Treatment of anaemia with erythropoiesis-stimulating agents in patients with chronic kidney disease does not lower mortality and may increase cardiovascular risk: a meta-analysis.

BACKGROUND/AIMS: Interpretation of the results of earlier meta-analyses in chronic kidney disease (CKD) patients on the impact of anaemia treatment with erythropoiesis-stimulating agents (ESAs) on clinical outcomes has been hampered by the inclusion of small trials and trials of short duration. We re-evaluated the benefits and harms of treating anaemia, including only relevant clinical trials. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials performed in adults with CKD which allocated patients to different doses of ESAs, and we compared the effect of these interventions on vascular access thrombosis, stroke, risk of end-stage renal disease (ESRD) and all-cause mortality. Additional inclusion criteria were studies with a duration of at least 1 year and enrolling more than 500 participants. RESULTS: Five trials (7,902 participants) met the inclusion criteria and were included in the meta-analysis. The number of patients enrolled in each trial ranged from 596 to 4,038. The mean/median duration of follow-up ranged from 14 to 36 months. A higher haemoglobin target was associated with increased risk of vascular access thrombosis (RR 1.343; 95% CI 1.162-1.554; p = 0.0005) and stroke (RR 1.735; 95% CI 1.323-2.275; p = 0.0005), and no effect on risk of ESRD (RR 1.089; 95% CI 0.986-1.203; p = 0.094) or all-cause mortality (RR 1.148; 95% CI 0.977-1.350; p = 0.093). CONCLUSION: In CKD patients, treatment of anaemia with ESAs targeting a higher haemoglobin value does not lower mortality or reduce the risk of ESRD, and may increase cardiovascular risk.

[Hospital prevalence of kidney failure. Consequences and reflections for the planning of nephrology services]. / Prevalência hospitalar da insuficiência renal. Consequências e reflexões para a planificação de Serviços de Nefrologia.

A prospective prevalence study of Renal Failure (RF) in inhospital patients (creatinine > = 1.7 mg/dl) was carried out during March 1994, in two hospitals covering well defined and mutually exclusive populations. Cases were selected by screening all urea and creatinine blood tests performed in both laboratories, and registered in an individual form for daily follow-up of their nephrologic outcome. We registered 242 RF cases among 3525 patients admitted (6.8%), with an A.R.F. prevalence of 5.2%, 46% of all patients had a serum creatinine > 3 mg/dl and 71% were older than 65 years. In 55% RF was acquired inside the hospital. The most frequent cause of A.R.F. was pre-renal failure with 37%, followed by 32% of ischemic acute tubular necrosis and 13% toxic ATN. Nephrology was consulted in only 29% of all hospital RF cases. Only 17% of the RF patients were submitted to dialysis procedures, overall mortality was 31%, and 30% had normal renal function at discharge. Our results provide a data base to rethink the organization, staffing and role of nephrology departments inside general hospitals.

Mixed cryoglobulinemia in a heroin addict.

Several forms of glomerulopathies have been described in patients who use intravenous heroin, including focal glomerulosclerosis, membranous nephropathy associated with chronic hepatitis B antigenemia, and immune complex proliferative glomerulonephritis. This report describes a patient who was a heroin addict for 15 years and who developed membranoproliferative glomerulonephritis and cutaneous vasculitis due to mixed cryoglobulinemia; he also had a positive hepatitis C virus (HCV) antibody. Recently, an association has been described between "essential" mixed cryoglobulinemia and chronic HCV infection, which has a high prevalence in intravenous drug addict population. It is possible that mixed cryoglobulinemia-associated glomerulonephritis, occurring with chronic HCV infection, came to be considered a major cause of renal disease in heroin abusers. The possibility that HCV infection can be responsible for other types of renal involvement in intravenous drug addicts deserves further attention.

[Hemostatic changes associated with recombinant human erythropoietin (rHu Epo) treatment]. / Alterações hemostáticas associadas ao tratamento com eritropoietina humana recombinante (rHu Epo).

