Hematuria Remission and Prognosis in IgA Nephropathy: A Post hoc Analysis of The TESTING Randomized Clinical Trial

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Hematuria Remission and Prognosis in IgA Nephropathy: A Post hoc Analysis of The TESTING Randomized Clinical Trial

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Co-author 1

Jingyi Wu wujingyi0858@163.com Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China *

Co-author 2

Dana Kim dana.kim@sydney.edu.au University of New South Wales The George Institute for Global Health Sydney Australia -

Co-author 3

Ling Guo guoling0915@126.com Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China -

Co-author 4

Jinwei Wang gslzwjw@163.com Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China -

Co-author 5

Hongyu Yang 543834697@qq.com Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China -

Co-author 6

Pei Chen glhrp@163.com Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China -

Co-author 7

Jingyi Li jingyili93@163.com Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China -

Co-author 8

Helen Monaghan h.monaghan@unsw.edu.au University of New South Wales The George Institute for Global Health Sydney Australia -

Co-author 9

Muh Geot Wong muhgeot.wong@sydney.edu.au University of New South Wales The George Institute for Global Health Sydney Australia -

Co-author 10

Vlado Perkovic vlado.perkovic@unsw.edu.au University of New South Wales The George Institute for Global Health Sydney Australia -

Co-author 11

Jicheng Lv jichenglv75@gmail.com Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China -

Co-author 12

Hong Zhang hongzh@bjmu.edu.cn Peking University First Hospital Renal Division, Peking University Institute of Nephrology Beijing China -

Co-author 13

Co-author 14

Co-author 15

Introduction

Hematuria is a hallmark of IgA nephropathy (IgAN), yet its prognostic value remains controversial. This study aimed to evaluate the association between hematuria remission and long‑term kidney outcomes, utilizing post hoc data from the Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) randomized clinical trial (RCT).

Methods

We conducted a post hoc analysis of the TESTING RCT, including 491 participants with biopsy-confirmed IgAN and a median follow-up of 3.5 years. Hematuria remission was defined as time‑averaged hematuria ≤ 5 RBC/HPF, and proteinuria remission as time‑averaged proteinuria < 1.0 g/day. The primary outcome was a composite of ≥40% eGFR decline, kidney failure, or kidney-related death, in accordance with the TESTING protocol. Analyses included stepwise Cox proportional hazards modeling and Kaplan-Meier survival estimates.

Results

Figure 2. Kaplan-Meier analysis of the primary composite outcome according to different hematuria remission groups in all included participants with IgAN. (A) Hematuria non-remission (H+) and hematuria remission (H-). (B) History of macrohematuria (Macro+) and history of no macrohematuria (Macro-). Methylprednisolone therapy significantly increased rates of hematuria remission (50.8% vs 39.9%, P = 0.020) and proteinuria remission (33.9% vs 16.5%, P < 0.001) compared to placebo. Hematuria remission alone was not significantly associated with reduced risk of kidney progression (HR, 0.799; 95% CI 0.579-1.103; P = 0.173). In contrast, proteinuria remission significantly reduced the risk of kidney progression in both hematuria remission (HR, 0.193; 95% CI, 0.092-0.404; P < 0.001) and non-remission groups (HR, 0.070; 95% CI, 0.022-0.220; P < 0.001).

Conclusion

Glucocorticoid therapy was associated with greater rates of hematuria and proteinuria remission. While hematuria remission was not significantly associated with improved kidney outcomes, proteinuria remission showed a robust and independent association. These findings support proteinuria remission as a more reliable surrogate marker than hematuria remission for long-term kidney outcomes in IgAN.

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