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Randomized Controlled Trial
. 2020 Dec;33(6):1231-1239.
doi: 10.1007/s40620-020-00836-8. Epub 2020 Aug 27.

Single versus dual blockade of the renin-angiotensin system in patients with IgA nephropathy

David Paul Lennartz #  1 , Claudia Seikrit #  1 , Stephanie Wied  2 , Christina Fitzner  2 , Frank Eitner  1   3 , Ralf-Dieter Hilgers  2 , Thomas Rauen  1 , Jürgen Floege  4
Affiliations
Randomized Controlled Trial

Single versus dual blockade of the renin-angiotensin system in patients with IgA nephropathy

David Paul Lennartz et al. J Nephrol. 2020 Dec.

Abstract

Background: Inhibitors of the renin-angiotensin system (RAS) are cornerstones of supportive therapy in patients with IgA nephropathy (IgAN). We analyzed the effects of single versus dual RAS blockaQueryde during our randomized STOP-IgAN trial.

Methods: STOP-IgAN participants with available successive information on their RAS treatment regimen and renal outcomes during the randomized 3-year trial phase were stratified post hoc into two groups, i.e. patients under continuous single or dual RAS blocker therapy over the entire 3 years of the trial phase. Primary and secondary STOP-IgAN trial endpoints, i.e. frequencies of full clinical remission, eGFR-loss ≥ 15 and ≥ 30 ml/min/1.73 m2 and ESRD onset, were analyzed by logistic regression and linear mixed effects models.

Results: Among the 112 patients included in the present analysis, 82 (73%) were maintained on single and 30 (27%) on dual RAS inhibitor therapy throughout the trial. Neither RAS blocker strategy significantly affected full clinical remission, eGFR-loss rates, onset of ESRD. Proteinuria moderately increased in patients under dual RAS blockade by 0.1 g/g creatinine during the 3-year trial phase. This was particularly evident in patients without additional immunosuppression during the randomized trial phase, where proteinuria increased by 0.2 g/g creatinine in the dual RAS blockade group. In contrast, proteinuria decreased in patients under single RAS blocker therapy by 0.3 g/g creatinine. The course of eGFR remained stable and did not differ between the RAS treatment strategies.

Conclusion: In the STOP-IgAN cohort, neither RAS blocker regimen altered renal outcomes. Patients on dual RAS blockade even exhibited higher proteinuria over the 3-year trial phase.

Keywords: IgA nephropathy; RAS blockers; RAS system; Renin-angiotensin system; STOP-IgAN.

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Conflict of interest statement

J.F. has received consultant honoraria from Omeros, USA, Retrophin, USA and Calliditas, Sweden. The other authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Flowchart of analyzed patients
Fig. 2
Fig. 2
Urinary protein excretion (a) and eGFR (b) at enrollment, at randomization (i.e. at the end of the 6-month run-in phase) and at the end of the 3-year trial phase in patients under single versus dual RAS blockade
Fig. 3
Fig. 3
Aldosterone measurements in available serum samples obtained at the end of the trial phase according to continuous single or dual RAS blocker therapy during the randomized 3-year trial phase
See this image and copyright information in PMC

References

    1. Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med. 2013;368(25):2402–2414. doi: 10.1056/NEJMra1206793. - DOI - PubMed
    1. KDIGO Clinical Practice Guideline for Glomerulonephritis Kidney International Supplements. 2012;2(2):142. doi: 10.1038/kisup.2012.12. - DOI
    1. Rauen T, et al. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med. 2015;373(23):2225–2236. doi: 10.1056/NEJMoa1415463. - DOI - PubMed
    1. Ma, F., et al., Treatment for IgA nephropathy with stage 3 or 4 chronic kidney disease: low-dose corticosteroids combined with oral cyclophosphamide. J Nephrol, 2020. - PubMed
    1. Stefanski A, et al. Early increase in blood pressure and diastolic left ventricular malfunction in patients with glomerulonephritis. Kidney Int. 1996;50(4):1321–1326. doi: 10.1038/ki.1996.444. - DOI - PubMed

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