5.3.1. Vanin-1

Vanin-1, a 53 kDa protein, is expressed in the brush borders of the proximal tubule of the kidney [100]. By catabolizing pantetheine to cysteamine and pantothenic acid (a precursor of coenzymes), it has roles in metabolism and energy production. The function of kidney vanin-1 remains to be established. However, the fact that vanin-1 is located specifically in the brush borders suggests that the enzyme plays a pivotal role in pantothenic acid salvage and recycling. The proximal tubular cells bear microvilli with large apical surface areas within which many transporters and channels are found [101]. Vanin-1 in cellular membranes is anchored to glycosylphosphatidylinositol. The anchor may be cleaved and soluble vanin-1 then secreted or released into the extracellular matrix in response to various stimuli [102].

Urine vanin-1 levels are increased in patients with drug-induced AKI [103] and UUTO [23], and in rat models with high salt-induced kidney damage [104], diabetic nephropathy [105], and UUTO [102]. UUTO inhibits urine flow and increases intratubular pressure, causing renal tubular damage. Vanin-1 is then secreted into the urine by renal tubular cells. The level of vanin-1 in renal pelvic urine correlates highly with the severity of urinary tract obstruction [23]. The level of vanin-1 in renal pelvic urine is highly predictive (AUC-ROC value 0.98) of adult UUTO, more predictive than NGAL, KIM-1, or NAG levels. Vanin-1 levels decrease following UUTO relief in patients with moderate to severe UUTO [23].
