Narelle S Willis

Prevention and treatment of renal disease in Henoch-Schönlein purpura: a systematic review

Objective: To determine the benefits and harms of therapies used to prevent or treat renal involvement in Henoch-Schönlein purpura. Design: Systematic review of randomised controlled trials. Setting: Secondary and tertiary paediatric and paediatric nephrology services. Subjects: Ten trials involving 1230 children aged less than 18 years. Main outcome measures: Persistent proteinuria and/or haematuria. Results: Meta-analyses of four trials showed no significant difference in the risk of persistent kidney disease at 6 months (379 children; relative risk (RR) 0.51, 95% CI 0.24 to 1.11) and 12 months (498 children; RR 1.02, 95% CI 0.40 to 2.62) in children given prednisone for 14–28 days at presentation of Henoch-Schönlein purpura compared with placebo or supportive treatment. In children with severe renal disease, there was no significant difference in the risk of persistent renal disease with cyclophosphamide compared with supportive treatment (one trial; 56 children; RR 1.07, 95% CI 0.65 to 1.78) and with cyclosporin compared with methylprednisolone (one trial; 19 children; RR 0.39; 95% CI 0.14 to 1.06). Conclusions: Data from randomised trials for any intervention used to improve renal outcomes in children with Henoch-Schönlein purpura are very sparse except for short-term prednisone, which has not been shown to be effective.

How to write a Cochrane systematic review.

The Cochrane Collaboration is a global network whose aim is to improve health‐care decision making through systematic reviews of the effects of health‐care interventions. Cochrane systematic reviews are published in the Cochrane Database of Systematic Reviews within The Cochrane Library ( http://www.thecochranelibrary.com), and regularly updated as new evidence arises. Cochrane Reviews are undertaken by teams of volunteer authors, who have access to free training resources, reference texts and software for preparing and maintaining their review. Here we aim to describe the steps involved to undertake a new or update an existing Cochrane Review.

Corticosteroid therapy in nephrotic syndrome: a meta-analysis of randomised controlled trials

AIMS To determine the benefits and toxicity of different corticosteroid regimes in preventing relapse in steroid responsive nephrotic syndrome. DESIGN Meta-analysis of randomised controlled trials. SUBJECTS Twelve trials involving 868 children aged 3 months to 18 years. MAIN OUTCOME MEASURE Frequency of relapse. RESULTS A meta-analysis of five trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12–24 months (relative risk 0.73; 95% confidence interval 0.60 to 0.89) without an increase in adverse events. There was an inverse linear relation (relative risk 1.382 (SE 0.215) − 0.133 (SE 0.048) duration;r 2 = 0.66; p = 0.05) between the duration of treatment and risk of relapse. CONCLUSIONS Children in their first episode of steroid responsive nephrotic syndrome should be treated with prednisone for at least three months, with an increase in benefit being shown for up to seven months of treatment.

Interventions for renal vasculitis in adults. A systematic review

BackgroundRenal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney failure, haematuria and proteinuria. Treatment of these conditions involves the use of steroid and non-steroid agents with or without adjunctive plasma exchange. Although immunosuppression has been successful, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This systematic review was conducted to determine the benefits and harms of any intervention for the treatment of renal vasculitis in adults.MethodsWe searched the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group Specialised Register, MEDLINE and EMBASE to June 2009. Randomised controlled trials investigating any intervention for the treatment of adults were included. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio with 95% confidence intervals for dichotomous outcomes or mean difference for continuous outcomes.ResultsTwenty two studies (1674 patients) were included. Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at 12 months (five studies: RR 0.47, CI 0.30 to 0.75). Four studies compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leukopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against Azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or Leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in Wegeners granulomatosis.ConclusionsPlasma exchange is effective in patients with severe ARF secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil are also effective. Azathioprine, methotrexate and leflunomide are effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.

