losartan-potassium and Polycystic-Kidney-Diseases

Somatic cell gene therapy has made considerable progress last five years and has shown clear success in some clinical trials. In the field of nephrology, both the elucidation of pathophysiology of renal diseases and the development of gene transfer technique have become driving force for new therapy of incurable renal diseases, such as Alport syndrome and polycystic kidney disease. Gene therapy of renal cancer, although its application is limited to advanced cancer, is the front-runner of clinical application. Erythropoietin gene therapy has provided encouraging results for the treatment of anemia in uremic rats and recently progressed to the inducible one in response to hypoxia. Gene therapy for glomerulonephritis and renal fibrosis showed prominent impact on experimental models, although the safety must be confirmed for prolonged treatment. Transplant kidney is an ideal material for gene modification and induction of tolerance in the transplant kidney is an attractive challenge. Emerging techniques are becoming available such as stem cell technology and messenger RNA silencing strategies. We believe that the future of gene therapy research is exciting and promising and it holds an enormous potential for clinical application.

Topics: Adenoviridae; Anemia; Erythropoietin; Fibrosis; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Glomerulonephritis; Humans; Kidney Diseases; Kidney Transplantation; Lentivirus; Polycystic Kidney Diseases; Recombinant Proteins

Topics: Animals; Erythropoietin; Humans; Hypoxia; Kidney; Kidney Failure, Chronic; Parathyroidectomy; Polycystic Kidney Diseases; Polycythemia

Impaired immunological response in hemodialysis (HD) patients, which leads to inappropriate cytokine production, is partially caused by the hyperstimulation of both T lymphocytes and monocytes/macrophages. Recent data suggest that human recombinant erythropoietin (rhEPO) may have an immunological action. The goal of our study was to estimate the influence of rhEPO treatment on the production of the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) and antiinflammatory cytokin interleukin-10 (IL-10) in 10 HD patients receiving rhEPO for 6 months. The levels of cytokines were measured in the in vitro cultures of whole blood. The level of IL-10 increased in all treated patients during the therapy, and it was accompanied by a transitory decrease of TNFalpha. The results of our studies suggest that rhEPO may reduce the inflammatory process by decreasing production of TNFalpha and increasing production of IL-10.

Topics: Adult; Blood Cells; Cells, Cultured; Erythropoietin; Female; Glomerulonephritis; Humans; Interleukin-10; Kidney Failure, Chronic; Male; Middle Aged; Phytohemagglutinins; Polycystic Kidney Diseases; Pyelonephritis; Recombinant Proteins; Renal Dialysis; Tumor Necrosis Factor-alpha

Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients.

Topics: Administration, Intravenous; Aged; Anemia; Cohort Studies; Darbepoetin alfa; Drug Resistance; Erythropoietin; Female; Hematinics; Hemodiafiltration; Hemoglobins; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Polycystic Kidney Diseases; Recombinant Proteins; Renal Dialysis

In chronic kidney disease (CKD), anemia and hypertension are significant co-morbidities that contribute to cardiovascular and renal disease progression.. The purpose of the study was to identify correlations between changes in hematologic variables against markers of renal function, blood pressure, and erythropoietin (EPO) in a naturally occurring hypertensive model of CKD, the Lewis polycystic kidney (LPK) rat.. Complete blood count, systolic blood pressure, urea and creatinine concentration, urinary protein to creatinine ratio, and plasma EPO concentration were determined in control Lewis (n = 51) and LPK rats (n = 56) aged 6-24 weeks. Renal EPO gene expression and RBC osmotic fragility were also documented. Hematopoiesis in spleen and bone marrow were assessed.. Lewis polycystic kidney rats had increasing urea and creatinine concentrations, concurrent with the development of a nonregenerative normocytic/normochromic anemia and hypertension, with a significant negative correlation between both HGB and HCT with urea concentration and blood pressure (P < .01). HCT was also significantly negatively correlated with creatinine concentration (P = .014). WBC was significantly negatively correlated with urea (P < .01). Plasma EPO concentration was increased and renal EPO mRNA expression was significantly upregulated in LPK animals. The former was significantly positively correlated with blood pressure and platelet count (P < .05). RBC osmotic fragility was normal in LPK rats and there was no evidence for increased RBC elimination or extramedullary hematopoiesis.. Marked anemia in the LPK CKD rodent model in the presence of elevated EPO suggests inefficient erythropoiesis that is correlated with plasma urea concentration and blood pressure.

