High-Target Hemodiafiltration Convective Dose Achieved in Most Patients in a 6-Month Intermediary Analysis of the CONVINCE Randomized Controlled Trial.

Introduction: High convection volumes in hemodiafiltration (HDF) result in improved survival; however, it remains unclear whether it is achievable in all patients. Methods: CONVINCE, a randomized controlled trial, randomized patients with end-stage kidney disease 1:1 to high-dose HDF versus high-flux hemodialysis (HD) continuation. We evaluated the proportion of patients achieving high-dose HDF target: convection volume per visit of ≥23 l (range ±1 l) at baseline, month 3, and month 6. We compared baseline characteristics in the following 2 ways: (i) patients on target for all 3 visits versus patients who missed target on ≥1 visits and (ii) patients on target for all 3 visits or missing it once versus patients who missed target on ≥2 visits. Results: A total of 653 patients were randomized to HDF. Their mean age was 62.2 (SD 13.5) years, 36% were female, 81% had fistula vascular access, and 33% had diabetes. Across the 3 visits, 75 patients (11%), 27 patients (4%), and 11 patients (2%) missed the convection volume target once, twice, and thrice, respectively. Apart from diabetes, there were no apparent differences in patient characteristics between patients who always achieved the high-dose target (83%) and those who missed the target either once or more (17%) or twice or more (6%). Conclusion: Achieving high-dose HDF is feasible for nearly all patients in CONVINCE and could be maintained during the 6-month follow-up period. Apart from diabetes, there were no other indications for confounding by indication on multivariable analyses that may explain the potential survival advantage for patients receiving high-dose HDF.

Interventions for minimal change disease in adults with nephrotic syndrome.

BACKGROUND: Steroids have been used widely since the early 1970s for the treatment of adult-onset minimal change disease. The response rates to immunosuppressive agents in adult minimal change disease, especially steroids, are more variable than in children. The optimal agent, dose, and duration of treatment for the first episode of nephrotic syndrome, or for disease relapse(s) has not been determined. OBJECTIVES: To determine the benefits and harms of interventions for the nephrotic syndrome in adults caused by minimal change disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference articles and abstracts from conference proceedings, without language restriction. Search date: January 2007. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of any intervention for minimal change disease in adults over 18 years with the nephrotic syndrome were included. Studies comparing different routes, frequencies, and duration of immunosuppressive agents were selected. Studies comparing non-immunosuppressive agents were also assessed. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and results were expressed as a relative risk (RR) for dichotomous outcomes, or mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Three RCTs (68 participants) were identified. All treatment comparisons contained only one study. No significant difference was found between prednisone compared with placebo for complete (RR 1.44, CI 0.95 to 2.19) and partial remission (RR 1.00, CI 0.07 to 14.45) of the nephrotic syndrome due to minimal change disease. There was no difference between intravenous methylprednisolone plus oral prednisone compared with oral prednisone alone for complete remission (RR 0.74, CI 0.50 to 1.08). Prednisone, compared with short-course intravenous methylprednisolone, increased the number of subjects who achieved complete remission (RR 4.95, CI 1.15 to 21.26). The lack of statistical evidence of efficacy associated with prednisone therapy was based on data derived from a single study that compared 'alternate-day prednisone' to no immunosuppression' with only a small number of participants in each group. No RCTs were identified comparing regimens in adults with a steroid-dependent or relapsing disease course or comparing treatments comprising alkylating agents, cyclosporine, tacrolimus, levamisole, or mycophenolate mofetil. AUTHORS' CONCLUSIONS: Further comparative studies are required to examine the efficacy of immunosuppressive agents for achievement of sustained remission of nephrotic syndrome caused by minimal change disease. Studies are also needed to evaluate treatments for adults with steroid-dependent or relapsing disease.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis with the aim of preventing the clinical syndrome associated with CMV infection. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause mortality in solid organ transplant recipients. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. Date of last search: February 2007 SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications and comparing different regimens of the same antiviral medications in recipients of any solid organ transplant. DATA COLLECTION AND ANALYSIS: Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). Subgroup analysis and univariate meta-regression were performed using restricted maximum-likelihood to estimate the between study variance. Multivariate meta-regression was performed to investigate whether the results were altered after allowing for differences in drugs used, organ transplanted and recipient CMV serostatus at the time of transplantation. MAIN RESULTS: Thirty four studies (3850 participants) were identified. Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 studies; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 studies; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 studies; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (7 studies; RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduced the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but not fungal infection, acute rejection or graft loss. Meta-regression showed no significant difference in the relative benefit of treatment (risk of CMV disease or all-cause mortality) by organ transplanted or CMV serostatus; no conclusions were possible for CMV negative recipients of negative organs. In direct comparison studies, ganciclovir was more effective than aciclovir in preventing CMV disease (7 studies; RR 0.37, 95% CI 0.23 to 0.60). Valganciclovir and IV ganciclovir were as effective as oral ganciclovir. AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated mortality in solid organ transplant recipients. They should be used routinely in CMV positive recipients and in CMV negative recipients of CMV positive organ transplants.

