Several kinases were able to distinguish medullary sponge kidney disease from idiopathic calcium nephrolithiasis, and three ephrin receptors (EphA1, EphB3, and EphB6) were found to be the most significantly downregulated proteins in medullary sponge kidney disease versus idiopathic calcium nephrolithiasis. Here, EPHB6 is linked to Multiple small medullary renal cysts.