ABSTRACT The standard treatment of primary hypoparathyroidism (hypoPT) with oral calcium supplementation and calcitriol (or an analog), intended to control hypocalcemia and hyperphosphatemia and avoid hypercalciuria, remains challenging for both patients and clinicians. In 2015, human parathyroid hormone (hPTH) (1-84) administered as a daily subcutaneous injection was approved as an adjunctive treatment in patients who cannot be well controlled on the standard treatments alone. This open-label study aimed to assess the safety and efficacy of an oral hPTH(1-34) formulation as an adjunct to standard treatment in adult subjects with hypoparathyroidism. Oral hPTH(1-34) tablets (0.75 mg human hPTH(1-34) acetate) were administered four times daily for 16 consecutive weeks, and changes in calcium supplementation and alfacalcidol use, albumin-adjusted serum calcium (ACa), serum phosphate, urinary calcium excretion, and quality of life throughout the study were monitored. Of the 19 enrolled subjects, 15 completed the trial per protocol. A median 42% reduction from baseline in exogenous calcium dose was recorded (p = .001), whereas median serum ACa levels remained above the lower target ACa levels for hypoPT patients (>7.5 mg/dL) throughout the study. Median serum phosphate levels rapidly decreased (23%, p = .0003) 2 hours after the first dose and were maintained within the normal range for the duration of the study. A notable, but not statistically significant, median decrease (21%, p = .07) in 24-hour urine calcium excretion was observed between the first and last treatment days. Only four possible drug-related, non-serious adverse events were reported over the 16-week study, all by the same patient. A small but statistically significant increase from baseline quality of life (5%, p = .03) was reported by the end of the treatment period. Oral hPTH(1-34) treatment was generally safe and well tolerated and allowed for a reduction in exogenous calcium supplementation, while maintaining normocalcemia in adult patients with hypoparathyroidism. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Anaemia is present in approximately 40% of cases of congestive heart failure (CHF) and is associated with a higher mortality, a lower left ventricular ejection fraction, a lower cardiac functional status, a higher rate of hospitalization, signs of malnutrition, a lower exercise capacity, a progressive fall in renal function, an increased need for high dose diuretics, hyponatraemia, an increased plasma volume, a reduced red cell volume and a lower quality of life. In both uncontrolled and controlled studies, correction of the anaemia with subcutaneous erythropoietin and, in some cases, with the addition of intravenous iron, has been shown to improve these parameters. A vicious circle is present between CHF, chronic kidney insufficiency (CKI) and anaemia, each capable of causing or being caused by the other, the so-called cardio renal syndrome. If larger randomized, controlled, double-blind studies confirm these observations, correction of the anaemia may prove to be a useful addition to the prevention and progression of both CHF and CKI. Cooperation between nephrologists, cardiologists and other internists to identify and treat these anaemic CHF patients early will help prevent progression of both the cardiac and renal disease.

The incidence of both congestive heart failure (CHF) and end-stage renal disease both are increasing. Anemia is common in both conditions and is associated with a marked increase in mortality and morbidity in both CHF and chronic kidney insufficiency (CKI). Each of these 3 conditions can cause or worsen the other 2. In other words, a vicious circle frequently is present in which CHF can cause or worsen both anemia and CKI, in which CKI can cause or worsen both anemia and CHF, and in which anemia can cause or worsen both CHF and CKI. We have called this vicious circle the cardio renal anemia syndrome. Optimal treatment of CHF with all the recommended CHF medications at their recommended doses will, in our experience, frequently fail to improve the CHF and CKI if anemia is present and is not corrected. On the other hand, correction of the anemia with subcutaneous erythropoietin and intravenous iron has caused a great improvement in the CHF including a marked improvement in patient and cardiac function and a marked reduction in the need for hospitalization and for high-dose diuretics. It also frequently has caused renal function to improve or at least stabilize. In addition, patients' quality of life and exercise capacity also have improved with the correction of the anemia. In CKI patients, anemia also may play an important role in increasing the risk for death, coronary heart disease, stroke, and progression to end-stage renal disease. Erythropoietin may have a direct positive effect on the heart and brain unrelated to correction of the anemia by reducing cell apoptosis and by increasing neovascularization, both of which could prevent tissue damage. This could have profound therapeutic implications not only in CHF but in the future treatment of myocardial infarction, coronary heart disease, strokes, and renal failure.

