- Email: [email protected]
Cochrane renal group report
COCHRANE RENAL GROUP REPORT Ruth L. Mitchell, Grad Dip Lib Sci, Gail Y. Higgins, Grad Dip Lib Sci, and Jonathan C. Craig, MBChB, PhD
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HIS ISSUE’S selection of randomized controlled trials includes recent ongoing and published trials from our register added since June 2002. As before, they have been selected for their relevance and quality, including suitable sample size and use of clinically important and/or patientcentered outcomes. It is particularly interesting to see reports of two trials, those by McMurray et al in the American Journal of Kidney Diseases and Sehgal et al in Journal of the American Medical Association, using educational interventions to improve quality of life for hemodialysis patients. We maintain a full list of ongoing trials on our website (www.cochrane-renal.org), with links, where available, to further information. We also regularly update our list of current published trials and provide links from Medline-indexed trials to their PubMed abstract. The Cochrane Renal Group is keen to hear details of any ongoing trials in nephrology not already included on our website. Please contact us on [email protected] if you would like to contribute in this way. INDEX WORDS: Systematic review; randomized controlled trial; Cochrane Collaboration.
DECEMBER 2002 ONGOING TRIALS
Dialysis Dember L, Kaufman J, Beck G, et al: Dialysis Access Consortium (DAC) Trial Design: Clopidogrel prevention of early AV fistula thrombosis. [Study size: 1,490] J Am Soc Nephrol 10:229A, 2002 (Programs and Abstracts Issue). 35th Annual Meeting & Scientific Exposition, American Society of Nephrology, Philadelphia, PA, October 30-November 4, 2002
From the Cochrane Renal Group, Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia. Address reprint requests to Ruth L. Mitchell, Grad Dip Lib Sci, Trials Search Coordinator, Cochrane Renal Group, Centre for Kidney Research, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Email: [email protected] © 2003 by the National Kidney Foundation, Inc. 0272-6386/03/4104-0022$30.00/0 884
Dixon BS, Greene T, Beck GJ, et al: Dialysis Access Consortium (DAC) Trial Design: Sustained-release dipyridamole plus aspirin (D/A) to prevent graft failure. [Study size: 1,228] J Am Soc Nephrol 10:232A, 2002 (Programs and Abstracts Issue). 35th Annual Meeting & Scientific Exposition, American Society of Nephrology, Philadelphia, PA, October 30-November 4, 2002 Isoflavones and acute-phase response in chronic renal failure. [Study size: 52] National Institutes of Health, ClinicalTrials.Gov Randomized study of recombinant human growth hormone in patients on chronic hemodialysis or peritoneal dialysis. [Study size: 60] National Institutes of Health, ClinicalTrials.Gov General Nephrology Alternate day prednisone or daily fish oil supplements in patients with immunoglobulin A nephropathy. [Study size: 123] National Institutes of Health, ClinicalTrials.Gov Homocysteine Study (HOST). [Study size: 2,006] National Institutes of Health, ClinicalTrials.Gov A phase II/III study of the safety and efficacy of NC-503 in patients suffering from secondary (AA) amyloidosis. [Study size: 150] National Institutes of Health, ClinicalTrials.Gov A randomized trial comparing methotrexate versus mycophenolate mofetil for remission maintenance in Wegener’s granulomatosis and related vasculitides. [Study size: 75 ] National Institutes of Health, ClinicalTrials.Gov A randomized, double-blind, placebo-controlled, multicenter safety and efficacy trial of LJP 394 in systemic lupus erythematosus (SLE) patients with a history of renal disease. [Study size: 330] National Institutes of Health, ClinicalTrials.Gov A randomized trial examining the use of Daclizumab in Wegener’s granulomatosis. [Study size: 75] National Institutes of Health, ClinicalTrials. Gov A rotation study through the main therapeutic classes of antihypertensive in patients with polycystic kidney disease and hypertension. [Study size: 40] National Research Register,UK
American Journal of Kidney Diseases, Vol 41, No 4 (April), 2003: pp 884-890
COCHRANE RENAL GROUP REPORT
Drug therapy in lupus nephropathy. [Study size: 45] National Institutes of Health, ClinicalTrials.Gov Phase III randomized, double-blind study of potassium phosphate VS potassium citrate for absorptive hypercalciuria. [Study size: 300] National Institutes of Health, ClinicalTrials.Gov Wegener’s Granulomatosis Etanercept Trial (WGET). [Study size: 180] National Institutes of Health, ClinicalTrials.Gov Transplantation A phase II open label single center randomized study of tacrolimus plus sirolimus and corticosteroids compared with tacrolimus plus azathioprine and corticosteroids in de novo renal allografts recipients. [Study size: 60] National Research Register, UK The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT). [Study size: 400 ] National Institute of Diabetes & Digestive & Kidney Diseases PUBLISHED TRIALS
Dialysis ● Dogra GK, Herson H, Hutchison B, et al: Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate: A randomized controlled study. J Am Soc Nephrol 13:2133-2139, 2002 This trial examined the effect of a gentamicin/ citrate catheter-lock solution versus heparin on prevention of tunneled hemodialysis catheter-related infections (CRI) in 112 catheters (83 patients).
● Guo A, Wolfson M, Holt R: Early quality of life benefits of icodextrin in peritoneal dialysis. Kidney Int Suppl 81:72-79, 2002 This trial compared the effect of icodextrin dialysis solution versus dextrose on patient quality of life (mental health, muscle spasms, cramps, itchy skin, faintness) over 13 weeks in 93 peritoneal dialysis patients.
● Johnson DW, MacGinley R, Kay TD, et al: A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters. Nephrol Dial Transplant 17:1802-1807, 2002
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This trial examined the effect of thrice-weekly application of mupirocin ointment to tunneled, cuffed hemodialysis catheters versus no ointment on time to first infection, infection rates and catheter survival rates until catheter removal in 50 patients.
● Li PK, Law MC, Chow KM, et al: Comparison of clinical outcome and ease of handling in two double-bag systems in continuous ambulatory peritoneal dialysis: A prospective, randomized, controlled, multicenter study. Am J Kidney Dis 40:373-380, 2002 This trial examined the effect of the Stay-Safe versus the Ultrabag double-bag disconnect systems on peritonitis and exit-site infection rates over 18 months, and ease of handling immediately posttraining and after 1 month in 110 CAPD patients.
● Locatelli F, Baldamus CA, Villa G, et al: Once-weekly compared with three-timesweekly subcutaneous epoetin beta: results from a randomized, multicenter, therapeuticequivalence study. Am J Kidney Dis 40:119125, 2002 This trial compared the effect of once-weekly versus thrice-weekly subcutaneous epoetin beta on hematocrit and epoetin dose requirements over 24 weeks in 173 hemodialysis patients.
● McMurray SD, Johnson G, Davis S, et al: Diabetes education and care management significantly improve patient outcomes in the dialysis unit. Am J Kidney Dis 40:566575, 2002 This quasi-randomized trial examined the effect of the provision of diabetes education and a care manager on glycemic control, self-management behavior, complications (amputations, diabetes/ vascular-related admissions), and quality of life over 1 year in 83 dialysis patients with diabetes.
● Nissenson AR, Swan SK, Lindberg JS, et al: Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis 40:110-118, 2002 This trial compared the effect of once-weekly IV darbepoetin versus thrice-weekly IV epoetin on maintenance of hemoglobin concentrations over 28 weeks in 507 hemodialysis patients.
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● Santoro A, Mancini E, Basile C, et al: Blood volume controlled hemodialysis in hypotension-prone patients: A randomized, multicenter controlled trial. Kidney Int 62: 1034-1045, 2002 This crossover trial examined the effect of a blood volume tracking system versus conventional hemodialysis on treatment tolerance in 36 hypotension-prone hemodialysis patients.
● Schwab SJ, Weiss MA, Rushton F, et al: Multicenter clinical trial results with the LifeSite hemodialysis access system. Kidney Int 62:1026-1033, 2002 The randomized Phase 1 section of this trial examined a subcutaneous access device (LifeSite Hemodialysis Access System) plus antimicrobial solution (0.2% sodium oxychlorosene) versus a transcutaneous access device (Tesio-Cath Hemodialysis Catheter) on blood flow and infection rates over 6 months in 70 hemodialysis patients.
● Sehgal AR, Leon JB, Siminoff LA, et al:
This trial compared immunoprophylaxis via a single dose of daclizumab with noninduction on acute graft rejection and graft function over 12 months in 100 first-kidney transplant patients also receiving triple therapy with tacrolimus, mycophenolate mofetil (MMF), and prednisone.
● Budde K, Schmouder RL, Brunkhorst R, et al: First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J Am Soc Nephrol 13:10731083, 2002 This trial examined the pharmacokinetic and pharmacodynamic effects of FTY720 in ascending single oral dosages (0.25 to 3.5mg) on 20 stable renal transplant patients also receiving a cyclosporine-based regimen.
● Fine RN, Stablein D, Cohen AH, et al: Recombinant human growth hormone postrenal transplantation in children: A randomized controlled study of the NAPRTCS. Kidney Int 62:688-696, 2002
Improving the quality of hemodialysis treatment: A community-based randomized controlled trial to overcome patient-specific barriers. JAMA 287:1961-1967, 2002
This trial examined the effect of recombinant human growth hormone on growth velocity over 1 year post-transplantation in 68 growth-retarded pediatric transplant recipients.
This multicenter trial examined the effect of a study coordinator providing recommendations on appropriate hemodialysis practice to 44 nephrologists and 182 patients on hemodialysis dose and quality of life at 6 months.
● Flechner SM, Goldfarb D, Modlin C, et al:
● Wolfson M, Piraino B, Hamburger RJ, et al: Icodextrin Study Group. A randomized controlled trial to evaluate the efficacy and safety of icodextrin in peritoneal dialysis. Am J Kidney Dis 40:1055-1065, 2002 This article reports 2 trials: the first examined icodextrin solution versus 2.5% dextrose for ultrafiltration over 4 weeks in 175 CAPD patients. The second examined the same interventions for mortality, hospitalization, adverse events, edema and body weight gain over 1 year in 287 CAPD and APD patients. Transplantation ● Ahsan N, Holman MJ, Jarowenko MV, et al: Limited dose monoclonal IL-2R antibody induction protocol after primary kidney transplantation. Am J Transplant 2:568-573, 2002
Kidney transplantation without calcineurin inhibitor drugs: A prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 74:1070-1076, 2002 This trial compared the effects of sirolimus (initiated within 2 days of surgery) versus cyclosporine (initiated within 8 days) on patient and graft survival and acute rejection rates at 1 year after primary transplantation in 61 adults.
● Sadek S, Medina J, Arias M, et al: Shortterm combination of mycophenolate mofetil with cyclosporine as a therapeutic option for renal transplant recipients: A prospective, multicenter, randomized study. Transplantation 74:511-517, 2002 This three-arm trial compared the effect of MMF for 3 months followed by azathioprine (AZA) for 9 months versus MMF for 12 months versus AZA for 12 months on acute rejection rates and treatment failure in 477 transplant recipients also receiving cyclosporine and steroids.
COCHRANE RENAL GROUP REPORT
● Smak Gregoor PJ, de Sevaux RG, Ligtenberg G, et al: Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: A randomized, prospective, multicenter study. J Am Soc Nephrol 13:1365-1373, 2002 This three-arm trial examined the effect of withdrawal of cyclosporine 6 months post-transplantation, versus withdrawal of prednisone 6 months post-transplantation, versus continuation of triple drug therapy on acute and chronic rejection, graft loss, and mean arterial pressure over 2 years in 212 patients on cyclosporine, prednisone, and MMF.
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in 79 cardiac angiography patients with existing moderate renal impairment.
● Houssiau FA, Vasconcelos C, D’Cruz D, et al: Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus highdose intravenous cyclophosphamide. Arthritis Rheum 46:2121-2131, 2002 This trial compared low-dose versus high-dose intravenous cyclophosphamide (both followed by AZA) on remission over a median follow-up period of 41 months in 90 patients with lupus nephritis.
● Schrier R, McFann K, Johnson A, et al: Car-
Diabetic Nephropathy ● Hansen HP, Tauber-Lassen E, Jensen BR, et al: Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy. Kidney Int 62:220-228, 2002
diac and renal effects of standard versus rigorous blood pressure control in autosomaldominant polycystic kidney disease: Results of a seven-year prospective randomized study. J Am Soc Nephrol 13:1733-1739, 2002
This trial examined the effect of a low-protein diet (0.6 g/kg/d) versus normal protein diet on survival and progression to end-stage renal failure over 4 years in 82 type 1 diabetes patients with diabetic nephropathy.
This trial compared the effect of rigorous (⬍120/80 mmHg) versus standard (135-140/85-90 mmHg) blood pressure control on left ventricular mass index and renal function in 75 hypotensive autosomal-dominant polycystic kidney disease patients with left ventricular hypertrophy.
● Schrier RW, Estacio RO, Esler A, et al: Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int 61:1086-1097, 2002 This trial compared the effect of intensive blood pressure control (nisoldipine or enalapril to achieve 10 mmHg below baseline diastolic BP) versus moderate (placebo to maintain 85 to 89 mmHg) on renal function, retinopathy progression, and strokes over 5 years in 480 normotensive type 2 diabetes patients. General Nephrology ● Durham JD, Caputo C, Dokko J, et al: A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography. Kidney Int 62:22022207, 2002 This trial compared the effects of N-acetylcysteine plus IV hydration versus placebo plus IV hydration for prevention of contrast nephropathy
Acute Renal Failure ● Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, et al: Effects of early highvolume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial. Crit Care Med 30:2205-2211, 2002 This trial examined the effect of early highvolume hemofiltration versus early and late lowvolume hemofiltration on mortality and recovery of renal function over 28 days in 106 oliguric, acute renal failure patients.
● Phu NH, Hien TT, Mai NT, et al: Hemofiltration and peritoneal dialysis in infectionassociated acute renal failure in Vietnam. N Engl J Med 347:895-902, 2002 This trial examined venovenous hemofiltration versus peritoneal dialysis on mortality and cost per survivor in 70 adult patients with infectionrelated acute renal failure.
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Cochrane Reviews are regularly updated as new information becomes available and in response to comments and criticisms. The reader shuld consult The Cochrane Library for the latest version of a Cochrane Review. Information on The Cochrane Library can be found at www.update-software.com
Short Versus Standard Duration Oral Antibiotic Therapy for Acute Urinary Tract Infection in Children Reviewers: M. Michael, E.M. Hodson, J.C. Craig, S. Martin, and V.A. Moyer ● Background: The optimal duration of oral antibiotic therapy for urinary tract infection (UTI) in children has not been determined. A number of studies have compared single-dose therapy to standard therapy for UTI, with mixed results. A course of antibiotics longer than a single dose but shorter than the usual 7 to 10 days might decrease the relapse rate and still provide some of the benefits of a shortened course of antibiotics. Objectives: The objective of this review was to assess the benefits and harms of short-course (2 to 4 days) compared to standard duration (7 to 14 days) oral antibiotic treatment for acute UTI in children. Search strategy: We searched the Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002), MEDLINE (1966 –September 2002) and EMBASE (1988 –September 2002) without language restriction. Selection criteria: Randomized and quasi-randomized controlled trials comparing short-term (2 to 4 days) with standard (7 to 14 days) oral antibiotic therapy were selected if they studied children aged 3 months to 18 years with culture-proven symptomatic UTI. Data collection & analysis: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (95% CI). Main results: Ten trials were identified in which 652 children with lower tract UTI were evaluated. There was no significant difference in the frequency of positive urine cultures between the short (2 to 4 days) and standard duration oral antibiotic therapy (7 to 14 days) for UTI in children at 0 to 10 days after treatment (8 studies: RR, 1.06; 95% CI, 0.64 to 1.76) and at 1 to 15 months after treatment (10 studies: RR, 0.95; 95% CI, 0.70 to 1.29). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (1 study: RR, 0.57; 95% CI, 0.32 to 1.01) or in recurrent UTI (3 studies: RR, 0.39; 95% CI, 0.12 to 1.29). Reviewers’ conclusions: A 2- to 4-day course of oral antibiotics appears to be as effective as 7 to 14 days in eradicating lower tract UTI in children.