Treatment for peritoneal dialysis-associated peritonitis.

BACKGROUND: Peritonitis is a common complication of peritoneal dialysis (PD) and is associated with significant morbidity. Adequate treatment is essential to reduce morbidity and recurrence. OBJECTIVES: To evaluate the benefits and harms of treatments for PD-associated peritonitis. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE and reference lists without language restriction. Date of search: February 2005 SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs assessing the treatment of peritonitis in peritoneal dialysis patients (adults and children) evaluating: administration of an antibiotic(s) by different routes (e.g. oral, intraperitoneal, intravenous); dose of an antibiotic agent(s); different schedules of administration of antimicrobial agents; comparisons of different regimens of antimicrobial agents; any other intervention including fibrinolytic agents, peritoneal lavage and early catheter removal were included. DATA COLLECTION AND ANALYSIS: Two authors extracted data on study quality and outcomes. Statistical analyses were performed using the random effects model and the dichotomous results were expressed as relative risk (RR) with 95% confidence intervals (CI) and continuous outcomes as mean difference (WMD) with 95% CI. MAIN RESULTS: We identified 36 studies (2089 patients): antimicrobial agents (30); urokinase (4), peritoneal lavage (1) intraperitoneal (IP) immunoglobulin (1). No superior antibiotic agent or combination of agents were identified. Primary response and relapse rates did not differ between IP glycopeptide-based regimens compared to first generation cephalosporin regimens, although glycopeptide regimens were more likely to achieve a complete cure (3 studies, 370 episodes: RR 1.66, 95% CI 1.01 to 3.58). For relapsing or persistent peritonitis, simultaneous catheter removal/replacement was superior to urokinase at reducing treatment failure rates (1 study, 37 patients: RR 2.35, 95% CI 1.13 to 4.91). Continuous IP and intermittent IP antibiotic dosing had similar treatment failure and relapse rates. IP antibiotics were superior to IV antibiotics in reducing treatment failure (1 study, 75 patients: RR 3.52, 95% CI 1.26 to 9.81). The methodological quality of most included studies was suboptimal and outcome definitions were often inconsistent. There were no RCTs regarding duration of antibiotics or timing of catheter removal. AUTHORS' CONCLUSIONS: Based on one study, IP administration of antibiotics is superior to IV dosing for treating PD peritonitis. Intermittent and continuous dosing of antibiotics are equally efficacious. There is no role shown for routine peritoneal lavage or use of urokinase. No interventions were found to be associated with significant harm.

[Evidence-based guidelines and nephrological clinical practice: the GRADE system for rating of evidence]. / Applicabilità delle Linee Guida basate sull'evidenza e alla comune pratica clinica: il sistema GRADE.

It has become widely accepted that decision-making should be based on the best available evidence. The preparation of evidence-based guidelines in the interest of improving long-term outcomes has been a challenging task for many societies. Although nephrology is a relatively young medical discipline and therefore presumably well-disposed towards evidence-based decision making, many problems exist and evidence-based approaches to guidelines have also been widely criticized. One key issue has been the availability of only few and suboptimal randomized trials in this discipline. Considerable variation in the grading systems used to assess existing evidence in nephrology guidelines highlights the need for a better tool. Tools that rigidly assess existing evidence need to also explore the applicability to current practice. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system, developed and implemented in 2004 by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines panel, is the most advanced tool in this direction.

Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial.