The incidence of both congestive heart failure (CHF) and end-stage renal disease both are increasing. Anemia is common in both conditions and is associated with a marked increase in mortality and morbidity in both CHF and chronic kidney insufficiency (CKI). Each of these 3 conditions can cause or worsen the other 2. In other words, a vicious circle frequently is present in which CHF can cause or worsen both anemia and CKI, in which CKI can cause or worsen both anemia and CHF, and in which anemia can cause or worsen both CHF and CKI. We have called this vicious circle the cardio renal anemia syndrome. Optimal treatment of CHF with all the recommended CHF medications at their recommended doses will, in our experience, frequently fail to improve the CHF and CKI if anemia is present and is not corrected. On the other hand, correction of the anemia with subcutaneous erythropoietin and intravenous iron has caused a great improvement in the CHF including a marked improvement in patient and cardiac function and a marked reduction in the need for hospitalization and for high-dose diuretics. It also frequently has caused renal function to improve or at least stabilize. In addition, patients’ quality of life and exercise capacity also have improved with the correction of the anemia. In CKI patients, anemia also may play an important role in increasing the risk for death, coronary heart disease, stroke, and progression to end-stage renal disease. Erythropoietin may have a direct positive effect on the heart and brain unrelated to correction of the anemia by reducing cell apoptosis and by increasing neovascularization, both of which could prevent tissue damage. This could have profound therapeutic implications not only in CHF but in the future treatment of myocardial infarction, coronary heart disease, strokes, and renal failure. Semin Nephrol 25:397-403 © 2005 Elsevier Inc. All rights reserved.

BACKGROUND:Many patients with congestive heart failure (CHF) have chronic kidney insufficiency (CKI) and anemia.AIMS:The purpose of this review is to clarify the relationship between these three factors and to study the effect of correction of anemia in CHF and CKI.FINDINGS:Anemia, CHF and CKI are each capable of causing or worsening each other. Thus they form a vicious circle which can result in progressive CHF, CKI and anemia. Aggressive therapy of CHF, CKI and control of the associated anemia with erythropoietin and i.v. iron can prevent the progression of CHF and CKI, reduce hospitalization, and improve quality of life.CONCLUSION:CHF patients are a major source of end-stage renal failure patients and deserve special attention. If treated well and early, progressive heart failure and renal failure can be prevented. Cooperation between nephrologists, cardiologists, and other internists will improve the care of all three conditions and prevent their progression.

Purpose of reviewRecent findings on the relationship between congestive heart failure and renal failure are summarized in this review. Recent findingsCongestive heart failure is found in about one-quarter of cases of chronic kidney disease. The most common cause of congestive heart failure is ischemic heart disease. The prevalence of congestive heart failure increases greatly as the patient's renal function deteriorates, and, at end-stage renal disease, can reach 65-70%. There is mounting evidence that chronic kidney disease itself is a major contributor to severe cardiac damage and, conversely, that congestive heart failure is a major cause of progressive chronic kidney disease. Uncontrolled congestive heart failure is often associated with a rapid fall in renal function and adequate control of congestive heart failure can prevent this. The opposite is also true: treatment of chronic kidney disease can prevent congestive heart failure. There is new evidence showing the cardioprotective effect of carvedilol in patients on dialysis, and of simvastatin and eplerenone in patients with congestive heart failure. Use of non-steroidal anti-inflammatory drugs doubles the rate of hospitalization in patients with congestive heart failure. Anemia has been found in one-third to half the cases of congestive heart failure, and may be caused not only by chronic kidney disease but by the congestive heart failure itself. The anemia is associated with worsening cardiac and renal status and often with signs of malnutrition. Control of the anemia and aggressive use of the recommended medication for congestive heart failure may improve the cardiac function, patient function and exercise capacity, stabilize the renal function, reduce hospitalization and improve quality of life. Congestive heart failure, chronic kidney disease and anemia therefore appear to act together in a vicious circle in which each condition causes or exacerbates the other. Both congestive heart failure and anemia are often undertreated. Cooperation between nephrologists and other physicians in the treatment of patients with anemic congestive heart failure may improve the quality of care and the subsequent prognosis for both congestive heart failure and chronic kidney disease. SummaryAdequate and early detection and aggressive treatment of congestive heart failure and chronic kidney disease and the associated anemia may markedly slow the progression of both diseases.

