Effectiveness of low-dose erythropoietin in predialysis chronic renal failure patients

Recombinant human erythropoietin (rHuEpo) has been shown tobe both effective and usually safe in patients with chronicrenal failure who have not yet reached the stage requiring dialysis.There are, however, disturbing reports on the possibility ofdeterioration of the reserve renal function in association withrHuEpo therapy. Most of the published studies have used rHuEpoin doses of 50–150 U/kg three times weekly subcutaneously.An open-label trial of rHuEpo therapy was conducted on 21 patientswith chronic renal failure treated sequentially at a referralhospital, rHuEpo was used in doses of 50 U/kg twice weekly for4 weeks followed by 25 U/kg twice weekly for 8 weeks subcutaneously,a regimen substantially lower than current recommendations.This was associated with a gentle but significant increase inhaematocrit (P<0.05) and haemoglobin (P<0.05), while theserum creatinine and the reciprocal of the creatinine remainedstable, with a tendency to improve rather than worsen (P=0.06).We conclude that there is no need to aim at a rapid increasein haematocrit and haemoglobin by rHuEpo therapy; rather a gentleincrease using modest doses is both effective and safe.     

A study of erythropoiesis inhibitory factors in chronic renal failure sera

Summary: Three separate high molecular weight fractions, designated as FI, FII and FIII, were isolated from sera of chronic renal failure (CRF) patients by precipitate with ammonium sulfate of different concentrations and DEAE celluose. All fractions had obvious suppressive effect on red blood cell growth, both erythroid colony (CFU-E) and BFU-E in vitro , but the maximal inhibitory rate that may be found in Fl or in FII and FIII depends entirely on individuals. the study also showed that none of these fractions was a homogeneous substance in SDS-PAGE electrophoresis. As well, a close correlationship between serum erythropoietin level and the inhibitory rate of the isolated fractions was observed. It is suggested that the inhibitory factors might exist in CRF sera and play a role in triggering the anaemia of CFR.     

Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure.

BACKGROUND: The bone abnormalities that lead to symptomatic renal osteodystrophy commence early in the course of renal failure, but the optimal time to start treatment needs clarifying. The present study examined the effect of alfacalcidol treatment on bone metabolism and bone density in patients with pre-dialysis chronic renal failure (CRF) in a prospective, randomized, placebo-controlled double blind design. METHODS: Repetitive measures of bone mineral density (BMD) estimated by dual energy X-ray absorptiometry and plasma levels of biochemical markers of bone turnover [osteocalcin, bone alkaline phosphatase, propeptide of type-I collagen (PICP) and telopeptide of type-I collagen] and parameters of calcium homeostasis were performed in 36 patients with a glomerular filtration rate (GFR) of 6-60 ml/min. RESULTS: A significant difference in BMD between the treatment groups in favour of the alfacalcidol-treated patients was found in the spine (4.2%), the femoral neck (4.9%) and the total femur (3.0%) (P<0.05). In the alfacalcidol group, plasma levels of parathyroid hormone 1-84 decreased from baseline values by 47+/-9%, and p-osteocalcin and bone alkaline phosphatase decreased by 24+/-9% and 48+/-8%, respectively (P<0.05). In the placebo group, PICP increased by 32+/-26% (P<0.05). No significant changes were found in plasma levels of vitamin D metabolites. GFR decreased significantly from baseline values in the alfacalcidol group (by 28+/-4 ml/min) and in the placebo group (by 26+/-5 ml/min) (P<0.05), with no difference being detected between the groups. CONCLUSIONS: Long-term treatment with alfacalcidol is safe and might be beneficial for the preservation of bone mass in the pre-dialysis stages of CRF, most likely through a reduction in bone turnover as estimated from the changes of the biochemical bone markers.     

Uraemic symptoms, nutritional status and renal function in pre-dialysis end-stage renal failure patients.

