Heart and iron deficiency anaemia in rats with renal insufficiency: the role of hepcidin

Aim: Anaemia is prevalent in chronic kidney disease (CKD) and induces significant changes in heart and kidney. In this study, we evaluated the relationship between iron metabolism, hepcidin and inflammation focusing on left ventricular (LV) function, in a remnant kidney rat model. Methods: Rats with 5/6 subtotal nephrectomy (STNx) and sham operation. Haemoglobin (Hb), serum iron (SI), fractional shortening (FS%) by echocardiograms were evaluated. Six months after STNx, the heart and kidney were processed by immunohistochemistry with antibodies against hypoxia-inducible factors (HIF)-1α, erythropoietin (EPO), pro-hepcidin, caspase-3, tumour necrosis factor (TNF)-α and interleukin (IL)-6. Results: Hb (g/dL) STNx: 10.8 ± 0.8, sham: 14.7 ± 0.6 (P < 0.01); SI (µg/dL) STNx: 154.5 ± 24.5, sham: 287.5 ± 32.1 (P < 0.01); heart weight (g) STNx: 2.21 ± 0.15, sham: 1.12 ± 0.12 (P < 0.01); FS% STNx: 28.4 ± 2.5, sham: 45.1 ± 4.1 (P < 0.01). There was a correlation between Hb and FS% (r = 0.95; P < 0.01) and between SI and FS% (r = 0.86; P < 0.01) in the STNx group. Tissue ferritin was reduced in heart and in kidney in the STNx group (P < 0.01). HIF-1α was expressed in cardiomyocytes (positive cells/area) STNx: 32 ± 5, sham: 4 ± 1; and tubular cells in STNx group: 70 ± 16, sham: 10 ± 3, P < 0.01. Hepcidin (% staining/area) in heart STNx: 6.6 ± 0.8, sham: 0.8 ± 0.1; in kidney STNx: 9.7 ± 2.6, sham: 3.7 ± 0.9, P < 0.01. EPO (% staining/area) in heart STNx: 2.6 ± 0.4, sham: 0.8 ± 0.2; in kidney STNx: 10.2 ± 1.4, sham: 1.2 ± 0.6; P < 0.01. In STNx group positive caspase-3, TNF-α and IL-6 were detected in heart and renal cells. Conclusion: Low LV performance is associated with iron deficiency anaemia in rats with CKD. Furthermore, overproduction of HIF-1α and the activation of caspase-3 seem to be associated with iron deficiency and with inflammatory markers. Hepcidin seems to plays a key role in this mechanism.     

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.     

Folic acid 5 or 15 mg/d similarly reduces plasma homocysteine in patients with moderate-advanced chronic renal failure

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease with a remarkable prevalence in patients with chronic renal failure (CRF). Low doses of folic acid (FA) with or without vitamin B6 and B12 has been shown to effectively reduce plasma homocysteine (Hcy). The aim of this study was to compare the short-term effects of two different oral doses of FA (5 vs 15 mg/d) on plasma Hcy levels in subjects suffering from moderate-severe CRF. METHODS: A double-blind, double-dummy, comparative, two-stage randomised study was performed. Seventeen patients aged 45-71 years, with glomerular filtration rates between 15.4-50 mL/min 1.73/m2 were randomly assigned to receive FA 5 mg/d (FA-5, n: 8) or FA 15 mg/d (FA-15, n: 9) for 30 days. At the end of this 30-day double-blind period, all the participants were placed on FA 5 mg/d (open period), for 5 additional months. Both groups were also supplemented with vitamins B1, B6 and B12 throughout the trial. Blood samples were drawn at 0, 15, 30, 90 and 180 days to assess Hcy, complete blood count (CBC) and sequential multichannel analysis (SMA). Chest X-ray and a 12-lead electrocardiogram (ECG) were also performed. RESULTS: Plasma Hcy (mean +/- SEM) decreased from 27.9 +/- 1.4 (baseline) to 15.1 +/- 0.6, 13.3 +/- 0.9, 14.1 +/- 0.5 and 13.8 +/- 0.5 micromol/L (FA-5) and from 28.8 +/- 2.7 to 15.6 +/- 1.2, 14.4 +/- 1.3, 13.0 +/- 0.7 and 13.1 +/- 0.6 micromol/L (FA-15) at days 15, 30, 90 and 180, respectively. (P < 0.01 from day 15 to 180 vs baseline for both groups with no differences between them). Renal function remained stable throughout the entire period of the study in all but one patient in whom it deteriorated to pre-end stage disease. No adverse cardiovascular events developed during the trial. CONCLUSION: Both folic acid doses induced a significant and similar decrease in plasma Hcy in subjects with moderate-severe chronic renal failure. The possible dose-related effect of this approach in reducing the risk of accelerated sclerotic vascular disease and cardiovascular events in this especially vulnerable population should be a matter of further investigation.     

