Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme-immunoassay was developed to evaluate the presence of anti-erythropoietin antibodies in plasma samples obtained from renal failure patients treated with recombinant human erythropoietin (rh-EPO). The assay was specific and reproducible. Normal donors had no antibodies to EPO, while 67% of treated patients were positive to the assay. While the specificity of anti-EPO IgG antibodies was high, their affinity for the antigen was low. This finding can be explained by the very small differences in the structure of rh-EPO compared to that of natural EPO. The assay described could be useful in evaluating the long-term effects of rh-EPO treatment on the control of anaemia in renal failure patients.
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PMID:Detection of anti-erythropoietin antibodies in haemodialysis patients treated with recombinant human-erythropoietin. 1067 83

The mortality among end-stage renal failure (ESRF) patients undergoing renal replacement therapy (RRT) remains high. An important proportion of these patients die shortly after the initiation of RRT. The present study aims to determine the best predictors for the early mortality in a group of 140 ESRF patients who initiated RRT between october 96 and december 99. The mean age of the study group was 61 +/- 13 years, and the mean follow-up time was 20 +/- 12 months. Diabetic nephropathy was the most prevalent etiology of renal failure (30%). The following data, collected immediately before the initiation of RRT, were included as independent variables: demographic and clinical characteristics, including the nutritional status established by the Subjective Global Assessment (SGA), follow-up time in the predialysis clinic (less or longer than 3 months), EPO therapy, vascular access, renal function (creatinine and urea clearances, and Kt/V urea), hematological and biochemical data including serum albumin, bicarbonate, transferrin, PTH and C-Reactive protein, as well as the protein catabolic rate and the percent of lean body mass normalized for ideal body weight, calculated from the 24 h total urine excretion of nitrogen and creatinine. The Cox proportional hazard regression model, stratified for an age over or less than 65 year, was utilized to determine the best predictors for the mortality during the study period. Sixty percent of patients had at least one comorbid condition, and 35% had cardiovascular diseases. Mild-moderate or severe malnutrition was observed in 48% of patients. The creatinine clearance and Kt/V urea before the initiation of RRT were: 9.50 +/- 2.64 ml/min/1.73 m2 and 1.47 +/- 0.44, respectively. Forty-one patients died during the study period (annual death rate: 17%). The best predictor of mortality was the nutritional status assessed by the SGA (OR: 2.32, IC 95% 1.54-3.48, p < 0.0001). In a second analysis in which the SGA was removed from the model, the previous history of cardiovascular diseases (OR: 2.07, CI 95%: 1.06-4.06, p = 0.032), and the percent of lean body mass/ideal weight (OR: 0.96; IC 95%: 0.93-0.99; p = 0.042), proved to be the best predictor of mortality. In conclusion, nutritional indices prior to the initiation of RRT, and the previous history of cardiovascular diseases were the best predictors of the early mortality in this unselected population on dialysis. Because nutritional status appeared to be a marker of the severity of the comorbid conditions, a better control of the number and severity of these comorbid conditions may be the best way for reducing the mortality in patients on RRT.
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PMID:[Predictors of early death during dialysis]. 1147 8

High concentration of intraerythrocyte ATP is a common phenomenon in patients with chronic renal failure (CRF). It is likely that this is a result of increased plasma concentration of adenine--one of purine moiety donors which is necessary for ATP synthesis. In the present study we monitored changes of both adenine and intraerythrocyte ATP concentration during renal replacement therapy. We have also estimated the influence of erythropoietin treatment. 4 groups of patients were included into the study: 22 patients with CRF, 22 patients on maintenance hemodialysis treatment (11 patients with EPO therapy), 19 patients after kidney transplantation (7 patients with insufficiency of transplanted kidney) and 26 healthy volunteers served as a control group. The measurements were performed in plasma and erythrocyte extracts using HPLC. Significant decrease of high plasma adenine concentration was observed after both HD session and successful kidney transplantation, however the achieved values were still higher than in healthy volunteers. Kidney transplantation resulted in a permanent decrease of plasma adenine concentration, but along with the deterioration of transplanted kidney function, the plasma adenine concentration reincreased. Also, it started to increase right after HD session had ended. On the other hand, the intraerythrocyte concentration of adenine and ATP after successful kidney transplantation and single HD session came back to normal values. Also in this case, along with the deterioration of transplanted kidney function, both studied parameters reincreased. We have not observed any significant influence of erythropoietin treatment on studied adenine nucleotide concentration in hemodialysis patients. The present study confirms the strong interrelationship between the adenine nucleotide metabolism abnormalities and the advancement of renal failure. The abnormalities intensify along with the disease progression and the renal replacement therapy results in partial their correction.
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PMID:[Renal replacement therapy results in correction of plasma and erythrocyte adenine nucleotide abnormalities in patients with chronic renal failure]. 1202 34

