Biomedical subjects

G F M Strippoli

Publications and source records attributed to G F M Strippoli.

At least 19 recordsLinked to original sources

PubMed2006

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).

Anemia↗

PubMed2006

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.

Calcium↗

PubMed2006

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.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

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.

Anti-Infective Agents↗

PubMed2005

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. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing antiviral medications with placebo or no treatment, trials comparing different antiviral medications and trials comparing different regimens of the same antiviral medications in recipients of any solid organ transplant. DATA COLLECTION AND ANALYSIS: Two reviewers 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). 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 two trials (3737 participants) were identified. Prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment significantly reduced the risk for CMV disease (19 trials; RR 0.42, 95% CI 0.34 to 0.52), CMV infection (17 trials; RR 0.61, 95% CI 0.48 to 0.77), and all-cause mortality (17 trials; RR 0.63, 95% CI 0.43 to 0.92) primarily due to reduced mortality from CMV disease (seven trials; 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 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 trials, ganciclovir was more effective than aciclovir in preventing CMV disease (seven trials; RR 0.37, 95% Cl 0.23 to 0.60). Valganciclovir and intravenous 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.

Acyclovir↗

PubMed2005

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.

Albuminuria↗

PubMed2005

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.

Bone Diseases↗

PubMed2004

Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) is used as substitutive treatment of renal function in a large proportion (15-50%) of the end-stage kidney disease (ESRD) population. The major limitation is peritonitis which leads to technique failure, hospitalisation and increased mortality. Oral, nasal, topical antibiotic prophylaxis, exit-site disinfectants and other antimicrobial interventions are used to prevent peritonitis. OBJECTIVES: The objective of this systematic review of randomised controlled trials (RCTs) was to evaluate what evidence supports the use of different antimicrobial approaches to prevent peritonitis in PD. SEARCH STRATEGY: The Cochrane CENTRAL Registry (issue 1, 2004), MEDLINE (1966-May 2003), EMBASE (1988-May 2003) and reference lists were searched for RCTs of antimicrobial agents in PD. SELECTION CRITERIA: Trials of the following agents were included: antibiotics by any route (oral, nasal, topical), exit-site disinfectants (chlorhexidine, povidone iodine, soap and water), vaccines, and ultraviolet germicidal devices. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data on the number of patients with one or more episodes and rates of peritonitis and exit-site/tunnel infection, catheter removal, catheter replacement, technique failure, toxicity of antibiotic treatments, all-cause mortality. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Nineteen trials, enrolling 1949 patients met our inclusion criteria. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (one trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (one trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). Perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (four trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (three trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). No intervention reduced the risk of catheter removal or replacement. REVIEWERS' CONCLUSIONS: This review demonstrates that nasal mupirocin reduces exit-site/tunnel infection but not peritonitis. Preoperative intravenous prophylaxis reduces early peritonitis but not exit-site/tunnel infection. No other antimicrobial interventions have proven efficacy. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered RCTs to inform decision making about strategies to prevent peritonitis is striking.

Anti-Bacterial Agents↗

PubMed2004

Catheter type, placement and insertion techniques for preventing peritonitis in peritoneal dialysis patients.

BACKGROUND: As many as 15-50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter-related interventions have been purported to reduce the risk of peritonitis in PD. OBJECTIVES: To evaluate the use of catheter-related interventions for the prevention of peritonitis in PD. SEARCH STRATEGY: The Cochrane Renal Group's specialised register (June 2004), The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library Issue 2 2004), MEDLINE (1966-April 2004), EMBASE (1988-April 2004) and reference lists were searched without language restriction SELECTION CRITERIA: Trials comparing different catheter insertion techniques, catheter types, use of immobilisation techniques or different break in periods were included. Trials of different PD sets were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Seventeen eligible trials (1089 patients) were identified, eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, one of single cuff versus double cuff catheters and one of an immobiliser device. The methodological quality was suboptimal. There were no significant differences with laparoscopy compared with laparotomy for peritonitis, the peritonitis rate, exit-site/tunnel infection or catheter removal/replacement. Standard insertion with resting but no subcutaneous burying of the catheter versus implantation and subcutaneous burying was not associated with a significant reduction in peritonitis rate, exit-site/tunnel infection rate or all-cause mortality. Midline compared to lateral insertion showed no significant difference in the risk of peritonitis or exit-site/tunnel infection. There was no significant difference in the risk of peritonitis, peritonitis rate, exit-site/tunnel infection, exit-site/tunnel infection rate or catheter removal/replacement between straight versus coiled intraperitoneal portion catheters. One trial compared single versus double cuffed catheters and showed no significant difference in the risk of peritonitis, exit-site/tunnel infection or catheter removal/replacement. One trial compared immobilisation versus no immobilisation of the PD catheter and showed no significant difference in the risk of peritonitis and exit-site/tunnel infection. No trials of different break-in periods were identified. REVIEWERS' CONCLUSIONS: No major advantages from any of the catheter-related interventions which have been purported to reduce the risk of PD peritonitis could be demonstrated in this review. The frequency and quality of available trials are suboptimal.

