Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients.

BACKGROUND: Partial correction of anaemia with recombinant human erythropoietin (rHuEpo) has been shown to markedly improve the general condition and quality of life of predialysis patients, but the effects of rHuEpo therapy on blood pressure and the rate of progression of chronic renal failure (CRF) are still disputed. In particular, no study evaluated the time duration until the start of maintenance dialysis in treated patients, compared to untreated predialysis patients. METHODS: We retrospectively evaluated the rate of decline of creatinine clearance (Delta Ccr) and the duration of the predialysis period in 20 patients with advanced CRF treated with rHuEpo (Epo+ group), and in 43 patients with a similar degree of CRF but with less marked, asymptomatic anaemia, not requiring rHuEpo therapy (Epo- group). All patients were submitted to identical clinical and laboratory surveillance. All received similar oral supplementation with B(6), B(9), and B(12) vitamins and oral iron supplementation. Maintenance dose of subcutaneous epoetin was 54.3+/-16.5 U/kg/week (median dose 3300 U/week). RESULTS: Initial and final haemoglobin (Hb) levels were 8.8+/-0.7 and 11.3+/-0.9 g/dl in the Epo+ group, vs 10.9+/-1.2 and 9.5+/-0.9 g/dl in the Epo- group. In the Epo+ group, Delta Ccr declined from 0.36+/-0.16 during the preceding 24 months to 0.26+/-0.15 ml/min/ 1.73 m(2)/month after the start of rHuEpo therapy (P<0.05). No significant variation was observed in the Epo- group. Time duration until the start of dialysis was 16.2+/-11.9 in the Epo+ group, compared to 10.6+/-6.1 months in the Epo- group (P<0.01). Slowing of progression was observed in 10 Epo+ patients, whereas no significant variation in Delta Ccr occurred in the other 10. There was no difference in previous Delta Ccr rate, nor in Hb or blood pressure levels while on rHuEpo therapy between the two subgroups. CONCLUSIONS: Our study affords conclusive evidence that rHuEpo therapy did not result in accelerated progression of CRF in any treated predialysis patients, nor deleterious increase in blood pressure, but instead resulted in significant slowing of progression and substantial retardation of maintenance dialysis. Such encouraging results remain to be validated in a large prospective, randomized study.     

Cost of treating predialysis patients with recombinant human erythopoietin

Treatment of the anaemia of predialysis patients with recombinanthuman erythropoietin (rHuEpo) is likely to become a widely acceptedpractice during the coming years. We estimated the impact onhealth care expenditures with the example of the French populationof end-stage renal disease patients. Using retrospective data,we calculated the percentage of predialysis patients with advancedchronic renal failure who would be eligible for treatment accordingto two different criteria based on haemoglobin and clinicalcondition, the total duration of treatment, and the total amountof rHuEpo delivered. We estimate that the total cost of treatingFrench predialysis patients could vary between 2.2 and 6.5 millionSwiss francs, or 50 000 to 140 000 Swiss francs per millionpopulation, using rHuEpo dosage from 50 to 150 IU/kg week.     

Low-dose subcutaneous recombinant erythropoietin in children with chronic renal failure

In a multicentre trial, low-dose subcutaneous recombinant human erythropoietin (r-Hu EPO) was evaluated in 22 children aged 4 months to 16 years with anaemia of chronic renal failure over a 12-month period. A starting dosage of 50 U/kg twice weekly was given until a target haemoglobin of 9–11 g/dl was achieved. The dosage was increased by 50 U/kg per week, each 4 weeks, if the haemoglobin did not increase by 1 g/dl per month. When the target haemoglobin was achieved, the same weeekly dosage was given as a single injection. After 10 weeks, the mean haemoglobin increased from 6.7±0.7 to 9.6±1.9 g/dl (P<0.001) and the haematocrit from 19.8%±2.4% to 29.3%±6.3% (P<0.001). By 4 months the target haemoglobin was achieved in 19 patients on 50 U/kg twice weekly and 1 patient on 75 U/kg twice weekly. Two children with severe renal osteodystrophy failed to respond to 95 U/kg and 150 U/kg twice weekly. The maintenance weekly dose of r-Hu EPO in 9 children over 4–12 months ranged between 45 and 125 U/kg. The Wechsler intelligence score increased in 11 children from 92±16 to 97±17 over the 12-month period (P=0.007). No adverse effects were recorded. A starting dose of r-Hu EPO of 50 U/kg subcutaneously twice weekly is recommended as effective and safe for the majority of children with anaemia of chronic renal failure.     

