LAUSR

We thank our colleague Dr Patoulias for pointing out that sodium glucose transporter (SGLT)2 inhibition (SGLT2i) could mediate nephroprotection in patients with lupus nephritis (LN) and ANCAassociated vasculitis (AAV) via specific mechanisms within the tubular cell compartment independent of the presence of diabetes mellitus. As discussed by Dr Patoulias, kidney injury molecule1 (KIM1) is affected by SGLT2i correlating with improvements in albuminuria, a hallmark of chronic kidney damage. KIM1, however, is not only a mere marker of tubular injury, but it is actively involved in diverse pathogenic actions. Hence, its expression, for example, in diabetic kidney disease accelerates kidney injury via fatty acid uptake coupled with tubular glucose reabsorption in renal proximal tubular cells, resulting in various detrimental stress responses. Upregulation of KIM1 and the ensuing tubular cell responses illustrate the close relationship between diseased glomeruli and subsequent tubulointerstitial fibrosis in response to increased tubular workload, thereby diseases traditionally considered primarily of glomerular origin such as diabetic kidney disease, and also inflammatory diseases such as LN and AAV, illustrate the therapeutic potential of innovative therapies such as SGLT2i by limiting permanent and progressive damage especially to the tubulointerstitial tissue. The concept of nephron overload has been very recently proposed to be the final result of various and diverse pathogenic insults in most forms of chronic kidney disease. Since SGLT2i substantially reduce tubular workload, they belong to the most efficient therapeutic interventions impacting nephron overload, suggesting also significant nephroprotective effects in LN and AAV.