Microalbuminuria is a strong, consistent and independent risk factor for cardiovascular and renal disease in patients with diabetes and/or hypertension and in the general population. Several randomized trials have shown the efficacy of inhibiting the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) to prevent cardiovascular events and the progression of kidney disease. These 2 classes of drugs are equally effective for renal outcomes in patients with diabetic nephropathy, but only ACEIs have been found to significantly impact the risk of all-cause mortality, predominantly cardiovascular, in patients with diabetic nephropathy. Studies on the cardiorenal efficacy of combined therapy with ACEIs and ARBs in individuals with microalbuminuria or macroalbuminuria and other cardiovascular risk factors have been inconclusive. The Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) study aims to address existing questions in this setting. This is a phase III, randomized, comparative, pragmatic trial with prospective randomized open blinded endpoint (PROBE) design. It will evaluate the comparative efficacy of combined therapy with ACEIs and ARBs versus monotherapy with either ACEIs or ARBs in improving cardiovascular and renal outcomes in microalbuminuric or macroalbuminuric individuals at cardiorenal risk. The study will enroll 2,100 patients, selected in a network of internal medicine, diabetology or nephrology outpatient clinics. Patients will be randomly allocated to ACEIs, ARBs or their combination. The study has been approved and funded by the Agenzia Italiana del Farmaco (A.I.F.A.) within the 2005 funding plan for independent research on drugs.

Interventions for preventing bone disease in kidney transplant recipients.

BACKGROUND: Patients with chronic kidney disease have significant abnormalities of bone remodeling and mineral homeostasis and are at increased risk of fracture. The fracture risk for a kidney transplant recipient is four times that of the general population and higher than for a patient on dialysis. Randomised controlled trials (RCTs) report the use of bisphosphonates, vitamin D sterols, calcitonin, and hormone replacement therapy to treat bone disease following transplantation. OBJECTIVES: To evaluate the use of interventions for treating bone disease following kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library), Cochrane Renal Group's specialised register, MEDLINE, EMBASE, reference lists, and conference proceedings abstracts without language restriction. Date of last search: May 2006 SELECTION CRITERIA: RCTs and quasi-RCTs comparing different treatments for kidney transplant recipients of any age were selected. We excluded all other transplant recipients, including kidney-pancreas transplant recipients. DATA COLLECTION AND ANALYSIS: Two authors 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 (CI) for dichotomous variables and mean difference (MD) for continuous outcomes. MAIN RESULTS: Twenty-four trials (1,299 patients) were included. No individual intervention (bisphosphonates, vitamin D sterol or calcitonin) was associated with a reduction in fracture risk compared with placebo. Combining results for all active interventions against placebo demonstrated any treatment of bone disease was associated with a reduction in the RR of fracture (RR 0.51, 95% CI 0.27 to 0.99). Bisphosphonates (any route), vitamin D sterol, and calcitonin all had a beneficial effect on the bone mineral density at the lumbar spine. Bisphosphonates and vitamin D sterol also had a beneficial effect on the bone mineral density at the femoral neck. Bisphosphonates had greater efficacy for preventing bone mineral density loss when compared head-to-head with vitamin D sterols. Few or no data were available for combined hormone replacement, testosterone, selective oestrogen receptor modulators, fluoride or anabolic steroids. Other outcomes including all-cause mortality and drug-related toxicity were reported infrequently. AUTHORS' CONCLUSIONS: Treatment with a bisphosphonate, vitamin D sterol or calcitonin after kidney transplantation may protect against immunosuppression-induced reductions in bone mineral density and prevent fracture. Adequately powered trials are required to determine whether bisphosphonates are better than vitamin D sterols for fracture prevention in this population. The optimal route, timing, and duration of administration of these interventions remains unknown.

Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is the most common virus causing disease and death in solid organ transplant recipients during the first six months post-transplant. Previous systematic reviews have demonstrated the efficacy of antiviral medications used prophylactically or pre-emptively in preventing CMV disease. In this review the efficacy of older agents (immunoglobulins (IgG), anti CMV vaccines and interferon) are examined. OBJECTIVES: To assess the benefits and harms of IgG, anti CMV vaccines or interferon for preventing symptomatic CMV disease in solid organ transplant recipients. SEARCH STRATEGY: We searched the Cochrane Renal Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. Date of last search: December 2005 SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing IgG, anti CMV vaccine or interferon with placebo or no treatment, IgG alone or combined with antiviral medications with antiviral medications or IgG alone in recipients of any solid organ transplant. DATA COLLECTION AND ANALYSIS: Two of four authors independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Thirty seven trials (2185 participants) were included in this review. There was no significant difference in the risk for CMV disease (16 trials, 770 patients: RR 0.80, 95% CI 0.61 to 1.05), CMV infection (14 trials, 775 patients: RR 0.94, 95% CI 0.80 to 1.10) or all-cause mortality (8 trials, 502 patients: RR 0.57, 95% CI 0.32 to 1.03) with IgG compared with placebo/no treatment. However IgG significantly reduced the risk of death from CMV disease (6 trials, 346 patients: RR 0.33, 95% CI 0.14 to 0.80). There was no difference in the risk for CMV disease (4 trials, 298 patients: RR 1.17, 95% CI 0.74 to 1.86), CMV infection (4 trials, 298 patients: RR 1.16, 95% CI 0.89 to 1.52) or all-cause mortality (2 trials, 217 patients: RR 0.92, 95% CI 0.37 to 2.29) between antiviral medication combined with IgG and antiviral medication alone. There was no significant difference in the risk of CMV disease with anti CMV vaccine or interferon compared with placebo or no treatment. AUTHORS' CONCLUSIONS: Currently there are no indications for IgG in the prophylaxis of CMV disease in recipients of solid organ transplants.

Choice of extracorporeal dialysis modality: can it be evidence based?

The incidence of end stage kidney disease is increasing worldwide and extracorporeal renal replacement techniques are widely used to treat these patients. Convective dialytic therapies such as hemodiafiltration are claimed to be superior to diffusive techniques such as hemodialysis given the higher clearance rates, hemodynamic stability and possibly reduced morbidity and mortality rates. Although observational studies have held this contention, randomized trials failed to do so. In this article, we present a case report and review available trial and systematic review evidence on the benefits-harms of various extracorporeal techniques. Both convective and diffusive clearance techniques were found to have similar all-cause mortality and hospitalization rates. Data on quality of life, dialysis related amyloidosis and procedure related outcomes such as hypotension have not been well studied. Most of the unbiased information, in the form of randomized trials, are only deriving from few and very small studies while large trials are lacking. Currently, there are three ongoing randomized clinical trials analyzing the efficacy of various extracorporeal techniques with focus on hard end points and their results will shed more light on this topic. Until then, since both convective and diffusive therapies have not been found to be different with respect to major patient-level outcomes but only some surrogates of uncertain clinical importance, the choice of renal replacement therapy should be based on other factors such as patients' preference, availability of dialysis centers and cost.

[Patient satisfaction in hemodialysis: a pilot cross-sectional analysis and a review]. / Valutazione del grado di soddisfazione da trattamento nel paziente in emodialisi: metologia di ricerca, strumenti, limiti e studio pilota trasversale.

BACKGROUND: Assessment of patient satisfaction is not performed routinely in many healthcare institutions. In this review, we discuss methodological aspects of assessment of patient satisfaction in hemodialysis. We also present a pilot study conducted in the Gambro Healthcare Italy dialysis clinics network. METHODS: Patient satisfaction was assessed in a network of hemodialysis units by using an internally validated Italian translation of the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) questionnaire. A cross-sectional analytic study design was used and data analysed with univariate and multivariate hierarchical logistic regression to explore correlates of the risk of being unsatisfied with dialysis treatment. Covariates which were considered include a series of over 20 clinical, demographic, organizational and structural aspects. In addition, unexplained inter-centre residual variability due to 'case-mix' was explored and plotted. RESULTS: Seventeen dialysis units participated in this cross-sectional analysis and 758/1001 (75.7%) provided answers to the questionnaires. There was a statistically significant association on multivariate hierarchical analysis between the risk of being unsatisfied with dialysis treatment and interdialysis body weight gain (unit of increase: 1 kg, p=0.004). On the contrary, the risk of unsatisfaction with dialysis treatment was significantly lower in patients with higher dry weight (unit of increase: 1 kg, p=0.002). Our multivariate hierarchical analysis identified some residual variability between dialysis units (n=6 outliers) which may not be explained by any of over 20 potential confounding covariates which were explored. CONCLUSIONS: Assessment of ''customer satisfaction'' is standard practice in private for profit product companies in general but needs to be increasingly recognized as a standard in both public and private providers of healthcare services. Social research methods, which are used for this type of analysis, need to be fine tuned and actively implemented in order to better understand how we may influence the quality of service we provide to our patients and the level at which they rate it.