Renal function in predialysis children with chronic renal failure treated with erythropoietin

To assess the effect of long-term administration of human recombinant erythropoietin (EPO) on renal function, 11 anemic children aged 1.4 – 17.2 years were followed for 10 – 61 (mean 31) months on treatment. During EPO therapy the mean hemoglobin rose from 8.1 to 11.1 g/dl at the last observation. The final maintenance dose ranged between 70 and 300 U/kg per week. The rate of deterioration of renal function was calculated by comparing the slope of the regression lines of reciprocal serum creatinine values (SCr) derived from a mean of 20 values per patient obtained over 8 – 50 (mean 29) months before and a mean of 24 SCR values during EPO therapy. The individual slopes improved after initiation of EPO therapy in all but 3 patients, but the mean change of slope (from –0.0521 to –0.0299) was not significant. The study suggests that in most children with predialysis chronic renal failure long-term administration of EPO is not associated with accelerated deterioration but rather with delayed deterioration of renal function. Received August 30, 1995; received in revised form November 16, 1995; accepted April 10, 1996     

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.     

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease?

In an uncontrolled open study 13 patients with moderate to preterminalrenal failure were treated with low doses (average 0.36 µg/day)of calcitriol up to the time of renal transplantation, whichwas performed before dialysis had been initiated. A transiliacbone biopsy was obtained both at the start and at the end ofthe treatment period, the latter coinciding with renal transplantation.All patients who started calcitriol treatment at a creatinineclearance (C_cr) above 30 ml/min had normal bone histology atthe time of transplantation, but this was not observed whencalcitriol treatment was started at C_cr below 30 ml/min. The study suggests that full benefit of calcitriol at the bonelevel is obtained only if prophylactic administration is startedearly in the course of renal failure.     

Sustained reduction of hyperhomocysteinaemia with folic acid supplementation in predialysis patients.

BACKGROUND: Moderate hyperhomocysteinaemia, as occurs in chronic renal failure patients, is an established independent risk factor for atherosclerotic arterial occlusive accidents, the incidence of which is abnormally high in such patients. Folic acid supplementation has been shown to reduce plasma homocysteine level in end-stage renal disease patients treated with haemodialysis or peritoneal dialysis, but its long-term effects in predialysis patients had not been assessed. METHODS: We prospectively treated a total of 78 predialysis patients with folic acid for at least 1 year (range 12-74 months) together with oral pyridoxine and vitamin B12 supplements. Of the patients, 67 received 5 mg folic acid three times per week, whereas the other 11 patients who were treated with recombinant erythropoietin received 5 mg/day. Plasma fasting total homocysteine concentration was determined at baseline, after 3 months and at the end of follow-up. RESULTS: Mean (+/-SD) plasma total homocysteine level decreased from 21.2+/-6.4 micromol/l at baseline to 14.2+/-4.6 at 3 months and remained at 12.8+/-3.7 micromol/l at the end of follow-up (average duration 2.8 years), whereas plasma creatinine rose from 268+/-129 to 399+/-234 micromol/l. Mean plasma folate concentration rose from 19+/-12 to 47+/-13 nmol/l and mean plasma vitamin B12 rose from 237+/-119 to 347+/-191 pmol/l from baseline to end of follow-up. CONCLUSIONS: Moderate folic acid supplementation (2.15 mg/day) allows a substantial (40% as a mean) and sustained (up to 6 years) reduction of plasma total homocysteine level in predialysis uraemic patients without any detectable side effect. Folic acid supplementation may thus contribute to lower the risk of accelerated atherosclerosis in such patients.     

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 ± 10.8 years; serum creatinine 2.7 ± 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)₂D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)₂D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = −0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)₂D (β = 0.434) was a significant predictor of decreases in total and trabecular BMD (R ² = 0.188, P < 0.01; and R ² = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)₂D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.     

