Discussion
death, CKD, proteinuria, ESRD, decline in renal function
END-STAGE RENAL DISEASE, DISEASE, ESRD
In this pragmatic clinical trial, prednisolone or doxycycline did not significantly improve renal function, 6 months after the commencement of treatment. A comprehensive understanding of the natural history of a disease is a prerequisite for designing, implementing and interpreting interventional studies. It was challenging to decide on study endpoints (development of CKD, end-stage renal disease (ESRD), renal replacement therapy (RRT) or death), duration of the study and biomarkers or surrogate end points (serum creatinine, eGFR, proteinuria) as this was the first prospective clinical trial on AIN of unknown aetiology with limited information on the natural history of the disease [According to the study results, by 6 months, 55% (30/54) of trial participants have reached < 60 ml/min/1.73mSteroid treatment is recommended to be commenced early, at least within 7 days from initial injury for better outcomes. Nevertheless, treatments in this trial were commenced at 20 (17–34) median (IQR) days after the onset of symptoms. Until substantial knowledge is available on the time and sources of exposure and detection of suspected toxin(s) in human tissues, it is difficult to target the initial injury. According to this study, the progression in prednisolone-treated patients (none reached < 30 GFR) was relatively slower than not so treated patients (17% reached < 30GFR). Of AIN patients of Nicaragua who were followed up for 90 days after the acute onset of decline in renal function, only 21/247 (8.5%) had progressed to CKD without specific interventions [