Furthermore, in obese patients, the accumulation of fat in proximal tubular cells reduced their ability to secrete ammonia, resulting in urine acidification, which could contribute to stone progression [40] Significantly increased levels of osteopontin and biomarkers associated with inflammatory responses and accumulation of pro-inflammatory macrophages were also observed in animal experiments in high-fat-fed mice, ultimately leading to crystal and mineral deposition in the tubular lumen of the kidneys and resulting in the progression of kidney stones [41]. Here, SPP1 is linked to nephrolithiasis.