Purpose of review Recent findings on the relationship between congestive heart failure and renal failure are summarized in this review. Recent findings Congestive heart failure is found in about one-quarter of cases of chronic kidney disease. The most common cause of congestive heart failure is ischemic heart disease. The prevalence of congestive heart failure increases greatly as the patient's renal function deteriorates, and, at end-stage renal disease, can reach 65-70%. There is mounting evidence that chronic kidney disease itself is a major contributor to severe cardiac damage and, conversely, that congestive heart failure is a major cause of progressive chronic kidney disease. Uncontrolled congestive heart failure is often associated with a rapid fall in renal function and adequate control of congestive heart failure can prevent this. The opposite is also true: treatment of chronic kidney disease can prevent congestive heart failure. There is new evidence showing the cardioprotective effect of carvedilol in patients on dialysis, and of simvastatin and eplerenone in patients with congestive heart failure. Use of non-steroidal anti-inflammatory drugs doubles the rate of hospitalization in patients with congestive heart failure. Anemia has been found in one-third to half the cases of congestive heart failure, and may be caused not only by chronic kidney disease but by the congestive heart failure itself. The anemia is associated with worsening cardiac and renal status and often with signs of malnutrition. Control of the anemia and aggressive use of the recommended medication for congestive heart failure may improve the cardiac function, patient function and exercise capacity, stabilize the renal function, reduce hospitalization and improve quality of life. Congestive heart failure, chronic kidney disease and anemia therefore appear to act together in a vicious circle in which each condition causes or exacerbates the other. Both congestive heart failure and anemia are often undertreated. Cooperation between nephrologists and other physicians in the treatment of patients with anemic congestive heart failure may improve the quality of care and the subsequent prognosis for both congestive heart failure and chronic kidney disease. Summary Adequate and early detection and aggressive treatment of congestive heart failure and chronic kidney disease and the associated anemia may markedly slow the progression of both diseases.

Anaemia is frequently found in patients with chronic heart failure (CHF) and has been associated with an increase in mortality and morbidity, impaired cardiac and renal function and a reduced quality of life (QoL) compared with non-anaemic CHF patients. Correction of anaemia with recombinant human erythropoietin (epoetin) has been associated with an improvement in CHF in both controlled and uncontrolled studies. The present study describes our findings in a series of 78 consecutive patients with symptomatic CHF and anaemia (haemoglobin (Hb) level <12.0 g/dl) treated with epoetin beta and, if necessary, intravenous iron sucrose. Over a mean observation period of 20.7 ± 12.1 months, mean Hb levels increased from 10.2 ± 1.1 to 13.5 ± 1.2 g/dl, p < 0.01. New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) were significantly improved and the number of hospitalizations was significantly reduced with the period before treatment (all p < 0.01). Serum creatinine and creatinine clearance (CCr) were 2.2 ± 0.9 mg/dl and 32.5 ± 26.5 ml/min, respectively, at baseline, and remained stable over the observation period. Interestingly, >90% of the patients had concomitant mild-to-moderate chronic kidney disease at baseline and study end (CKD), as defined by the accepted diagnostic criterion of a CCr <60 ml/min. Conclusions: The correction of the anaemia with epoetin beta together with initial intravenous iron supplementation, resulted in significant improvements in NYHA class and cardiac function, and a reduction in hospitalization rate. Moreover, renal function was maintained stable in most patients.

