with other etiological forms of arterial hypertension, only a very short-term suppression of erythropoietin levels was observed during hyperoxemia. No significant changes in blood pressure during breathing with pure oxygen were found in any of the studied groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Pressure; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Hypertension; Hypertension, Renal; Hypertension, Renovascular; Iron; Male; Middle Aged; Oxygen

Intracellular free calcium concentration ([Ca2+]i) was examined in the platelets of 15 control subjects (NT), 6 predialysis patients with chronic renal failure (CRF), 17 patients on hemodialysis (HD), 20 patients on continuous ambulatory peritoneal dialysis (CAPD), 10 normotensive persons with genetic hypertension (GHT) and 8 essential hypertensive patients (EHT). Levels of [Ca2+] i in the platelets were measured by the fluorescent calcium indicator Fura-2. Resting [Ca2+] i in CRF and HD patients was higher than the value in NT and that in CAPD patients was similar to NT. rHuEPO significantly increased the level of [Ca2+] i in CRF and HD patients compared to those in NT. Under resting and EPO-stimulated conditions, the levels of [Ca2+] i in GHT and EHT were higher than those in NT. rHuEPO increased the levels of [Ca2+] i in the absence of extracellular calcium in NT, GHT and EHT. In addition, EPO-stimulated calcium influx in GHT and EHT was greater than that in NT. Thus, it appears that the mechanism of rHuEPO-induced hypertension may be mainly due to elevation of [Ca2+] i. EPO may contribute to the development of genetic hypertension.

Topics: Adult; Aged; Blood Platelets; Calcium; Erythropoietin; Female; Humans; Hypertension; Hypertension, Renal; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins

A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.01-1 microM. Structure-activity studies showed the quinoline nitrogen atom and a short alkyl chain at the quinoline 2-position to be essential for receptor binding. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-2.0 mg/kg. One of the compounds, 2-ethyl-4-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy]quinoline (5g), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg in AII-infused, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model, compound 5g showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg. On the basis of its profile, this compound, designated ICI D8731, has been selected for clinical evaluation.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Antihypertensive Agents; Binding, Competitive; Blood Pressure; Dose-Response Relationship, Drug; Guinea Pigs; Hydrogen Bonding; Hypertension, Renal; In Vitro Techniques; Male; Models, Molecular; Molecular Conformation; Quinolines; Radioligand Assay; Rats; Rats, Wistar; Receptors, Angiotensin; Structure-Activity Relationship; X-Ray Diffraction

In 24 hypertensive patients with unilateral renal disease, the erythropoietin (Epo) concentration ratio in the renal veins was compared with the renin ratio. Seven patients showed moderately elevated peripheral Epo values. Epo and plasma renin activity were significantly positively correlated both in peripheral and renal veins. This suggests that the reduction of renal blood flow was a common, but not unique, stimulating factor of Epo and renin secretion. Epo ratio appeared insensitive since it was greater than 1.5 in only 30% of patients with a renin ratio > 2. Our results indicate that the Epo concentration ratio in renal veins cannot be proposed as a substitute for the currently used renin ratio.

Topics: Adolescent; Adult; Aged; Blood Pressure; Erythropoietin; Female; Humans; Hypertension, Renal; Hypertension, Renovascular; Male; Middle Aged; Renal Veins; Renin

Topics: Adrenergic beta-Antagonists; Anemia, Hemolytic; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Diuretics; Erythropoietin; Humans; Hypertension, Renal; Kidney Failure, Chronic; Renal Dialysis; Sympatholytics

The substitution of recombinant human erythropoietin (rhEPO) in chronic hemodialysis patients is often associated with the development of severe hypertension. In the present study, a systematical echocardiographic analysis was performed in 25 patients on maintenance hemodialysis during rhEPO therapy for at least 4 months. Referred to the total group, indices of left ventricular size decreased significantly. Left ventricular total volume and left ventricular mass were reduced considerably. Fractional fiber shortening and ejection fraction showed an impressing improvement. At a constant heart rate, stroke volume and cardiac output were reduced. Myocardial thickness did not alter under chronic rhEPO therapy. When subgroups were formed with respect to changes in blood pressure, all parameters investigated behaved very similar to the total group, irrespective of changes in blood pressure. Five patients with coronary heart disease and clinical signs of myocardial insufficiency were evaluated separately. These patients showed a decrease in left ventricular size and no evidence of a deterioration of myocardial function. We conclude from our results that rhEPO therapy in patients on maintenance renal replacement therapy has beneficial effects on left ventricular size and function; these effects are not significantly counteracted by the development of hypertension.