BACKGROUND: Deciding on the right moment to initiate dialysis and finding the best method to establish this critical stage of chronic renal failure are both controversial issues. This study attempted to address this subject by correlating a uraemic score with the most common clinical methods for assessing renal function in pre-dialysis chronic renal failure (end-stage renal disease, ESRD) patients. METHODS: The study group consisted of 201 non-selected ESRD patients. A uraemic score, composed of the uraemic symptoms, the subjective global assessment of nutritional status, serum albumin concentration, and protein catabolic rate normalized for ideal body weight, was taken as a clinical marker of uraemic toxicity. Correlations that best fit this uraemic score with creatinine clearance (Ccr), the arithmetic mean of Ccr, urea clearance (Ccr-Cu) and Kt/V urea were then investigated. RESULTS: Thirty-six per cent of patients had malnutrition. By multiple logistic regression analysis, the presence of comorbidity, Ccr-Cu and haematocrit were the best determinants of malnutrition. The correlation that best fit Ccr or Ccr-Cu with the uraemic score was a cubic curve (r=0.38, P<0.0001, and r=0.42, P<0.0001, respectively), in which an ascending inflection was observed when Ccr and Ccr-Cu fell below 12-13 and 10 ml/min, respectively. However, the relationship between Kt/V urea and the uraemic score was less predictable, especially in male patients. CONCLUSION: Ccr or Ccr-Cu are reliable methods for establishing the degree of severity of chronic renal failure below which the development of symptoms and malnutrition are highly prevalent. In contrast, Kt/V urea may be a less sensitive and specific method for assessing the severity of uraemia in ESRD patients.     

Endothelin in chronic renal failure.

The aims of the present study were to determine plasma endothelin (ET) in chronically uraemic patients, the renal clearance of endogenous ET in normal dog and man, and the effect of acute volaemic expansion on ET. The mean plasma ET concentration in haemodialysis patients was 57.5 +/- 5 pg/ml before haemodialysis and remained unchanged at 52.5 +/- 5 pg/ml after haemodialysis. They were thus significantly elevated both before and after haemodialysis (P less than 0.01) compared with plasma ET in normal subjects of 20.8 +/- 0.8 pg/ml. There was no evidence of ET clearance across the cuprophane membrane of the dialyser. Resting plasma ET values in the 15 non-dialysed uraemic patients ranged between 20 and 52.5 pg/ml (mean 38.2 +/- 2.3 pg/ml), significantly greater than those observed in controls (P less than 0.01). In CAPD patients, plasma ET was also significantly (P less than 0.01), elevated (63 +/- 10 pg/ml) when compared to controls, and similar to those observed in patients before haemodialysis. In dogs, mean ET did not diminish between the aorta and the renal vein (28.1 +/- 1 versus 28.4 +/- 2 pg/ml). In man mean ET did not significantly decline between the renal artery and the renal vein (17 +/- 3 to 13 +/- 0.8 pg/ml). In the seven healthy subjects who received 2000 ml of isotonic saline intravenously ET remained unchanged (24 +/- 2; 23 +/- 1 and 23 +/- 2 pg/ml before and 1 and 2 h after starting hydration respectively). We have thus shown that plasma ET is elevated in patients with chronic renal failure especially those on dialysis and CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomized study of oral vs intravenous iron supplementation in patients with progressive renal insufficiency treated with erythropoietin.

BACKGROUND: Correction of anaemia as a result of renal failure improves cardiovascular function and also provides significant cognitive and emotional benefits. The most appropriate route for iron supplementation has not been determined for patients with chronic renal failure who are not yet on dialysis. METHODS: Forty-five anaemic patients with progressive renal insufficiency (PRI) were prospectively randomized to receive oral (ferrous sulphate 200 mg tds) or intravenous (300 mg iron sucrose monthly) iron treatment. Erythropoietin (rHuEpo) was simultaneously commenced and the dose adjusted according to a pre-established protocol. RESULTS: There were no significant differences in baseline patient characteristics between the two groups. The average follow-up was 5.2 months. Three patients suffered possible allergic reactions to iron sucrose. Haemoglobin response and changes in red cell hypochromasia were similar in the two groups, but serum ferritin was significantly higher in the intravenous group. The starting dose of rHuEpo could be temporarily discontinued in 43% of patients on oral iron and 33% of patients receiving iron sucrose (NS). rHuEpo was increased after 3 months in 9% of patients on oral iron and 19% of patients receiving iron sucrose (NS). Final doses of rHuEpo were 33.5 (0-66) and 41.6 (0-124) U/kg/week respectively in the oral and intravenous groups (NS). Although gastro-intestinal symptoms were more commonly reported in patients taking oral iron, these were mild according to scores on visual analogue scales. Dietary protein and energy intake were not significantly different in the two groups at 0, 3 and 6 months. CONCLUSIONS: In pre-dialysis patients, the efficacy of monthly 300 mg iron sucrose given intravenously is not superior with regard to haemoglobin response and rHuEpo dose as compared with a daily oral dose of 600 mg of ferrous sulphate or equivalent. Where intravenous iron is preferred, lower doses may help to reduce the incidence of allergic or "free iron" reactions, especially in patients with low body mass.     