Catheterization↗

PubMed2004

Treatment for lupus nephritis.

BACKGROUND: Lupus nephritis is the renal manifestation of systemic lupus erythematosus (SLE) - a disease mainly affecting young women with substantial morbidity and mortality. It is classified by the World Health Organization (WHO) criteria I - VI based on histology. WHO Class IV is a diffuse proliferative glomerulonephritis which has the worst prognosis without treatment, with a reported 17% five year survival in the era 1953-1969. This survival was 82% in the early 1990's and continues to improve. An important factor behind this has been the use of cytotoxics such as cyclophosphamide in addition to steroids. OBJECTIVES: To assess the benefits and harms of different treatments in biopsy-proven proliferative lupus nephritis (LN). SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (January 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 1, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing treatments for PLN in both adult and paediatric patients with Class III, IV, Vc, Vd lupus nephritis were included. All treatments were considered. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Of 920 articles identified, 25 were RCTs suitable for inclusion, which enrolled 915 patients. The majority compared cyclophosphamide or azathioprine plus steroids versus steroids alone. Cyclophosphamide plus steroids reduced the risk of doubling of serum creatinine (RR 0.59, 95% CI 0.40 to 0.88) compared to steroids alone but had no impact on mortality (RR 0.98, 95% CI 0.53 to 1.82). The risk of ovarian failure was significantly increased (RR 2.18, 95% CI 1.10 to 4.34). Azathioprine plus steroids reduced the risk of all cause mortality compared to steroids alone (RR 0.60, 95% CI 0.36 to 0.99), but did not alter renal outcomes. Neither therapy was associated with increased risk of major infection. No benefit was found with addition of plasma exchange to cyclophosphamide or azathioprine plus steroids for mortality ( RR 0.71, 95% CI 0.50 to 1.02), doubling of serum creatinine (RR 0.17, 95% CI 0.02 to 1.26) or end-stage renal failure (RR 1.24, 95% CI 0.60 to 2.57). There was also no increased risk of major infection (RR 0.69, 95% CI 0.35 to 1.37). REVIEWER'S CONCLUSIONS: Until future RCTs of newer agents are completed, the current use of cyclophosphamide combined with steroids remains the best option to preserve renal function in proliferative LN. The smallest effective dose and shortest duration of treatment should be used to minimise gonadal toxicity, without compromising efficacy.

Azathioprine↗

PubMed2003

Immunosuppressive agents for treating IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a world-wide disease and the cause of end-stage renal failure (ESRF) in 15 to 20% of patients within 10 years and in 30 to 40% of individuals within 20 years from the apparent onset of disease. No specific treatment has yet been established but many approaches have been investigated. OBJECTIVES: To assess the benefits and harms of immunosuppressive treatment for IgAN. SEARCH STRATEGY: We searched The Cochrane Renal Group's specialized register (May 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and handsearched reference lists of retrieved articles and conference proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing treatment of IgAN with immunosuppressive agents against placebo, no treatment, other immunosuppressive or non-immunosuppressive agents. DATA COLLECTION AND 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) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: Thirteen eligible RCTs involving 623 patients were identified. All identified RCTs had a placebo, no treatment or warfarin/dipyridamole control group. Seven trials used steroids, three used alkylating agents/cyclosporin and three used combinations of steroids and alkylating agents/cyclosporin. No trial directly compared steroids versus alkylating agents/cyclosporin. Quality was sub-optimal. Steroids were associated with a lower risk of progression to ESRF (RR 0.44, 95% CI 0.25 to 0.80) and lower urinary protein excretion (WMD -0.49 g/24h, 95% CI -0.72 to -0.12). Urinary protein excretion was lower for patients treated with alkylating agents/cyclosporin compared to placebo/no treatment (WMD -0.94 g/24h, 95% CI -1.43 to -0.46). There was no significant reduction of urinary protein excretion with combination treatment of steroids and alkylating agents compared with placebo/no treatment. REVIEWER'S CONCLUSIONS: The optimal management of IgAN remains uncertain. The RCTs identified were small, of sub-optimal methodological quality and tended to only report favorable and surrogate outcomes without a thorough reporting of treatment harms. All outcomes favor the use of immunosuppressive interventions, with steroids appearing to be the most promising. Further study, in the form of RCTs, is necessary to ascertain which patients would benefit from these interventions, whether they are the ones with early signs of renal dysfunction or those with more advanced renal impairment.

