losartan-potassium and Albuminuria

Hypertension involves the entire cardiovascular system, and hypertensive vascular disease may promote and exacerbate cardiac and renal dysfunction. We discuss the coexistence of cardiorenal disease as a manifestation of vascular involvement in hypertension, and the relationship of biomarkers of renal vascular involvement in hypertension with cardiovascular endpoints.. Markers of renal dysfunction, especially microalbuminuria, have been considered recently as potent predictors of cardiovascular morbidity and mortality in all explored populations, including hypertensive individuals. Microalbuminuria, per se, is related to vascular injury and to the increased glomerular permeability of albumin as a direct manifestation of renal vascular involvement in hypertension, a systemic vascular disease. Left ventricular hypertrophy in hypertension develops even before proteinuria or impairment of renal function. Factors including anemia, inflammation and hyperuricemia are either induced or exacerbated by renal vascular disease, and each of these may exert additional influence in determining the increased incidence of cardiovascular events with progressive renal dysfunction.. The development and progression of vascular disease is the primary determinant in the progressive cardiac and renal dysfunction observed in hypertension and, therefore, is the underlying mechanism of the overall clinical manifestations of cardiorenal disease. Commonly used biomarkers of renal and vascular function are important tools for determination of the progression and, hence, management of hypertensive disease and its complications.

Topics: Albuminuria; Biomarkers; C-Reactive Protein; Disease Progression; Erythropoietin; Glomerular Filtration Rate; Humans; Hypertension; Hyperuricemia; Natriuretic Peptide, Brain; Renal Insufficiency; Uric Acid

The rising incidence of type 2 diabetes mellitus and of its complications will make it the most important health care challenge in the first quarter of the 21st Century. Diabetic nephropathy left unchecked will overwhelm the renal resources. Simple methods (proper diet and exercise, prevention of obesity) are successful in preventing type 2 diabetes in the great majority of the persons at risk. In patients with established type 2 diabetes, nephropathy can be prevented or greatly delayed by strict metabolic control, strict control of blood pressure using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers as the first line of drugs, tight control of serum lipids using statins as indicated, low protein diet, avoidance of smoking and other nephrotoxic influences, prevention of abnormalities in calcium/phosphorus metabolism, and prevention of renal anemia by the early use of erythropoietin. Current research offers the promise of definitive prevention of both type 2 diabetes and diabetic nephropathy.

Topics: Albuminuria; Anemia; Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Erythropoietin; Glomerular Filtration Rate; Humans; Hypertension; Mitochondria

To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.. We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.. ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.

Topics: Acute Kidney Injury; Albuminuria; Double-Blind Method; Erythropoietin; Female; Gestational Age; Glomerular Filtration Rate; Humans; Hypertension; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins; Renal Insufficiency, Chronic

Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb) and erythropoietin (EPO) levels. We evaluated the correlation between reduced albuminuria and decreased hemoglobin concentrations after treatment with an angiotensin II receptor blocker (ARB). Two hundred forty-five non-diabetic hypertensive participants with established albuminuria and relatively preserved renal function were treated with an ARB (40 mg/day olmesartan) for eight weeks. Subsequent changes in various clinical parameters, including Hb, EPO, and albuminuria, were analyzed following treatment. After the 8-week treatment with an ARB, Hb and EPO levels significantly decreased. Patients with a greater decrease in Hb exhibited a greater reduction in 24-hour urinary albumin excretion compared with patients with less of a decrease or no decrease in Hb, whereas no associations with a decline in renal function and EPO levels were noted. Multivariate logistic regression analysis demonstrated a correlation between the reduction of urine albumin excretion and the decrease in Hb levels (after natural logarithm transformation, adjusted odds ratio 1.76, 95% confidence interval 1.21-2.56, P = 0.003). Linear regression analysis also supported this positive correlation (Pearson correlation analysis; R = 0.24, P < 0.001). Decreased Hb concentrations following ARB treatment were positively correlated with reduced albuminuria in non-diabetic hypertensive patients, regardless of decreased blood pressure and EPO levels or renal function decline.

Topics: Albuminuria; Angiotensin Receptor Antagonists; Case-Control Studies; Erythropoietin; Female; Hemoglobins; Humans; Hypertension; Male; Middle Aged; Olmesartan Medoxomil; Receptors, Angiotensin; Renin-Angiotensin System; Treatment Outcome

Erythropoietin (EPO) is reported to be mainly produced by renal peritubular interstitial cells. Serum levels of EPO may provide new information on the tubulointerstitial lesions in patients with diabetic nephropathy. We determined EPO, hemoglobin (Hb), and Hb x EPO in 63 diabetic patients who showed normo-, micro- or macroalbuminuria with normal or reduced renal function (creatinine clearance, Ccr, > or = 60 ml/min or < 60 ml/min). In addition, we followed up Ccr during a mean of 26 months in 13 patients with overt nephropathy and normal renal function. The following results were obtained: (1) Hb, EPO, and Hb x EPO values gradually decreased along with advancing stages of nephropathy, and (2) 6 patients with rapidly decreasing renal function showed significantly lower initial EPO and Hb x EPO values than 7 patients without it (p < 0.01). We conclude that EPO and Hb x EPO values may be a new marker predicting future chronic renal failure in diabetic overt nephropathy.