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.     

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.     

Prevalence of vascular risk factors and vascular disease in predialysis chronic renal failure

Patients with end-stage renal disease have a high mortality, with the majority of deaths due to vascular disease. The prevalence of vascular risk factors and vascular disease in predialysis chronic renal failure (CRF) is poorly characterized. The aim of the present study was to determine the prevalence of vascular risk factors and clinically overt vascular disease in an Australian cohort of patients with predialysis CRF. We performed a retrospective chart review of outpatients with CRF and noted demographic data, the cause of renal failure, the presence or otherwise of vascular risk factors and vascular disease and calculated glomerular filtration rate. The prevalence of overt vascular disease and modifiable vascular risk factors was calculated. One hundred and eighty patients completed the study. Eighty-nine per cent of patients had hypertension, 68% had dyslipidaemia, 32% were diabetic and 38% were previous smokers. The subgroup with diabetic nephropathy had significantly more risk factors (P < 0.001) than other groups. Twenty-seven per cent of the group had cardiovascular disease, 22% had cerebrovascular disease, 23% had peripheral vascular disease and 9% had renal artery stenosis. Patients with ischaemic nephropathy had significantly more vascular disease than other groups (P < 0.001). Patients with overt vascular disease were older, had a higher number of risk factors and a higher calcium phosphate product than those without vascular disease. In conclusion, the present study suggests a high prevalence of vascular risk factors and vascular disease in predialysis CRF. Early detection provides an opportunity for early intervention and may help reduce the development of vascular disease, and the associated mortality, once these patients progress to dialysis.     

Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients.

BACKGROUND: Intravenous iron is a recognized therapy of anaemia in chronic haemodialyzed patients, especially in those receiving erythropoietin (Epo), while its role in the anaemia of pre-dialyzed chronic renal failure (CRF) patients is much less clear. This study attempted to evaluate the effects of intravenous iron in anaemic pre-dialyzed patients. METHODS: Sixty anaemic (haemoglobin<11 g/dl) non-diabetic patients with moderate CRF [32 males, 28 females; mean age 52.2+/-12.5 years; mean glomerular filtration rate 36.2+/-5.2 ml/min], without iron deficiency, iron overload or inflammation, without concomitant erythropoietin treatment and without any previous iron therapy were enrolled. Intravenous iron was administered as iron sucrose, 200 mg elemental iron per month for 12 months, with 1 month pre-study survey and 1 month follow-up after the last iron dose. RESULTS: Intravenous iron supplementation was associated with a significant increase in haemoglobin (from 9.7+/-1.1 at the baseline to 11.3+/-2.5 g/dl after 12 months, a mean increase of 1.6 g/dl), a further 36% of patients reaching the target haemoglobin of 10 g/dl. There was a significant increase in serum iron from 73.9+/-17.2 to 101.8+/-12.2 microg/dl, in serum ferritin from 98.0 (24.8-139.0) to 442.5 (86.0-496.0) microg/l and in transferrin saturation from 21.6+/-2.6 to 33.6+/-3.2%. No worsening of renal function, no increase in blood pressure and no other side effects were noted. CONCLUSIONS: Intravenous iron therapy in pre-dialysis patients with no Epo seems often to ameliorate the anaemia, avoiding the necessity of Epo or blood transfusions in one-third of pre-dialyzed non-diabetic patients. Intravenous iron supplementation appears to be an effective and safe treatment for anaemia in pre-dialysis CRF patients.     