Haemoglobin and haematocrit targets for the anaemia of chronic kidney disease.

BACKGROUND: Anaemia affects 60% to 80% of patients with chronic kidney disease (CKD) reduces quality of life and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO) and darbepoetin alfa. Recently higher haemoglobin (Hb) and haematocrit (HCT) targets have been widely advocated because of positive associations with improved survival and quality of life from observational studies. OBJECTIVES: To assess the benefits and harms of different Hb or HCT targets in CKD patients receiving any treatment for anaemia. SEARCH STRATEGY: We searched The Cochrane Renal Group's specialised register, Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library) MEDLINE (from 1966), EMBASE (from 1980) and reference lists of retrieved articles. Date of most recent search: April 2006 SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing different Hb/HCT targets in patients with the anaemia of CKD. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as relative risks (RR) for dichotomous outcomes and weighted mean difference (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: Twenty two trials (3707 patients) were included. Hb > or = 133 g/L was not associated with a reduction in the risk of all-cause mortality compared with 120 g/L in dialysis and pre-dialysis patients. In pre-dialysis patients, there was a significantly lower end of treatment creatinine clearance with Hb < 120 g/L compared to > 130 g/L (MD -4.17, 95% CI -6.33 to -2.02) but no significant difference in the risk of end-stage kidney disease (ESKD) (RR 1.05, 95% CI 0.50 to 2.22). Lower Hb targets resulted in an increased risk for seizures (RR 5.25, 95% CI 1.13 to 24.34) and a reduced risk of hypertensive episodes (RR 0.50, 95% CI 0.33 to 0.76). There were no significant differences in the risk of vascular access thrombosis. AUTHORS' CONCLUSIONS: There was no significant difference in the risk of death for low (< 120 g/L) versus higher Hb targets (>133 g/L). Lower Hb targets were significantly associated with an increased risk for seizures but a reduced risk of hypertension. In general study quality was poor. There is a need for more adequately powered, well-designed and reported trials. Trials should be pragmatic, focusing on hard end-points (mortality, ESKD, major side effects) or outcomes which were previously not studied adequately (e.g. seizures, quality of life).

Pre-emptive treatment for cytomegalovirus viraemia to prevent cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment with antiviral agents of patients with CMV viraemia has been widely adopted as an alternative to routine prophylaxis to prevent CMV disease. OBJECTIVES: This review was conducted to evaluate the efficacy of pre-emptive treatment in preventing symptomatic CMV disease. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library Issue 2, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005) and reference lists and conference proceedings were searched. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of pre-emptive treatment versus placebo, no treatment or antiviral prophylaxis in solid organ transplant recipients. DATA COLLECTION AND ANALYSIS: Two authors assessed the quality and extracted all data. Analysis was with a random-effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI). MAIN RESULTS: Ten eligible trials (476 patients) were identified, six of pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), three of pre-emptive treatment versus antiviral prophylaxis and one of oral versus intravenous pre-emptive treatment. Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (six trials, 288 patients: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (three trials, 185 patient: RR 1.06, 95% CI 0.64 to 1.76) or all-cause mortality (two trials, 176 patients: RR 1.23, 95% CI 0.35 to 4.30). Comparative trials of pre-emptive therapy versus prophylaxis showed no significant difference in the risks of CMV disease, acute rejection or all-cause mortality. AUTHORS' CONCLUSIONS: Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care, but additional head-to-head trials are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients.