Topics: Albuminuria; Biomarkers; Diabetic Nephropathies; Disease Progression; Erythropoietin; Female; Follow-Up Studies; Hemoglobinometry; Humans; Male; Middle Aged

1. In experimental studies, activation of renal sympathetic nerves attenuates the natriuretic response to atrial natriuretic factor. We therefore investigated the response to low-dose infusion of atrial natriuretic factor in renal transplant recipients. 2. Eight male cyclosporin-treated renal transplant recipients received human-alpha atrial natriuretic factor (1-28) at a dose of 1.2 pmol min-1 kg-1 or placebo for 2 h in a placebo-controlled, randomized, cross-over study. The plasma atrial natriuretic factor concentration rose from 18.5 to 49.2 pmol/l in association with an immediate natriuresis (a rise of 49.1 mumol/min in the first 30 min, P less than 0.05; peaking at a 61% increase from baseline, P less than 0.01), diuresis (from 3.37 to 7.46 ml/min) and a threefold rise in urinary cyclic GMP excretion. 3. In response to infusion of atrial natriuretic factor, the packed cell volume rose by 4.2% (P less than 0.001) and the filtration fraction by 5% (from 22 to 27%, P less than 0.05), but there was no significant change in renal plasma flow, glomerular filtration rate or mean arterial blood pressure. Likewise, the plasma catecholamine concentrations, plasma renin activity and serum erythropoietin concentration remained unchanged. 4. The sensitivity of the renal allograft to plasma atrial natriuretic factor concentrations in the high physiological range suggests a role for endogenous atrial natriuretic factor in the modulation of graft function. Furthermore, the immediate natriuretic response to atrial natriuretic factor in the effectively denervated transplant kidney, in contrast to the delayed response seen in normal subjects, may imply that sympathetic nerves have an inhibitory effect on the renal response to atrial natriuretic factor in normal man.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Albuminuria; Atrial Natriuretic Factor; Cyclic GMP; Diuresis; Erythropoietin; Hematocrit; Hemodynamics; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Random Allocation

In patients with heart failure (HF), serum erythropoietin (EPO) levels are elevated and associated with disease severity and outcome. Whether endogenous EPO levels are prospectively associated with the development of HF or cardiovascular events in the general population is unknown.. Serum EPO levels were measured at baseline in 6686 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Mean age (±SD) was 53 ± 12 years, 49.8% were male, and the median (interquartile range) EPO level was 7.7 (5.9-10.2) IU/L. During a median follow-up of 8.3 (7.7-8.8) years, 209 (3.1%) subjects were newly diagnosed with HF, 97 (1.5%) died of a cardiovascular cause, and 386 (6.0%) subjects had a non-fatal cardiovascular event (277 cardiac events and 93 strokes). Each doubling of EPO level was multivariably associated with new-onset HF [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.03-1.69, P = 0.031]. EPO levels showed interaction with urinary albumin excretion (P = 0.006) and were only associated with HF in subjects with albuminuria (HR 1.51, 95% CI 1.13-2.03, P = 0.005). There was an independent association of EPO levels with stroke in women (HR 1.82, 95% CI 1.24-2.65, P = 0.002), but not in men. No association was observed for EPO levels with other cardiovascular events or cardiovascular mortality.. High serum EPO levels are independently associated with an increased risk of new-onset HF in subjects with albuminuria. More research into the pathophysiological mechanisms linking EPO levels to HF is needed to understand this association.

Topics: Adult; Aged; Albuminuria; Cardiovascular Diseases; Erythropoietin; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Netherlands; Prognosis; Proportional Hazards Models; Sex Factors; Stroke

Erythropoietin (EPO) is a glycoprotein hormone produced predominantly in the kidneys. The protective effect of exogenous EPO in hypoxic-ischemic brain injury has been thoroughly examined in neonates. However, the metabolism of endogenous EPO in neonates remains unclear.. We aimed to evaluate the concentration of urinary EPO (uEPO) in critically ill neonates and to identify possible clinical and laboratory variables that may be associated with uEPO levels.. The concentrations of EPO, cystatin-C, microalbumin, and α1-microglobulin in the first available urine sample during the initial 72 h of life were measured in 103 critically ill neonates. Clinical and laboratory data were collected for each neonate.. There was a positive correlation between uEPO levels and urinary levels of cystatin-C (r = 0.265, p = 0.008), microalbumin (r = 0.422, p < 0.001), and α1-microglobulin (r = 0.421, p < 0.001). The concentration of uEPO was elevated in neonates who developed acute kidney injury (AKI) during the first week of life compared with those without AKI (p = 0.002) and was also elevated in neonates with brain injury, as demonstrated by ultrasound or magnetic resonance imaging, compared to neonates without brain injury (p = 0.008). An increased log10 uEPO level was associated with the occurrence of AKI (OR 2.70, p = 0.007) and brain injury (OR 2.33, p = 0.016).. An increased urinary EPO level in the early postnatal period is significantly associated with kidney and brain injury in critically ill neonates.