Corticosteroid Therapy for Nephrotic Syndrome in Children Reviewers: E.M. Hodson, J.F. Knight, N.S. Willis, and J.C. Craig ● Background: In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinemia and generalized edema. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. However, about 70% of children experience a relapsing course with recurrent episodes of edema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However, corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, and adrenal suppression. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. Objectives: The aim of this review was to determine the benefits and harms of different corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). Search strategy: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), Cochrane Renal Group Specialised Register (July 2002), MEDLINE (1966 –July 2002), and EMBASE (1980 –July 2002) without language restriction, reference lists of articles, abstracts from proceedings, and contact with known investigators in the area. Selection criteria: Randomized controlled trials were included if they were carried out in children (3 months to 18 years of age) in their initial or subsequent episode of SSNS; if they compared different durations, total doses. or other dose strategies using prednisone or other corticosteroid agent; and if they had outcome data at 6 months or more. Data collection & analysis: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality, and extracted data. The principle outcome measure was the number of children with and without relapse after 6 and 12 to 24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk [RR], risk difference [RD]) after testing for heterogeneity. Metaregression was used to explore potential between-study differences due to the baseline risk of relapse, study quality, and types of interventions used. Main results: Five additional trials were included in the review for a total of 17 trials. A meta-analysis of 6 trials, which compared 2
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months of prednisone with 3 months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 to 24 months (RR, 0.70; 95% confidence interval [CI], 0.58 to 0.84) without an increase in adverse events. There was an inverse linear relationship between the duration of treatment and risk of relapse (RR ⴝ 1.26 to 0.112 duration; r2 ⴝ 0.56; P ⴝ 0.03). The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without an increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR, 0.44; 95% CI, 0.25 to 0.78). Reviewers’ conclusions: Children in their first episode of SSNS should be treated for at least 3 months with an increase in benefit being demonstrated for up to 7 months of treatment. In a population with a baseline risk for relapse following the first episode of 60% with 2 months of prednisone, daily prednisone for 4 weeks followed by alternate-day therapy for 6 months would be expected to reduce the number of children experiencing a relapse by about 33%. In children who relapse frequently, deflazacort deserves further study.
Long-Term Antibiotics for Preventing Recurrent Urinary Tract Infection in Children Reviewers: G. J. Williams, A. Lee, and J.C. Craig ● Background: Acute urinary tract infection (UTI) is common in children. By the age of 7 years, 8.4% of girls and 1.7% of boys will have suffered at least 1 episode. Symptoms are systemic rather than localized in early childhood and consist of fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and treatment consists of a course of antibiotics. Because of the unpleasant acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children receive long-term antibiotics aimed at preventing recurrence. However, these medications may cause side effects and promote the development of resistant bacteria. Objectives: To determine the efficacy and side effects of long-term antibiotics administered prevent recurrent UTI in children. Search strategy: We conducted a search of MEDLINE (1966 to September 2002), EMBASE (1988 to September 2002), the Cochrane Controlled Trials Register (Cochrane Library, Issue 3, 2002), and the Cochrane Renal Group Specialised Register (September 2002) for relevant randomized controlled trials without language restriction; reference lists of review articles; and contact with content experts. Selection criteria: Randomized comparisons of 2 or more antibiotics and placebo with 1 or more antibiotics to prevent recurrent UTI. Data collection & analysis: Two reviewers independently assessed and extracted information. For each trial, information was collected on the methods of the trial, participants, interventions, and outcomes. A random-effects model was used to estimate a summary relative risk (RR) and a summary risk difference (RD) for recurrent UTI. Heterogeneity tests and subgroup analyses were carried out based on a priori hypothesis of plausible effect modification. Main results: There were 3 trials (n ⴝ 151) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied among the studies (10 weeks to 12 months). The method of allocation concealment in the 3 trials was inadequate, unclear, and adequate. The overall rate of recurrent UTI in the placebo/no treatment group was 63% (48/76). Compared to placebo/no treatment, antibiotics reduced the risk of recurrent UTI (RR, 0.36; 95% confidence interval [CI], 0.16 to 0.77; RD, ⴚ46%; 95% CI, ⴚ59% to ⴚ33%). No side effects were described in any of these 3 trials. There was 1 double-blinded trial (n ⴝ 120) with unclear allocation concealment that compared 2 different types of antibiotics to prevent recurrent UTI. Nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a 6-month period (RR, 0.48; 95% CI, 0.25 to 0.92; RD, ⴚ18%; 95% CI, ⴚ34% to ⴚ3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) than were patients receiving trimethoprim (RR, 3.17; 95% CI, 1.36 to 7.37; RD, 22%; 95% CI, 8% to 36%). Reviewers’ conclusions: Most published studies to date have been poorly designed with biases known to overestimate the true treatment effect. Large, properly randomized, double-blinded trials are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.
Hemoglobin and Hematocrit Targets for the Anemia of Chronic Renal Failure Reviewers: G.F.M. Strippoli, MD, J.C. Craig, PhD, MBChB, C. Manno, MD, and F.P. Schena, MD ● Background: Anemia affects 60% to 80% of patients with renal impairment, reduces quality of life, and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO), and darbepoietin. Recently, higher hemoglobin (Hb) and hematocrit (Hct) targets have been widely advocated because of positive data from observational studies. However, these may lead to access thrombosis and hypertension and are costly. This review
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assessed the benefits and harms of low (Hb <100 g/L, Hct <30%) and high (Hb >100 g/L, Hct >30%) targets in predialysis and postdialysis patients receiving any treatment for anemia. Methods: The Cochrane Renal Group Specialised Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE, and article reference lists were searched for randomized or quasirandomized trials. Two independent reviewers assessed studies for inclusion criteria (randomized Hb targets, patients with anemia of chronic renal failure) and extracted data on their effect on mortality, cardiovascular events, hypertension, seizures, stroke, hyperkalemia, access thrombosis, and quality of life. Data were analyzed with a random effects model. Results: From 1,365 abstracts retrieved, 43 full-text articles were analyzed for eligibility and 15 (2,096 patients) were included. Different targets were achieved by placebo and EPO in 12 trials (673 patients) or 2 EPO doses in 3 trials (1,423 patients). Hb values of 100 g/L are associated with lower mortality compared to Hb values of 140 g/L or more in the population with chronic renal failure and cardiovascular impairment. These targets also imply a reduced risk for hypertension but an increased risk for seizures. Conclusions: From the available trial evidence, the benefits associated with higher Hb targets (reduced seizures) are outweighed by the harms (increased risk of hypertension and death). INDEX WORDS: Anemia; chronic renal failure (CRF); hemoglobin (Hb); hematocrit (Hct).
