A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD.