Effects of dapagliflozin in IgA-nephropathy in real clinical practice

Introduction. IgA-nephropathy (IGAN) is the most common glomerulopathy worldwide leading to chronic kidney disease (CKD) progression and end stage renal disease. In the last decade sodium-glucose cotransporter type 2 inhibitors (iSGLT2) including dapagliflozin are considered to be the excellent  option for CKD treatment. However, the efficacy of dapagliflozin in patients with IgAN was analyzed only in few studies which had some serious limitations. We conducted the present study to reveal the effects of the drug in the real clinical practice.

Methods. In this retrospective study we enrolled patients with IGAN (n=30) who were diagnosed and treated in nephrology clinic of Pavlov University during 2022. Inclusion criteria were: primary variant of IgAN, eGFR≥25 ml/min/1.73 m² at the time of the diagnosis, follow-up period ≥6 months (mo) from the time of diagnosis/ dapagliflozin initiation, absence of diabetes mellitus. Patients were divided on 2 groups: on dapagliflozin treatment 10 mg/day (Dapa+, n=19) and without iSGLT2 therapy (Dapa-, n=11). In all patients we evaluated basic clinical and demographic parameters including 24h proteinuria and eGFR at the time of kidney biopsy and at 6, 12, 18 and 24 mo of follow-up. All tissue samples were classified by MEST-C (Oxford classification). Tubular atrophy/ interstitial fibrosis was estimated semiquantitatively as T0, T1 and T2 corresponding to < 25%, 25-50% and >50% of cortex involved, respectively.

Results. Basic clinical and morphological parameters were compared between Dapa+ and Dapa-. Reduction of 24h-proteinuria in Dapa+ was greater than in Dapa- at 12 mo (M (IQR): -1.14 [-2.04;-0.31] vs -0.5 [-1.26;+0.34] g/day, p=0,042), 18 mo (M (IQR): -1.09 [-1.98;-0.4] vs -0.84 [-2.4;+0.73] g/day, p=0,042), and 24 mo (M (IQR): -1.34 [-1.68;-0.86] vs -0.78 [-1.02;+0.32] g/day, p=0,021). There was no difference in eGFR changes between two groups. In patients with T<2 decrease in 24h-proteinuria in Dapa+ was better than in Dapa- at 6 mo (M (IQR): -0.94 [-1.21;-0.58] vs -0.58 [-0.58;-1.13] g/day, p=0,042), 12 mo (M (IQR): -0.77 [-1.14;-0.31] vs -0.5 [-0.5;+0.34] g/day, p=0,042) and 24 mo (M (IQR): -0.86 [-1.34;-0.3] vs -0.32 [-1.02;+0.32], g/day, p=0,042).

Conclusion. Dapagliflozin showed the distinct nephroprotective effect in patients with IgAN including those who had mild-moderate tubulointerstitial fibrosis. This finding supports the idea to initiate the iSGLT2 treatment in early CKD stages aiming to achieve better proteinuria reduction and slow CKD progression.

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