Objectives: To find the prevalence of anemia in patients hospitalized with the primary diagnosis of congestive heart failure (CHF). Background: There is growing evidence that anemia is common in CHF and may contribute to the high morbidity and mortality associated with this condition. However, there is considerable disagreement about the prevalence of anemia in this condition. Methods: In 338 consecutive patients who were admitted to the medical wards with a primary diagnosis of CHF we extracted from the charts the hemoglobin (Hb), serum creatinine, age, sex, New York Heart Association (NYHA) functional class, presence of smoking, diabetes, hypertension, hyperlipidemia and the primary cardiac etiology of the CHF. Anemia was considered to be present when the Hb on admission was < 12 g/dl. Results: All the patients were NYHA functional class III-IV One hundred seventy seven (52.4%) of the 338 patients had a Hb on admission that was < 12 g/dl. The mean Hb for the entire group was 12.0 +/- 1.8 g/dl. One hundred three (51.0%) of the 202 males were anemic compared to 74 (54.4%) of the 136 women. The mean serum creatinine was 1.7 +/- 1.1 mg/dl. The prevalence of renal insufficiency (serum creatinine >1.5 mg%) was 47.6%. There was a negative correlation between the level of serum creatinine and Hb (r = -0.294) P < 0.00001. Of the 177 patients who were anemic, most of 114 (64.4%) had a serum creatinine >1.5 mg/dl. Conclusions: Anemia is a common finding in patients hospitalized with CHF and most anemic CHF patients have some degree of renal insufficiency. In view of the negative effect of anemia on cardiac function, it may be a common and important contributor to the mortality and morbidity of CHF in these patients. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Background & aim: Congestive heart failure (CHF) and anemia were reported to affect resting energy expenditure (REE). The aim of this study was to evaluate the effect of the correction of anemia on REE in subjects with CHF.Patients and methods: Nine anemic patients with compensated CHF and CRF were studied before and after correction of anemia. REE was studied by an open circuit indirect calorimeter, body composition by dual-energy-X-ray absorption and total body and extracellular water by multi-frequency bioelectrical impedence. Four anemic and 5 non-anemic CHF patients who did not receive any new treatment served as controls.Results: After the correction of their anemia patients tended to increase weight (P<0.06), but no significant changes were observed in body composition. Daily caloric intake increased significantly (P<0.02). Ejection fraction increased (P<0.05) and pulse rate decreased significantly (P<0.001). REE and REEPP were in the normal range before correction but increased significantly afterwards (1402+/-256 vs. 1496+/-206 kcal/d, and 101+/-9 vs. 109+/-8, P<0.023 and P<0.006, respectively).Conclusion: Correction of anemia in patients with CHF increases their REE. This can be related either to improved tissue oxygenation and/or to increased caloric intake. (C) 2003 Elsevier Ltd. All rights reserved.

BACKGROUNDIt is suggested that either arginine or its metabolites, nitric oxide and polyamines play a role in the renal hemodynamic alterations observed in the early stages of diabetes. Yet, the regulation of arginine transport in diabetic kidneys has never been studied.METHODSArginine uptake was determined in glomeruli harvested from control rats; diabetic rats (2 weeks following an intraperitoneal injection of streptozotocin, 60 mg/kg body weight); rats, 4 days following left nephrectomy (a nondiabetic model of hyperfiltration); diabetes + lysine (0.5% in the drinking water to attenuate arginine uptake); and control + lysine.RESULTSGlomerular arginine transport was significantly increased in diabetic rats, but remained unchanged following uninephrectomy. Lysine abolished the increase in arginine uptake in diabetic rats but had no effect in controls. The increase in creatinine clearance observed in diabetes was completely abolished by lysine. Using reverse transcription-polymerase chain reaction (RT-PCR), Northern blotting, and immunohistochemistry, we found a significant increase in glomerular cationic amino acid transporter-1 (CAT-1) expression in diabetic animals, which was unaffected by lysine. When human endothelial cells were incubated with arginine end products no effect on arginine transport was observed. However, only in the presence of 0.5 mM/L sodium nitroprusside (SNP) an augmented steady-state CAT-1 mRNA was demonstrated by RT-PCR.CONCLUSIONIn a rat model of early diabetes, glomerular arginine uptake is elevated through modulation of CAT-1 expression, thus, contributing to the pathogenesis of hyperfiltration. Increased nitric oxide formation may play a role in this process.

BACKGROUND:Congestive heart failure is extremely common in octogenarians and is associated with severe fatigue, shortness of breath, recurrent hospitalizations, and death. These patients, many of whom are anemic, are often resistant to standard CHF therapy including angiotensin-converting enzyme inhibitors, beta-blockers and diuretics.OBJECTIVES:To examine whether correction of the anemia (hemoglobin < 12 g/dl) in CHF patients can improve their clinical condition.METHODS:Forty octogenarians with anemia and severe resistant CHF were administered a combination of subcutaneous erythropoietin and intravenous iron sucrose.RESULTS:This combination therapy led to a marked improvement in cardiac function, shortness of breath and fatigue, a marked reduction in the rate of hospitalization and a stabilizing of renal function.CONCLUSION:Anemia appears to be an important but ignored contributor to the progression of CHF, and its correction may improve cardiac and renal status as well as the quality of life in elderly patients.