Back pain in chronic renal failure.

Back pain in chronic renal failure Patient SK, a 40-yr-old female, resident of Bhagalpur villagein Bihar, India, was operated for gallstones 3 years previously.On pre-operative checkup, mild renal dysfunction was detected.She was asymptomatic for renal disease with serum creatinineof 159 µmol/l (1.8 mg/dl), bland urinary sediment     

Hot bath for the treatment of chronic renal failure

Background: Dialysis and its complications were debated recently. There was lack of an adjuvant renal replacement method to reduce the complications of patients with chronic renal failure and dialysis itself. Materials and methods: In this article, we reviewed the role of thermal sweating in treating of the patients with chronic renal failure, and the role of traditional Chinese medicine in the therapy of chronic kidney diseases. Results: Thermal sweating can reduce interdialytic weight gain and improve the patients’ blood pressure; Chinese herbal medicine can promote the excretion of uremic toxicities and relieve the skin disorders of these patients. Conclusions: Traditional Chinese medicine-mediated hot bath could be one of the adjuvant renal replacement methods.     

Benchmarking iron dextran sensitivity: reactions requiring resuscitative medication in incident and prevalent patients.

BACKGROUND: Reliable information on the incidence of severe reactions to iron dextran is limited. Administration of agents of resuscitation in acute anaphylaxis may serve as a marker to quantify life-threatening adverse drug reactions. METHODS: To determine the incidence of the most serious reactions to intravenous (i.v.) iron dextran, we searched the Gambro Healthcare US medical database for evidence of same-day administration of both i.v. iron dextran and parenteral adrenaline, corticosteroids or antihistamines. We confirmed each case as an iron dextran sensitivity reaction by direct inquiry. We also determined the total reported number of suspected adverse iron dextran reactions. RESULTS: During the 16 month study period, we determined that 1,066,099 doses of i.v. iron dextran were given to 48,509 patients, including 20,213 patients who had not previously received iron dextran (iron dextran na?ve). We identified seven patients who experienced reactions requiring resuscitative agents, all in response to a test dose (five patients) or first therapeutic dose (two patients), and therefore all in the iron-na?ve (incident) group. Thus, we found the incidence of iron dextran reactions requiring resuscitative agents to be 0.035% (7 out of 20,213). No reaction was fatal. In a combined group of incident and prevalent patients, we found 337 total reports of suspected adverse reactions to iron dextran, without regard to severity of reaction, yielding an overall per patient adverse drug event (ADE) rate of 0.69% (337 out of 48,509) and per exposure rate of 0.03% (337 out of 1,066,099). CONCLUSIONS: The incidence of reactions to iron dextran requiring resuscitative medications, per exposure or per patient, is approximately 0.035%. Reactions of this severity occur after either the test dose or first dose of iron dextran.     

Effect of recombinant human erythropoietin on erythropoiesis in homozygous sickle-cell anaemia and renal failure.