Incidence of side-effects associated with high-dose ferric gluconate in patients with severe chronic renal failure

SUMMARY: Ferric gluconate complex in sucrose (Ferrlecit™) has been associated with less side-effects than iron dextran; however, the recommended dose of 62.5–125 mg per treatment is only suitable for haemodialysis (HD) patients. We retrospectively analysed the incidence of the side-effects associated with a high dose of Ferrlecit™ infusion (20 treatments in 13 patients; 10 treatments of 250 mg/3–4 h, and 10 treatments of 500 mg/5 h infusion). The patients were in the age range of 32–75 years old, seven with chronic renal failure (CRF), and six on dialysis treatment. One (10%) of the 10 treatments using a 250 mg dose was complicated with severe nausea/vomiting, diarrhoea and a burning sensation in the feet. Three (30%) of the 10 treatments using a 500 mg dose were complicated with: chills, severe nausea/vomiting, hypotension and syncope in one; severe nausea/vomiting, diarrhoea and hypotension in one; and an episode of vomiting in one patient. A single treatment with a 250 mg dose resulted in no significant change in haematological parameters. A single treatment with a 500 mg dose resulted in a significant increase in haemoglobin (Hgb) and haematocrit (Hct), but only a rising trend in serum iron,% transferrin saturation and ferritin pre versus 1–2 months postinfusion. In conclusion, Ferrlecit™ doses of 250 or 500 mg are complicated with significant untoward reactions in 10–30% of patients, in a dose-dependent fashion.     

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.     

Atherosclerosis and folic acid supplementation trial in chronic renal failure: baseline results

BACKGROUND: Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is a randomized placebo controlled trial assessing whether high-dose folic acid can reduce cardiovascular events and atherosclerosis progression in patients with chronic renal failure (CRF). Here we report the baseline results and compare indices of arterial structure (carotid intima-medial thickness (IMT)) and function (systemic arterial compliance (SAC)), pressure augmentation index (AI(x)) and pulse wave velocity (PWV a-f and PWV f-d)) to age- and sex-matched controls. METHODS: Three hundred and fifteen subjects with CRF (serum creatinine > or = 0.40 mmol/L) aged 24-79 years (mean +/- SD: 56.6 +/- 13.6 years) and 213 healthy controls (58.2 +/- 10.2 years) were studied. Fasting blood samples were assayed for lipids (both groups), total homocysteine (tHcy), red cell folate, cobalamin and fibrinogen (CRF group). Ultrasound B mode measurements were used to determine mean carotid IMT and applanation tonometry techniques to determine SAC, AI(x), PWV (a-f), PWV (f-d) and central pressures. RESULTS: Ninety-six per cent of the CRF group had at least one of: hypertension, hypercholesterolaemia, diabetes or smoking; 35% had established cardiovascular disease. The mean IMT was greater in CRF patients than in controls (0.86 +/- 0.19 vs 0.68 +/- 0.11 mm, P < 0.001). The SAC was significantly lower, and PWV (a-f) and AI(x) significantly higher. The tHcy was increased in 97% of the CRF group (27.3 +/- 2.9 micromol/L (normal < 13)). Total homocysteine did not correlate with IMT or any other measure of arterial function. However, those in the upper quantile of tHcy (> or =25 micromol/L) did have higher PWV (a-f) and lower SAC than those in the lower quantile. CONCLUSIONS: Compared to normals, patients with CRF exhibited a 10-15-year shift to the right in age-related increases in carotid IMT and PWV (a-f), and significantly increased central pressure augmentation. This 5-year study is examining the impact of high-dose folic acid therapy on cardiovascular end-points, IMT progression and arterial function in CRF.     

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.     

Colchicine myoneuropathy in chronic renal failure patients with gout

Colchicine myoneuropathy is a rare and often underdiagnosed disease. It often presents as painless subacute muscle weakness. We present a case of painful colchicine myoneuropathy in a 76-year-old man with chronic renal failure and gout. Published work about clinical presentations of colchicine myoneuropathy in gouty arthritis patients are reviewed. During the previous year, the patient had a drug regimen of colchicine 0.5 mg three times per day for a 3 day course each month. He developed bilateral lower leg weakness and severe myalgia. His serum creatinine level was 680.7 micromol/L and creatinine kinase was 959 IU/L on admission. Laboratory findings included decreasing amplitude of motor and sensory nerve conduction velocity and an electromyogram showed small amplitude, short duration polyphasic waves over the right biceps. A muscle biopsy disclosed vacuolar changes in the cytoplasm. These results all supported a diagnosis of colchicine myoneuropathy. After cessation of colchicine, the creatinine kinase level decreased approximately 50% in 6 days, myalgia subsided and his muscle weakness improved gradually over the next 2 weeks.     

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.     

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.     

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.     

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.