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HIS ISSUE’S selection of randomized controlled trials includes recent ongoing and published trials from our register added since June 2002. As before, they have been selected for their relevance and quality, including suitable sample size and use of clinically important and/or patientcentered outcomes. It is particularly interesting to see reports of two trials, those by McMurray et al in the American Journal of Kidney Diseases and Sehgal et al in Journal of the American Medical Association, using educational interventions to improve quality of life for hemodialysis patients. We maintain a full list of ongoing trials on our website (www.cochrane-renal.org), with links, where available, to further information. We also regularly update our list of current published trials and provide links from Medline-indexed trials to their PubMed abstract. The Cochrane Renal Group is keen to hear details of any ongoing trials in nephrology not already included on our website. Please contact us on [email protected] if you would like to contribute in this way. INDEX WORDS: Systematic review; randomized controlled trial; Cochrane Collaboration.
DECEMBER 2002 ONGOING TRIALS
Dialysis Dember L, Kaufman J, Beck G, et al: Dialysis Access Consortium (DAC) Trial Design: Clopidogrel prevention of early AV fistula thrombosis. [Study size: 1,490] J Am Soc Nephrol 10:229A, 2002 (Programs and Abstracts Issue). 35th Annual Meeting & Scientific Exposition, American Society of Nephrology, Philadelphia, PA, October 30-November 4, 2002
From the Cochrane Renal Group, Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, New South Wales, Australia. Address reprint requests to Ruth L. Mitchell, Grad Dip Lib Sci, Trials Search Coordinator, Cochrane Renal Group, Centre for Kidney Research, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Australia. Email: [email protected] © 2003 by the National Kidney Foundation, Inc. 0272-6386/03/4104-0022$30.00/0 884
Dixon BS, Greene T, Beck GJ, et al: Dialysis Access Consortium (DAC) Trial Design: Sustained-release dipyridamole plus aspirin (D/A) to prevent graft failure. [Study size: 1,228] J Am Soc Nephrol 10:232A, 2002 (Programs and Abstracts Issue). 35th Annual Meeting & Scientific Exposition, American Society of Nephrology, Philadelphia, PA, October 30-November 4, 2002 Isoflavones and acute-phase response in chronic renal failure. [Study size: 52] National Institutes of Health, ClinicalTrials.Gov Randomized study of recombinant human growth hormone in patients on chronic hemodialysis or peritoneal dialysis. [Study size: 60] National Institutes of Health, ClinicalTrials.Gov General Nephrology Alternate day prednisone or daily fish oil supplements in patients with immunoglobulin A nephropathy. [Study size: 123] National Institutes of Health, ClinicalTrials.Gov Homocysteine Study (HOST). [Study size: 2,006] National Institutes of Health, ClinicalTrials.Gov A phase II/III study of the safety and efficacy of NC-503 in patients suffering from secondary (AA) amyloidosis. [Study size: 150] National Institutes of Health, ClinicalTrials.Gov A randomized trial comparing methotrexate versus mycophenolate mofetil for remission maintenance in Wegener’s granulomatosis and related vasculitides. [Study size: 75 ] National Institutes of Health, ClinicalTrials.Gov A randomized, double-blind, placebo-controlled, multicenter safety and efficacy trial of LJP 394 in systemic lupus erythematosus (SLE) patients with a history of renal disease. [Study size: 330] National Institutes of Health, ClinicalTrials.Gov A randomized trial examining the use of Daclizumab in Wegener’s granulomatosis. [Study size: 75] National Institutes of Health, ClinicalTrials. Gov A rotation study through the main therapeutic classes of antihypertensive in patients with polycystic kidney disease and hypertension. [Study size: 40] National Research Register,UK
American Journal of Kidney Diseases, Vol 41, No 4 (April), 2003: pp 884-890
COCHRANE RENAL GROUP REPORT
Drug therapy in lupus nephropathy. [Study size: 45] National Institutes of Health, ClinicalTrials.Gov Phase III randomized, double-blind study of potassium phosphate VS potassium citrate for absorptive hypercalciuria. [Study size: 300] National Institutes of Health, ClinicalTrials.Gov Wegener’s Granulomatosis Etanercept Trial (WGET). [Study size: 180] National Institutes of Health, ClinicalTrials.Gov Transplantation A phase II open label single center randomized study of tacrolimus plus sirolimus and corticosteroids compared with tacrolimus plus azathioprine and corticosteroids in de novo renal allografts recipients. [Study size: 60] National Research Register, UK The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT). [Study size: 400 ] National Institute of Diabetes & Digestive & Kidney Diseases PUBLISHED TRIALS
Dialysis ● Dogra GK, Herson H, Hutchison B, et al: Prevention of tunneled hemodialysis catheter-related infections using catheter-restricted filling with gentamicin and citrate: A randomized controlled study. J Am Soc Nephrol 13:2133-2139, 2002 This trial examined the effect of a gentamicin/ citrate catheter-lock solution versus heparin on prevention of tunneled hemodialysis catheter-related infections (CRI) in 112 catheters (83 patients).
● Guo A, Wolfson M, Holt R: Early quality of life benefits of icodextrin in peritoneal dialysis. Kidney Int Suppl 81:72-79, 2002 This trial compared the effect of icodextrin dialysis solution versus dextrose on patient quality of life (mental health, muscle spasms, cramps, itchy skin, faintness) over 13 weeks in 93 peritoneal dialysis patients.
● Johnson DW, MacGinley R, Kay TD, et al: A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters. Nephrol Dial Transplant 17:1802-1807, 2002
885
This trial examined the effect of thrice-weekly application of mupirocin ointment to tunneled, cuffed hemodialysis catheters versus no ointment on time to first infection, infection rates and catheter survival rates until catheter removal in 50 patients.