Glomerulonephritis, IGA↗

PubMedDate not supplied

[Randomized controlled trials: a controversial past and a future of regulation and rejection].

The quality of randomized controlled clinical trials has a pivotal role in their external validity. There are no definite protocols to evaluate the quality of already published studies, whereas international guidelines for the preparation of randomized controlled trials are available. This review outlines some milestones in the development of guidelines for randomized controlled trials and presents the Revised Consort Statement which includes 22 items, sub divided into sections (title and abstract, introduction, methods, results and discussion) and a flow chart. The aim of this analysis is to provide clinical researchers with a valuable working tool. Finally, future guidelines for systematic reviews of randomized controlled studies are presented according to the Cochrane Collaboration model.

Double-Blind Method↗

PubMedDate not supplied

[Prevalence of malnutrition in uremic patients undergoing hemodialysis therapy in Puglia and Lucania].

BACKGROUND: Calorie-protein malnutrition is associated with increased morbidity and mortality in hemodialysis patients. The aim of this study was to evaluate the prevalence of malnutrition in uremic patients treated with hemodialysis in two areas of Southern Italy. METHODS: A questionnaire was sent out to all Dialysis Centers in the two regions to select and enrol eligible patients by considering these parameters: Body Mass Index (BMI), serum albumin, serum creatinine, urea, calcium, phosphate, triglycerides, cholesterol, body weight. Enrolment criteria were patients on dialysis for at least six months and BMI less than 21 kg/m2. The dialytic dose was evaluated by reporting the hours of dialysis and filter surfaces. The number of weekly sessions (n. 3) remained unchanged over time. RESULTS: Twenty-three Dialysis Centers in the two Regions replied to our questionnaire and 149 patients were enrolled in the study out of the 1546 patients examined. The overall prevalence of calorie-protein malnutrition was observed in 9.6% of the patients. The prevalence of malnutrition was found to be higher in males and in patients on dialysis for longer time. We observed no correlation with the hypoproteic diet administered in the pre-dialysis phase. Malnourished patients showing progressive weight loss were older and had undergone dialysis for a longer time. CONCLUSIONS: This retrospective study indicates low prevalence of malnutrition in the two regions examined. The lack of correlation between the hypoproteic diet and dialytic dose suggests the need for further studies to evaluate if increased dialytic dose or early start of dialysis could improve the nutritional status and quality of life in elderly patients.

Adult↗

PubMedDate not supplied

[Prevalence of pre-obesity and obesity in uremic hemodialysis patients from Puglia and Lucania].

BACKGROUND: Obesity is a well-known cause of increased morbidity and mortality in the general population, while its influence on the hemodialysis population is yet to be defined. Obesity probably has a protective effect on survival in hemodialysis. In this study, we evaluated the prevalence of obesity in the hemodialysis population of Puglia and Lucania, two regions of Southern Italy, by using simple and easily accessible parameters collected by the participating centres. METHODS: One thousand five hundred and forty-six patients on stable hemodialysis for at least 6 months from 23 Centres were studied. One hundred and sixty patients had a body mass index (BMI) more than 25 kg/m2; "preobesity" was defined as a BMI ranging between 25 and 30 kg/mq, while "obesity" as a BMI > 30. All data regarding the underlying renal disease, the use of low-protein diet before beginning hemodialysis, weight and height at the beginning of treatment and the different kinds of treatment were collected. A careful analysis of the last dialysis treatment by means of biochemical data was carried out. RESULTS: The prevalence of preobesity and obesity was 3.1 and 7.3%, respectively. Eighty-three percent of patients in the preobesity group and seventy-two percent in the obesity group were female (p<0.001). The prevalence of diabetes was 19 and 24% in the preobesity and obesity groups, respectively, while it was 8% in patient with normal BMI (p<0.0001). Age and duration of low-protein diet were similar to those observed in the general population, while dialytic age was greater in preobesity group (p<0.01). Conclusions. Our study has shown that the prevalence of obese people undergoing hemodialysis is increasing. It is therefore necessary to introduce new measures to obtain a good nutritional status in end stage renal disease patients; in particular fat free mass is to be increased, since an improvement in the patient's nutritional status acts as a protecting factor against morbidity and mortality.

Adult↗

PubMedDate not supplied

[Chorea in hemodialysis: Is chorea just a neurological syndrome or is it related to uremia or dialysis?].