Anemia (Hemoglobin of < 12 to 13 g/dl) is frequently encountered in patients with congestive heart failure (CHF). This anemia may be partly due to hemodilution, partly to the associated reduction in renal function, and partly to the use of ACE inhibitors and aspirin. However, there is evidence that CHF alone--through excessive cytokine production may also reduce the bone marrow and cause anemia. In several recent studies anemia has been found to be associated with a more severe degree of CHF, a higher rate of death, renal failure, hospitalization and evidence of malnutrition. In both uncontrolled and controlled studies correction of anemia with erythropoietin with or without the addition of i.v. iron has been attempted. The correction of anemia has been associated with a marked improvement in New York Heart Association (NYHA) functional cardiac class and Left Ventricular Ejection Fraction, a marked reduction in the need for hospitalization and high dose oral and i.v. diuretics, and an improvement in exercise capacity, peak exercise oxygen utilization and quality of life. The serum creatinine, which had been increasing steadily before treatment, stabilized with the correction of anemia. All this suggests that control of anemia in CHF could become a valuable addition to the therapeutic armamentarium of CHF and might also play a major role in the prevention of progressive renal failure.

BACKGROUND:Up to 64% of patients referred to nephrologists with chronic kidney insufficiency (CKI) have evidence of congestive heart failure (CHF), and most of these patients are also anemic. We have called this triad of anemia, CKI, and CHF the cardio renal anemia (CRA) syndrome. The 3 components of this syndrome form a vicious circle, with each one capable of causing or worsening the other 2. Anemia is found in one-third to one-half of CHF patients and can either cause or worsen the CHF, and can increase the mortality, hospitalization, and malnutrition in this condition. Anemia is also associated with a worsening of renal function in CHF and CKI, causing a more rapid progression to dialysis than is found in those without anemia. Uncontrolled CHF can cause rapid deterioration of renal function and may also cause anemia. Chronic kidney insufficiency can cause anemia and worsen the CHF.METHODS:Aggressive therapy of CHF with all the accepted CHF medications in the accepted doses will often fail to improve the CHF if anemia is also present but is not corrected. However, when the anemia was corrected with subcutaneous erythropoietin and, in some cases, with intravenous iron, the cardiac and patient function and quality of life improved, the need for hospitalization and for high-dose oral and intravenous diuretics was strikingly reduced, and renal function, which had previously been deteriorating, stabilized.RESULTS:Nephrologists should carefully assess the cardiac status of all CKI patients, including routinely getting an echocardiogram and possibly measuring B-type natriuretic peptide. Where CHF is present, the indicated CHF agents in the indicated doses should be used.CONCLUSION:Studies show that most cardiologists and internists do not recognize, investigate, or treat the anemia frequently seen in their CHF patients. In our experience cooperation between nephrologists and these specialists has increased their awareness about anemia, resulting in its earlier correction, and thus preventing the deterioration of the CHF, the CKI, and the anemia itself.

UNLABELLED:L-Arginine supplementation was found to have a reno-protective effect in different models of chronic renal failure (CRF) in spite of normal plasma levels. Experiments were designed to determine if changes in glomerular uptake of arginine occur in 5/6 nephrectomized rats as a model of CRF. Renal function and glomerular uptake of radiolabeled arginine {[3H] L-arginine} was measured in sham operated, 5/6 nephrectomy, and right nephrectomy rats. Renal failure and proteinuria was found in the CRF animals only. Arginine uptake by glomeruli harvested from rats with CRF was significantly lower than that by glomeruli from sham operated and unilateral nephrectomy rats.IN CONCLUSION:glomerular arginine uptake is decreased in CRF. This phenomenon can explain the beneficial effect of L-arginine supplementation in CRF.