● Li PK, Law MC, Chow KM, et al: Comparison of clinical outcome and ease of handling in two double-bag systems in continuous ambulatory peritoneal dialysis: A prospective, randomized, controlled, multicenter study. Am J Kidney Dis 40:373-380, 2002 This trial examined the effect of the Stay-Safe versus the Ultrabag double-bag disconnect systems on peritonitis and exit-site infection rates over 18 months, and ease of handling immediately posttraining and after 1 month in 110 CAPD patients.
● Locatelli F, Baldamus CA, Villa G, et al: Once-weekly compared with three-timesweekly subcutaneous epoetin beta: results from a randomized, multicenter, therapeuticequivalence study. Am J Kidney Dis 40:119125, 2002 This trial compared the effect of once-weekly versus thrice-weekly subcutaneous epoetin beta on hematocrit and epoetin dose requirements over 24 weeks in 173 hemodialysis patients.
● McMurray SD, Johnson G, Davis S, et al: Diabetes education and care management significantly improve patient outcomes in the dialysis unit. Am J Kidney Dis 40:566575, 2002 This quasi-randomized trial examined the effect of the provision of diabetes education and a care manager on glycemic control, self-management behavior, complications (amputations, diabetes/ vascular-related admissions), and quality of life over 1 year in 83 dialysis patients with diabetes.
● Nissenson AR, Swan SK, Lindberg JS, et al: Randomized, controlled trial of darbepoetin alfa for the treatment of anemia in hemodialysis patients. Am J Kidney Dis 40:110-118, 2002 This trial compared the effect of once-weekly IV darbepoetin versus thrice-weekly IV epoetin on maintenance of hemoglobin concentrations over 28 weeks in 507 hemodialysis patients.
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● Santoro A, Mancini E, Basile C, et al: Blood volume controlled hemodialysis in hypotension-prone patients: A randomized, multicenter controlled trial. Kidney Int 62: 1034-1045, 2002 This crossover trial examined the effect of a blood volume tracking system versus conventional hemodialysis on treatment tolerance in 36 hypotension-prone hemodialysis patients.
● Schwab SJ, Weiss MA, Rushton F, et al: Multicenter clinical trial results with the LifeSite hemodialysis access system. Kidney Int 62:1026-1033, 2002 The randomized Phase 1 section of this trial examined a subcutaneous access device (LifeSite Hemodialysis Access System) plus antimicrobial solution (0.2% sodium oxychlorosene) versus a transcutaneous access device (Tesio-Cath Hemodialysis Catheter) on blood flow and infection rates over 6 months in 70 hemodialysis patients.
● Sehgal AR, Leon JB, Siminoff LA, et al:
This trial compared immunoprophylaxis via a single dose of daclizumab with noninduction on acute graft rejection and graft function over 12 months in 100 first-kidney transplant patients also receiving triple therapy with tacrolimus, mycophenolate mofetil (MMF), and prednisone.
● Budde K, Schmouder RL, Brunkhorst R, et al: First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J Am Soc Nephrol 13:10731083, 2002 This trial examined the pharmacokinetic and pharmacodynamic effects of FTY720 in ascending single oral dosages (0.25 to 3.5mg) on 20 stable renal transplant patients also receiving a cyclosporine-based regimen.
● Fine RN, Stablein D, Cohen AH, et al: Recombinant human growth hormone postrenal transplantation in children: A randomized controlled study of the NAPRTCS. Kidney Int 62:688-696, 2002
Improving the quality of hemodialysis treatment: A community-based randomized controlled trial to overcome patient-specific barriers. JAMA 287:1961-1967, 2002
This trial examined the effect of recombinant human growth hormone on growth velocity over 1 year post-transplantation in 68 growth-retarded pediatric transplant recipients.
This multicenter trial examined the effect of a study coordinator providing recommendations on appropriate hemodialysis practice to 44 nephrologists and 182 patients on hemodialysis dose and quality of life at 6 months.
● Flechner SM, Goldfarb D, Modlin C, et al:
● Wolfson M, Piraino B, Hamburger RJ, et al: Icodextrin Study Group. A randomized controlled trial to evaluate the efficacy and safety of icodextrin in peritoneal dialysis. Am J Kidney Dis 40:1055-1065, 2002 This article reports 2 trials: the first examined icodextrin solution versus 2.5% dextrose for ultrafiltration over 4 weeks in 175 CAPD patients. The second examined the same interventions for mortality, hospitalization, adverse events, edema and body weight gain over 1 year in 287 CAPD and APD patients. Transplantation ● Ahsan N, Holman MJ, Jarowenko MV, et al: Limited dose monoclonal IL-2R antibody induction protocol after primary kidney transplantation. Am J Transplant 2:568-573, 2002
Kidney transplantation without calcineurin inhibitor drugs: A prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 74:1070-1076, 2002 This trial compared the effects of sirolimus (initiated within 2 days of surgery) versus cyclosporine (initiated within 8 days) on patient and graft survival and acute rejection rates at 1 year after primary transplantation in 61 adults.
● Sadek S, Medina J, Arias M, et al: Shortterm combination of mycophenolate mofetil with cyclosporine as a therapeutic option for renal transplant recipients: A prospective, multicenter, randomized study. Transplantation 74:511-517, 2002 This three-arm trial compared the effect of MMF for 3 months followed by azathioprine (AZA) for 9 months versus MMF for 12 months versus AZA for 12 months on acute rejection rates and treatment failure in 477 transplant recipients also receiving cyclosporine and steroids.
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● Smak Gregoor PJ, de Sevaux RG, Ligtenberg G, et al: Withdrawal of cyclosporine or prednisone six months after kidney transplantation in patients on triple drug therapy: A randomized, prospective, multicenter study. J Am Soc Nephrol 13:1365-1373, 2002 This three-arm trial examined the effect of withdrawal of cyclosporine 6 months post-transplantation, versus withdrawal of prednisone 6 months post-transplantation, versus continuation of triple drug therapy on acute and chronic rejection, graft loss, and mean arterial pressure over 2 years in 212 patients on cyclosporine, prednisone, and MMF.