1,019 adult patients with terminal renal failure were treated with dialysis (D) in the first part of the year 2000 in the Republic of Macedonia. 1,010 patients (99%) were treated with chronic intermittent (maintenance) hemodialysis (HD) while nine patients (1%) were on continuous ambulatory peritoneal dialysis (CAPD). For the children, a special peritoneal dialysis program was developed; 509 patients per million of the population (PMP) were on dialysis. The Republic of Macedonia is, therefore, among those central and eastern European countries with a higher PMP number in the treatment of end-stage renal disease, following Croatia, the Czech Republic and Slovenia. The patients were treated at 18 Centers in a network of HD Centers at a distance of 30-50 km. from their place of residence in order to facilitate their access to treatment and to work. All patients who have had symptoms indicating need for treatment with D were accepted for treatment. The government payed all the expenses of the treatment and the salaries of the staff. 56% were male and 44% were female patients. The youngest patient was aged 9 and the oldest was 82 years old. There has been an increase in the age of the patients on D as well as an increase in their number. In 1993 we had 727 patients being treated with D, and now we have 1,019 with a constant increase in the number of patients with ESRD and a need for D and renal transplantation. Mortality per year at the different Centers ranged from 8-19% in 1999 and the average is 12%. Glomerulonephritis (GN)--both primary and secondary--is the main cause of renal failure (RF) in some Centers up to 45%. Tubulo-interstitial disease follows GN. ADPKD patients constitute 9.4% with a difference among the Centers of 3-29%, and diabetic nephropathy is found in 10%, 5-15% in different Centers. 11-61% of patients have an unknown etiology. 352 patients are on treatment with human recombinant erythropoietin (rhuEPO) - in some Centers up to 60%. The mode of application was subcutaneous and the initial dose is 20 U/kg body weight and the mean maintenance dose of EPO per patient weekly is 4,000 U. The Cimino-Brescia arteriovenous fistula is being applied as a standard vascular access. The survival rate of our patients treated with maintenance HD at 5 years was 58%. CAPD and particularly renal transplantation are to be further developed as alternative methods in treating terminal renal failure.
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PMID:Dialysis in adults in year 2000 in the Republic of Macedonia. 1207 35

The aim of this study was to determine the effect of rh-EPO on the redox-sensitive transcription factor (NF-kappaB) in vivo and in vitro. Ten patients (7 female, 3 male), mean age 69.2 +/- 11 years, with end-stage renal failure and anemia prior to initiation of regular hemodialysis were enrolled and divided into 2 groups (group A "good responder", 7 patients and group B "poor responder", 3 patients) in accordance to the response to rh-EPO therapy. Nuclear binding activity of NF-kappaB was determined in ex vivo isolated mononuclear cells before, 4 and 8 weeks after onset of regular hemodialysis and rh-EPO therapy by electrophoretic mobility shift assays (EMSA). In group A, a reduction of NF-KB binding activity from 100% to 56 +/- 6% was observed within the first four weeks of rh-EPO treatment, while mean hemoglobin rose from 8.2 +/- 0.4 g/dl to 11.1 +/- 0.2 g/dl. However, this effect was abrogated after another 4 weeks of treatment when NF-kappaB signal increased back to 85.2 +/- 10.6% despite consistent mean hemoglobin level of 11.3 +/- 0.4 g/dl. Group B demonstrated a slight increase of NF-kappaB signal from 100% to 129 +/- 18.5%, while mean hemoglobin only moderately rose from 7.6 +/- 0.3 g/dl to 8.3 +/- 0.1 g/dl within the first 4 weeks, and it further rose to 180 +/- 45% after 8 weeks of treatment, while mean hemoglobin (9.5 +/- 0.1 g/dl) remained low. The NF-kappaB binding activity differed significantly when comparing both groups (p = 0.007). Binding activity of Oct-1, serving as control, did not change notably in either group (p = 0.34). In vitro studies showed that rh-EPO did not directly affect NF-KB binding activity in THP-1 cells. However, coincubation of THP-1 cells with erythrocytes led to a reduction of NF-kappaB binding activity only in THP-1 cells with a hemoglobin level adjusted to 11 g/dl compared to 8 g/dl in the presence of rh-EPO. In vivo and in vitro data implicate a complex interaction between rh-EPO, stimulated RBC and the redox-sensitive transcription factor NF-kappaB in mononuclear cells.
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PMID:Erythropoietin-mediated decrease of the redox-sensitive transcription factor NF-kappaB is inversely correlated with the hemoglobin level. 1235 90

We describe a patient with end-stage renal failure (ESRF) who developed anti-erythropoietin (anti-EPO) antibodies and pure red-cell aplasia (PRCA) after using Eprex (Janssen-Cilag, Sydney). Anti-EPO antibodies were detected with an immunoprecipitation technique and were shown to inhibit erythropoiesis in vitro. Antibody levels waned upon ceasing Eprex. The patient required transfusions for 21 months then recovered after immunosuppression.
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PMID:Recovery of pure red-cell aplasia secondary to antierythropoietin antibodies after cessation of recombinant human erythropoietin. 1451 Dec 2