BACKGROUNDA mild anaemia is often found in patients with congestive heart failure (CHF), but its significance is uncertain. In an open uncontrolled study we investigated the effect of correcting this anaemia [haemoglobin (Hb) 9.5-11.5 g%] with subcutaneous (s.c.) erythropoietin (Epo) and intravenous (i.v.) iron (Fe) in 179 patients, 84 type II diabetics and 95 non-diabetics, with moderate to severe CHF which was resistant to maximally tolerated doses of standard CHF medications.METHODSEpo, s.c., was given every 1-3 weeks to achieve and maintain the Hb at 12.5 g%. Fe (Fe sucrose-Venofer) was added i.v. as necessary to maintain the Fe stores. Duration of treatment was 11.8 + 8.2 months.RESULTSWith the Epo-Fe treatment the Hb increased from 10.41 +/- 1.0 to 13.1 +/- 1.3 g% in diabetics and from 10.5 +/- 1.0 to 12.9 +/- 1.2 g% in non-diabetics. Comparing the diabetics and non-diabetics, the New York Heart Association functional class improved by 34.8 and 32.4%, respectively. breathlessness and/or fatigue, as measured by a self-administered Visual Analogue Scale, improved by 69.7 and 67.4%, and the left ventricular ejection fraction improved by 7.4 and 11.5%, respectively. The number of hospitalizations fell by 96.4 and 95.3%, respectively, compared with the pre-treatment period. Although the glomerular filtration rate (GFR) was falling at a rate of approximately 1 ml/min/month before the study in both groups, neither the mean serum creatinine nor the GFR changed significantly during the study period. The mean dose of Epo needed, measured in IU/week/kg body weight, was similar in the two groups.CONCLUSIONThe correction of the mild anaemia that was found in diabetics and non-diabetics with resistant CHF and mild to moderate chronic renal failure improved the cardiac function and patient functional status, stabilized the renal function and markedly reduced the need for hospitalization.

Anemia is commonly seen in mild to moderate Chronic Kidney Insufficiency (CKI) and in Congestive Heart Failure (CHF) as well. The purpose of this study was to examine the relative contribution of CHF and CKI to the production of the anemia of CHF. Material and Methods. We compared the prevalence of anemia in the following groups of patients taken from the Nephrology and the special Cardiology CHF outpatient clinics. Group 1 Patients with CHF and normal renal function (serum creatinine <1.5 mg). Group 2 Patients with CKI (serum creatinine 1.5-2.5 mg%). Group 3 Patients with both CHF and CKI (serum creatinine 1.5-2.5 mg%). Anemia was defined as a Hb of < 12g%. Results. The prevalence of anemia in the CHF group without CKI (Group 1) 32.1% and the CKI group without CHF (Group 2)-22.4% was not significantly different. In those in Group 3 with both CHF and CKI the prevalence of anemia was significantly higher (66.2%) and the level of Hb was significantly lower than in either Group 1 or Group 2 and the effect appeared to be additive. Combining all the CHF patients in Groups 1 and 3 there was a negative correlation between the level of creatinine and Hb (r=0.286) p<0.01. Conclusion. Our findings suggest that CHF itself is an important cause of the anemia. In the group of patients with both CHF and CKI patients 2/3 were anemic, about twice as many as in. the patients with CHF alone and CKI alone. This suggests that CHF and CKI have an equal and additive effect on the production of anemia.

