Biomarker evidence for distal tubular damage but cortical sparing in hospitalized diabetic patients with acute kidney injury (AKI) while on SGLT2 inhibitors.

BACKGROUND

Inhibitors of sodium-glucose co-transporter-2 (SGLT2i) were found to improve renal outcome in diabetic patients in large prospective randomized trials. Yet, SGLT2i may acutely reduce kidney function through volume depletion, altered glomerular hemodynamics or intensified medullary hypoxia leading to acute tubular injury (ATI). The aim or this study was to prospectively assess the pathophysiology of acute kidney injury (AKI) in patients hospitalized while on SGLT2i, differing ATI from pre-renal causes using renal biomarkers.

METHODS

Serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Ischemia Molecule (KIM)-1, markers of distal and proximal tubular injury, respectively, were determined in 46 diabetic patients who were on SGLT2i upon hospitalization with an acute illness.

RESULTS

Serum and urine NGAL, but not KIM-1, were significantly increased in 21 of the patients who presented with AKI upon admission, as compared with 25 patients that maintained kidney function. Both serum and urinary NGAL correlated with the degree of impaired renal function, which in many cases was likely the result of additional acute renal perturbations, such as sepsis.

CONCLUSIONS

Increased urinary and serum NGAL indicates that ATI, principally affecting distal tubular segments, may develop in some of the patients hospitalized with an acute illness and AKI while on SGLT2i. It is suggested that intensified medullary hypoxia by SGLT2i might be detrimental in this injury. By contrast, concomitantly unaltered KIM-1 might reflect improved cortical oxygenation by SGLT2i, and may explain an overall reduced risk of AKI with SGLT1i in large series. The independent potential of SGLT2i to inflict medullary hypoxic damage should be explored further.