Topics: Anemia; Animals; Blood Cell Count; Blood Pressure; Blood Urea Nitrogen; Cohort Studies; Creatinine; Disease Models, Animal; Disease Progression; Erythropoietin; Female; Hypertension; Kidney; Kidney Function Tests; Male; Polycystic Kidney Diseases; Rats; Rats, Inbred Lew; Renal Insufficiency, Chronic

Some chronic hemodialysis (HD) patients can maintain normal hemoglobin levels without requiring erythropoiesis-stimulating agents (ESAs). However, the prevalence and the factors associated with this condition in Chinese chronic HD patients have not been reported. The aim of this study was to investigate clinical features, iron metabolism, and other characteristics to survey the prevalence rate and the related factors of this condition among Chinese chronic HD patients.. A total of 1,318 chronic HD patients participated in this study. The patients were classified into a non-ESA group (n = 11) and an ESA group (n = 1,307). The r-HuEPO-independent (non-ESA) HD patients were defined as having hemoglobin greater than 12 g/dl for more than 6 months without r-HuEPO injection, blood transfusion, or androgen therapy. Epidemiological and laboratory data were collected. Renal sonography was also performed on each patient to evaluate the formation of renal and liver cysts, and the number and size of the cysts were recorded.. Approximately 0.84 % of all HD patients were found to be r-HuEPO independent. The non-ESA group had a higher proportion of men (79.6 vs. 58.3 %), a longer duration of renal replacement therapy (RRT) (8.6 ± 6.1 vs. 5.1 ± 3.3 years), a higher prevalence of adult polycystic kidney disease (APKD) (46.3 vs. 9.7 %), a higher prevalence of hepatitis C virus (HCV) liver disease (26.2 vs. 3.2 %, P < 0.01), and had older patients (63.3 ± 13.6 vs. 49.6 ± 13.5 years). Endogenous erythropoietin levels in the non-ESA group were significantly higher than those in the ESA group (61.8 ± 27.1 vs. 29.3 ± 11.7 mU/ml). Non-ESA patients had a significantly higher number of renal (38.1 vs. 13.2 %) and hepatic cysts (9.3 vs. 1.9 %), which were also larger in size (2.9 ± 1.6 vs. 1.3 ± 0.3 cm) compared with those of patients in the ESA group. No significant difference in iron metabolism was found between two groups. In the multivariate Cox analysis, the independent predictor factors for the absence of anemia in these HD patients were the number of renal cysts >6 cysts (95 % CI 1.058-1.405; P = 0.00), endogenous erythropoietin levels (95 % CI 1.139-1.361; P = 0.05), HCV+ liver disease (95 % CI 1.129-1.316; P = 0.01), and time on RRT (95 % CI 1.019-1.263; P = 0.05).. To our knowledge, this study is the first to report on r-HuEPO independence among Chinese HD patients. The prevalence among Chinese chronic HD patients is significantly lower than that reported in the literature. Factors contributing to this condition are complex and multiple. The frequency of this condition is higher in men and in older patients with long-term RRT, in patients with HCV+ liver disease, and in APKD patients. This condition is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

Topics: Adult; Age Factors; Aged; Anemia; China; Cross-Sectional Studies; Cysts; Erythropoietin; Female; Hematinics; Hemoglobins; Hepatitis C; Humans; Iron; Liver Diseases; Male; Middle Aged; Polycystic Kidney Diseases; Prevalence; Recombinant Proteins; Renal Dialysis; Renal Insufficiency, Chronic; Time Factors; Ultrasonography