Reliability of DMSA for the diagnosis of renal parenchymal abnormality in children

Abstract The objective of this study was to evaluate the variability of technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy interpretation by four nuclear medicine physicians for the diagnosis of renal parenchymal abnormality in children, and to compare variability among three different DMSA methods in clinical use: planar alone, single-photon emission tomography (SPET) alone, and planar with SPET. One hundred consecutive DMSA studies were independently interpreted 3 times by four participating nuclear medicine specialists from different departments and in random order. All scans were classified by the presence or absence of renal parenchymal abnormality using the modified four-level grading system of Goldraich. Indices of agreement were the percentage of agreement and the kappa statistic. Disagreement was analysed using children, kidneys and kidney zones (three zones per kidney). Using patients as the unit of analysis, agreement for planar and planar with SPET methods was 87%–88% (kappa 0.74) for the normal-abnormal scan classification. The corresponding agreement value for the SPET alone method was 78% (kappa 0.56). Similarly, substantial disagreement (disagreement ≥2 categories) occurred in 2.5% and 1.3% of comparisons between observers for planar alone and planar with SPET, respectively, but in 5.2% of comparisons for SPET alone. These results did not vary appreciably whether interpretation of patients, kidneys or kidney zones was compared. It is concluded that the four experienced nuclear medicine physicians showed substantial agreement in the interpretation of planar alone and planar with SPET DMSA scintigraphic images. Interpretation of SPET DMSA images, without planar images, was significantly more variable than interpretation using the two other methods, disagreement occurring in more than 20% of comparisons. SPET DMSA scintigraphy, when used without planar images, does not provide a firm basis for clinical decision making in the care of children who may have renal damage. There is no apparent benefit of reduced variability from the extra provision of SPET data to nuclear medicine physicians who already have planar images.

Celebrating 20 years of evidence from the Cochrane Collaboration: what has been the impact of systematic reviews on nephrology?

It has been 20 years since the Cochrane Collaboration started the global effort to synthesize evidence to improve healthcare. Since 1997, the Cochrane Renal Group has produced over 100 systematic reviews that have collectively had an important impact on nephrology care, guidelines and policy. In this article, we reflect on the ongoing need for randomized trials and systematic reviews in contemporary nephrology and the achievements of the Cochrane Collaboration so far. We also describe some of the challenges in clinical research still faced by the nephrology community today.

Reply to the letter from P. Geier et al.

Sirs, We appreciate the opportunity to respond to the thoughtful comments of Dr. Geier and his colleagues [1] about our article “Evidence-based management of steroidsensitive nephrotic syndrome” in Pediatric Nephrology [2]. We do not agree that the results of our systematic review [3] fail to inform clinicians about the management of a child with his/her initial episode of SSNS. The primary purpose of a systematic review is to present an unbiased synthesis of the best available research information relevant to the clinical question, rather than to provide rigid recommendations for treatment. The latter require additional considerations including availability of interventions and estimation of baseline risks. The conclusions drawn are designed to help people to understand the implications of the evidence when making practical decisions based on local conditions. However, we would suggest that the trial data available to inform clinicians about steroid use for this indication are relatively numerous, especially in comparison with many other clinical problems in paediatric nephrology. Dr. Geier and colleagues imply that because the evidence base is not perfect, “experts” should decide, and that the experts should weight the findings of the Arbeitsgemeinschaft für Pädiatrische Nephrologie (APN) trial [4] over the ten other trials, which are relevant, and ignore the data showing that courses longer than 3 months reduce the likelihood of relapses. We disagree. The data from our systematic review of randomised controlled trials of steroid therapy in initial episodes of SSNS demonstrate that prolonged courses of therapy should be administered in the initial episode of SSNS and suggest that courses should exceed 3 months [3]. The total dose and duration of daily and alternate-day steroids used in four trials comparing 3 months of therapy with 6 months differed though two well designed trials [5, 6] used the APN 3 month regimen [4] in their control groups. Nevertheless no heterogeneity existed among studies allowing the conclusion that 6 months of therapy are more effective than 3 months. The meta-analysis carried out by Dr Geier and his colleagues [1], which compared the results of the 6-month therapy arms from the four trials with those of the 3-month therapy arm in the APN trial [4], is not an appropriate method for comparing results across trials. One should not compare the outcome of one arm of one trial with the outcome of a second arm in another trial. This type of analysis ceases to be a randomised comparison because any differences in outcome between the two groups may be due to differences in baseline risks. Standard meta-analytic methods estimate the weighted average of within-trial treatment effects. The results of Dr Geier’s analysis are simply not valid [1]. We agree that further well designed and adequately powered randomised controlled trials are required to determine the optimal duration and total dose of steroids in the initial episode of SSNS. It would certainly be an advantage if such trials tested different interventions against a standard intervention such as the APN 3-month regimen [4]. We support the suggestion of Dr Geier and Pediatr Nephrol (2006) 21:1781–1782 DOI 10.1007/s00467-006-0207-2