Haemodynamic changes induced by the correction of anaemia by erythropoietin: role of antiplatelet therapy

BACKGROUND.: In a restrospective study, antiplatelet therapy has been shownto be associated with a decreased incidence of erythropoietin-inducedhypertension. In order to ascertain the role of antiplateletdrugs in the haemodynamic response to the correction of anaemiaby rHuEpo, 18 patients on chronic haemodialysis who startedrHuEpo therapy were prospectively studied. METHODS.: The subjects were randomly assigned to receive or not, one ofthe following antiplatelet drugs: ditazole (3 patients), ticlopidine(3 patients) or aspirin plus dipyridamole (3 patients). Cardiacindex (CI) by echo-Doppler, total peripheral resistance (TPR)and mean arterial pressure (MAP) were determined at baseline10 and 20 weeks following the initiation of rHuEpo therapy.rHuEpo therapy was administered subcutaneously at the same dose(40 U/kg thrice weekly) during the first 10 weeks. Ten uraemicpatients on haemodialysis who had never received rHuEpo therapyserved as the control group. RESULTS.: One patient in the group without antiplatelet drugs discontinuedthe study due to the development of severe hypertension after12 weeks on rHuEpo therapy. There were no significant differencesin the haemodynamic parameters at baseline. At 10 weeks, MAPwas higher in patients without than with antiplatelet drugsor controls untreated with rHuEpo (128.5 ± 28 versus100.6 ± 13.5 versus 98.7 ± 14 mmHg respectively,P = 0.0047), TPR was also higher in patients without antiplateletdrugs than in the 2 other groups (1919 ± 433 versus 1576± 359 versus 1418 ± 324 din.seg.cm^–5 m²respectively, P = 0.0231), but CI did not differ among the threegroups. At 20 weeks, MAP was still higher in patients withoutantiplatelet drugs than in patients with antiplatelet drugsor controls not on rHuEpo therapy respectively (112.9 ±24.6 versus 91.0 ± 9.0 versus 101.7 ± 14.1 mmHgrespectively, P = 0.075), but at this stage TPR and Cl did notdiffer among the three groups. CONCLUSIONS.: These data reinforce the previous observation that antiplatelettherapy may prevent the development of rHuEpo-induced hypertension.     

Peripheral blood mononuclear cells from patients with chronic renal failure release factors which suppress erythropoietin secretion in vitro

Decreased production of erythropoietin (Epo) as a result ofreduced renal mass is considered the main factor underlyingthe anaemia that is invariably associated with chronic renalfailure (CRF). Other mechanisms such as accumulation of inhibitorsof Epo also contribute. In this study we show that supernatantfrom peripheral blood mononuclear cells (PBMC) cultured frompatients with CRF inhibits Epo release by Hep G2 cells in vitro.Ten patients (5 male) with CRF (mean age 42 years, range 25–60)were studied. Five were approaching end-stage renal failureand five were maintained on haemodialysis (HD). Ten apparentlyhealthy volunteers were used as controls. Full blood countsand serum Epo (RIA) levels were determined and adherent PBMCwere cultured for 48 h with and without LPS. There was a significantrise in TNF- and IL1-ß levels measured in monocytesupernatant (MS) from patients and controls after LPS stimulation(P<0.05) and in IL-l levels in patients (P<0.05). IL-1ßlevels were higher in patients compared to controls both beforeand after stimulation with LPS (P<0.05). Hep G2 cells werecultured in 5% CO₂ and 20% O₂ and incubated with MS from patientsand controls for 24 h. Hep G2 harvest fluids were then analysedfor Epo levels, which were expressed as a function of totalcell protein (mU/mg). Epo production was inhibited by MS frompatients compared to controlsboth before and after stimulationwith LPS (P<0.0001). There was, however, no direct correlationbetween the degree of Epo suppression and concentrations ofMS TNF-, IL-l, and IL-ß. Inhibition byspecific polyclonalanti-TNF- antibodies and anti-IL-ß antibodies didnot abrogate the inhibition ofEpo release by Hep G2 cells. Theseresults demonstrate that although PBMC from patients with CRFproduce factors that inhibit Hep G2 cell secretion of Epo invitro, this effect does not appear to be directly related tothe proinflammatory cytokines TNF-, IL-l, and IL-ß.     