The development of end-stage renal disease (ESRD) in patients with sickle-cell anaemia results in increased transfusion dependence, increasing the risk of iron overload. Correction of anaemia with recombinant human erythropoietin (rHuEpo) in dialysis patients might also result in stimulation of haemoglobin F production, which protects against sickling, although very high doses were required to achieve this effect in non-uraemic animals. rHuEpo was administered to three transfusion-dependent patients with ESRD and homozygous sickle-cell disease (initial dose 100 U/kg twice weekly, increasing to 125 U/kg at 6 weeks, and to 150 U/kg at 9 weeks in two patients). This resulted in reticulocytosis and increased circulating erythroid blast-forming units. Total haemoglobin was predominantly HbA (i.e. transfused blood) at the start of the study, reflecting transfusion dependence, but after 3 months' treatment was between 60 and 94% HbS. No sickling crises occurred. Haemoglobin F remained at less than 3% of total haemoglobin. One patient was withdrawn at 10 weeks with CAPD peritonitis. The other two patients completed 12 weeks' treatment without transfusion but final Hb concentrations were 4.5 and 5.5 g/dl. Whether larger doses of rHuEpo will be more successful in managing such patients remains unclear. No effect on HbF production can be expected.     

Quality of sleep in patients with chronic kidney disease.

BACKGROUND: Sleep disorders are common in patients with renal failure on dialysis; however, the prevalence of "poor sleep" in patients with chronic kidney disease (CKD) not yet on dialysis is not known. This study aimed to measure the prevalence of "poor sleep" in CKD patients and to examine the association between quality of sleep and the degree of renal impairment in this population. METHODS: Quality of sleep was measured using the Pittsburgh Sleep Quality Index (PSQI) in 120 prevalent CKD patients. RESULTS: Sixty-three subjects (53%) had "poor sleep" defined as a global PSQI score >5. There was no statistically significant relationship between the global PSQI score and the blood urea nitrogen level (BUN), serum creatinine level or calculated creatinine clearance, but the sleep efficiency component score correlated with BUN (r = 0.19, P = 0.04) and serum creatinine (r = 0.20, P = 0.03). A history of depression was the only independent predictor of "poor sleep" (global PSQI >5). CONCLUSIONS: "Poor sleep" is common in CKD patients. Quality of sleep decreases in the early stages of CKD and does not appear to be associated with the subsequent degree of renal failure. Large prospective longitudinal studies of quality of sleep in CKD patients are needed to confirm the high prevalence of impaired quality of sleep in this population and examine the association between renal function and quality of sleep while controlling for potential confounding variables.     

Efficacy prospective study of different frequencies of Epo administration by i.v. and s.c. routes in renal replacement therapy patients.

BACKGROUND: The problem of pure red cell aplasia (PRCA) prompted nephrologists to revert to a wider intravenous (i.v.) utilization of erythropoeitin (Epo). Once weekly i.v. Epo administration has been suggested to be as effective as the twice/thrice weekly i.v. dose. The aim of the present study was to test whether once weekly i.v. Epo administration is equally as cost-effective as once weekly subcutaneous (s.c.) and 2-3 times weekly i.v. administration. METHODS: We prospectively studied 41 patients (23 males, aged 28-82 years), on renal replacement therapy for 18-286 months, stabilized on twice or thrice weekly s.c. Epo-alpha (basal). The patients were treated for three consecutive 6 month periods with once weekly s.c. (OWSC), once weekly i.v. (OWIV) and twice/thrice weekly i.v. (TWIV) Epo-alpha. The initial dose for each period was equal to the final dose of the previous one; when necessary, the dose was adjusted according to DOQY guidelines. Iron, folic acid and vitamin B(12) supplementations were given throughout all the study periods. At the end of each of the four study periods, the following parameters were evaluated: haemoglobin, haematocrit, hypochromic red blood cells (RBCs), iron, serum ferritin, transferrin, folate, vitamin B(12), C-reactive protein (CRP), Kt/V, parathyroid hormone (PTH) and weekly dose of Epo-alpha. RESULTS: Thirty-three out of 41 enrolled patients completed the study (there were five deaths, two renal transplants and one transfer). No significant changes were observed as regards iron, serum ferritin, transferrin, folate, vitamin B(12), CRP, Kt/V or PTH level. Haemoglobin levels were not different at the end of the basal (11.7+/-1.21), OWSC (11.8+/-0.86) and TWIV (12.1+/-1.04) periods, while significantly lower levels were observed after the OWIV period (11.0+/-0.97, P<0.01). Weekly Epo consumption (Epo U/week/kg body weight/g haemoglobin) was: basal 11.57+/-5.96; OWSC 10.22+/-4.53; OWIV 15.99+/-7.7*(a); and TWIV 11.89+/-6.3*(a) (*P<0.01 vs basal; (a)P<0.01 vs OWSC). CONCLUSIONS: From our results, the OWIV schedule seems to have less efficacy in the control of anaemia of chronic renal failure patients on dialysis treatment than either OWSC or TWIV schedules.     

