The aim of this study was to explore the etiology, long-term renal outcomes and affecting factors of acute tubulointerstitial nephritis (ATIN). Patients with biopsy-proven ATIN from 1 January 2005 to 31 December 2013 at Peking University First Hospital were enrolled in the study and received scheduled follow-up for at least 24 months. The causes of ATIN were defined at biopsy and reclassified during follow-up. Factors affecting renal recovery at 6 months post-biopsy and estimated glomerular filtration rate (eGFR) at 12 months post-biopsy and at the end of follow-up were analyzed. A total of 157 ATIN patients were enrolled, with an average follow-up of 48 months (range 24-108 months). A modified etiology spectrum was identified, with a decreased proportion of drug-induced ATIN (D-ATIN, 64% at biopsy to 50% after follow-up) and an increase in autoimmune-related ATIN (22-41%) with late-onset systemic manifestations in patients who had been classified as D-ATIN or ATIN of unknown cause. Recurrent kidney injury was observed in 51% of the patients with tubulointerstitial nephritis and uveitis syndrome (TINU), 53% of those with an autoimmune disease and 8% of those with D-ATIN, resulting in prolonged immunosuppressive treatment. By 12 months, decreased eGFR (<60 mL/min/1.73 m2) was observed in 47% of the patients with D-ATIN, 74% of those with TINU and 57% of those with other autoimmune diseases. In multivariable analysis, female sex, older age, presence of hypertension and recurrent kidney injury were independent risk factors for worse renal outcomes. Our data demonstrate that autoimmune-related ATIN may present with systemic manifestations after kidney injury and is, therefore, commonly misdiagnosed. Repeated kidney injury is not uncommon in patients with ATIN. Scheduled follow-up is, therefore, critical for defining the exact etiology and proper management of ATIN.