04352nas a2200625   4500000000100000008004100001260001700042653001000059653001100069653001100080653002400091653000900115653001600124653001400140653002800154653002500182653003100207653002800238653002000266653002300286653001600309100001800325700001700343700001400360700001300374700001400387700001100401700001600412700002100428700001900449700001800468700001800486700001900504700001900523700001500542700001500557700002500572700001700597700001700614700001800631700001900649700002100668700001800689700001300707700001700720700001900737700001900756700001700775700002400792245013200816300001200948490000800960520274400968022001403712       2017                            d  c18277394411110aAdult10aFemale10aHumans10aDouble-Blind Method10aMale10aMiddle Aged10aInfection10aKidney Failure, Chronic10aAdministration, Oral10aGlomerular Filtration Rate10aGlomerulonephritis, IGA10aGlucocorticoids10aMethylprednisolone10aProteinuria1 aWoodward Mark1 aLevin Adeera1 aCass Alan1 aWong Muh1 aJardine M1 aJha V.1 aWu Yangfeng1 aRemuzzi Giuseppe1 aMonaghan Helen1 aJohnson David1 aFeehally John1 aBillot Laurent1 aPerkovic Vlado1 aLv Jicheng1 aZhang Hong1 aHladunewich Michelle1 aZhao Minghui1 aBarbour Sean1 aReich Heather1 aCattran Daniel1 aGlassock Richard1 aWheeler David1 aChan Tak1 aLiu Zhi-Hong1 aFloege Jürgen1 aAgarwal Raj iv1 aWang Hai-Yan1 aTESTING Study Group00aEffect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial.  a432-4420 v3183 a<p>
<b>Importance: </b>Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.
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<b>Objective: </b>To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression.
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<b>Design, Setting, and Participants: </b>The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred.
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<b>Interventions: </b>Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.
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<b>Main Outcomes and Measures: </b>The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years.
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<b>Results: </b>After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P &lt; .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2.5%-17.9%]; P = .02).
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<b>Conclusions and Relevance: </b>Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.
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<b>Trial Registration: </b>clinicaltrials.gov Identifier: NCT01560052.
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