Interventional trials indicate adverse outcomes when hemoglobin >13 g/dL is targeted in patients with chronic kidney disease (CKD) who receive erythropoiesis-stimulating agents (ESAs). It is not clear whether high-achieved hemoglobin with minimal to no ESA administration as observed in some patients with polycystic kidney disease (PKD) is also associated with poor outcomes. Survival models were examined to assess the association between hemoglobin increments and mortality in a 6-year cohort of 2,402 PKD and 110,875 non-PKD hemodialysis patients across infrequent versus frequent ESA therapy defined as ESA < 25% of cohort time versus otherwise, respectively. Mortality risk was estimated by Cox proportional regression [hazard ratio (HR) and 95% of confidence interval] analysis. Patients with PKD were aged 58 ± 13 years and included 46% women 14% Blacks, respectively. Fully adjusted death HRs of time-averaged hemoglobin increments <11.0, 12.0 to <13.0 g/dL (reference: 11.0 to <12.0 g/dL) for frequent ESA therapy were 2.57 (1.48-4.48), 0.60 (0.43-0.82), and 0.81 (0.50-1.29), whereas for infrequent ESA therapy they were 1.33 (0.47-3.78), 0.28 (0.13-0.61), and 0.22 (0.09-0.57), respectively. Hence, in patients with PKD who require infrequent ESA, incrementally higher achieved hemoglobin including > 13.0 g/dL exhibits better survival; this incremental survival gain of higher hemoglobin is not observed in patients with PKD receiving frequent ESA administration, in whom hemoglobin concentration > 13 exhibits increased mortality.

Topics: Aged; Cohort Studies; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Polycystic Kidney Diseases; Renal Dialysis; Survival Rate

Topics: Erythropoietin; Hemoglobins; Humans; Polycystic Kidney Diseases

In polycystic kidney disease (PKD), erythropoietin (EPO) production and interstitial vascularization are increased compared with other kidney diseases. EPO and several angiogenic factors are controlled by hypoxia-inducible transcription factors (HIFs), which are composed of a constitutive beta-subunit and two alternative alpha-subunits (HIF-1alpha, HIF-2alpha). We hypothesized that cyst expansion may result in pericystic hypoxia and consecutive up-regulation of HIF and thus examined the expression of HIF-alpha and HIF target genes in human PKD and in a rodent PKD model. HIF-1alpha and HIF-2alpha were found to be up-regulated in cyst epithelium and cells of cyst walls, respectively. The distinct expression pattern of the HIF-alpha isoforms closely resembles the respective pattern in normal kidneys under systemic hypoxia. Pimonidazole staining, a marker for tissue hypoxia, confirmed the existence of regional hypoxia in polycystic kidneys. Immunohistochemistry for selected target genes implicated a role for HIF-1alpha in vascular endothelial growth factor and Glut-1 activation and HIF-2alpha in endoglin and EPO stimulation. Polycystin-deficient cells showed physiological, oxygen-dependent HIF-alpha modulation, excluding a direct influence of polycystin deficiency on HIF-alpha regulation. In conclusion, HIF accumulation in human and rat PKD seems to be responsible for increased EPO production and pericystic hypervascularity and may have an impact on progression of PKD.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Hypoxia; Erythropoietin; Female; Gene Expression; Glucose Transporter Type 1; Heme Oxygenase-1; Humans; Immunoblotting; Immunohistochemistry; Male; Middle Aged; Polycystic Kidney Diseases; Rats; TRPP Cation Channels; Vascular Endothelial Growth Factor A

Renal anaemia is caused by a relative erythropoietin (EPO) deficiency. Due to difficult interpretation of serum EPO concentrations adapted to anaemia and renal function, the diagnostic value of measuring serum EPO concentrations is limited.. We retrospectively analysed the relationship between haemoglobin and serum EPO concentrations routinely measured in in- and out-patients of our university hospital from 2001-04. Patients under EPO substitution or those with acute renal failure, polycystic kidney disease, renal carcinoma or polycythaemia due to pulmonary disease were excluded. The study population (n = 500) was then stratified according to the presence or absence of chronic kidney disease (CKD) and to the stage if CKD was present. EPO concentrations were expressed in percentiles corrected for the severity of anaemia and based on the EPO response in patients without CKD.. In patients without CKD (n = 167) there was a strong parametric correlation between severity of anaemia and increase in EPO (r = -0.81). Linear regression of the log-transformed EPO values revealed the equation log EPO (mIU/ml) = -0.135 x Hb (g/dl) + 2.821 (r(2) = 0.65). With increasing stages of CKD the correlation between haemoglobin and EPO concentrations was gradually attenuated and was completely lost in CKD stage four and five. In anaemic patients with Hb < 11 g/dl, relative EPO deficiency defined as EPO concentrations below the 25th percentile was present in 38%, 67%, 93% and 100% of the patients with CKD stages 1-5, respectively.. Expression of EPO concentrations in percentiles improves the diagnostic value of measuring EPO concentrations for diagnosing relative EPO deficiency and renal anaemia.

