Article Text

SGLT2 inhibitors in lupus nephropathy, a new therapeutic strategy for nephroprotection
  1. Enrique Morales1,
  2. Maria Galindo2
  1. 1 Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain
  2. 2 Rheumatology, Hospital Universitario 12 de Octubre, Madrid, Spain
  1. Correspondence to Dr Enrique Morales, Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain, Spain; emoralesr{at}

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Systemic lupus erythematosus (SLE) is a chronic autoimmune condition characterised by heterogeneous clinical features. The patients with SLE are known to have an increased risk of cardiovascular events, due to both traditional and disease-specific risk factors, including inflammation, endothelial dysfunction, accelerated atherosclerosis and lupus nephritis (LN). Since chronic kidney disease (CKD) is per se one of the strongest CV risk factors, any manoeuvres to prevent CKD progression, including reduction of albuminuria and prevention of estimated glomerular filtration decline, will likely have profound influences on patient outcomes.1 2

All patients with LN have by definition CKD, since they display albuminuria to varying degrees. While albuminuria is a classical sign of renal damage, a substantial portion of patients will also have structural and functional impairment of their kidney function as hallmark of CKD, that is, glomerular hyperfiltration and albuminuria. In the past, renin–angiotensin–aldosterone system inhibitors (RAASi) has already conferred nephroprotective potential in patients with LN; however, a substantial residual renal risk remains in all forms of CKD. In the last few years, novel treatment strategies are therefore required to further decrease proteinuria and to slow kidney function decline.3

Sodium–glucose cotransporter-2 inhibitors (SGLT2i) have recently been demonstrated to exert profound cardio and nephroprotection in large cardiovascular outcome trials. An initial drop of eGFR after SGLT-2i administration (2–5 mL/min) is detected during the first weeks of treatment reflecting a reduction of intraglomerular pressure. A similar effect was observed with mineralocorticoid receptor blockers and ACE inhibitor.4 SGLT2i inhibits the sodium proton exchanger, further increasing the delivery of sodium to the loop of Henle, which results in activation of TGF feedback response with consequent attenuation of glomerular hyperfiltration. They reduce progression of CKD including albuminuria and improve outcomes in heart failure patients with and without type 2 diabetes on top of angiotensin-blocking agents.5 Since many aetiologies of non-diabetic nephropathy are characterised by intraglomerular hypertension, we hypothesise that SGLT2i acutely decrease GFR and proteinuria in patients without diabetes at risk of progressive kidney function loss via a glucose independent haemodynamic mechanism. Furthermore, distinct complications of SLE may also seem to be amenable to the therapeutic potential with SGLT2i such as the increased occurrence of pulmonary hypertension, metabolic syndrome and increased blood pressure.6 Patients with LN were excluded from such studies due to potential necessities of acute immunosuppression.7

The aim of this study was to analyse the effect of SGLT2i in patients with LN in chronic and stable treatment with immunosuppression and residual proteinuria.

Five patients with histologically confirmed LN on immunosuppressive therapy with mean proteinuria of 2.2 g/day had empaglifozin 10 mg/day added. Within 8 weeks of starting treatment, the patients experienced a dramatic decrease in proteinuria (49.9%) with minimal change in glomerular filtration rate (table 1, online supplemental figure 1).

Table 1

Main effects of sodium–glucose cotransporter-2 inhibitors (empaglifozin 10 mg) lupus nephritis

This pilot trial evaluates the antiproteinuric and nephroprotective effect of SGLT2i in patients with LN. Landmark studies have unequivocally demonstrated the renoprotective effect of SGLT2i in addition to the standard of care (RAASi) in different chronic proteinuric nephropathies. For this reason, we believe that these drugs combined with RAASi may be an effective alternative in the management of residual proteinuria in patients with lupus nephropathy with adequate immunosuppression due to their nephroprotective and cardioprotective effects. Prospective randomised studies are needed to demonstrate the potential beneficial effect of SGT2 inhibitors in patients with LN.

Ethics statements

Patient consent for publication

Ethics approval

The institution’s Ethical and Research Committee approved the study (approval number 17/061). Comité de Etica de la Investigación del Hospital Universitario 12 de Octubre, Madrid, Spain exempted this study. Participants gave informed consent to participate in the study before taking part.


We thank all patients for their participation.


Supplementary materials

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  • Handling editor Josef S Smolen

  • Contributors EM and MG conceived and designed the study, drafted the manuscripts and approval of the final version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.