RESUMO
We herein report a case of acute kidney injury (AKI) due to tubulointerstitial nephritis (TIN) after starting empagliflozin in a diabetic patient. The patient developed stage 1 AKI with proteinuria and elevated tubulointerstitial markers. A renal biopsy showed acute TIN with lymphocytic infiltration into the interstitium. The patient's renal function improved after discontinuation of empagliflozin and steroid administration. Sodium-glucose cotransporter 2 (SGLT2) inhibitor-induced AKI has been reported, but the underlying mechanism remains unclear, potentially because few patients with SGLT2-inhibitor-induced AKI have undergone a renal biopsy. We report the present case in the hope that it will help clarify the mechanism.
Assuntos
Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Nefrite Intersticial , Humanos , Injúria Renal Aguda/induzido quimicamente , Compostos Benzidrílicos/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Glucose , Hipoglicemiantes/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/diagnóstico , Sódio , Transportador 2 de Glucose-Sódio/efeitos adversosRESUMO
Iron is an essential mineral for oxygen delivery and for a variety of enzymatic activities, but excessive iron results in oxidative cytotoxicity. Because iron is primarily used in red blood cells, defective erythropoiesis caused by loss of the erythroid growth factor erythropoietin (Epo) elevates iron storage levels in serum and tissues. Here, we investigated the effects of iron in a mouse model of Epo-deficiency anemia, in which serum iron concentration was significantly elevated. We found that intraperitoneal injection of iron-dextran caused severe iron deposition in renal interstitial fibroblasts, the site of Epo production. Iron overload induced by either intraperitoneal injection or feeding decreased activity of endogenous Epo gene expression by reducing levels of hypoxia-inducible transcription factor 2α (HIF2α), the major transcriptional activator of the Epo gene. Administration of an iron-deficient diet to the anemic mice reduced serum iron to normal concentration and enhanced the ability of renal Epo production. These results demonstrate that iron overload due to Epo deficiency attenuates endogenous Epo gene expression in the kidneys. Thus, iron suppresses Epo production by reducing HIF2α concentration in renal interstitial fibroblasts.