Topics: Adult; Aged; Anemia; Chemistry, Clinical; Erythropoietin; Female; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Models, Biological; Polycystic Kidney Diseases; Regression Analysis; Retrospective Studies

Most hemodialysis patients exhibit renal anemia mainly due to erythropoietin deficiency as a result of impaired erythropoetin production in the kidney. However, erythrocytosis in patients with renal failure requiring hemodialysis is extremely rare. We report the development of erythrocytosis in a patient with a polycystic kidney disease on hemodialysis for 13 years. She had erythrocytosis with increased serum erythropoietin levels despite severe secondary hyperparathyroidism, which is known to depress erythrocytosis. Since neither renal disease (renal cell carcinoma) nor extrarenal diseases (hypoxia, hepatoma, cerebellar diseases) linked with erythropoietin production could be proven, this case might be one with inappropriate idiopathic erythropoietin production after 13 years of hemodialysis, the longest duration of dialysis in the literature before erythrocytosis was observed.

Topics: Erythropoietin; Female; Humans; Kidney Failure, Chronic; Middle Aged; Obesity; Polycystic Kidney Diseases; Polycythemia; Renal Dialysis; Time Factors

Dose requirements of epoetin vary considerably among patients with end-stage renal disease (ESRD), whereas determinants of epoetin sensitivity are poorly understood. Fat mass is an important source of adipokines, including interleukin 6 (IL-6), which is associated with decreased epoetin sensitivity. Furthermore, the adipokine leptin stimulates human erythroid development in vitro. In the present study, we investigate the impact of fat mass and leptin level on epoetin sensitivity in patients with ESRD.. One hundred sixty-six patients with ESRD (107 men; 64%) with a mean age of 56.9 +/- 0.9 years were studied in a post hoc cross-sectional analysis. Body composition was analyzed by dual-energy X-ray absorptiometry and correlated with serum markers of inflammation and leptin (analyzed by enzyme-linked immunosorbent assays), as well as with epoetin dose, in international units administered per week (IU/wk). To correct for differences in body mass and hemoglobin (Hb) levels, epoetin sensitivity was approximated as epoetin/Hb ratio, ie, epoetin dose per unit of Hb (IU/wk/g/dL) and epoetin/Hb/kg ratio, ie, epoetin dose per unit of Hb and kilogram of patient body weight (IU/wk/Hb/kg).. Patients were divided into 3 groups according to epoetin/Hb/kg ratio (no-epoetin group, low-epoetin group, and high-epoetin group). The 3 groups had significantly different serum levels of high-sensitivity C-reactive protein (hsCRP; median, 8.6 versus 3.1 and 8.0 mg/L, respectively; P < 0.05), neopterin (median, 112.4 versus 94.3 and 96.1 ng/L, respectively; P < 0.05), and IL-6 (median, 6.8 versus 4.1 and 6.5 ng/mL, respectively; P < 0.05). Significant between-group differences also were found in fat mass and leptin levels (median, 14.8 versus 10.5 and 7.9 ng/mL, respectively; P = 0.02). In univariate analyses, significant relationships between epoetin sensitivity indices, leptin levels, and levels of the inflammatory markers hsCRP and IL-6 were found. In a multivariate stepwise regression model, log ferritin, parathyroid hormone, log leptin, log IL-6, and polycystic kidney disease were significantly associated with the epoetin/Hb ratio.. The present study shows that leptin level may be a predictor of epoetin sensitivity. The effect could be either direct stimulation of erythropoiesis or indirect stimulation by associated adipokines. Although truncal fat is associated with secretion of proinflammatory cytokines, this secretion appears not to have inhibitory effects on epoetin sensitivity in the presence of high leptin levels.