because of Conclusion: In conclusion, low protein vegetarian diet supplemented with alpha-chetoanalogues is a useful tool in chronic renal failure diabetic patients, allowing a good compliance and without relevant side-effects. One of the causes of anemia in chronic renal failure (CRF) is reduced production of erythropoietin (EPO) by the kidneys. Quinolinic acid (QA) is one of the products of the tryptophan oxidation via kynurenic pat- way. The aim of the study was to assess of QA impact on the process of erythropoiesis. We induced various degrees of CRI model. Blood from rats with CRF was used for the study, as well as HepG2 hepatic cells line, which are characterised by the ability to synthesise EPO in conditions of induced hypoxia.QA concentration in the plasma of the control rats was 346.4+74nM.In animals with CRF, a statistically signifi- cant increase in the concentration of the studied parameter was observed (moderate 973.7+88.7, p < 0.01, severe 2134.3+489.4nM, p < 0.001). The level of creatinine positively correlated with the plasma QA (r=0.847, p < 0.05).On the other hand, the high concentration of QA negatively correlated with: hematocrit (r=-0.843, p < 0.05), hemoglobin (r=-0.704, p < 0.01) and red blood cells count (r=-0.841, p < 0.07). The changes were accompanied by a slight decrease of the concentration of endogenic erythropoietin in plasma, from 29.1+4.1 mIU/ml in control to 24.1+6.1 mIU/ml (NS) in animals with CRF. In vitro study in the conditions of hy- poxia showed that QA (10, 100, 1000 uM) inhibited, the release of EPO from HepG2 cells to the culture base: 36.5+16.4 (p < 0.05), 54.9+24.3 (p < 0.01), 83.7+24.9 (p < 0.001) % of control, respectively. The inhibitory activity of QA (10, 100 uM) on EPO production had no effect on cell viability. In conclusion, an importance erythropoiesis in CRF could be attributed to the increase of QA. Thus, we propose that QA can be a uremic toxin responsible for the development of anemia in CRF. the genomic organisation of both the murine and human orthologues of ERIC-1 and have identified areas with up to 80% sequence homology. Sequence data indicate both genes CAAT Highly conserved gions and murine haematopoietic as AML-1a and GATA-1/2 predicted binding sites within these conserved regions. Luciferase assays utilising murine genomic sequence 5 prime to the transcription start site of mERIC-1 (maximally 3548 bp upstream) in both human (Hep3B) and murine (Hepa1c1c7) cell lines have identified regions of regulatory importance. The highest luciferase activity was detected using sequences 500 to 700 bp upstream of ERIC-1 transcription initiation. Targeted mutation of putative transcription factor binding motifs and alteration of the cellular oxygen should further regulatory mechanisms of this gene. two plasma with antioxidant and anti-inflammatory properties. PAF-AH is associated with low- and high-density lipoproteins (LDL and HDL, respectively), PON1 with HDL. Both hy- drolyze and inactivate potent proinflammatory oxidized phospholipids well as platelet-activating Serum PAF-AH activity in ure- mic patients is significantly higher compared with healthy volunteers. evaluated the effect of on serum PAF-AH PON1 activities of patients with chronic renal failure in relation to the rEPO effect on patient’s hematocrit and lipoprotein profile. We investigated the effect of correction of anemia on OS in patients with CHF plus CRF. 48 patients, 71.6 ± 12.7 yrs, M/F27/21, were referred for treatment of anemia (Hb < 12g%; mean Hb 10.5 ± 0.9g.). They all had severe resistant CHF and moderate CRF (mean s. creat 2.4 ± 1.2 mg%). They were treated with subcutaneous EPO weekly and had their iron stores maintained with IV Iron (iron sucrose). The final mean Hb was 12.7 ± 1.2mg%. The mean % Fe sat and serum ferritin at onset were D. of the CREATE Study Group. The Cardiovascular risk Reduction by Early Anaemia Treatment with Epoetin beta (CREATE)study is a large, multicentre, international trial in chronic renal failure (CRF) patients not yet receiving renal replacement therapy (RRT) currently in progress. Patients with Hb 11.0-12.5 g/dl and creatinine clearance of 15-35 ml/min are being randomized to one of two treatment groups; an early anaemia correction group is starting epoetin beta (NeoRecormon  ) therapy immediately to attain a target Hb level of 13-15 g/dl, while a late anaemia correction group will only begin treatment once their Hb has declined below 10.5 g/dl, with a target level of 10.5-11.5 g/dl. This report provides an overview of the baseline characteristics among the 385 patients enrolled to date. in The target level of Hematocrit (Hct) with rHuEPO therapy in pre-dialysis renal failure patients is still obscure. To date, the efficacy of a high level of Hct (33-36%) has been confirmed in several countries in ESRD pa- tients, on the basis of several parameters, especially in cardiovascular function. To investigate the effect of rHuEPO (Epoetin-beta, Chugai, Japan) therapy with a target Hct of 33-36%, a multicenter preliminary non-controlled trial in CRF was carried out. rHuEPO was given at a dose of 6000 IU per week, subcutaneously, with the goal of maintaining the Hct level at 33-36% (24 Weeks). Echocardiography was performed blindly every 12 weeks by an expert cardiologist. Twenty-six patients (17 females, 9 males) were enrolled in this trial (CGN: 14, DM: 