End-stage chronic renal failure (CRF) is often associated with platelet' disfunction and therefore with impaired hemostasis. Several investigators have reported that rHu Epo, used in the treatment of CRF anaemia, is able to activate a broad spectrum of hematopoietic stem cells, and therefore is able to increase the number of platelets and to induce correction of platelet disfunction. In order to investigate hemostasis changes associated with rHu Epo we studied 8 dialysis patients before and 12 weeks after rHu Epo. RHu Epo did not induce any change in the number of platelets (187710 +/- 52690 vs 204430 +/- 68710; p = NS), but seemed to improve its function (MI% of aggregation with ADP: 46.3 +/- 4.4% vs 49.1 +/- 5.3%; p less than 0.05). There was an improvement in PT (79.0 +/- 3.0% vs 87.5 +/- 8.9%; p less than 0.02) and aPTT (33.3 +/- 5.9" vs 29.3 +/- 2.1"; p less than 0.05) suggesting an improvement in platelet coagulant activities. These preliminary results indicate that rHu Epo does not increase the number of platelets but can induce a correction of platelet disfunction.

[Treatment of anemia in patients with chronic kidney insufficiency in hemodialysis with erythropoietin]. / Tratamento da anemia dos doentes insuficientes renais crónicos em hemidiálise com eritropoietina.

A group of 50 patients (26 men and 24 women, mean age 50 +/- 19 years and range 21 to 67) on chronic hemodialysis (HD) and with basal levels of hemoglobin (Hb) less than or equal to 8 g/dl was treated with recombinant human erythropoietin (r-HuEpo) during 3 months. r-HuEpo was started at 50 U/kg I.V. 3 times a week, immediately after each session of HD, for 4 weeks, and this dose was increased in steps of 25 U/kg until a Hb level of 12 g/dl or a maximum dose of 100 U/kg were reached. Complete blood counts and biochemical profile were performed before the first dose of r-HuEpo and once weekly and monthly respectively during the period of treatment. In 8 patients the red-cell life span was studied with cromium 51 labelled erythrocytes just before and after treatment. One patient had a grand mal seizure and the r-HuEpo was discontinued. In 44 patients the mean hematocrit increased from 21.8% to 32.1% and in the other 5 there were no response because of iron deficiency. There were no changes in leucocytes and platelets counts and consistent decreases in iron and ferritin serum concentrations were observed despite oral supplementation of iron. In the 8 patients studied the shortened erythrocyte survival did not suffer any significant variation with r-HuEpo. Predialysis creatinine, urea and phosphorus blood levels increased significantly at 3th month of treatment but there was no increase in potassium. In 32.6% of previously normotensive and hypertensive patients an increase in blood pressure was founded. Thrombosis of arteriovenous fistulas and other severe clinical side effects were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Arterial hypertension in patients with chronic kidney insufficiency in hemodialysis with erythropoietin]. / Hipertensão arterial nos doentes insuficientes renais crónicos em hemodiálise tratados com eritropoietina.

The purpose of this study was to evaluate the effect of the partial correction of anaemia with recombinant human erythropoietin (rHuEPO) on the blood pressure (BP) of patients on chronic haemodialysis (HD). A group of 50 patients (26 men and 24 woman, mean age of 50 +/- 19.0 and range of 21 to 67) with basal levels of haemoglobin (Hb) less than or equal to 8 g/dl was evaluated before and during treatment with rHuEPO. Recombinant erythropoietin was started at 50 U/kh I.V. 3 times a week, immediately after each session of HD, for 4 weeks, and this dose was increased in steps of 25 U/kg until and Hb level of 12 g/dl or a maximum dose of 100 U/kg were reached. Before the administration of rHuEPO 33 patients (67.3%) were normotensives and 16 (32.6%) were hypertensives treated and well controlled. During the period of administration of rHuEPO 10 of the normotensives (30.3%) and 5 (31.3%) of the hypertensives patients showed an increase in the B.P. There was no correlation between the frequency of increase in B.P. and sex, age, length of time on HD and previous levels of B.P., but that frequency was higher in the patients with the lowest basal levels of haematocrit (Hct) and with the greatest increases in Hct (delta Hct). An immediate effect of I.V. administration of rHuE-PO on B.P. levels was not found. Finally we discuss the etiopathologic factors eventually responsible for the increase in BP and suggest some rules to be observed in the therapeutic use of rHuEPO.