Chronic renal failure and haemodialysis patients are prone to develop encephalopathy. The causes of encephalopathy are often unclear. Clinical signs of encephalopathy in the uraemic patient often overlap with several other affections causing neurological disorders. Whenever basal ganglia are anatomically involved, movement disorders arise, including chorea. Some acute and chronic neurological syndromes associated with chronic uraemia have consistently been reported (uraemic encephalopathy, dialysis disequilibrium syndrome, dialysis dementia, nephroangiosclerosis neuropathy and ageing neuropathy). Other clinical conditions in which neurological involvement exists are not so frequent in both haemodialysis patients and in the general population (Wernicke's encefalopathy, Creutzfeldt-Jacob disease). Because of the non specific symptoms and the very heterogeneous aetiology, a careful physical examination should be performed in haemodialysis patients with clinical signs of encephalopathy and the main metabolic alterations should be sought; moreover, central nervous system imaging examination is often appropriate. In case of basal ganglia anatomical involvement, supported by findings of imaging techniques, it is necessary to evaluate individual causes of encephalopathy by means of more accurate tests including analysis of cerebro-spinal fluid, measurement of plasma levels of vitamin B components and laboratory tests searching for more uncommon diseases such as Huntington's chorea and Wilson's disease.

Aged↗

PubMedDate not supplied

[Nephrology evidence and guidelines: current tools and several still open questions].

BACKGROUND: It is widely accepted that decision making should be based on evidence. Although nephrology is a relatively young discipline of internal medicine that should be quick to adopt evidence-based decision making policies, several problems are slowing the progress to an era of evidence-based nephrology. These problems may be identified as: a) an inadequate knowledge-base for problems related to the utilization of evidence-based research resources; b) the unavailability of adequate evidence sources in nephrology; and c) the small investment and funding for clinical research. METHODS: This review outlines the major problems of evidence-based nephrology and looks particularly at the strengths and weaknesses of study designs for evidence-based nephrology. The primary guidelines for evidence-based preparation are presented together with possible strategies to meet the challenge of adopting evidence-based policies in nephrology. CONCLUSIONS: This challenge is particularly important now; after several years of extraordinary basic science research, we face the problem of improving clinical practice by applying this same progress in basic science. This transition has failed because of the small investment provided for clinical research.

Evidence-Based Medicine↗

PubMedDate not supplied

[Causality in nephrology: study design and objectives of future research].

BACKGROUND: Causality has to be assessed by randomised controlled trials. However, since these are not always ethically or technically possible, other study designs such as cohort studies, case-control and cross-sectional analytic studies may be used. METHODS: In this review, we focus on the strengths and limitations of epidemiological studies whose aim is to identify the causal relationship between study factor and outcome (cohort studies, case-control studies, cross-sectional analytic studies). We also introduce the absolute and non-absolute parameters useful in determining the causal relationship in epidemiological studies. RESULTS: To establish a causal relationship between a factor and an outcome, exposure must precede the outcome, the association must not be due to chance, bias, confounding or misclassification. It is important when reading this kind of research papers that all these factors are properly considered. Studies in which strong associations are documented, whereby a dose-effect relationship exists, and those which are consistent with the results of previous epidemiological studies and document biologically plausible associations are generally stronger evidence than those in which these criteria are not found. CONCLUSIONS: The design and conduct of valid cohort, case-control and other type of studies, when randomised trials are unfeasible or unethical to answer causality and intervention questions, is a challenge for the nephrology community, presently lacking valid clinical evidence and adequate answers to many questions.

Biomedical Research↗

PubMedDate not supplied

[Critical appraisal of systematic reviews of randomised trials in nephrology: theory and practice for interpreting level I evidence].

INTRODUCTION: Systematic reviews represent the primary level of evidence (level I evidence) and an excellent answer to causality questions. They should be based upon high quality standards and the critical appraisal of such study design is fundamental. METHODS: In this review we introduce the primary indicators of quality and guide our readers through the process of critical appraisal of systematic reviews. RESULTS: The main criteria in critically appraising systematic reviews in nephrology are the adequate presentation of a research question, adequate selection of studies, comprehensiveness of search strategies, the quality assessment of included studies, the fact that all procedures have been performed independently by at least 2 investigators, the exploration of heterogeneity, the type of results and their applicability. In nephrology we still lack a large number of systematic reviews because of the lack of randomised trials. CONCLUSIONS: Preparing a large number of systematic reviews is an important challenge for the nephrology community. This community should prepare more randomised trials to answer intervention questions and should make an effort to synthesise the evidence in the form of systematic reviews. It is essential that available systematic reviews be critically appraised and their results implemented in the clinical practice whenever they are based on high methodological standards.

Nephrology↗