Chronic Tubulointerstitial Nephritis: Hypokalemia, Hyperoxaluria, and Hyperuricemia

Important mechanisms of interstitial kidney disease have been described in association with non-immune metabolic causes of chronic interstitial nephritis. For example, as an end product of ammoniagenesis, ammonia accumulation in the medulla leads to activation of the alternative complement pathway in hypokalemic interstitial nephritis. On the other hand, oxalate and urate crystals activate the NALP-3 inflammasome in the interstitial cells, resulting in maturation of proinflammatory IL-1ß and IL-18. Also, uric acid directly stimulates the nuclear factor- κB (NF-κB) signaling pathway. In this section, these metabolic causes are discussed.