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in 79 cardiac angiography patients with existing moderate renal impairment.
● Houssiau FA, Vasconcelos C, D’Cruz D, et al: Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus highdose intravenous cyclophosphamide. Arthritis Rheum 46:2121-2131, 2002 This trial compared low-dose versus high-dose intravenous cyclophosphamide (both followed by AZA) on remission over a median follow-up period of 41 months in 90 patients with lupus nephritis.
● Schrier R, McFann K, Johnson A, et al: Car-
Diabetic Nephropathy ● Hansen HP, Tauber-Lassen E, Jensen BR, et al: Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy. Kidney Int 62:220-228, 2002
diac and renal effects of standard versus rigorous blood pressure control in autosomaldominant polycystic kidney disease: Results of a seven-year prospective randomized study. J Am Soc Nephrol 13:1733-1739, 2002
This trial examined the effect of a low-protein diet (0.6 g/kg/d) versus normal protein diet on survival and progression to end-stage renal failure over 4 years in 82 type 1 diabetes patients with diabetic nephropathy.
This trial compared the effect of rigorous (⬍120/80 mmHg) versus standard (135-140/85-90 mmHg) blood pressure control on left ventricular mass index and renal function in 75 hypotensive autosomal-dominant polycystic kidney disease patients with left ventricular hypertrophy.
● Schrier RW, Estacio RO, Esler A, et al: Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney Int 61:1086-1097, 2002 This trial compared the effect of intensive blood pressure control (nisoldipine or enalapril to achieve 10 mmHg below baseline diastolic BP) versus moderate (placebo to maintain 85 to 89 mmHg) on renal function, retinopathy progression, and strokes over 5 years in 480 normotensive type 2 diabetes patients. General Nephrology ● Durham JD, Caputo C, Dokko J, et al: A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography. Kidney Int 62:22022207, 2002 This trial compared the effects of N-acetylcysteine plus IV hydration versus placebo plus IV hydration for prevention of contrast nephropathy
Acute Renal Failure ● Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, et al: Effects of early highvolume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial. Crit Care Med 30:2205-2211, 2002 This trial examined the effect of early highvolume hemofiltration versus early and late lowvolume hemofiltration on mortality and recovery of renal function over 28 days in 106 oliguric, acute renal failure patients.
● Phu NH, Hien TT, Mai NT, et al: Hemofiltration and peritoneal dialysis in infectionassociated acute renal failure in Vietnam. N Engl J Med 347:895-902, 2002 This trial examined venovenous hemofiltration versus peritoneal dialysis on mortality and cost per survivor in 70 adult patients with infectionrelated acute renal failure.
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Cochrane Reviews are regularly updated as new information becomes available and in response to comments and criticisms. The reader shuld consult The Cochrane Library for the latest version of a Cochrane Review. Information on The Cochrane Library can be found at www.update-software.com
Short Versus Standard Duration Oral Antibiotic Therapy for Acute Urinary Tract Infection in Children Reviewers: M. Michael, E.M. Hodson, J.C. Craig, S. Martin, and V.A. Moyer ● Background: The optimal duration of oral antibiotic therapy for urinary tract infection (UTI) in children has not been determined. A number of studies have compared single-dose therapy to standard therapy for UTI, with mixed results. A course of antibiotics longer than a single dose but shorter than the usual 7 to 10 days might decrease the relapse rate and still provide some of the benefits of a shortened course of antibiotics. Objectives: The objective of this review was to assess the benefits and harms of short-course (2 to 4 days) compared to standard duration (7 to 14 days) oral antibiotic treatment for acute UTI in children. Search strategy: We searched the Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002), MEDLINE (1966 –September 2002) and EMBASE (1988 –September 2002) without language restriction. Selection criteria: Randomized and quasi-randomized controlled trials comparing short-term (2 to 4 days) with standard (7 to 14 days) oral antibiotic therapy were selected if they studied children aged 3 months to 18 years with culture-proven symptomatic UTI. Data collection & analysis: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (95% CI). Main results: Ten trials were identified in which 652 children with lower tract UTI were evaluated. There was no significant difference in the frequency of positive urine cultures between the short (2 to 4 days) and standard duration oral antibiotic therapy (7 to 14 days) for UTI in children at 0 to 10 days after treatment (8 studies: RR, 1.06; 95% CI, 0.64 to 1.76) and at 1 to 15 months after treatment (10 studies: RR, 0.95; 95% CI, 0.70 to 1.29). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (1 study: RR, 0.57; 95% CI, 0.32 to 1.01) or in recurrent UTI (3 studies: RR, 0.39; 95% CI, 0.12 to 1.29). Reviewers’ conclusions: A 2- to 4-day course of oral antibiotics appears to be as effective as 7 to 14 days in eradicating lower tract UTI in children.