Topics: Acute Kidney Injury; Albuminuria; Alpha-Globulins; Biomarkers; Brain Injuries; Critical Illness; Cystatin C; Erythropoietin; Female; Humans; Infant, Newborn; Linear Models; Logistic Models; Magnetic Resonance Imaging; Male; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Prognosis; Risk Factors; Time Factors; Ultrasonography, Doppler, Transcranial; Up-Regulation

Podocyte damage and accumulation of advanced glycation end products (AGEs) are characteristics of diabetic nephropathy (DN). The pathophysiology of AGE-challenged podocytes, such as hypertrophy, apoptosis, and reduced cell migration, is closely related to the induction of the cell cycle inhibitor p27(Kip1) and to the inhibition of neuropilin 1 (NRP1). We have previously demonstrated that treatment with erythropoietin is associated with protective effects for podocytes in vitro. db/db mice with overt DN aged 15-16 wk were treated with either placebo, epoetin-β, or continuous erythropoietin receptor activator (CERA) for 2 wk. db/db mice compared with nondiabetic db/m control mice revealed the expected increases in body weight, blood glucose, albumin-to-creatinine ratio, and AGE accumulation. Whereas there were no differences in body weight, hyperglycemia and AGEs were observed among diabetic mice that received epoetin-β compared with CERA and placebo treatment, indicating that epoetin-β/CERA treatment does not interfere with the development of diabetes in this model. However, the albumin-to-creatinine ratio was significantly lower in db/db mice treated with epoetin-β or CERA. Furthermore, kidney weights in db/db mice were increased compared with db/m control mice, indicating renal hypertrophy, whereas the increase in renal weight in epoetin-β- or CERA-treated db/db mice was significantly lower than in placebo-treated control mice. Induction of p27(Kip1) and suppression of NRP1 were significantly reduced in the epoetin-β treatment group versus the CERA treatment group. Furthermore, erythropoietin treatment diminished the diabetes-induced podocyte loss. Together, independently from hematopoetic effects, epoetin-β or CERA treatment was associated with protective changes in DN, especially that NRP1 and p27(Kip1) expressions as well as numbers of podocytes returned to normal levels. Our data show, for the first time, that medication of overt DN with erythropoietin for a short time can ameliorate albuminuria and podocyte loss.

Topics: Albuminuria; Animals; Cyclin-Dependent Kinase Inhibitor p27; Diabetic Nephropathies; Erythropoietin; Glycation End Products, Advanced; Male; Mice; Neuropilin-1; Podocytes; Polyethylene Glycols; Recombinant Proteins

Hypoxia-inducible factor (HIF) activity during the course of chronic kidney disease (CKD) development is poorly defined, and the effect of HIF activation on CKD is still controversial. The purpose of the present study was to characterize HIF expression during the course of CKD development, and to investigate the effect of HIF activation on CKD by using prolyl hydroxylase (PHD) inhibitor L-mimosine.. Rats with remnant kidneys (RK) were killed at week 1, 2, 4, 6, 8, 12 after subtotal nephrectomy. An additional group of RK rats was treated with L-mimosine to study the effect of HIF-α activation.. Tubulointerstitial hypoxia in the remnant kidney began at week 1 and continued, albeit attenuated, until week 12, the last time point examined. The nuclear expression of HIF-1α and HIF-2α, as well as typical HIF target genes VEGF (vascular endothelial growth factor), HO-1 (heme oxygenase-1), GLUT-1 (glucose transporter-1) and EPO (erythropoietin), were all upregulated in the early stage of RK when renal function was stable, and returned to the basal level later, accompanied by impaired renal function and interstitial fibrosis. L-mimosine administered from week 5 to week 12 led to accumulation of HIF-1α and HIF-2α proteins, increased expression of VEGF, HO-1 and GLUT-1, and improved renal function. Furthermore, fibrosis markers α-smooth muscle actin (α-SMA) and Collagen III, as well as peritubular capillary rarefaction index, were all significantly decreased after L-mimosine treatment.. There was a transient HIF-α activation in the remnant kidney of rats at the early stage following subtotal nephrectomy. L-mimosine administered in later stages re-activated HIF-α and reduced tubulointerstitial fibrosis.

Topics: Albuminuria; Animals; Blood Pressure; Disease Models, Animal; Erythropoietin; Glucose Transporter Type 1; Heme Oxygenase-1; Hypoxia-Inducible Factor 1, alpha Subunit; Kidney; Kidney Function Tests; Mimosine; Nephrectomy; Procollagen-Proline Dioxygenase; Rats; Renal Insufficiency; Up-Regulation; Vascular Endothelial Growth Factor A

To evaluate the renal production of erythropoietin (EPO) in relation to filtration function in patients with diabetic kidney lesion.. The investigation enrolled 183 patients with types 1 and 2 diabetes mellitus (DM), of whom 128 were diagnosed as having diabetic kidney lesion. Serum EPO levels were measured by enzyme immunoassay. Patients who had a glomerular filtration rate (GFR) of below 15 ml/min/1.73 m2 and received erythropoiesis-stimulating agents were excluded from the investigation.. The mean serum EPO levels in the patients with diabetic kidney lesion did not vary with the presence or absence of anemia, the degree of albuminuria, or GFR. A physiological inverse relationship was found between the level of EPO and that of hemoglobin in the blood of the patients with DM without kidney disease and in those with renal lesion and GFR > or = 60 ml/min/1.73 m2. The magnitude of the association of the values increased as GFR was higher. The level of EPO was found to be unassociated with hemoglobin in patients with GFR < 60 ml/min/1.73 m2.. In the patients with diabetic kidney lesion, serum EPO concentrations did not depend on the stage of chronic kidney disease and the degree of albuminuria in spite of more severe anemia as renal failure progressed. These patients showed inadequate EPO production just in early diminished renal filtration function.

