Acute Interstitial Nephritis After Treatment With Liraglutide

Abstract

An 83-year-old man with type 2 diabetes and stage G3A2 chronic diabetic nephropathy (serum creatinine, 2.14 mg/dL, corresponding to estimated glomerular filtration rate [eGFR] of 32 mL/min/1.73 m2 calculated using the 4-variable MDRD Study equation) presented with acute kidney injury. The patient’s recent medical history revealed a modification of his diabetes treatment: exenatide was introduced 2 months earlier and then rapidly switched to liraglutide for practical reasons. Physical examination showed bilateral leg edema and basal fine crackles on lung auscultation. The patient’s serum creatinine level was 9.3 mg/dL, corresponding to eGFR of 6 mL/min/1.73 m2. Urinalysis showed nondysmorphic red blood cells (79/μL) and white blood cells (79/μL; 35% eosinophils). Blood eosinophil count was normal (100/μL). A kidney biopsy showed diffuse tubulointerstitial infiltration with numerous eosinophils in addition to features of diabetic nephropathy (Fig 1). The diagnosis of acute interstitial nephritis was made, likely induced by liraglutide with a possible cross-reaction to exenatide. Investigations excluded other possible causes, such as infection or immunologic disease.1Kodner C.M. Kudrimoti A. Diagnosis and management of acute interstitial nephritis.Am Fam Physician. 2003; 67: 2527-2534PubMed Google Scholar The patient received steroids and transient dialysis, and liraglutide therapy was discontinued. After this, a progressive improvement in kidney function was observed (serum creatinine, 3.58 mg/dL; eGFR, 18 mL/min/1.73 m2). Glucagon-like peptide-1 (GLP-1) agonists are widely used in patients with type 2 diabetes.2Martin J.H. Deacon C.F. Gorrell M.D. Prins J.B. Incretin-based therapies—review of the physiology, pharmacology and emerging clinical experience.Intern Med J. 2011; 41: 299-307Crossref PubMed Scopus (54) Google Scholar Most of the few reported adverse kidney events have been caused by gastrointestinal-induced dehydration.3Narayana S.K. Talab S. Elrishi M. Liraglutide-induced acute kidney injury.Pract Diabetes. 2012; 29: 380-382Crossref Scopus (6) Google Scholar To our knowledge, this is the first case of liraglutide-induced acute interstitial nephritis second to any GLP-1 agonists.4Nandakoban H. Furlong T.J. Flack J.R. Acute tubulointerstitial nephritis following treatment with exenatide.Diabet Med. 2013; 30: 123-125Crossref PubMed Scopus (21) Google Scholar This injury could be immune mediated. Antibody production is described with both exenatide and liraglutide because these GLP-1 agonists present only a partial homology to human GLP-1.5Buse J.B. Garber A. Rosenstock J. et al.Liraglutide treatment is associated with a low response or increased frequency of adverse events: results from the Liraglutide Effect and Action in Diabetes (LEAD) trials.J Clin Endocrinol Metab. 2011; 96: 1695-1702Crossref PubMed Scopus (109) Google Scholar Financial Disclosure: The authors declare that they have no relevant financial interests.