The oto-renal axis describes the relationship between hearing loss and chronic nephropathy. Several clinical studies have investigated the incidence of hypoacusia in patients affected by chronic renal failure, but the etiopathogenic mechanism is not fully understood. In this context, there is a general agreement that hypoacusia is usually neurosensorial and the cochlea is the main site of lesion. Inner ear and kidney present an interesting similarity in terms of structure and function. In particular, the presence of pericytes and podocytes in inner ear and in glomeruli, respectively, evidence common characteristics of microcirculation. Defects in microcirculation in the inner ear mainly cause an electrolytic imbalance with the consequent impairment of endocochlear potential and sensorial transduction. In kidney, microvessels and podocytes contribute to glomerular stability and function. Microcirculation dysfunction often occurs during the inflammatory status, frequently reported both in chronic nephropathy and in cardiovascular disease. Clinical studies aimed to describe the hypoacusia in nephropathy patients are summarized. Then, in order to speculate the etiopathogenic mechanism of hearing loss in chronic nephropathy, we report the similarities between pericytes and podocytes in inner ear and glomeruli microcirculation in terms of structure and function. Finally, we propose a model in which inflammation plays an important role in oto-renal dysfunction. Our model proposes the inflammation, as an etiopathogenic mechanism of hypoacusia in chronic nephropathy and the defective cross-talk between pericytes/podocytes and vascular endothelium, as the initial event of the degenerative process.