Topics: Adult; Albuminuria; Anemia; Diabetes Complications; Diabetes Mellitus; Erythropoietin; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged

Recent preclinical data have indicated that erythropoietin (Epo) can protect organs from ischemic damage. We evaluated the ability of Epo to protect the kidney from the effects of ischemia.. Thirty dogs underwent a laparoscopic nephrectomy and were allowed to recover for 2 weeks. The dogs were then divided into five groups. Animals in groups 1 and 2 underwent 1.5 hours of abdominal insufflation with placebo (saline) injection (group 1) or Epo injection (group 2) before; groups 3 to 5 underwent 1 hour of laparoscopic renal artery clamping after placebo injection (group 3), Epo injection (group 4), or mannitol injection (group 5). Serum evaluations and 24-hour urine collections were performed weekly. After 28 days, the animals were sacrificed. Statistical analysis was performed with the Kruskal-Wallis test.. After recovery from the initial nephrectomy, all dogs had similar serum hematocrit and creatinine levels. Hematocrit was not significantly affected by Epo administration at any time point. Immediately after the second surgery, dogs that underwent renal artery clamping (groups 3-5) had significantly lower 24-hour urine creatinine levels than those that were not clamped (groups 1-2). After 4 weeks of recovery, the dogs that had received Epo before ischemia (group 4) had recovered significantly more renal function than the dogs that received placebo or mannitol before ischemia (urine creatinine level = Epo 149.1 mg/dL v placebo 70.7 mg/dL v mannitol 80.7 mg/dL). At sacrifice, microalbuminuria was also significantly less in dogs receiving Epo before ischemia than their mannitol or placebo counterparts.. The current study demonstrates that administering Epo before warm ischemia can improve the recovery of renal function after ischemia better than placebo or mannitol.

Topics: Albuminuria; Animals; Creatinine; Dogs; Dose-Response Relationship, Drug; Erythropoietin; Humans; Kidney; Kidney Function Tests; Recombinant Proteins; Time Factors; Warm Ischemia

To investigate the relationship between Erythropoietin (EPO) and 1,25-dihydroxyvitamin D levels, and tubular damage in patients with diabetes mellitus (DM) without persistent microalbuminuria.. We measured serum EPO and 1,25-dihydroxyvitamin D levels and tubular injury markers such as urinary N-acetyl-beta-d-glucosaminidase (NAG) and retinol binding protein (RBP) levels in 41 non-diabetic controls, 40 patients with Type 1 and 40 with Type 2 DM.. Median serum EPO levels were lower in Type 1 (2.57 mIU/ml: p<0.001) and Type 2 DM (5.69 mIU/ml: p=0.044) than in controls (8.76 mIU/ml), though haemoglobin levels did not differ. Median 1,25-dihydroxyvitamin D levels were lower in Type 1 (41.0 pmol/l: p=0.001) and Type 2 DM (41.8 pmol/l: p=0.035) than in controls (56.1 pmol/l), though serum creatinine, calcium, phosphate and PTH levels did not differ. Median RBP excretion was higher in Type 2 DM (0.35 mg/l vs. 0.23 mg/l: p=0.013) than in controls. Median NAG excretion was higher in Type 1 DM (1,079 micromol/h vs.1,030 micromol/h: p=0.048) compared to controls.. Tubulo-interstitial damage with low levels of EPO and 1,25-dihydroxyvitamin D occurs early in Type 1 and Type 2 DM before persistent microalbuminuria.

Topics: Adult; Albuminuria; Blood Glucose; Blood Pressure; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Erythropoietin; Female; Glycated Hemoglobin; Humans; Kidney Tubules; Male; Middle Aged; Reference Values; Vitamin D; Young Adult

Topics: Age Factors; Aged; Albuminuria; Antihypertensive Agents; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Erythropoietin; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Radioimmunoassay

The present study investigated the relationship between hemoglobin (Hb) levels and autonomic failure using a sensitive marker, coefficient of variation of R-R intervals in electrocardiogram (CVR-R) in order to clarify a cause of normocytic normochromic anemia in type 1 diabetic patients without overt nephropathy. We recruited 46 patients with type 1 diabetes and measured creatinine clearance (Ccr), HbA1c, albuminuria, Hb levels and CVR-R of all patients. In addition, the status of diabetic retinopathy and neuropathy were also evaluated. Serum erythropoietin (EPO), Fe, total iron binding capacity, lactate dehydrogenase, total bilirubin levels and number of reticulocytes and mean corpuscular volume were also measured to distinguish types of anemia. To survey the statistical correlation existing between Hb and body mass index (BMI), Ccr, HbA1c, albuminuria or retinopathy, multiple regression analysis was performed. Serum EPO, Fe, TIBC, LDH and TB levels and number of reticulocytes and MCV were within normal limits. Multiple regression analysis disclosed that HbA1c, nephropathy evaluated by albuminuria and Ccr, and retinopathy has no concern with Hb level. There is only significant relationship between Hb levels and CVR-R. Similar results were obtained even if we analyzed a group of male and female separately. We conclude that CVR-R has the strong relationship on anemia without overt nephropathy in type 1 diabetes, indicating that autonomic failure contributes on the progression of anemia via a poor response of EPO to anemia.