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure

Darbepoetin alfa (DA) is a unique long-acting treatment for anaemia in patients with chronic renal failure (CRF). This study assessed the mean dose of DA to achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF children aged 11 years to 18 years. This observational, prospective study was conducted in 39 patients treated with DA. Twenty-nine patients were switched from recombinant human erythropoietin (r-HuEPO), and ten patients were naive to r-HuEPO. Naive patients received initial doses of 0.45 μg/kg of DA. Switched patients received a dose adjusted to the prior dose of r-HuEPO (200 IU r-HuEPO:1 μg DA). Among the switched patients, 79.3% received dialysis. No naive patients underwent dialysis. Overall, 74% of patients showed increased Hb level, with a mean value of 11.6 ± 1.6 g/dl, using a mean DA dose of 0.63 ± 0.48 μg/kg per week, and 66.7% patients reached the target Hb level. Hb increased in naive patients from 9.5 (95% CI: 7.7, 11.4) to 11.7 (95% CI: 10.9, 12.6) g/dl and in switched patients from 11.1 (95% CI: 10.6, 11.5) to 11.5 (95% CI: 10.8, 12.2) g/dl). Higher doses of DA were needed in the “switched” than in the “naive” patients to maintain Hb levels over 11 g/dl, respectively 0.73 (95% CI: 0.54, 0.92) and 0.34 (95% CI: 0.16, 0.52) μg/kg per week. Our results indicate the doses of DA necessary to treat CRF patients aged 11 years to 18 years. DA was an effective treatment to stabilise CRF patients at extended dosing intervals. A prospective observational study, on behalf of the French Society for Pediatric Nephrology. Preliminary results of this study were published in part as an abstract and presented as a poster at the European Society of Pediatric Nephrology in Istanbul 11–13 September 2005 and at the ASN Renal Week in Philadelphia (Pennsylvania) 8–13 November 2005.     

Incidence of anaemia, and use of epoetin therapy in pre-dialysis patients: a prospective study in 403 patients.

BACKGROUND: Recent American and European guidelines recommend that epoetin therapy should be considered whenever the blood haemoglobin (Hb) level is <10-11 g/dl in dialysis patients and in pre-dialysis patients. Thus, data on the current prevalence of anaemia with respect to the degree of chronic renal insufficiency are needed in order to determine the potential indications of epoetin therapy in the pre-dialysis period. METHODS: We prospectively studied 403 consecutive ambulatory pre-dialysis patients whose serum creatinine (Scr) was 200 micro mol/l or more at their first passage at our out-patient clinic between January 1 and June 30, 1999. Hb and Scr values were determined at each visit until June 30, 2000, or until the start of maintenance dialysis. Patients had a clinical and laboratory evaluation every 2-3 months, and monthly when treated with epoetin. RESULTS: The mean (+/-SD) age of patients was 60.9+/-17.2 years at presentation. The Hb level was <11 g/dl in 62% of patients with Scr > or =400 micro mol/l, and in 58% of patients with an estimated creatinine clearance (Ccr) <20 ml/min/1.73 m(2). The proportion of anaemic patients was higher for any given Ccr value in females than in males. A total of 136 patients were treated with epoetin during the observation period. At the start of epoetin, their mean Hb value was 9.5+/-0.6 g/dl and Ccr level 13.9+/-4.9 ml/min/1.73 m(2). Among the 123 patients who began maintenance dialysis therapy during the observation period, 85 (or 69%) received epoetin therapy before the start of dialysis. Their mean Hb value at the start of dialysis was 10.8+/-1 g/dl compared with 10.5+/-1.1 g/dl in the 41 dialysed patients who did not require epoetin therapy during the pre-dialysis period. CONCLUSIONS: Based on the data gained in a large cohort of patients receiving regular pre-dialysis nephrological care, the proportion of subjects with a Hb level <11 g/dl may be estimated at approximately 60% when the Ccr is <20 ml/min/1.73 m(2). If the Hb level is to be maintained at no less than 11 g/dl, at least two-thirds of patients at this advanced stage of chronic renal failure should require pre-dialysis epoetin therapy.     

