Abstract
Background and Aims
SGLT-2 inhibitors are effective anti-hyperglycemic agents with proved cardiovascular and renal benefits. However, there have been post marketing reports of episodes of acute kidney injury (AKI), some requiring hospitalization and even dialysis in patients receiving SGLT2 inhibitors. This phenomenon may be related to volume contraction and hemodynamic changes, particularly in patients with other risk factors (such as patients on RAAS blocking agents or NSAIDS, patients with CKD). We present a case of acute interstitial nephritis (AIN) and acute tubular necrosis related to an SGLT2-inhibitor.
Method
Case report description.
Results
A 67-year-old women was admitted with weakness, dizziness and abdominal pain. Her medical history was remarkable for hypertension, diabetes mellitus, ischemic heart disease and peripheral vascular disease. Her medications included bisoprolol, losartan, amlodipine, sitagliptin and aspirin. Two months prior the current presentation, empagliflozin was prescribed by her primary physician for her diabetes mellitus. However, several days after initiation of empgliflozin she felt weak and dizzy and empagliflozin was discontinued. A week before the current presentation, empagliflozin was re-initiated by her cardiologist.
The patient reported no recent illness, fevers, rash, arthralgias, respiratory symptoms or bone pain. She denied exposure to other new medications (including NSAIDS and antibiotics).
On admission, blood pressure was 165/76 mm Hg. The rest of the physical examination was unremarkable. Laboratory studies revealed acute kidney injury (creatinine 3.19 mg/dL, BUN 28 mg/dL, baseline creatinine 0.9 mg/dL). Complete blood count demonstrated no eosinophilia or thrombocytopenia.
Urinalysis showed a few leukocytes but no red cells or casts. The urine protein to creatinine ratio was 5160 mg of protein per gram creatinine. Abdominal ultrasonography showed normal-size kidneys and no hydronephrosis.
Immunologic and infectious serologies were unremarkable. over several days the patient became oligo-anuric and creatinine peaked to 9.22 mg/dL and hemodialysis was initiated. Empiric treatment with prednisone was given and a renal biopsy was performed. Four glomeruli were seen on light microscopy. The glomeruli were normocellular. An interstitial infiltrate of lymphocytes and small numbers of eosinophils were seen. Thining of the renal tubular brush border with intra-tubular necrotic content was a also seen. Immunofluorescence was negative. The findings were compatible with acute interstitial nephritis and acute tubular necrosis (Figure 1).
The patient was discharged with a regimen of intermittent hemodialysis and steroid therapy. Three months later, urine output and kidney function improved, and the patient was weaned off dialysis.
Conclusion
In this case report, we describe previously unreported histologically proven AIN likely related to empagliflozin exposure. Although SGLT2 inhibitors have been reported to be associated with AKI it has been supposed to be related to volume contraction and hemodynamic changes. As virtually any drug can cause AIN, further proof of the drug's causation in our case was an onset of renal dysfunction with re- institution of empagliflozin, biopsy-proven AIN and absence of other drugs, infection or systemic disease that might cause AIN. With the dramatic increase in use of SGLT-2 inhibitors worldwide, treating physicians should be aware of AIN as a possible cause of AKI in this context.
Diagnosing acute interstitial nephritis: considerations for clinicians