Topics: Adult; Aged; Albuminuria; Anemia; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Electrocardiography; Erythropoietin; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Sensitivity and Specificity

In order to determine the possible origins of undetectable EPO profiles in athletes' urine, we analyzed the data obtained from a large number of official anti-doping urine tests aimed at detecting recombinant erythropoietin. The following variables were considered as potential causes for lack of EPO detection: athlete's gender, competition effect, urine specific gravity as well as possible usage of proteasic adulterants to evade doping detection.. Statistical analyses indicated that undetectable EPO profiles were clearly related to urine properties such as low EPO concentrations or extreme specific gravities. The addition of very small quantities of protease was shown to remove all traces of EPOs in urine. This finding led to the development of a simple, specific and sensitive test that reveals proteasic activity based on albumin digestion.. Urine characteristics clearly affect the detectability of an EPO profile. At the same time, addition of anti-proteases prevents the adulteration of urine. These two findings have clear practical implications with regards to the timing of urine collection as well as the entire anti-doping control procedure.

Topics: Albuminuria; Erythropoietin; Female; Humans; Isoelectric Focusing; Male; Recombinant Proteins; Sex Characteristics; Trypsin; Urine

Anaemia is a common finding in patients with diabetic nephropathy. Impaired production of erythropoietin is thought to be the predominant cause, as a result of renal microvascular disease. This study aims to determine the prevalence of functional erythropoietin deficiency in a cross-sectional survey of patients with Type 2 diabetes.. Clinical data on 604 patients with Type 2 diabetes were obtained, including a full blood count, iron indices and detailed history of diabetic complications. Erythropoietin levels were correlated with the presence of anaemia, iron deficiency and renal dysfunction. Functional erythropoietin deficiency was defined by erythropoietin levels in the normal range despite the presence of anaemia.. Nineteen per cent of patients (n = 112) were anaemic, among whom erythropoietin deficiency (76%) and reduced iron availability (58%) were common findings. Over 90% of patients had erythropoietin deficiency, once those with reduced iron stores or availability were excluded. Most of these patients had moderate renal impairment (60%, n = 67). However, even in the absence of renal impairment, 71% of anaemic patients (n = 32/45) had functional erythropoietin deficiency, although most had other evidence of nephropathy. In addition, two-thirds of patients with reduced iron availability were unable to increase erythropoietin above the normal range.. These findings confirm the failure of the kidney to produce erythropoietin in response to a falling haemoglobin is a key component to anaemia in diabetes. The likelihood of functional erythropoietin deficiency as a cause of anaemia is not dependent on the severity of renal impairment or excluded in diabetic patients with reduced iron stores or availability.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Anemia; Biological Availability; Blood Pressure; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Iron; Iron Deficiencies; Kidney; Male; Middle Aged

This case-control study was undertaken in 75 subjects categorized into 3 equal groups (A: diabetic subjects with macroalbuminuria, B: non-diabetic subjects with macroalbuminuria and C; control subjects). Serum erythropoietin (EPO) was estimated and analyzed in relation to hemoglobin levels in the three groups. The Pearson's coefficient (r) for hemoglobin and log natural EPO was significant for groups A (0.01), B (0.05) and C (0.01). Linear regression analysis of hemoglobin and log natural EPO showed significant differences between the study and control groups; however no significant difference could be demonstrated amongst the study groups. Hence, it was concluded that an inadequate EPO production occurs in renal failure, which accounts for the anaemia and diabetes does not confer an additional discrepancy in this mechanism over non-diabetic macroalbuminuria.

Topics: Adult; Aged; Albuminuria; Anemia; Case-Control Studies; Diabetic Nephropathies; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged

Low plasma erythropoietin (EPO) is a key causal factor in the anaemia of diabetic patients. The aim of this study was to investigate the prevalence of anaemia in relation to EPO in patients with Type 2 diabetes.. In a clinic-based cross-sectional study of 161 Type 2 diabetes patients, we measured EPO, ferritin and full blood count. The patients were classified on the basis of the urine albumin:creatinine excretion ratio as normo-, micro- or macroalbuminuric. Serum creatinine, cystatin C and glomerular filtration rate (GFR) calculated from cystatin C were used as markers of renal function. All the patients were assessed for symptoms and signs of diabetic complications, including diabetic peripheral sensory neuropathy (PSN).. Twenty-one (13.0%) patients were anaemic; 80 patients (49.7%) had low EPO (< 5 mU/ml), of whom 28.8% had a GFR < 60 ml/min per 1.73 m2; 57.5% were normoalbuminuric, 33.7% were microalbuminuric and 8.8% macroalbuminuric. Although EPO was significantly higher in anaemic patients compared with non-anaemic patients, the EPO response was inappropriate for the degree of anaemia. Of patients with PSN, 66.7% had low EPO but there was no significant difference in EPO between patients with and without PSN. Log EPO correlated significantly with urine microalbumin:creatinine ratio and logistic regression analysis showed that haemoglobin, age and urine microalbumin: creatinine ratio were the main determinants of EPO.. The degree of microalbuminuria is the most significant determinant of plasma EPO, which is often low or inappropriately normal in diabetic patients with and without anaemia.