BACKGROUND: Calcimimetic agents have recently been evaluated in the treatment of secondary hyperparathyroidism (SHPT) as add-on therapy to calcitriol and vitamin D analogues and dietary phosphate binders. OBJECTIVES: To evaluate the benefits and harms of calcimimetics for the prevention of secondary hyperparathyroid bone disease (including osteitis fibrosa cystica and adynamic bone disease) in dialysis patients with chronic kidney disease (CKD). SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and conference proceedings were searched for randomised controlled trials (RCTs) evaluating any calcimimetic against placebo or another agent in pre-dialysis or dialysis patients with CKD. SELECTION CRITERIA: We included all RCTs of any calcimimetic agent, cinacalcet HCl (AMG-073, Sensipar), NPS R-467 or NPS R-568 administered to patients with CKD for the treatment of SHPT. DATA COLLECTION AND ANALYSIS: Data were extracted on all relevant patient-centred and surrogate outcomes. Analysis was by a random effects model and results expressed as relative risk (RR) or weighted mean difference (MD) with 95% confidence intervals. MAIN RESULTS: Eight studies (1429 patients) were identified, which compared a calcimimetic agent plus standard therapy to placebo plus standard therapy. The end of treatment values of parathyroid hormone (pg/mL) (MD -290.79, 95% CI -360.23 to -221.34), serum calcium (mg/dL) (MD -0.85, 95% CI -1.14 to -0.56), serum phosphorus (mg/dL) (MD -0.29, 95% CI -0.50 to -0.08) and the calcium by phosphorus product (mg(2)/dL(2))(MD -7.90, 95% CI -10.25 to -5.54) were significantly lower with calcimimetics compared to placebo. No significant effects on patient-based endpoints were demonstrated except for the risk of hypotension which was significantly reduced with calcimimetics compared to placebo (RR 0.53, 95%CI 0.36 to 0.79). AUTHORS' CONCLUSIONS: Calcimimetic treatment of SHPT leads to significant improvements in biochemical parameters that observational studies have shown to be associated with increased mortality, cardiovascular risk and osteitis fibrosa, but patient-based benefits have not yet been demonstrated in trials. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until further RCTs become available.

Haemodiafiltration, haemofiltration and haemodialysis for end-stage kidney disease.

BACKGROUND: Renal replacement therapy (RRT) for end-stage kidney disease (ESKD) can be achieved by several interventions including haemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation. HD, haemofiltration (HF), haemodiafiltration (HDF) and acetate-free biofiltration (AFB) are extracorporeal RRT methods. It has been suggested that HF and HDF may reduce the frequency and severity of intradialytic and post-dialytic adverse symptoms and may be more effective than HD in the removal of high molecular weight molecules. OBJECTIVES: To compare convective modes of extracorporeal RRT (HF, HDF or AFB) with HD and to establish if any of these techniques is superior to each other in patients with ESKD. SEARCH STRATEGY: We searched MEDLINE (1966-2006), EMBASE (1980-2006), Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library issue 2, 2006) and CINAHL (1872-2006). Authors of included studies were contacted, reference lists of identified RCTs and relevant narrative reviews were screened. SELECTION CRITERIA: RCTs comparing HF, HDF, AFB and HD for ESKD were included. Trials enrolling any patient undergoing RRT for ESKD were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weighted mean difference (MD) for continuous data with 95% confidence intervals (CI). Heterogeneity was measured using the Chi-square (chi(2)) and I(2) statistic. MAIN RESULTS: Twenty studies (657 patients) were included. Seventeen studies compared HF, HDF or AFB with HD, two compared HDF with AFB and one compared HF with HDF. The studies were generally small with suboptimal quality. Convective modalities (HF, HDF, AFB) did not differ significantly from HD for mortality (RR 1.68, 95% CI 0.23 to 12.13; chi(2)= 2.58, P = 0.11, I(2) = 61.2%), number of hospital admissions/year (MD 0.20, 95% CI -0.07 to 0.47) and dialysis adequacy (Kt/V: MD 0.09, 95% CI 0.02 to 0.17; chi(2) = 3.73, P = 0.29, I(2) = 19.6%). No study assessed number of dialysis treatments associated with "any adverse symptoms", sessions that were stopped early, change of dialysis modality or dialysis-related amyloidosis. AUTHORS' CONCLUSIONS: We were unable to demonstrate whether convective modalities (either HF, HDF or AFB) have significant advantages over HD with regard to clinically important outcomes of mortality, dialysis-related hypotension and hospitalisation. More adequately-powered good quality RCTs assessing clinically important outcomes (mortality, hospitalisation, quality of life) are needed.