Whole body and regional body composition in patients with chronic renal failure

BACKGROUND.: Nutritional state is a powerful prognostic factor in chronicrenal failure (CRF). Techniques for the assessment of nutritionhave limitations which are often most marked in the presenceof renal disease. We have used techniques of body compositionanalysis to assess the nutritional state of groups of patientswith CRF. METHODS.: Body composition was measured in groups of patients with advancedCRF on conservative treatment, peritoneal dialysis, and haemodialysisand the results compared with a healthy control group. The selectioncriteria for the CRF patients ensured that they were ‘stable’with no recent intercurrent illness, and dialysis adequacy wassatisfactory according to currently accepted targets. RESULTS.: Whole body dual energy X-ray absorptiometry (DEXA) found significantreduction in lean tissue in haemodialysis patients and femaleperitoneal dialysis patients. Regional analysis with DEXA showedreduction in limb (especially arm), lean tissue in CRF patients,with arm lean tissue being reduced in all three CRF groups forfemales and both dialysis groups for males. Limb/trunk leantissue ratios were significantly reduced for all CRF groups.Bioelectrical impedance showed reductions of fat-free mass inthe same groups who had reduced whole body lean tissue withDEXA, but skinfold anthropometry failed to detect any significantreduction in fat-free mass. CONCLUSIONS.: We conclude that even in ‘healthy’ groups of CRFpatients receiving adequate dialytic and dietary management,lean tissue depletion is a common problem. Regional analysisby DEXA, with measurement of limb lean tissue mass is a moresensitive method for the detection of lean tissue depletionthan measurement of whole body lean tissue in patients withCRF.     

Effect of anaemia on mortality, cardiovascular hospitalizations and end-stage renal disease among patients with chronic kidney disease

Objective:   To determine whether an independent association exists between anaemia and chronic kidney disease (CKD) outcomes in a quasi-incidence cohort when patients' most recent laboratory values are considered.
Methods:   We conducted a dynamic, retrospective cohort study among patients with incident CKD in a large health maintenance organization administrative data set. CKD was defined by two estimated glomerular filtration rates (eGFR). We measured the absolute rates for all-cause mortality, cardiovascular hospitalizations and end-stage renal disease.
Results:   Our completed cases Cox regression model followed 5885 patients with both CKD and haemoglobin measures. For patients with the most severe anaemia (haemoglobin <10.5 g/dL), we estimated an increased rate of mortality (hazard ratio (HR) = 5.27, CI 4.37–6.35), cardiovascular hospitalizations (HR = 2.18, CI 1.76–2.70) and end-stage renal disease (HR = 5.46, CI 3.38–8.82) when compared with patients who were not anaemic; the HR reflect time-varying haemoglobins and eGFR.
Conclusion:   Anaemia is a predictor of excess mortality, excess cardiovascular hospitalizations and excess end-stage renal disease even when the progression of CKD is considered by controlling for time-varying eGFR values.     

狄克片治疗慢性肾衰竭的临床疗效

目的探讨狄克片对慢性肾衰竭（CRF）的临床疗效。方法将140例CRF患者随机分为狄克片组和艾西特组,各组70例。狄克片组在常规治疗基础上加用狄克片。艾西特组在常规治疗基础上加艾西特。观察二者的治疗效果。结果狄克片组的血肌酐、尿素氮、肌酐清除率均有显著改善（P〈0．01）,其显效率、总有效率分别为31．4％、84．2％;而艾西特组分别为17．2％、58．6％,两组比较均差异有统计学意义（P〈0．01）。狄克片组疗效明显优于艾西特组。结论狄克片治疗CRF疗效明显优于艾西特组。