Topics: Aged; Albuminuria; Anemia; Angiotensin-Converting Enzyme Inhibitors; Creatinine; Cross-Sectional Studies; Cystatin C; Cystatins; Diabetes Mellitus, Type 2; Erythropoietin; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged

The aim of this study was to analyze the effects of elevated parathyroid hormone (iPTH) and C-reactive protein (CRP) on rHuEPO requirements and associated clinical and biochemical parameters of hemodialysis patients.. A total of 127 hemodialysis patients were included. Laboratory values from the previous 3 months (monthly measured CRP, iPTH, albumin, prealbumin, calcium, phosphorus, and hemoglobin) and clinical findings (rHuEPO requirements, iron supplements, Kt/V) were recorded retrospectively. Patients were subgrouped according to presence of hyperparathyroidism (mean iPTH > 350 pg/mL) and chronic inflammation (mean CRP > 8.5 mg/L) as group I (low iPTH, low CRP, n = 32), group II (high iPTH, low CRP, n = 32), group III (low iPTH, high CRP, n = 32), and group IV (high iPTH, high CRP, n = 31).. We found that group IV had lowest hemoglobin (P < .0001, .0001, .01, respectively), albumin (P < .0001), prealbumin (P < .0001, .0001, .02, respectively), and highest rHuEPO requirements (P < .0001, .0001, .01, respectively) compared to other groups despite of similar iron indices. Group III also had lower albumin (P < .002, .0001, respectively), prealbumin (P < .001, .01, respectively), hemoglobin (P < .001, .005, respectively), but higher rHuEPO requirements (P < .01) compared to group I and group II.. We propose that hyperparathyroidism increases rHuEPO requirements and aggravates the negative effects of chronic inflammation in hemodialysis patients.

Topics: Adult; Aged; Albuminuria; C-Reactive Protein; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Hyperparathyroidism; Inflammation; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Topics: Albuminuria; Anemia; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Erythropoietin; Europe; Humans; Practice Guidelines as Topic; Prognosis; Quality of Life

Recombinant erythropoietin upregulates the expression of the vascular endothelial growth factor (VEGF) receptors, Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), in endothelial cells. The integrity of the VEGF system seems to be crucial for the regulation of endothelial permeability and thus for the avoidance of renal protein leakage. As albuminuria/proteinuria is a hallmark of diabetic nephropathy, we examined cross-sectionally in 35 type 1 and 37 type 2 diabetic patients with various degrees of renal dysfunction and albuminuria whether there was an interrelationship between intrinsic erythropoietin (EPO) and VEGF/Flt-1.. In patients with plasma creatinine values < or =1.5 (n = 53) or >1.5 mg/dL (n = 19), the mean serum EPO was 5.6 +/- 4.4 and 10.2 +/- 7.0 mU/mL (P = 0.02), respectively. In the two groups, urinary and serum VEGF(165) concentrations were similarly distributed (mean 94.3 +/- 91.8 vs 108 +/- 72.2 ng/L and 91.7 +/- 76.8 vs 91.9 +/- 74.9 ng/L, respectively; both P = NS). The mean urinary Flt-1 for the two groups amounted to 0.14 +/- 0.35 and 0.51 +/- 0.93 ng/mL (P = 0.045), respectively. No correlation between VEGF or Flt-1 and EPO was apparent.. Our data suggest that in vivo EPO does not affect the functionality and/or production of components of the VEGF/Flt-1 system in diabetics with normal or reduced renal function.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Anemia; Cross-Sectional Studies; Diabetic Nephropathies; Erythropoietin; Female; Humans; Kidney; Male; Middle Aged; Renal Insufficiency; Solubility; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

Diabetes mellitus is associated with an increased prevalence of anemia, particularly in patients with nephropathy. We undertook this survey to determine the relationship between anemia and the renal production of erythropoietin in patients with diabetes mellitus.. The clinical data of 722 patients were obtained, including markers of diabetic complications. Erythropoietin levels were measured in the same samples. Patients with a full blood cell count, iron indexes, and renal function within the normal range (n = 151) were used to define the reference range for this population. Anemic patients who had erythropoietin levels within this range were defined as having an "inappropriate erythropoietin response to anemia.". Of the 722 patients, 168 (23.3%) had anemia, of whom 130 (77.4%) had erythropoietin levels inappropriately within the normal range. Although 55.4% of anemic patients had moderate renal impairment, erythropoietin levels were also inappropriately low in 69.2% of anemic patients with normal renal function. However, most of these patients (17 of 26) had diabetic kidney disease, as denoted by albuminuria.. The failure to produce erythropoietin in response to a declining hemoglobin level is a common contributor to anemia in patients with diabetes mellitus. This seems to be a manifestation of diabetic kidney disease, in the presence or absence of renal impairment.

Topics: Aged; Albuminuria; Anemia; Diabetes Mellitus; Diabetic Nephropathies; Erythropoietin; Female; Follow-Up Studies; Glomerular Filtration Rate; Hemoglobins; Humans; Kidney; Male; Middle Aged; Multivariate Analysis

