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Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study

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Abstract

Introduction

The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown.

Methods

Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up.

Results

After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52–4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52–4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99–73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18–3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63–2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m2 greater in the aliskiren group (12.83 vs 5.08; 95% CI − 0.17 to 15.66; P = 0.055).

Conclusion

Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.

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Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ACEi:

Angiotensin converting enzyme inhibitor

ARB:

Angiotensin receptor blocker

AKI:

Acute kidney injury

ALTITUDE:

The aliskiren trial in type 2 diabetes using cardiorenal endpoints

ASTRONAUT:

The aliskiren trial on acute heart failure outcomes

CAPD:

Continuous ambulatory peritoneal dialysis

CKD:

Chronic kidney disease

DRI:

Direct renin inhibitor

DBP:

Diastolic blood pressure

eGFR:

Estimated glomerular filtration rate

Gd-IgA1:

Galactose-deficient immunoglobulin A1

PSM:

Propensity score-matched

RAAS:

Renin angiotensin aldosterone system

RENAAL:

Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan

SBP:

Systolic blood pressure

UPCR:

Urine protein-to-creatinine ratio

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Acknowledgements

This study was supported by the Hong Kong Society of Nephrology Research Grant (awarded to DNWL), and by philanthropic donations from Dr. Rita T Liu SBS of L & T Charitable Foundation Ltd. & Bingei Family of Indo Café, Mr. Winston Leung, Mr. K.K. Chan, Ms. Siu Suet Lau and an Endowment Fund established at the University of Hong Kong for the Yu Professorship in Nephrology awarded to SCWT.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 4/F Professorial Block, 102 Pokfulam Road, Hong Kong SAR, China

    Davina N. W. Lie, Kam Wa Chan, Anthony T. P. Chan, Gary C. W. Chan, Kar Neng Lai & Sydney Chi-Wai Tang

  2. Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China

    Alexander H. N. Tang

Authors
  1. Davina N. W. Lie
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  2. Kam Wa Chan
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  4. Anthony T. P. Chan
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  5. Gary C. W. Chan
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  6. Kar Neng Lai
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  7. Sydney Chi-Wai Tang
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Contributions

SCWT conceived the study. DNWL and ATPC collected the data. AHNT performed all the MEST-C scoring on kidney biopsies. KWC and DNWL performed the statistical analysis and drafted the manuscript. SCWT, DNWL, KWC, GCWC and KNL were involved in the interpretation of data and manuscript revision.

Corresponding author

Correspondence to Sydney Chi-Wai Tang.

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Conflict of interest

The authors declared that they have no conflict of interest.

Ethical approval

This project was approved by the joint Institutional Review Board and Ethics Committee of the Hong Kong Hospital Authority and the University of Hong Kong. This study is reported according to STROBE.

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Not applicable. No personal information was included.

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Lie, D.N.W., Chan, K.W., Tang, A.H.N. et al. Long-term outcomes of add-on direct renin inhibition in igA nephropathy: a propensity score-matched cohort study. J Nephrol 36, 407–416 (2023). https://doi.org/10.1007/s40620-022-01530-7

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  • DOI: https://doi.org/10.1007/s40620-022-01530-7

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