TESTING
Trial question
What is the effect of oral methylprednisolone in patients with IgA nephropathy and persistent proteinuria who are at risk of progression?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
37.0% female
63.0% male
N = 262
262 patients (96 female, 166 male).
Inclusion criteria: patients with IgA nephropathy and persistent proteinuria > 1 g/d and eGFR of 20-120 mL/min/1.73 m² after at least 3 months of BP control and RAS blockade who are at risk of progression.
Key exclusion criteria: strong indication or contraindication for corticosteroid therapy, or the use of systemic immunosuppressive therapy in the previous year.
Interventions
N=136 oral methylprednisolone (0.6-0.8 mg/kg/d; maximum 48 mg/d for 2 months, with subsequent weaning over 4-6 months).
N=126 placebo (matching placebo for 2 months).
Primary outcome
End-stage kidney disease, death due to kidney failure, or a ≥ 40% decline in eGFR
5.9%
15.9%
15.9 %
11.9 %
8.0 %
4.0 %
0.0 %
Oral
methylprednisolone
Placebo
Significant
decrease ▼
NNT = 10
Significant decrease in end-stage kidney disease, death due to kidney failure, or a ≥ 40% decline in eGFR (5.9% vs. 15.9%; HR 0.37, 95% CI 0.17 to 0.85).
Secondary outcomes
Significant increase in death, ESRD, or ≥ 40% decline in eGFR (7.4% vs. 15.9%; ARR 8.5, 95% CI 0.7 to 16.6).
No significant difference in the incidence of eGFR decline (-1.79 mL/min/1.73 m²/year vs. -6.95 mL/min/1.73 m²/year; MD -5.15, 95% CI -9.89 to 0.42).
Safety outcomes
Significant differences in serious adverse events (14.7% vs. 3.2%, p = 0.001; risk difference 11.5%, 95% CI 4.8-18.2%), mostly due to excess serious infections (8.1% vs. 0, p < 0.001; risk difference 8.1%, 95% CI 3.5-13.9%).
Conclusion
In patients with IgA nephropathy and persistent proteinuria > 1 g/d and eGFR of 20-120 mL/min/1.73 m² after at least 3 months of BP control and RAS blockade who are at risk of progression, oral methylprednisolone was superior to placebo with respect to a end-stage kidney disease, death due to kidney failure, or a ≥ 40% decline in eGFR.
Reference
Lv J, Zhang H, Wong MG et al. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432-442.
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