Erythropoietin (EPO)-deficient anaemia has been described in Type 1 diabetic patients with both severe autonomic neuropathy (AN) and proteinuria. This study was aimed at distinguishing between the effects of AN and nephropathy on haemoglobin and EPO levels in Type 2 diabetic patients at an early stage of diabetic nephropathy.. In 64 Type 2 diabetic patients (age 52 +/- 10 years, duration 10 +/- 9 years) without overt nephropathy and other causes of anaemia or EPO deficit, we assessed cardiovascular tests of AN, 24-h blood pressure (BP) monitoring, urinary albumin excretion rate (UAE), a full blood count, and serum EPO.. Although the Type 2 diabetic patients with AN did not show differences in haemoglobin and EPO when compared with patients without AN, the presence of haemoglobin < 13 g/dl was associated with the presence of AN (chi(2)= 3.9, P < 0.05) and of postural hypotension (chi(2)= 7.8, P < 0.05). In a multiple regression analysis including as independent variables gender, body mass index, duration of diabetes, smoking, creatinine, 24-h UAE, 24-h diastolic BP, ferritin, erythrocyte sedimentation rate, and autonomic score, we found that the only variables independently related to haematocrit were autonomic score, ferritin and erythrocyte sedimentation rate. Finally, the physiological inverse relationship between EPO and haemoglobin present in a control group of 42 non-diabetic non-anaemic subjects was completely lost in Type 2 diabetic patients. The slopes of the regression lines between EPO and haemoglobin of the control subjects and the Type 2 diabetic patients were significantly different (t = 14.4, P < 0.0001).. This study documents an early abnormality of EPO regulation in Type 2 diabetes before clinical nephropathy and points to a contributory role of AN in EPO dysregulation.

Topics: Adult; Aged; Albuminuria; Autonomic Nervous System Diseases; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Erythropoietin; Female; Hemoglobins; Humans; Hypotension, Orthostatic; Male; Middle Aged

We report the case of a 52-year-old woman with long-term type 1 diabetes mellitus, complicated with proliferative retinopathy, autonomic neuropathy and microalbuminuria and moderate renal failure. A normochromic, normocytic are generative anaemia had been diagnosed for three years. Clinical and biological investigations for the aetiology of anaemia remained normal or negative. Anaemia was associated with a concentration of erythropoietin (EPO) in the normal range, but inappropriately low regarding anaemia. Treatment with recombinant EPO induced a rapid increase in haemoglobin level and improved the patient's quality of life. The role of diabetic neuropathy in the genesis of anaemia, in conjunction with a modest renal impairment is discussed.

Topics: Albuminuria; Anemia; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Electrocardiography; Erythropoietin; Female; Hemoglobins; Humans; Hypotension, Orthostatic; Kidney Failure, Chronic; Middle Aged; Quality of Life; Recombinant Proteins

The estimation of cord blood erythropoietin in subjects with pre-eclampsia and eclampsia.. Erythropoietin was measured, using ELISA, in the cord blood of infants born to 83 mothers with pre-eclampsia, and 7 with eclampsia. Another 90 subjects with no evidence of pre-eclampsia or eclampsia were taken as control subjects. Maternal parity, gestational age, blood pressures, 24-h urine protein and Apgar scores of the infants delivered were also noted.. Cord blood erythropoietin levels were statistically significantly higher (P<0.001) in infants born to mothers with pre-eclampsia and eclampsia. There was a significant positive correlation (P<0.01) between cord blood erythropoietin levels and maternal blood pressure (systolic and diastolic) and albuminuria. A negative correlation (P<0.01) was observed with the birth weights of infants.. Pre-eclampsia and eclampsia are associated with higher levels of cord blood erythropoietin.

Topics: Adult; Albuminuria; Apgar Score; Biomarkers; Birth Weight; Blood Pressure; Case-Control Studies; Eclampsia; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Fetal Blood; Gravidity; Humans; Hydrogen-Ion Concentration; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Uric Acid

To discover whether Type 1 diabetic patients with autonomic neuropathy might be anaemic and erythropoietin (EPO)-depleted.. Fifteen Type 1 diabetic patients with serious complications (DM-COMP) were selected because of severe symptomatic autonomic neuropathy, including significant postural hypotension. All had proteinuria from nephropathy (three microalbuminuria and 12 macroalbuminuria), but a normal serum creatinine (< 122 micromol/l). They were compared to age and duration matched Type 1 diabetic controls without autonomic neuropathy (DM-controls) and non-diabetic patients with and without hypochromic, microcytic anaemia.. The DM-COMP patients were anaemic (mean haemoglobin (Hb) 11.1+/-1.2 g/dl), sometimes severely (minimum Hb 9.2 g/dl), compared to non-neuropathic DM-controls (Hb 13.7+/-0.7 g/dl; P < 0.001). Furthermore, EPO failed to increase in association with anaemia in the DM-COMP group compared to the progressive increase in the non-diabetic, anaemic patients (difference of regression lines P < 0.001), indicating EPO depletion in the anaemic, diabetic patients. There was no other demonstrable cause for the anaemia. Treatment with EPO in 5 DM-COMP patients led to a rapid increase in haemoglobin (range 1.7-5.0 g/dl) with improvement in wellbeing.. Some Type 1 diabetic patients with autonomic neuropathy present with an EPO-depleted anaemia, which responds to treatment with EPO. This observation supports the concept of autonomic neuropathy as a cause of anaemia with EPO depletion, although the role of established renal damage cannot be excluded.

Topics: Adult; Albuminuria; Anemia; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Diabetic Neuropathies; Erythropoietin; Female; Hemoglobins; Humans; Middle Aged; Proteinuria

The effects of recombinant human erythropoietin (rHuEPO) administration on blood pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a week) for 6 weeks. Control animals received the vehicle only (0.25 mL of physiological saline). An angiotensin converting enzyme inhibitor was administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once a week. No significant differences in SBP were observed between rHuEPO and vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v 172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/- 7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg, respectively); UAE was significantly higher in groups treated with rHuEPO than in control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4 +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v 143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin treatment causes an increase in arterial pressure in SHR only, and an increase in UAE in both normotensive and hypertensive rats. The albuminuric effect was not entirely dependent on increased blood pressure. The treatment with an angiotensin converting enzyme inhibitor did not modify either the proteinuric or the pressor effects.

Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Weight; Drinking; Erythropoietin; Hematocrit; Hemoglobins; Humans; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Recombinant Proteins; Sodium; Urodynamics

Angiotensin-converting enzyme (ACE) inhibitor therapy has recently been shown to be effective in the treatment of post-renal transplant erythrocytosis (PTE). In an attempt to assess the effect of drug treatment on serum erythropoietin level, glomerular filtration rate, and urinary protein excretion, we prospectively evaluated 8 consecutive cadaveric renal transplant recipients with PTE treated with ACE inhibitor therapy for 3 months. In response to ACE inhibition, the mean hematocrit (HCT) value decreased from 53.7 +/- 0.6% before treatment to 42.7 +/- 2.2% at the conclusion of the study (p = 0.03). However, 1 patient failed to respond to ACE inhibition (HCT > 50%), and 2 patients with PTE developed anemia (HCT < 35%) while maintained on drug treatment. Although the mean serum erythropoietin level decreased during ACE inhibition (from 22.8 +/- 8.4 to 9.4 +/- 5.3 mU/ml; p = 0.06), a consistent change in individual erythropoietin levels was not identified. At the conclusion of the study, the serum erythropoietin levels were undetectable in 4 patients, decreased in 1, unchanged in 2, and increased in the only patient with PTE who failed to respond to drug treatment. All patients tolerated the ACE inhibitor therapy without developing cough or hyperkalemia. In addition, serum creatinine levels, 125I-iothalamate clearances, and mean arterial blood pressures were unchanged throughout the study. Microalbuminuria (spot urinary albumin/creatinine ratio between 30 and 200 mg/g) developed in 5 patients with PTE and coincided with the onset of erythrocytosis (25.2 +/- 7 mg/g before PTE and 76.3 +/- 36.7 mg/g at the time of PTE detection).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Chronic Disease; Contrast Media; Erythropoietin; Female; Glomerular Filtration Rate; Humans; Iodine Radioisotopes; Iothalamic Acid; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Polycythemia; Prospective Studies

Recent data indicated the importance of urinary losses of erythropoietin (Epo) in the pathogenesis of anaemia in patients with nephrotic syndrome. In the present study we aimed to investigate plasma and urinary Epo levels and their renal handling in relation to beta 2-microglobulin (beta 2m), sodium metabolism and the renin-angiotensin-aldosterone system (RAAS), respectively, in patients with sub-nephrotic range proteinuria (SNP), microalbuminuric diabetics and hypertensives, and in healthy subjects studied on a standardized diet containing 120 mmol sodium and 70 g protein per day. We found that patients with SNP were characterized by lower plasma levels of Epo than healthy subjects but no differences were found in urinary excretion of Epo, endogenous Epo clearance and its fractional excretion (FEEpo). There were no differences between groups in FE beta 2m and FENa and plasma aldosterone levels but plasma renin activity was higher in patients with SNP than in the controls. No relationships were found between Epo levels and activity of the RAAS and sodium metabolism, respectively. Our data suggest that lower levels of plasma Epo in patients with SNP and normal renal excretory function are not due to urinary losses of Epo but rather to the decreased production/degradation ratio.

Topics: Adult; Albuminuria; beta 2-Microglobulin; Diabetes Mellitus, Type 2; Erythropoietin; Humans; Hypertension; Nephrotic Syndrome; Proteinuria; Renin-Angiotensin System; Sodium

To investigate the possible effect of preeclampsia on erythropoietin metabolism, we measured plasma and urine erythropoietin concentrations and complete blood count in 19 women with preeclampsia and nine healthy gravidas. Hemoglobin concentration and hematocrit values in the preeclamptic patients did not differ significantly from those of the normal pregnant controls. However, the plasma erythropoietin concentration tended to be higher in the preeclamptic group than in the normal pregnant controls (26.9 +/- 31.2 versus 11.2 +/- 9.9 mU/mL), though the difference was not statistically significant. Plasma erythropoietin concentration correlated negatively with both hemoglobin concentration and hematocrit (r = -0.85, P less than .01). The pattern and magnitude of the erythropoietin response to anemia paralleled that previously reported in individuals with iron deficiency anemia. No significant correlation was found between urinary erythropoietin excretion and blood pressure, qualitative albumin excretion, hematocrit, hemoglobin concentration, or plasma erythropoietin concentration. Based on our results, the erythropoietin response to anemia appears to be intact in preeclampsia, at least in the absence of renal failure.

Topics: Adult; Albuminuria; Blood Cell Count; Blood Pressure; Creatine; Erythropoietin; Female; Humans; Pre-Eclampsia; Pregnancy; Proteinuria; Thrombocytopenia; Uric Acid

Topics: 2,3-Diphosphoglycerate; Adult; Albuminuria; Blood Cell Count; Creatine; Diphosphoglyceric Acids; Enzymes; Erythrocytes; Erythropoietin; Exercise; Ferritins; Humans; Iron; Male; Middle Aged