Topics: Adipose Tissue; Anemia; Body Composition; C-Reactive Protein; Cross-Sectional Studies; Darbepoetin alfa; Drug Resistance; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Organ Size; Polycystic Kidney Diseases; Renal Dialysis; Sweden

Topics: Anemia; Drug Resistance; Erythropoietin; Female; Humans; Hypothyroidism; Middle Aged; Polycystic Kidney Diseases

Recombinant human erythropoietin (rHuEPO) is primarily used for patients with anemia associated with end-stage renal disease. We evaluated the efficacy of EPO gene therapy using adenovirus vector for chronic renal failure mice expressing severe renal anemia.. Recombinant HuEPO gene transfer to mesothelial cells was performed in vitro and in vivo. Recombinant replication-deficient adenoviruses containing rHuEPO cDNA (AdCMVEPO), E. coli lacZ gene (AdCMVlacZ), or an nonexogenous gene (AdNull as control vector) driven by the cytomegalovirus promotor/enhancer were constructed. The oligosaccharides associated with the rHuEPO from AdCMVEPO-treated mesothelial cells were analyzed. For in vivo study, the DBA/2FG-pcy mouse, a model for human autosomal recessive polycystic kidney disease resulting in chronic renal failure with progressive anemia, was used.. The sialylated oligosaccharides associated with the rHuEPO produced in AdCMVEPO-treated mesothelial cells occupied 78 +/- 0.7% of the total oligosaccharide pool. A single intraperitoneal administration of AdCMVEPO induced rHuEPO synthesis in the peritoneal cells and a marked increase in erythrocyte production. The maximal increase in hematocrit (43 +/- 4%) was observed on day 28, and it remained elevated for 40 days.. These results indicate that intraperitoneal administration of AdCMVEPO improves renal anemia in mice with chronic renal failure and that the mesothelial cell is an appropriate target cell for gene transfer.

Topics: Adenoviridae; Anemia; Animals; Blotting, Northern; Blotting, Western; Cell Line; CHO Cells; Cricetinae; Erythropoietin; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Hematocrit; Humans; Mice; Mice, Inbred CBA; Mice, Mutant Strains; Polycystic Kidney Diseases; Rats; Recombinant Proteins

Topics: Anemia; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Middle Aged; Polycystic Kidney Diseases; Recombinant Proteins

A 49-year-old woman had been on hemodialysis for 18 years. She presented with left back pain and macrohematuria. Radiologic studies demonstrated a left renal tumor with acquired cystic disease of the kidney. Her serum erythropoietin (EPO) level was 78.4 U/L despite no history of EPO supplementation. Left radical nephrectomy was performed. Pathologic examination revealed EPO-producing renal cell carcinoma. After surgery, the patient's serum EPO level decreased markedly to 15.1 U/L. The measurement of serum EPO levels may be useful for detecting and monitoring a recurrence of renal cell carcinoma with acquired cystic disease of the kidney in patients on long-term hemodialysis.

Topics: Carcinoma, Renal Cell; Erythropoietin; Female; Humans; Immunohistochemistry; Kidney Neoplasms; Middle Aged; Nephrectomy; Polycystic Kidney Diseases; Tomography, X-Ray Computed

Concentration of erythropoietin (Epo) and iron reserves (IR) belong to the essential factors determining erythropoiesis in haemodialysis patients. Patients on dialysis with acquired kidney disease (ACKD+) can control anaemia better than patients without acquired kidney disease (ACKD-). Therefore we decided to check if plasma Epo levels and IR differ significantly in both groups of patients. Forty chronically haemodialyzed patients after ultrasound diagnosis were divided into 18 patients (45%) with ACKD+ and 22 (55%) without ACKD-. In both groups of patients we compared their plasma levels of Epo and IR. Plasma erythropoietin and ferritin levels were measured by enzymatic immunoassay. Iron reserves were estimated by the formula: IR = 400 x [ln (ferritin)-ln (50)]. In the ACKD+ group 72% of patients and in the ACKD- group 32% of patients did not require rHu Epo therapy. Plasma levels of erythropoietin and iron reserves did not differ significantly between ACKD+ and ACKD- patients. There must be also other factors than erythropoietin levels and iron reserves regulating erythropoiesis in these patients.

