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Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. While decades of research have focused on the molecular mechanisms of solute supersaturation and crystal formation, the pathomechanisms of crystal-induced renal inflammation remain largely unknown. The recent discovery of the intracellular NLRP3 inflammasome as a pattern recognition platform that translates crystal uptake into innate immune activation via secretion of IL-1β and IL-18 revised the pathogenesis of gout, silicosis, asbestosis, atherosclerosis and other crystal-related disorders. As a proof of concept, the NLRP3 inflammasome was now shown to trigger inflammation and acute kidney injury (AKI) in oxalate nephropathy. It seems likely that this and potentially other innate immunity mechanisms drive crystalline nephropathies (CNs) that are associated with crystals of calcium phosphate, uric acid, cysteine, adenine, certain drugs or contrast media, and potentially of myoglobin during rhabdomyolysis and of light chains in myeloma. Here, we discuss the proven and potential mechanisms of renal inflammation and kidney injury in crystal-related kidney disorders. In addition, we list topics for further research in that field. This perspective may also provide novel therapeutic options that can help to avoid progressive tissue remodeling and chronic kidney disease in patients with kidney stone disease or other CNs.

Urinary tract obstruction and vesicoureteral reflux, which are often associated with urinary tract infections, may lead to progressive renal damage. Relatively little is known about the pathophysiology of this process, and a need exists for noninvasive methods of its detection in its early stages. Because urine is refluxed into the venous and lymphatic drainage of the kidney in severe vesicoureteral reflux and urinary tract obstruction, an immune response to urinary tract components might play a role in the pathophysiology of progressive renal damage and serve as a serologic marker for its presence. A solid-phase radioimmunoassay for a protein found only in the urine (Tamm-Horsfall protein [THP]) was developed and used to measure antibody to THP in the serum of 60 subjects. Significant elevations of antibody to THP were observed in five of 15 patients with obstruction and infection of the urinary tract and in one of 10 patients with infection alone, when these patients were compared with 12 healthy control subjects. Similar elevations of antibody to THP were not seen in uninfected patients with urinary tract obstruction or in patients with low-grade vesicoureteral reflux or sepsis of nonrenal origin. These results suggest that the measurement of antibody to THP might be useful in the identification of patients with obstruction and infection of the urinary tract.

Concanavalin A (Con A)-inducible suppressor cell activity in peripheral blood lymphocytes (PBL) of urologic cancer patients and of appropriate controls with benign urologic disorders was measured concurrently. Although the proliferative responses to Con A of the cancer patients were significantly lower than those of controls, no difference in Con A-induced suppressor cell activity was demonstrated between cancer patients and controls when tested under a variety of conditions. Moreover, regression analysis revealed no correlation between the proliferative response to Con A and suppressor cell activity in either cancer patients or controls. The results indicated that Con A-inducible suppressor cell activity was unaltered in urologic cancer patients and suggested that suppressor cells of the type that can be activated by Con A were not involved in the general immunologic impairment frequently associated with urologic cancer.