Background/Purpose:

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are currently recommended for patients with lupus nephritis (LN) as an adjunctive therapy for the optimal control of proteinuria. However, that recommendation is mainly extrapolated from studies in diabetes, hypertension and IgA nephropathy with no supportive evidence from patients with LN. The aim of this study was to assess the impact of such treatment on proteinuria in active LN.

Methods:

Patients from our long-term longitudinal cohort who were treated with glucocorticosteroids (GCS) and mycophenolate mofetil (MMF, 2-3g/day) or azathioprine (AZA, 2mg/kg) for their first episode of active LN after 2001 were included. They had at least one year of follow-up with visits at 6 and 12 months. Individuals with end-stage renal disease (eGFR≤15ml/min/1.73m²) or LN class VI at baseline were excluded. Patients were divided into two groups according to the concurrent treatment with ACEIs/ARBs or not. Demographic, clinical, immunological and therapeutic variables were compared at baseline; cumulative GCS dose and blood pressure at baseline, 6 and 12 months were also assessed. Proteinuria (24h) and eGFR were compared at 6 and 12 months after therapy initiation. Complete renal response was defined as proteinuria<500mg/day. Statistical analysis was performed with SAS 9.4; p<0.05 was considered significant.

Results:

One hundred forty three patients were included (77 with concomitant ACEI/ARB treatment and 66 without). There were no significant differences concerning age at LN diagnosis, gender, race, disease duration, SLEDAI-2K and SLICC/Damage Index as well as LN histopathologic class, eGFR and blood pressure at baseline. Severity of proteinuria (2.2±1.5 vs. 2.1±1.8g/day, p=0.78) and nephrotic syndrome (proteinuria>3g/day) were also similar (15.6% vs. 18.2%, p=0.68). There were no differences in the initial GCS and MMF/AZA doses as well as antimalarial usage. Cumulative GCS dose at 12 months and blood pressure at 6 and 12 months were also comparable. Overall, 55.2% of the patients achieved a complete renal response with a significant mean reduction (60%) in proteinuria at 6 and 12 months. Prevalence of complete renal response, level of proteinuria and eGFR between groups are shown in Table 1.

A sub-analysis of the patients who were treated only with MMF (n=81, 51 with concomitant ACEI/ARB treatment and 31 without) yielded similar results.

Conclusion:

A majority of patients achieved complete renal response at 12 months without significant differences between groups. Similarly, there was a significant improvement in proteinuria at 6 and 12 months with no significant deterioration of the eGFR and no difference between groups. Renin angiotensin system blockade may not be necessary in the acute phase of LN.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/does-renin-angiotensin-system-blockade-in-addition-to-immunosuppressive-therapy-improve-proteinuria-in-acute-lupus-nephritis/