Topics: Adult; Erythropoietin; Female; Humans; Iron; Male; Middle Aged; Polycystic Kidney Diseases; Renal Dialysis

We studied serum concentrations of erythropoietin (EPO) in the cord blood of 31 newborns. In patients with renal agenesis (n = 6), the EPO levels were 68.2 (23-177) mU/ml (median, range). These values are clearly above EPO levels in the reference groups (median/range: < 30 weeks 11.0 (5.5-17.5) mU/ml; 30-32 weeks 18.1 (5.5-136) mU/ml; 33-34 weeks 17.7 (8.3-423) mU/ml; 35-37 weeks 17.3 (5.5-272) mU/ml; > or = 38 weeks 17.8 (8.7-40.3) mU/ml). Neonates with polycystic kidney diseases (n = 12, EPO 23.5 (9.7-491) mU/ml) and with severe bilateral hydronephrosis due to obstructive uropathy (n = 13, 18.6 (7.5-30.7) mU/ml) showed no difference to the reference groups. In all groups there were only slight differences in haemoglobin/haematocrit values.. In spite of renal agenesis and severe congenital kidney diseases, erythropoiesis is sufficiently maintained during fetal life. The liver of congenitally kidney-damaged fetuses is sufficiently able to compensate the reduction in--or lack of--renal EPO production.

Topics: Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobinometry; Humans; Hydronephrosis; Infant, Newborn; Kidney; Male; Polycystic Kidney Diseases; Reference Values

Post-transplant erythrocytosis (PTE) has been increasingly recognized as a complication of kidney transplantation, and several risk factors have been defined. Recent evidence suggests renal function may also play a role in hematological recovery after transplantation and risk of PTE. In this study of kidney transplant recipients (n = 123), simultaneous Tc99m DTPA GFR (n = 710) and hemoglobin levels were compared with possible clinical determinants. The frequency histogram of post-transplant hemoglobin was bell-shaped and continuously distributed above and below the arbitrary definition of PTE, suggesting that PTE is not a separate disease entity. Hemoglobin reached a plateau at 12 months after transplantation and was correlated with isotopic GFR (r = 0.46, p < 0.001). This consistent and statistically independent relationship became prominent 3 months after transplantation. Hemoglobin was independently predicted by multivariate analysis by time after transplantation, presence of polycystic renal disease, greater serum albumin and reduced serum urea (which in turn were reflected by number of infective and rejection episodes), shorter kidney anastomosis time and a higher GFR, but not by immunosuppressive therapy. Rejection or infection episodes impaired hematological recovery. The independent determinants of GFR included hematological recovery. The independent determinants of GFR included hemoglobin level, kidneys from young, male donors, fewer HLA-DR mismatches and rejection episodes, shorter time on dialysis and greater azathioprine dose. Renal function was not altered by therapeutic phlebotomy. Determination of hemoglobin level by both donor and recipient variables supports the relevance of tubular and glomerular function in control of erythrocystosis after renal transplantation. A role for renin-angiotensin mediation in the alteration of intraglomerular hemodynamics and erythropoietin secretion is postulated.

Topics: Adult; Erythropoietin; Female; Glomerular Filtration Rate; Graft Rejection; Hemoglobinometry; Histocompatibility Testing; Humans; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Male; Middle Aged; Polycystic Kidney Diseases; Polycythemia; Postoperative Complications; Renin-Angiotensin System; Risk Factors; Treatment Outcome

Topics: Adult; Aged; Erythropoiesis; Erythropoietin; Female; Glomerular Filtration Rate; Glomerulonephritis; Hemoglobinometry; Humans; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Nephritis, Interstitial; Polycystic Kidney Diseases

Two anephric patients in the course of one year erythropoietin therapy improved their anemic status without changes in Mean Arterial Blood Pressure. The discordant time course behaviour of hematocrit and blood pressure points to the importance of residual renal tissue for blood pressure to develop during erythropoietin therapy in the renoprival status.

