While the association between HK and low eGFR and/or metabolic acidosis is clear-cut, the relationship with diabetes is more complex, with several factors playing a role; it depends, in fact, not only on insulin deficiency and an increased use of RAASI, but also on hyporeninemic hypoaldosteronism ascribed to impairment to the juxtaglomerular apparatus, autonomic dysfunction and/or renal salt retention with dependent volume expansion suppressing renin synthesis [32]. This evidence concerns the gene REN and Abnormal autonomic nervous system physiology.