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JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362.

Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial.

Author information

1
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China2The George Institute for Global Health, University of New South Wales, Sydney, Australia.
2
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
3
The George Institute for Global Health, University of New South Wales, Sydney, Australia.
4
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
5
The George Institute for Global Health, New Delhi, India5University of Oxford, Oxford, United Kingdom.
6
The University of British Columbia, Vancouver, British Columbia, Canada.
7
University Health Network, Toronto, Ontario, Canada.
8
David Geffen School of Medicine, University of California-Los Angeles.
9
Royal Free and University College Medical School, London, United Kingdom.
10
The George Institute for Global Health, University of New South Wales, Sydney, Australia10The George Institute for Global Health, University of Oxford, Oxford, United Kingdom11Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland.
11
University of Hong Kong, Hong Kong, China.
12
Research Institute of Nephrology, Jinling Hospital, Nanjing, China.
13
Australasian Kidney Trials Network, University of Queensland, Brisbane, Australia.
14
The George Institute for Global Health, University of New South Wales, Sydney, Australia15Menzies School of Health Research, Charles Darwin University, Darwin, Australia.
15
University of Leicester, Leicester, United Kingdom.
16
Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.
17
Mario Negri Institute for Pharmacological Research and Clinical Research Centre for Rare Diseases, Bergamo, Italy.
18
Peking University Clinical Research Institute, Beijing, China.
19
Indiana University School of Medicine, Indianapolis.

Abstract

Importance:

Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.

Objective:

To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression.

Design, Setting, and Participants:

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.

Interventions:

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.

Main Outcomes and Measures:

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.

Results:

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 < .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).

Conclusions and Relevance:

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.

Trial Registration:

clinicaltrials.gov Identifier: NCT01560052.

PMID:
28763548
PMCID:
PMC5817603
DOI:
10.1001/jama.2017.9362
[Indexed for MEDLINE]
Free PMC Article

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