Semaglutide-associated kidney injury

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are multipurpose agents effective in improving glycemic control in patients with type 2 diabetes while also achieving weight loss and risk reduction of major cardiovascular (CV) events and chronic kidney disease progression. With their increased utility in diabetes, obesity, CV health and renal protection, the use of GLP-1RAs has increased. However, with this increased use, there have also been increased reports of associated kidney adverse events, including case reports of acute interstitial nephritis (AIN) associated with GLP-1RA use. We report the data from the Food and Drug Administration adverse event reporting system (FAERS) in relation to GLP-1RA use and adverse kidney events, with acute kidney injury being the most common. In addition, we report two cases of semaglutide-associated biopsy-proven AIN and one with associated podocytopathy. To our knowledge, this is the first case of biopsy-proven AIN with podocytopathy associated with semaglutide use. Both patients experienced complete remission shortly after discontinuing semaglutide and undergoing immunosuppressive therapy. Further analysis of the FAERS database revealed 17 cases of proteinuria and 1 case of glomerulonephritis associated with semaglutide in the FAERS database, however no further information was available. While further research is needed to establish causality, this case series adds to the growing body of literature that semaglutide is associated with AIN and adds a new association, semaglutide with AIN and podocytopathies. While the overall clinical and mortality benefits of GLP-1RAs may outweigh the rarer risks, prescribers need to be aware of these associations, particularly as the use of GLP-1RAs continues to expand.

Keywords: AIN; AKI; GLP1 agonist; acute interstitial nephritis; diffuse podocytopathy; minimal change disease; podocytopathy; semaglutide.

Figure 1:

From Case 1. Image (A) periodic acid–Schiff (PAS) Patchy infiltrates with associated tubulitis and tubular injury characterized by epithelial flattening and attenuated brush borders (PAS ×200). Image (B) hematoxylin and eosin (H&E) 20, H&E 40: infiltrates comprising of mononuclear inflammatory cells with scattered eosinophils. There is evidence of acute tubular injury with flattening of epithelial cells and focal mild tubulitis (H&E ×200; H&E ×400).