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Review
. 2020 Jul 15;9(7):2243.
doi: 10.3390/jcm9072243.

Nephroprotection by SGLT2 Inhibition: Back to the Future?

Luca De Nicola  1 , Francis B Gabbai  2 , Carlo Garofalo  1 , Giuseppe Conte  1 , Roberto Minutolo  1
Affiliations
Review

Nephroprotection by SGLT2 Inhibition: Back to the Future?

Luca De Nicola et al. J Clin Med. .

Abstract

The introduction of sodium/glucose cotransporter 2 inhibitors (SGLT2i) has opened new perspectives for the management of diabetic population at risk of or with chronic kidney disease (CKD). More important, recent, large real-world studies have repositioned the nephroprotective efficacy of SGLT2i emerged from randomized trials within the frame of effectiveness. Furthermore, the salutary effects of these agents may extend to the nondiabetic population according to the positive results of current studies. Nevertheless, the clear benefits of these agents on the prevention of organ damage contrast with their unexpected, limited use in clinical practice. One potential barrier is the acute decline in glomerular filtration rate (GFR) commonly observed at the beginning of treatment. This phenomenon is reminiscent of the early response to the traditional nephroprotective interventions, namely blood pressure lowering, dietary protein and salt restriction and the inhibition of the renin-angiotensin system. Under this perspective, the "check-mark" sign observed in the GFR trajectory over the first weeks of SGT2i therapy should renew interest on the very basic goal of CKD treatment, i.e., alleviate hyperfiltration in viable nephrons in order to prolong their function.

Keywords: SGLT2-inhibition; chronic kidney disease; nephroprotection.

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Conflict of interest statement

L.D.N. has received fees for scientific consultation and/or lectures from Astellas, AstraZeneca, Mundibiopharma and Vifor Pharma. R.M. was a member of advisory boards for Astellas and an invited speaker at meetings supported by Amgen and Vifor Pharma. F.G., G.C and C.G. do not have any conflict of interest to declare.

Figures

Figure 1
Figure 1
Check-mark sign in randomized trials reporting GFR values by period of follow up. Solid line represents changes in active arm, while dotted line refers to placebo arm. Trials are described in Table 1. GFR decline is absolute (upper panel) or percentual (lower panel) and calculated from baseline to the first 6 months and from 6 months to the end of trial. Absolute changes are calculated as weighted means in order to take into account the different sample size in trials, and are expressed as mL/min/month to take into account the different timing of GFR assessment in different trials. The initial period occurred after 5.1 ± 1.5 months and end of trial after further 43.3 ± 17.8 months for trials with SGLT2i and after 5.6 ± 3.1 months and end of trial after further 41.6 ± 13.8 months for trials with other interventions.
Figure 2
Figure 2
Intrarenal hemodynamic mechanisms of nephroprotection by SGLT2 inhibition. SGLT2, sodium/glucose cotransporter 2; Rprox Na, proximal tubular reabsorption of sodium; TGF, tubuloglomerular feedback; ECV, extracellular volume; GBM, glomerular basal membrane.
See this image and copyright information in PMC

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