Detailed Causality between Sodium-glucose Cotransporter 2 Inhibitor and Tubulointerstitial Nephritis

To the Editor Konta et al. reported a patient who had sodium-glucose cotransporter 2 inhibitor (SGLT2i)-induced acute kidney injury (AKI) due to suspected tubulointerstitial nephritis (TIN), which was demonstrated by a renal biopsy (1). These findings remind us that TIN can be a cause of SGLT2i-induced AKI.

Renal impairment can be observed approximately one month following the initiation of SGLT2i as an “initial drop” (2). We in general continue SGLT2is for reno-protective effects against such transient renal impairment. However, according to the authors' report, some such cases can be due to drug-related TIN, instead of an initial drop, so specific intervention along with termination of the SGLIT2i is required (1).

It is challenging to monitor markers of tubular injury frequently. Do the authors have any recommended methodologies for easily distinguishing drug-related TIN from the initial drop? We should avoid unnecessary termination of SGLT2is. Did the authors monitor tubular markers following the termination of empagliflozin and initiation of steroid therapy?

There were no signs of tubulitis in their renal biopsy specimen (1). Without tubulitis, interstitial infiltration might indicate non-specific changes or sampling bias, instead of typical TIN.

Detailed location of interstitial infiltration might clarify the causality between SGLT2is and TIN. SGLT2 is located on the proximal convoluted tubule S1-S2. Was the inflammation located around this area? Or did the inflammatory cells invade non-specifically and diffusely around interstitial tissues? In addition, the patient had hypouricemia. Did the patient have Fanconi's syndrome due to proximal convoluted tubular impairment?

The authors state that they have no Conflict of Interest (COI).