7, oth- ers: 5), with a mean age of 59.3 ± 7.3 yr, and a mean serum creatinine 3.5 ± 1.4 mg/dL. The mean Hct level at the start was 28.0 ± 2.3%, and this increased to 36.6 ± 3.5% (12 W) and 32.8 ± 2.7% (24 in- temporary CA1 area neuronal loss and passive avoidance test recombinant significantly reduced delayed neuronal death in the CA1 area of hippocampus and prevented cognition impairment in the passive avoidance test. These data indicate that recombinant human erythropoietin neuroprotec- tive effect in brain ischemia are associated with preservation of learning function. Serumtransferrin receptor(TfR)hasbeensuggestedto provideasensitive indicator of an early iron deficiency. Calculation of the ratio TfR/log ferritin (TfR-F index) is a way of combining TfR and ferritin results. We compared TfR and TfR-F index to ferritin, transferrin The aim of this prospective, randomized, double blind, crossover, and placebo-controlled study was to evaluate the effect of parenteral vitamin C on erythropoietin (EPO) response in haemodialysis (HD) patients. Sixty HD patients were recruited. All patients were dialyzed thrice-weekly using bicarbonate dialysate bath. Both haematocrit levels and dose of EPO were stable for at least 3 months and all patients were on maintenance parenteral iron treatment. During the first 6-months pe- riod, 30 patients were administrated intravenous vitamin C of 500 mg after each HD session (Group 1), whilst the remaining 30 patients were treated with placebo (Group 2). During the next 6-months period, Group 1 was administrated placebo and Group 2 vitamin C. Dose of iron was not changed throughout the study. EPO dose was arranged bimonthly according to haematocrit level by a physician, who was blind to the group of the patients. Both groups were similar in age, duration of HD, Kt/Vurea, dose of EPO, haematocrit, transferrin saturation, ferritin, PTH, and CRP at the baseline. At the end of the first period, Group 1 had significant increases in haematocrit and haemoglobin (29.5 ± 3.5% to 32.0 ± 4.5%, p=0.011 and 9.7 ± 1.1 to 11.3 ± 1.5, p < 0.001, respectively) and transferrin satura-tion (28.2 ± 10.0% to 38.4 ± 19.0%, p=0.008), and had a significant decrease in dose of EPO (148 ± 65 UI/kg/week to 124 ± 74, p=0.011), while In this prospective study, we aimed to investigate the effects of Valsar- tan, an angiotensin II type 1 (AT1) receptor blocker on erythropoietin (EPO) and haemoglobin levels in patients with reduced kidney function (creatinine 1.5-4 mg/dL) and hypertension. Twenty two patients (M: 12, F:10, mean age 56.8 ± 8.9, without any diseases and drugs affecting erythropiesis such as EPO, ACE inhibitor or AT-1 receptor blocker) with chronic renal failure and hypertension were treated with 80 mg Valsartan qd after three week washout period. The follow up time was 12 weeks. In two of the patients Valsartan has to be discontinued 6 days later due to hy-perkalemia. Hypertension could be controlled with Valsartan monother- apy in 12 patients. Amlodipine (for 8 pts) and furosemide (for 2 pts) were added to the regimen as needed. Biochemical parameters, haemoglobin and serum EPO levels were measured before and 12 weeks after treatment. Aditionally EPO levels were measured at days 3 and 6. Creatinine (2.7 ± 1.0 vs 2.5 ± 1.1) and haemoglobin (11.9 ± 2.2 vs 12.8 ± 1.8) values were not changed significantly. EPO levels were dropped significantly when compared to basal level as seen in the table. A dedicated anaemia co-ordinator improved anaemia management in all groups of pre-dialysis patients. Use of IV iron lowered EPO requirements in manypatients. Improvements inthe management ofanaemia in chronic renal insufficiency patients are possible using standardised protocols de-ployed by a specific nurse anaemia co-rdinator. These suggest that a decline in nNOS activity and abundance occurs rapidly after loss of a critical level of renal function, quite early after A/I. Ectopic calcification is common in renal disease, and renal calcification is thought to play a role in the PRD. We have shown that NH4Cl-induced acidosis protected against the PRD in 5/6 nephrectomized (NPX) rats on a high phosphate (PO4) diet (KI 58: 1023,2000). In the present study, we have used the same model to evaluate the effect of metabolic acidosis and PTX on renal function and kidney calcium deposition (kCa) in 5/6 NPX rats on a normal PO4 diet (0.6%). After a two-stages 5/6 NPX, rats received the diet for 30 days. The 5/6 NPX rats without PTX were acid-loaded with a 0.75% NH4Cl solution as drinking water, and 5/6 NPX- PTX rats with a 0.375% NH4Cl. Blood

Both Congestive Heart Failure (CHF) and Chronic Renal Failure (CRF) are increasing steadily in the community. We propose that there is a vicious circle established whereby CHF and CRF both cause anemia and the anemia then worsens both the CHF and CRF causing more anemia and so on. We call this the Cardio Renal Anemia (CRA) syndrome. By the combination of active treatment of the CHF and control of the anemia with subcutaneous erythropoietin and intravenous iron, the progression of both the CHF and the CRF can be slowed or stopped in most cases, the quality of life improved and the need for recurrent hospitalization reduced. This will involve cooperation between internists, cardiologists, and nephrologists to allow early and maximal therapy of both the CHF and the anemia.