Topics: Anemia; Cardiomegaly; Erythropoietin; Female; Humans; Hypertension, Renal; Kidney Failure, Chronic; Male; Recombinant Proteins; Renal Dialysis; Ultrasonography; Ventricular Function, Left

Recombinant human erythropoietin (rHu-EPO) was given during 12 to 20 months in 15 long term haemodialysis anaemic (mean Hb: 6.6 +/- 1 g/dl) patients who required no blood transfusion. Patients over 65, or with severe arterial disease or with uncontrolled hypertension were not included in this trial. Correction of anaemia (mean Hb 12.1 +/- 0.6 g/dl) was achieved in all patients and maintained all along the study. An improved sense of wellbeing and increased exercise tolerance were reported by all patients. Appropriate maintenance dosage of rHu-EPO was 74 +/- 6 U/kg i.v. twice weekly. High dose oral and/or intravenous iron therapy was necessary in the absence of previous marked iron overload. One retinal venous thrombosis was the sole severe side-effect encountered. A slight but significant increase of blood pressure was observed with the need of intensifying previous anti-hypertensive therapy in one patient and of starting one in one another. Fine adjustment of the dry weight was necessary to maintain blood pressure in the normal range. Heparin requirements increased in the majority of patients because of hollow fibre clotting but there was no evidence of decreased efficacy of dialysis. In two patients clotting of arteriovenous fistula was not obviously related to the rHu-EPO treatment.

Topics: Adult; Anemia; Body Weight; Drug Evaluation; Erythropoietin; Female; Humans; Hypertension, Renal; Iron; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retinal Vein Occlusion

For some unknown reason, the blood hematocrit will become elevated 50 percent or more in some cases of renal disease where hypertension is a factor. In the absence of other identifiable causes of erythrocytosis, this is believed to result from the formation of erythropoietin stimulating factor (ESF) by the kidney in response to some intrarenal hypoxic stimulus. In this study it could be demonstrated with the help of computer simulations, that the hypertension was caused by excess fluid being retained by the kidneys, whereas, the elevated hematocrit could only be attributed to primary increase in the resistance to blood flow. This suggests that the high hematocrit levels that have been reported probably could not have occurred, except for powerful excess vasoconstrictor activity affecting the whole circulation.

Topics: Blood Pressure; Cardiac Output; Erythropoiesis; Erythropoietin; Hematocrit; Hemodynamics; Homeostasis; Humans; Hypertension, Renal; Models, Biological; Oxygen; Polycythemia; Vascular Resistance

We evaluated propranolol effects on blood pressure, plasma renin activity, and erythrocyte production in nine chronically hemodialyzed and four nondialyzed patients with hypertension and high plasma renin concentrations. Propranolol, at a maximum daily dose of 240 mg, controlled blood pressure in 12 of the 13 patients. During propranolol treatment of dialyzed patients, mean blood pressure fell from 133 +/- 1 to 113 +/- 4 mm Hg (P less than 0.005) and plasma renin activity from 3093 +/- 423 to 689 +/- 218 ng/dl 3h (P less than 0.001). Similar results were obtained in nondialyzed patients. In both groups hematocrit and red cell mass were unchanged, although ferrokinetic measurements suggested a decrease in erythropoiesis. Thus propranolol alone reduces blood pressure and renin activity in chronically dialyzed patients with hypertension and high renin concentrations. No hematologic complications or other side effects were observed. These findings suggest that propranolol may be an effective alternative to bilateral nephrectomy in the control of renin-dependent hypertension in selected patients.

Topics: Adult; Blood Pressure; Erythrocytes; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Hypertension, Renal; Iron; Male; Middle Aged; Minoxidil; Propranolol; Renal Dialysis; Renin; Reticulocytes

Hypertension was found in four patients after unilateral renal-artery thrombosis following blunt abdominal trauma. In one patient, who was followed up from the time of injury, renin hypersecretion and secondary aldosteronism developed within a few days, and hypertension was present 12 weeks later. Increasing haemoglobin and raised blood-erythropoietin concentrations were also found. In the three other patients, hypertension was found casually within 3 years of trauma. In all patients, unilateral renin production by the affected kidney was significantly increased. Nephrectomy of the diseased kidney corrected hypertension and endocrine abnormalities in all patients. The delayed onset of hypertension despite early activation of the renin/angiotensin/aldosterone axis accords with the course of events observed in experimentally induced hypertension in rats, and suggests that several weeks or even months are required for hypertension to develop after sudden renal-artery occlusion in man. Slowly acting mechanisms, probably initiated by hypersecretion of renin, may be responsible for the hypertension.

Topics: Abdominal Injuries; Adult; Aldosterone; Angiotensin II; Blood Pressure; Erythropoietin; Female; Hemoglobins; Humans; Hypertension, Renal; Male; Middle Aged; Nephrectomy; Renal Artery; Renin; Sodium; Thrombosis

Plasma activities of renin and erythropoietin were determined in the renal veins of the right and left kidneys of hypertensive patients. The patients were divided into the following groups either according to the origin of the hypertension (group 1: control for essential hypertension, group 2: renovascular hypertension) or according to the hormone levels (group 3: renin activity exceeding 10 ng/litre in at least one of the renal veins and group 4: erythropoietin activity higher than 4% 59Fe incorporation in at least one of the renal veins). In groups 1, 2 and 3 a statistically significant difference in renin activity was found between the kidney with the higher renin activity and that with the lower activity. However, in group 4, the side, which showed elevated erythropoietin values also had higher renin activity as compared to the essential hypertensive group. Erythropoietin activity probably does not parallel the increased renin activity found in renovascular hypertension or in some cases of non-renovascular hypertension. However, in several cases of renal vascular alterations, both systems can be activated simultaneously.