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor antagonists (AIIRA) are considered to be equally effective for patients with diabetic kidney disease (DKD), but renal and not mortality outcomes have usually been considered. OBJECTIVES: To evaluate the benefits and harms ACEi and AIIRA in patients with DKD. SEARCH STRATEGY: We searched MEDLINE (1966 to December 2005), EMBASE (1980 to December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 4 2005) and contacted known investigators. SELECTION CRITERIA: Studies comparing ACEi or AIIRA with placebo or each other in patients with DKD were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). Heterogeneity among studies was explored using the Cochran Q statistic and the I(2) test, subgroup analyses and random effects metaregression. MAIN RESULTS: Fifty studies (13,215 patients) were identified. Thirty eight compared ACEi with placebo, five compared AIIRA with placebo and seven compared ACEi and AIIRA directly. There was no significant difference in the risk of all-cause mortality for ACEi versus placebo (RR 0.91, 95% CI 0.71 to 1.17) and AIIRA versus placebo (RR 0.99, 95% CI 0.85 to 1.17). A subgroup analysis of studies using full-dose ACEi versus studies using half or less than half the maximum tolerable dose of ACEi showed a significant reduction in the risk of all-cause mortality with the use of full-dose ACEi (RR 0.78, 95% CI 0.61 to 0.98). Baseline mortality rates were similar in the ACEi and AIIRA studies. The effects of ACEi and AIIRA on renal outcomes (ESKD, doubling of creatinine, prevention of progression of micro- to macroalbuminuria, remission of micro- to normoalbuminuria) were similarly beneficial. Reliable estimates of effect of ACEi versus AIIRA could not be obtained from the three studies in which they were compared directly because of their small sample size. AUTHORS' CONCLUSIONS: Although the survival benefits of ACEi are known for patients with DKD, the relative effects on survival of ACEi with AIIRA are unknown due to the lack of adequate direct comparison studies. In placebo controlled studies, only ACEi (at the maximum tolerable dose, but not lower so-called renal doses) were found to significantly reduce the risk of all-cause mortality. Renal and toxicity profiles of these two classes of agents were not significantly different.

Antimicrobial agents and catheter-related interventions to prevent peritonitis in peritoneal dialysis: Using evidence in the context of clinical practice.

BACKGROUND: Peritonitis still represents a common and major complication of peritoneal dialysis. The broader adoption of several strategies, including antimicrobial and catheter related interventions, has been advocated to prevent or reduce the risk of peritonitis in peritoneal dialysis. METHODS: In this article we start with the presentation of a clinical case where concern exists about the strategies for preventing peritoneal dialysis peritonitis. We then look at the available evidence in the form of systematic reviews of randomized trials and individual randomized trials of interventions to prevent peritonitis in peritoneal dialysis. A summary of the evidence is provided and then put in context with the clinical case scenario. RESULTS: Nineteen eligible trials (1949 patients) of antimicrobial agents and 37 (2822 patients) of catheter related interventions to prevent peritonitis in peritoneal dialysis were identified. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (1 trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (1 trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). As for antimicrobial strategies, perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (4 trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (3 trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). As for catheter related strategies, Y-set and twin-bag systems were superior to conventional spike systems (7 trials, 485 patients, RR 0.64, 95% CI 0.53 to 0.77) and no other catheter-related intervention was demonstrated to prevent peritonitis in PD. CONCLUSIONS: Evidence exists to support the use of perioperative intravenous antibiotic prophylaxis at the time of catheter placement, the twin-bag and Y-set system, as well as prophylaxis with mupirocin in Staphylococcus aureus nasal carriers. Despite lack of evidence, several other agents are used and recommended in major international guidelines, which is reasonable but requires further investigation.

[The Italian Society of Nephrology Guidelines (3rd Edition): principles and methods]. / I principi ed i metodi della III edizione delle Linee Guida della Società Italiana di Nefrologia (2005-2006).

Scientific Societies at both a local and international level are making big effort to prepare their clinical practice guidelines. The Italian Society of Nephrology has already published in two previous editions a series of guidelines relating to various aspects of management and diagnosis of different renal diseases. In this review we present the criteria of the 3(rd) edition of the Italian Society of Nephrology guidelines. This 3(rd) edition of guidelines will be based on the availability of scientific evidence in different areas of nephrology, dialysis and transplantation. Ten key intervention questions have been identified, based on the availability of systematic reviews of randomized trials or individual randomized address them. Systematic reviews and randomized trials are the optimal study design to address intervention questions. These have been summarized based upon rigid methodological criteria and strictly reflect the evidence basis. The different phases of development and publication of the 3(rd) edition of the Italian Society of Nephrology guidelines are presented.

Interventions for preventing bone disease in kidney transplant recipients.