The rate of decline of renal function (RDRF) in the pre-end stage renal disease setting (pre-ESRD) is highly variable. Several factors have been involved as potential modifiers of renal failure progression. This retrospective study attempts to establish which were the main determinants of the RDRF in pre-ESRD patients followed in the predialysis consult. The study group consisted of 230 patients with pre-ESRD not yet on dialysis who were referred to the predialysis consult from January 1998 to July 2002. The mean follow-up time per patient was 356 days. RDRF was assessed as delta of the average of creatinine and urea clearances (CrCl-UCl). Data obtained at time of referral to the predialysis consult were analyzed as potential predictors of the subsequent RDRF. These independent variables included: demographics, comorbid conditions, main hematological and biochemical data, antihypertensive and statin treatment, mean blood pressure, and CrCl-UCl at time of referral. The predictors of delta CrCl-UCl were determined by multiple linear regression analysis. The determinants of the survival without dialysis were established by the Cox regression hazard model, adjusted to renal function at time of referral. Mean CrCl-UCl at time of referral was 10.98 +/- 2.58 ml/min/1.73 m2, and mean delta CrCl-UCl was -0.37 +/- 0.46 ml/min/1.73 m2/month. Patients with diabetic nephropathy and chronic glomerulonephritis had the fastest RDRF, while patients with ischemic nephropathy and chronic interstitial nephritis had the slowest RDRF. Seventy-five patients (46%) required EPO therapy. The best determinants of delta CrCl-UCl were: the 24-hour proteinuria (p < 0.0001), and the hematocrit at time of referral (p = 0.0024). The best determinants of the survival rate without dialysis during the study period were: the proteinuria (in g/24 hours) (R 1, 16; p < 0.0001), the hematocrit at time of referral (OR: 0.88; p < 0.0001), the treatment with EPO (OR: 0.59; p = 0.02), and the diagnosis of diabetes mellitus (OR: 1.59; p = 0.01). In conclusion, apart from the rate of proteinuria, which could represent the best marker of the RDRF in chronic renal diseases, the development of anemia was associated with faster decline in renal function.
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PMID:[Progression of renal insufficiency in the pre-end-stage renal disease setting]. 1500 86

We reviewed clinical and molecular data of 23 consecutive unrelated patients affected by paroxysmal nocturnal hemoglobinuria (PNH) (19 with hemolytic PNH, 3 with aplastic anemia/PNH, and 1 with myelodysplasia/PNH syndrome) with a mean follow-up of 11.8 years. Five patients had thrombotic episodes, and 10 needed regular blood transfusions; 2 died for cerebral hemorrhage and kidney failure, and 2 spontaneously recovered from PNH. Twenty different PIG-A gene mutations were detected in 21/23 patients: 15 frameshift, 1 splicing, 2 nonsense, and 2 missense mutations. Two mutations (DelG341 and IVS2 +1g-a) were detected twice. A PIG-A mutated clone was also revealed in the two patients in complete clinical remission. One patient with aplastic anemia/PNH syndrome was treated with two courses of antilymphocyte globulin and cyclosporin with partial sustained response. Six patients were given rHu-EPO 150 U/kg/day s.c. for at least 6 months: one became transfusion-independent for 8 months and then discontinued treatment for clinical complications; one displayed a mean rise of Hb of 1.5 g/dL and is currently maintaining Hb levels higher than 9 g/dL after 54 months of therapy. Mutation specific quantitative-competitive PCR showed that the rise of hemoglobin was related to an increase of PIG-A negative molecules, suggesting that the efficacy of rHu-EPO therapy may be due to the stimulation of the abnormal clone.
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PMID:Clinical and molecular aspects of 23 patients affected by paroxysmal nocturnal hemoglobinuria. 1530 4

An 80-year-old man with chronic renal failure (CRF) had pure red cell aplasia (PRCA) 9 months after starting the subcutaneous administration of recombinant human erythropoietin alfa (rHuEPO-alpha). Owing to the advanced renal failure, conventional immunosuppressive therapies were not practicable. It was decided to administer rituximab (4 cycles of 375 mg/m2/wk). PRCA was treated successfully with rituximab. The administration of rHuEPO-alpha then was resumed via the intravenous route with a satisfactory correction of anemia (12 months after the EPO-alpha rechallenge the patient is still transfusion independent). To the authors' knowledge, this is the first report of (1) a successful treatment with rituximab with CD20 depletion in a CRF patient with PRCA and (2) a successful intravenous resumption of the same rHuEPO-alpha.
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PMID:Successful resumption of epoetin alfa after rituximab treatment in a patient with pure red cell aplasia. 1538 28

Anemia is an important cause of morbidity in patients suffering from chronic renal failure, and erythropoietin is a milestone of anemia treatment. Various factors may cause erythropoietin resistance. Herein, we describe the case of 32-year-old man who presented with anemia and weakness. He developed progressive renal failure secondary to recurrent kidney stones. One year before admission, he developed anemia for which he had been treated with erythropoietin. However, the anemia persisted. Examination of bone marrow biopsy specimen showed that the marrow was extensively replaced with oxalate crystals and fibrous connective tissue with severe decrease of hematopoietic cells. To the best of our knowledge, our patient represents the first case in the literature describing the association between the oxalate deposition and EPO resistance.
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PMID:Erythropoietin resistance as a result of oxalosis in bone marrow. 1590 2


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