Topics: Erythropoietin; Humans; Hypertension; Hypertension, Renal; Renin

Topics: Anthropometry; Erythropoietin; Humans; Hypertension, Renal; Juxtaglomerular Apparatus

Topics: Acute Kidney Injury; Erythropoietin; Gastrins; Glucose; Humans; Hypertension, Renal; Insulin; Kidney; Parathyroid Hormone; Renin; Vitamin D

During the study of an inbred strain of Wistar rats which spontaneously develop hypertension when they reach a weight of approximately 150 g, it was found that these animals also develop an erythrocytosis. A significant increase in red cell count was observed in spontaneously hypertensive (SH) rats (8-11 x 10(6) RBC/mm(3)) when compared with normotensive rats (6-7 x 10(6) RBC/mm(3)) of the same strain. This increase in red cell count paralleled the increase in body weight and the rise in blood pressure. Since the plasma volume, as measured with labeled albumin was normal, there was an absolute increase in red cells. The hematocrit and hemoglobin content of the blood measured in SH rats were only slightly greater than those found in normotensive rats. However, the mean cell volume (MCV) of the red cells in the SH rats was 45-47 mu(3) as compared with 51-53 mu(3) in normotensive rats.A fourfold increase in 24 hr (59)Fe incorporation into the red cells was found in the SH rats when compared with normotensive controls. The bone marrow of the SH rats showed erythroid hyperplasia. When the SH rats were treated with alpha-methyldopa (Aldomet 200 mg/kg daily, i.p.) the red cell count fell in parallel with the drop in blood pressure. No change in red cell count or blood pressure was observed in normotensive rats treated in the same manner. The erythropoietin titer was high in SH rats, and was undetectable in normotensive rats. These observations suggest a direct relationship between the hypertension and the erythrocytosis mediated by erythropoietin; both are genetically controlled.

Topics: Animals; Blood Pressure; Blood Pressure Determination; Body Weight; Cell Survival; Chromium Isotopes; Dihydroxyphenylalanine; Erythrocyte Count; Erythrocytes; Erythropoietin; Female; Hematocrit; Hemoglobins; Hypertension; Hypertension, Renal; Iron; Iron Isotopes; Leukocyte Count; Male; Plasma Volume; Polycythemia; Rats; Rats, Inbred Strains; Serum Albumin, Radio-Iodinated

Topics: Adolescent; Adult; Aged; Angiotensin II; Aortic Coarctation; Blood Pressure; Creatinine; Erythrocyte Count; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Hyperaldosteronism; Hypertension; Hypertension, Renal; Male; Middle Aged; Polycythemia; Potassium; Renin; Sodium; Urea; Water-Electrolyte Balance

Topics: Animals; Blood Pressure; Blood Volume; Body Weight; Diet, Sodium-Restricted; Erythropoietin; Hematocrit; Hypertension, Renal; Hypoxia; Juxtaglomerular Apparatus; Male; Nephrectomy; Rats; Renin; Reticulocytes

Topics: Aldosterone; Animals; Blood Pressure; Dogs; Erythropoiesis; Erythropoietin; Glucose; Humans; Hypertension, Renal; Insulin; Lipoproteins; Nephrectomy; Renal Dialysis; Renin; Saliva

Topics: Adolescent; Adult; Aged; Anemia; Angiotensin II; Blood Pressure; Blood Volume; Creatinine; Erythropoietin; Female; Hematocrit; Humans; Hypertension; Hypertension, Renal; Injections, Intravenous; Iron Isotopes; Male; Middle Aged; Potassium; Proteinuria; Renin; Sodium

Topics: Aldosterone; Angiotensin II; Erythropoietin; Hemodynamics; Humans; Hypertension, Renal; Kallikreins; Kidney; Prostaglandins; Renin

Topics: Adrenal Gland Neoplasms; Animals; Carcinoma; Cerebellar Neoplasms; Erythropoietin; Female; Hemangiosarcoma; Humans; Hypertension, Renal; Kidney; Kidney Diseases; Kidney Neoplasms; Liver Neoplasms; Neoplasms; Pheochromocytoma; Polycythemia; Polythiazide; Rats; Renin; Uterine Neoplasms

Topics: Aortography; Erythropoietin; Hematocrit; Humans; Hypertension, Renal; Male; Middle Aged; Polycythemia; Renal Artery Obstruction; Urography

Topics: Animals; Blood Flow Velocity; Dogs; Erythropoietin; Female; Glycolysis; Humans; Hypertension, Renal; Kidney; Male; Oxygen Consumption; Regional Blood Flow; Renal Artery Obstruction

Topics: Animals; Dogs; Erythropoietin; Hemodynamics; Hypertension, Renal; Juxtaglomerular Apparatus; Kidney; Renal Artery Obstruction

Topics: Adenocarcinoma; Animals; Erythropoietin; Hypertension, Renal; Ischemia; Kidney Diseases; Kidney Neoplasms; Male; Mercury; Nitrosamines; Radioisotopes; Rats