BACKGROUND: Patients with chronic kidney disease have significant abnormalities of bone remodelling and calcium homeostasis and are at increased risk of fracture. The fracture risk for a kidney transplant recipient is four times that of the general population and higher than that for a patient on dialysis. Trials reporting the use of bisphosphonates, vitamin D analogues, calcitonin, and hormone replacement therapy to treat bone disease following engraftment exist. OBJECTIVES: To evaluate the use of interventions for the treatment of bone disease following kidney transplantation. SEARCH STRATEGY: The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library - Issue 3 2004), MEDLINE (1966 to August 2004), EMBASE (1980- August 2004) and reference lists were searched without language restriction. SELECTION CRITERIA: Randomised trials of treatment of bone disease following kidney transplantation were included. Trials of recipients of any transplant other than a kidney transplant including trials of kidney-pancreas transplants were excluded. DATA COLLECTION AND ANALYSIS: Two authors assessed independently 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 (CI) for dichotomous variables. For continuous variables the weighted mean difference (WMD) and its 95% CI was used. MAIN RESULTS: Twenty-three eligible trials (1,209 patients) were identified. Seven trials compared more than two interventions. Nineteen trials compared active treatment with placebo, five vitamin D analogue and calcium, six vitamin D analogue alone, twelve bisphosphonates, and four nasal calcitonin. Eight trials compared two active treatments, one 17-beta oestradiol and medroxyprogesterone versus vitamin D analogue, five bisphosphonate versus vitamin D analogue, two vitamin D analogue and calcium versus calcium and one bisphosphonate versus calcitonin. Methodological quality was suboptimal. There were no significant differences between any treatment group for risk of fracture. Bisphosphonate, administered by any route, vitamin D analogue and calcitonin all had a beneficial effect on the bone mineral density at the lumbar spine. Bisphosphonates and vitamin D analogue had a beneficial effect on the bone mineral density at the femoral neck. Few or no data were available for combined hormone replacement, testosterone, selective oestrogen receptor modulators, fluoride or anabolic steroids. All-cause mortality and drug-related toxicity were reported infrequently and there was no statistical difference between treatment groups. AUTHORS' CONCLUSIONS: No benefit from any intervention known to reduce risk of fracture from bone disease could be demonstrated to reduce fracture incidence in kidney transplant recipients.

Antihypertensive agents for preventing diabetic kidney disease.

BACKGROUND: Twenty to sixty percent of diabetic patients are affected by hypertension and antihypertensive agents are used to treat this condition. These agents are also used to prevent the onset of kidney disease both in normotensive and hypertensive diabetics. OBJECTIVES: To evaluate the comparative effects of antihypertensive agents in patients with diabetes and normoalbuminuria. SEARCH STRATEGY: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, conference proceedings, and contact with investigators were used to identify relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any antihypertensive agent with placebo or another agent in hypertensive or normotensive patients with diabetes and no kidney disease (albumin excretion rate < 30 mg/d) were included. DATA COLLECTION AND ANALYSIS: Two investigators independently extracted data on renal outcomes and other patient relevant outcomes (all-cause mortality, serious cardiovascular events), and assessed quality of trials. Analysis was by a random effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI). MAIN RESULTS: Sixteen trials (7603 patients) were identified, six of angiotensin converting enzyme inhibitors (ACEi) versus placebo, six of ACEi versus calcium channel blockers (CCBs), one of ACEi versus CCBs or combined ACEi and CCBs and three of ACEi versus other agents. Compared to placebo, ACEi significantly reduced the development of microalbuminuria (six trials, 3840 patients: RR 0.60, 95% CI 0.43 to 0.84) but not doubling of creatinine (three trials, 2683 patients: RR 0.81, 95% CI 0.24 to 2.71) or all-cause mortality (four trials, 3284 patients: RR 0.81, 95% CI 0.64 to 1.03). Compared to CCBs, ACEi significantly reduced progression to microalbuminuria (four trials, 1210 patients: RR 0.58, 95% CI 0.40 to 0.84). AUTHORS' CONCLUSIONS: A significant reduction in the risk of developing microalbuminuria in normoalbuminuric patients with diabetes has been demonstrated for ACEi only. It appears that the effect of ACEi is independent of baseline blood pressure, renal function and type of diabetes, but data is too sparse to be confident that these are not important effect modifiers and an individual patient data meta-analysis is required.