Topics: Adult; Anemia; Blood Pressure; Combined Modality Therapy; Erythropoietin; Female; Glomerulosclerosis, Focal Segmental; Hematocrit; Humans; Hypertension; Kidney; Male; Nephrectomy; Polycystic Kidney Diseases; Renal Dialysis; Time Factors

DBA/2FG-pcy mice developed the chronic renal failure by the progressive polycystic formation at five months old. Their bilaterally enlarged kidneys occupied about 15% of the body weight. It was about 9 times larger than the normal kidney of DBA/2N mice. A large number of various-sized cysts appeared in cortex and medulla of bilateral light-yellow kidneys of sponge-like shape. Blood urea nitrogen and creatinine increased. Red blood cells (746 +/- 39 x 10(4)/mm3), hemoglobin (8.8 +/- 0.4 g/dl) and hematocrits (31.1 +/- 1.5%) were lower than those of normal control mice. Serum erythropoietin level and reticulocytes did not increase. In addition, the treatment with exogenous erythropoietin improved the anemia in DBA/2FG-pcy mice. It was suggested that the anemia in DBA/2FG-pcy mice was due to the disorder of erythropoietin production caused by the progressive polycystic formation in kidneys.

Topics: Anemia; Animals; Blood Urea Nitrogen; Creatinine; Erythrocyte Count; Erythropoietin; Female; Hematocrit; Hemoglobins; Kidney; Male; Mice; Mice, Inbred DBA; Polycystic Kidney Diseases; Recombinant Proteins; Reticulocytes; Rodent Diseases

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.

Topics: Anemia; Animals; Blood Urea Nitrogen; Bone Marrow; Colony-Forming Units Assay; Disease Models, Animal; Erythrocyte Count; Erythropoietin; Hematocrit; Kidney; Mice; Osmotic Fragility; Polycystic Kidney Diseases; Recombinant Proteins

Topics: Aldosterone; Anemia; Blood Pressure; Enalapril; Erythropoietin; Hematocrit; Humans; Hypertension; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Polycystic Kidney Diseases; Renal Dialysis; Renin-Angiotensin System

Acquired cystic kidney disease has been related to improvement of anemia in dialysis patients. It has been suggested that this could be due to erythropoietin production by the cysts. We studied 110 patients, 58 on hemodialysis and 52 on continuous ambulatory peritoneal dialysis, with an age of 48.6 +/- 14.78 years and a time on dialysis of 44.5 +/- 35.53 months. A renal echography was performed in every patient, evaluating presence and number of cysts. These findings were related to the blood levels of hemoglobin, ferritin, and erythropoietin as well as to the number of transfusions prescribed during the year of the study. The serum erythropoietin level was 18.23 +/- 12.14 U/l in hemodialysis patients, 15.04 +/- 12.35 in patients on continuous ambulatory peritoneal dialysis, and 12.4 +/- 4.7 U/l in the control group. Hemoglobin and erythropoietin were significantly higher in patients with polycystic kidney disease. Patients without cysts had the lowest levels of hemoglobin and erythropoietin, although no significant difference was found in those with multiple bilateral cysts or in those with 1-3 isolated cysts.

Topics: Anemia; Blood Transfusion; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Polycystic Kidney Diseases; Renal Dialysis

The treatment of renal failure includes dietary modification, drug treatment and hormonal supplements as well as renal transplantation. The rationale for these therapies and the associated problems likely to present to the GP are given practical consideration.

Topics: Acute Kidney Injury; Erythropoietin; Humans; Immunosuppressive Agents; Kidney Transplantation; Polycystic Kidney Diseases

Erythropoietin (EPO) formation in kidneys of 18 patients with autosomal dominant polycystic kidney disease (ADPKD) was investigated. In 12 patients on hemodialysis and in 6 patients with preterminal renal failure serum, EPO was 29 +/- 7 and 16 +/- 1.5 mU/ml and hemoglobin concentrations were 11.0 +/- 0.6 and 12.7 +/- 1.2 g/dl, respectively. Cyst fluid from a total of 357 renal cysts was obtained by either in vivo aspiration or immediately after nephrectomy. The cysts contained variable concentrations of bioactive EPO from undectable values up to 3.2 U/ml. A pronounced enrichment of EPO was observed in cysts with sodium concentrations greater than 100 mmol/liter, suggesting an association with proximal tubular malformations. The EPO concentrations in the cysts were neither correlated with the protein concentration nor with the oxygen pressure of the cyst fluid. Using a cDNA probe for human EPO, mRNA for EPO was localized in stroma cells of the cyst walls by an in situ hybridization technique. Our findings suggest that single interstitial cells juxtaposed to proximal tubular cysts may produce EPO independent of the oxygen pressure inside the cysts, which ameliorates the anemia during end-stage polycystic kidney disease.

