Suetonia C. Palmer

Meta-analysis: Erythropoiesis-stimulating agents in patients with chronic kidney disease

BACKGROUNDnPrevious meta-analyses suggest that treatment with erythropoiesis-stimulating agents (ESAs) in chronic kidney disease (CKD) increases the risk for death. Additional randomized trials have been recently completed.nnnPURPOSEnTo summarize the effects of ESA treatment on clinical outcomes in patients with anemia and CKD.nnnDATA SOURCESnMEDLINE (January 1966 to November 2009), EMBASE (January 1980 to November 2009), and the Cochrane database (to March 2010) were searched without language restriction.nnnSTUDY SELECTIONnTwo authors independently screened reports to identify randomized trials evaluating ESA treatment in people with CKD. Hemoglobin target trials or trials of ESA versus no treatment or placebo were included.nnnDATA EXTRACTIONnTwo authors independently extracted data on patient characteristics, study risks for bias, and the effects of ESA therapy.nnnDATA SYNTHESISn27 trials (10 452 patients) were identified. A higher hemoglobin target was associated with increased risks for stroke (relative risk [RR], 1.51 [95% CI, 1.03 to 2.21]), hypertension (RR, 1.67 [CI, 1.31 to 2.12]), and vascular access thrombosis (RR, 1.33 [CI, 1.16 to 1.53]) compared with a lower hemoglobin target. No statistically significant differences in the risks for mortality (RR, 1.09 [CI, 0.99 to 1.20]), serious cardiovascular events (RR, 1.15 [CI, 0.98 to 1.33]), or end-stage kidney disease (RR, 1.08 [CI, 0.97 to 1.20]) were observed, although point estimates favored a lower hemoglobin target. Treatment effects were consistent across subgroups, including all stages of CKD.nnnLIMITATIONSnThe evidence for effects on quality of life was limited by selective reporting. Trials also reported insufficient information to allow analysis of the independent effects of ESA dose on clinical outcomes.nnnCONCLUSIONnTargeting higher hemoglobin levels in CKD increases risks for stroke, hypertension, and vascular access thrombosis and probably increases risks for death, serious cardiovascular events, and end-stage renal disease. The mechanisms for harm remain unclear, and meta-analysis of individual-patient data and trials on fixed ESA doses are recommended to elucidate these mechanisms.nnnPRIMARY FUNDING SOURCEnNone.

Corticosteroid or Nonsteroidal Antiinflammatory Drugs for the Treatment of Acute Gout: A Systematic Review of Randomized Controlled Trials

Objective. Nonsteroidal antiinflammatory drugs (NSAID) are used as first-line agents to treat acute gout. Recent trials suggest a possible first-line role for corticosteroids. Methods. We conducted a metaanalysis of randomized controlled trials (RCT) evaluating corticosteroid versus NSAID therapy (nonselective and selective) as treatment for acute gout. MEDLINE, EMBASE, and CENTRAL were systematically searched through August 2016. Outcomes included pain, bleeding, joint swelling, erythema, tenderness, activity limitation, response to therapy, quality of life, time to resolution, supplementary analgesics, and adverse events. Evidence quality was summarized using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system. Results. Six eligible trials (817 patients) were identified. The mean study followup was 15 days (range 4–30). Risks of bias were generally low. In low- to moderate-quality evidence, corticosteroids did not have different effects on pain score at < 7 days [standardized mean difference (SMD) −0.09, 95% CI −0.26 to 0.08] or at ≥ 7 days (SMD 0.32, 95% CI −0.27 to 0.92) when compared with NSAID. There was no evidence of different risks of gastrointestinal bleeding [relative risk (RR) 0.09, 95% CI 0.01–1.67]. There was no evidence of different responses to therapy on pain at < 7 days (RR 1.07, 95% CI 0.80–1.44) and ≥ 7 days, time to disease resolution, or number of supplementary analgesics used (MD 2.10 drugs, 95% CI −1.01 to 5.21). There was a lower risk of indigestion (RR 0.50, 95% CI 0.27–0.92), nausea (RR 0.25, 95% CI 0.11–0.54), and vomiting (RR 0.11, 95% CI 0.02–0.56) with corticosteroid therapy. Conclusion. There is no evidence that corticosteroids and NSAID have different efficacy in managing pain in acute gout, but corticosteroids appear to have a more favorable safety profile for selected adverse events analyzed in existing RCT.

KHA-CARI commentary on the KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease

Due to the markedly accelerated risks of cardiovascular disease for people who have chronic kidney disease (CKD), lipid-lowering treatment represents a potentially effective intervention to reduce cardiovascular events, including death from cardiovascular disease. However, existing randomized trials have been inconsistent about whether statin therapy is beneficial for all patients with CKD, particularly those who are treated with dialysis, while data for recipients of a kidney transplant and children with CKD are sparse. Given the extensive trial data that have become available over recent years and in particular, information from the Study of Heart and Renal Protection (SHARP) trial of simvastatin/ezetimibe which involved more than 9000 adults with advanced kidney disease, lipid management is a highly relevant guideline for development by the Kidney Disease Improving Global Outcomes (KDIGO) group. The KDIGO ‘Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease’ was published in November 2013 and makes 13 recommendations. In this commentary, we consider the recommendations made in the KDIGO guideline with particular reference to the New Zealand and Australian context. Overall, the KDIGO guideline recommendations are suitable for Australasian clinical practice.

Statins for end-stage kidney disease treated with dialysis.

This systematic review summarized the available evidence for the efficacy and safety of statin therapy in adults with end-stage kidney disease treated with dialysis. The review assessed the efficacy and safety of statin drugs (atorvastatin, cerivastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin with or without combined ezetimibe therapy) against placebo or another statin. We focus here on the available evidence in placebo-controlled trials for treatment effects on mortality, cardiovascular, adverse event and lipid end-points.