Safety and efficacy of erythropoietin in children with chronic renal failure

 A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks (mean±SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease. Received: 12 March 1998 / Revised: 24 June 1998 / Accepted: 6 July 1998     

Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis

Aplastic bone disease (ABD) is a common form of renal osteodystrophyand is characterized by a defect in bone matrix formation andmineralization without an increase in osteoid thickness. Theprevalence and pathogenesis of ABD in predialysis patients islargely unknown. We prospectively studied 92 unselected predialysispatients with a creatinine clearance <10 ml/min/1.73 m² anda mean age of 45±2 years (61 M, 31 F). None of the studypatients had received any form of vitamin D therapy, and CaCO₃was the primary phosphate binder. Aplastic bone disease wasobserved in 30 (32%) patients. Stainable bone aluminium surfacewas <3% in all ABD patients. Patients with ABD were older(52±3 versus 42±2 years; P<0.01) and had reducedserum intact PTH compared to non-ABD patients (199±25versus 561 ±87 pg/ml; P<0.001). Patients with diabetesmellitus showed lower PTH values (179±31 versus 432±62pg/ml; P<0.001) and a lower incidence of advanced by chperparathyroidismbone lesions (16% versus 46%; P<0.05) than non-diabetic patients.However, diabetes was not clearly associated with low bone turnoverdisease (56% in diabetics versus 41% in non-diabetics; P=0.1). A second bone biopsy was obtained in eleven ABD patients aftera period of 16.6±2.2 months on maintenance dialysis witha dialysate calcium of 7 mg/dl. Bone histology was unchangedin 10 patients, and one evolved to mild hyperparathyroidism.Trabecular bone volume did not change (22.7± 1.7 versus20.7±1.7%), and the stainable bone aluminium surfaceremained <3%. In summary, ABD not associated with positive histological stainingfor aluminium is a common finding in asymptomatic end-stagerenal failure patients in the Canary Islands. Older age andrelatively low PTH values are associated with this form of bonedisease. After a period of 12–36 months of dialysis, progressiveosteopenia and other clinical problems do not occur.     

Influence of blood volume on the blood pressure of predialysis and peritoneal dialysis patients treated with erythropoietin

Twenty-seven patients with renal failure (16 on CAPD and 11predialysis) were treated with erythropoietin. At 12 weeks,the mean haemoglobin concentration (±SEM) in the CAPDpatients had increased from 7.07 ± 0.20 to 10.88 ±0.45 g/dl (two-tailed paired t test, P<0.0001) and in thepredialysis patients from 6.90 ±0.35 to 10.05 ±0.47 g/dl (P< 0.0001). Predialysis patients were taking moreantihypertensive medication at baseline. No increase was requiredin either group after erythropoietin; there was no change inblood pressure in the CAPD patients, though in the predialysispatients the systolic blood pressure rose slightly from 132to 146 mmHg (P=0.029) and the mean blood pressure from 95 to103 mmHg (P=0.028). In 12 patients (6 on CAPD and 6 predialysis) the red cell volume,plasma volume, and total blood volume were measured before andafter treatment. In the CAPD patients there was a marked expansionof the red cell volume from 912±127 to 1471±222ml (P=0.004) and a concomitant contraction of the plasma volumefrom 3932 ±250 to 3178 ±326 ml (P=0.005), leavingthe blood volume unchanged from 4843 ± 352 to 4649 ±503ml. Predialysis patients had a similar expansion of the redcell volume from 733 ± 59 to 1304± 161 ml (P=0.017)but no contraction of the plasma volume (from 3417 ±354to 3314 ±260 ml), so that the blood volume tended toexpand from 4149 ±347 to 4618 ±414 ml (P= 0.053).The mean contraction of the plasma volume in the predialysisgroup was trivial (– 102 ±214 ml), whereas in theCAPD group it was large (–754 ±158 ml, P=0.034,two-tailed unpaired t test). Thereby the predialysis group experiencedan expansion of the total blood volume of 469±186ml,whereas the CAPD group experienced a contraction of the bloodvolume of –195±189 ml(P=0.031). We conclude that (a) increased blood volume may contribute tothe exacerbation of hypertension induced by erythropoietin therapy;(b) gradual reduction of plasma volume, aiming for a stabletotal blood volume, is an important strategy for the preventionand control of erythropoietin-induced hypertension; (c) as reductionof plasma volume may be more problematic in predialysis patients,adequate blood pressure control may consequently be slightlymore difficult, placing more reliance on antihypertensive medication.     

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.     

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.