Topics: Animals; DNA; DNA Probes; Electrolytes; Erythropoietin; Female; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Mice; Middle Aged; Nucleic Acid Hybridization; Oxygen; Polycystic Kidney Diseases; Proteins; Radioimmunoassay; Renal Dialysis

Radioimmunoassays for erythropoietin are limited so far to a few specialized laboratories and this requires transport and storage of samples. We therefore tested the stability of immunoreactive erythropoietin in serum and plasma samples obtained from a uremic and a nonuremic anemic patient. No significant change in the concentration of immunoreactive erythropoietin was found in either serum or plasma samples for up to 14 days of storage. This type of stability was observed no matter whether the samples were stored at room temperature, 4 degrees C, or -20 degrees C. There was no difference between the estimates of erythropoietin in serum and heparinized plasma. Validity of the radioimmunoassay used in this study was demonstrated by parallelism of dilution curves of test specimens and the 2nd International Reference Preparation for erythropoietin and by a close correlation between the immunoreactivity and the bioactivity of the hormone, as assessed in the same samples by the exhypoxic polycythemic mouse bioassay. In conclusion the data obtained clearly indicate that the necessity of storage and transport of clinical samples does not limit the practicability of the radioimmunoassay for erythropoietin.

Topics: Anemia, Aplastic; Blood Preservation; Erythropoietin; Freezing; Humans; Kidney Failure, Chronic; Polycystic Kidney Diseases; Radioimmunoassay; Reference Standards; Renal Dialysis

Serum erythropoietin levels were randomly collected and measured by a sensitive radioimmunoassay in a hemodialysis population. For analysis, the patients were divided into two groups: those with polycystic kidney disease and those with other kidney diseases. In 12 polycystic kidney disease patients, serum erythropoietin was 22.6 +/- 2.4 mU/ml, hematocrit 29.7 +/- 1.0%, and absolute reticulocyte count 17.0 +/- 4.1 X 10(4)/microliters. In 24 other kidney disease patients, serum erythropoietin was 12.4 +/- 0.7 mU/ml, hematocrit 21.2 +/- 0.8%, and reticulocyte count 7.5 +/- 1.5 X 10(4)/microliters. Serum erythropoietin was 18.5 +/- 0.7 mU/ml in normal controls. Polycystic kidney disease patients manifested higher hematocrit, reticulocyte counts, and serum erythropoietin levels when compared to other kidney disease patients (p less than 0.01). The data suggest (1) an inappropriately low serum erythropoietin level for the severity of anemia in uremic hemodialysis patients and (2) that greater availability of erythropoietin results in more effective erythropoiesis, even in the uremic environment.

Topics: Adolescent; Adult; Anemia; Erythropoietin; Humans; Kidney Diseases; Kidney Failure, Chronic; Middle Aged; Polycystic Kidney Diseases; Renal Dialysis

Topics: Erythropoietin; Humans; Kidney Diseases, Cystic; Kidney Neoplasms; Polycystic Kidney Diseases

Topics: Adenocarcinoma; Aged; Erythropoietin; Female; Humans; Kidney Diseases; Kidney Failure, Chronic; Kidney Neoplasms; Kidney Transplantation; Male; Middle Aged; Polycystic Kidney Diseases

Topics: Cerebellar Neoplasms; Cerebral Ventriculography; Erythropoietin; Gastrointestinal Hemorrhage; Hemangiosarcoma; Humans; Male; Middle Aged; Polycystic Kidney Diseases; Polycythemia; Urography

Topics: Diagnosis, Differential; Epoetin Alfa; Erythropoietin; Humans; Kidney; Polycystic Kidney Diseases; Polycythemia; Polycythemia Vera

Topics: Epoetin Alfa; Erythrocyte Count; Erythropoietin; Humans; Hydronephrosis; Hypertension; Kidney; Nephrectomy; Polycystic Kidney Diseases; Polycythemia

Topics: Epoetin Alfa; Erythropoietin; Humans; Hydronephrosis; Kidney Diseases; Plasma; Polycystic Kidney Diseases; Polycythemia