Corticosteroid Therapy for Nephrotic Syndrome in Children Reviewers: E.M. Hodson, J.F. Knight, N.S. Willis, and J.C. Craig ● Background: In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinemia and generalized edema. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. However, about 70% of children experience a relapsing course with recurrent episodes of edema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However, corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis, and adrenal suppression. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. Objectives: The aim of this review was to determine the benefits and harms of different corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). Search strategy: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), Cochrane Renal Group Specialised Register (July 2002), MEDLINE (1966 –July 2002), and EMBASE (1980 –July 2002) without language restriction, reference lists of articles, abstracts from proceedings, and contact with known investigators in the area. Selection criteria: Randomized controlled trials were included if they were carried out in children (3 months to 18 years of age) in their initial or subsequent episode of SSNS; if they compared different durations, total doses. or other dose strategies using prednisone or other corticosteroid agent; and if they had outcome data at 6 months or more. Data collection & analysis: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality, and extracted data. The principle outcome measure was the number of children with and without relapse after 6 and 12 to 24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk [RR], risk difference [RD]) after testing for heterogeneity. Metaregression was used to explore potential between-study differences due to the baseline risk of relapse, study quality, and types of interventions used. Main results: Five additional trials were included in the review for a total of 17 trials. A meta-analysis of 6 trials, which compared 2
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months of prednisone with 3 months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 to 24 months (RR, 0.70; 95% confidence interval [CI], 0.58 to 0.84) without an increase in adverse events. There was an inverse linear relationship between the duration of treatment and risk of relapse (RR ⴝ 1.26 to 0.112 duration; r2 ⴝ 0.56; P ⴝ 0.03). The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without an increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR, 0.44; 95% CI, 0.25 to 0.78). Reviewers’ conclusions: Children in their first episode of SSNS should be treated for at least 3 months with an increase in benefit being demonstrated for up to 7 months of treatment. In a population with a baseline risk for relapse following the first episode of 60% with 2 months of prednisone, daily prednisone for 4 weeks followed by alternate-day therapy for 6 months would be expected to reduce the number of children experiencing a relapse by about 33%. In children who relapse frequently, deflazacort deserves further study.
Long-Term Antibiotics for Preventing Recurrent Urinary Tract Infection in Children Reviewers: G. J. Williams, A. Lee, and J.C. Craig ● Background: Acute urinary tract infection (UTI) is common in children. By the age of 7 years, 8.4% of girls and 1.7% of boys will have suffered at least 1 episode. Symptoms are systemic rather than localized in early childhood and consist of fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and treatment consists of a course of antibiotics. Because of the unpleasant acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children receive long-term antibiotics aimed at preventing recurrence. However, these medications may cause side effects and promote the development of resistant bacteria. Objectives: To determine the efficacy and side effects of long-term antibiotics administered prevent recurrent UTI in children. Search strategy: We conducted a search of MEDLINE (1966 to September 2002), EMBASE (1988 to September 2002), the Cochrane Controlled Trials Register (Cochrane Library, Issue 3, 2002), and the Cochrane Renal Group Specialised Register (September 2002) for relevant randomized controlled trials without language restriction; reference lists of review articles; and contact with content experts. Selection criteria: Randomized comparisons of 2 or more antibiotics and placebo with 1 or more antibiotics to prevent recurrent UTI. Data collection & analysis: Two reviewers independently assessed and extracted information. For each trial, information was collected on the methods of the trial, participants, interventions, and outcomes. A random-effects model was used to estimate a summary relative risk (RR) and a summary risk difference (RD) for recurrent UTI. Heterogeneity tests and subgroup analyses were carried out based on a priori hypothesis of plausible effect modification. Main results: There were 3 trials (n ⴝ 151) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied among the studies (10 weeks to 12 months). The method of allocation concealment in the 3 trials was inadequate, unclear, and adequate. The overall rate of recurrent UTI in the placebo/no treatment group was 63% (48/76). Compared to placebo/no treatment, antibiotics reduced the risk of recurrent UTI (RR, 0.36; 95% confidence interval [CI], 0.16 to 0.77; RD, ⴚ46%; 95% CI, ⴚ59% to ⴚ33%). No side effects were described in any of these 3 trials. There was 1 double-blinded trial (n ⴝ 120) with unclear allocation concealment that compared 2 different types of antibiotics to prevent recurrent UTI. Nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a 6-month period (RR, 0.48; 95% CI, 0.25 to 0.92; RD, ⴚ18%; 95% CI, ⴚ34% to ⴚ3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) than were patients receiving trimethoprim (RR, 3.17; 95% CI, 1.36 to 7.37; RD, 22%; 95% CI, 8% to 36%). Reviewers’ conclusions: Most published studies to date have been poorly designed with biases known to overestimate the true treatment effect. Large, properly randomized, double-blinded trials are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.
Hemoglobin and Hematocrit Targets for the Anemia of Chronic Renal Failure Reviewers: G.F.M. Strippoli, MD, J.C. Craig, PhD, MBChB, C. Manno, MD, and F.P. Schena, MD ● Background: Anemia affects 60% to 80% of patients with renal impairment, reduces quality of life, and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO), and darbepoietin. Recently, higher hemoglobin (Hb) and hematocrit (Hct) targets have been widely advocated because of positive data from observational studies. However, these may lead to access thrombosis and hypertension and are costly. This review
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assessed the benefits and harms of low (Hb <100 g/L, Hct <30%) and high (Hb >100 g/L, Hct >30%) targets in predialysis and postdialysis patients receiving any treatment for anemia. Methods: The Cochrane Renal Group Specialised Register, Cochrane Controlled Trial Registry, MEDLINE, EMBASE, and article reference lists were searched for randomized or quasirandomized trials. Two independent reviewers assessed studies for inclusion criteria (randomized Hb targets, patients with anemia of chronic renal failure) and extracted data on their effect on mortality, cardiovascular events, hypertension, seizures, stroke, hyperkalemia, access thrombosis, and quality of life. Data were analyzed with a random effects model. Results: From 1,365 abstracts retrieved, 43 full-text articles were analyzed for eligibility and 15 (2,096 patients) were included. Different targets were achieved by placebo and EPO in 12 trials (673 patients) or 2 EPO doses in 3 trials (1,423 patients). Hb values of 100 g/L are associated with lower mortality compared to Hb values of 140 g/L or more in the population with chronic renal failure and cardiovascular impairment. These targets also imply a reduced risk for hypertension but an increased risk for seizures. Conclusions: From the available trial evidence, the benefits associated with higher Hb targets (reduced seizures) are outweighed by the harms (increased risk of hypertension and death). INDEX WORDS: Anemia; chronic renal failure (CRF); hemoglobin (Hb); hematocrit (Hct).