Disorders of Oxalate Metabolism

Summary

Hyperoxaluria is one of the most important promoters of crystallization, which might induce a chronic inflammatory process if crystals are internalized in the tubular system, leading later to early end-stage renal failure (Kurts. Kidney Int. 2013;84(5):859–61; Beck et al. Pediatric kidney disease. New York: Elsevier/WB Saunders; pp. 1037–58). Urinary oxalate is mostly of endogenous origin, and only ~10% derive from the daily nutritional intake (Whittamore et al. Am J Physiol Gastrointest Liver Physiol. 2019;316(1):G82–94). Primary causes are distinguished from secondary ones: The autosomal recessive inherited primary hyperoxaluria (PH) types I, II, and III are defects of the glyoxylate metabolism leading to endogenous (primary) overproduction of oxalate (Hoppe. Nat Rev Nephrol. 2012;8(8):467–75; Belostotsky et al. Am J Hum Genet. 2010;87(3):392–9). A significant number of hyperoxaluric patients, who would classify for PH, have yet unknown genetic basis of disease; thus, further types of PH are likely to exist (unclassified PH). Urinary excretion of oxalate is strongly elevated (>1 mmol/1.73 m² BSA/day, normal <0.5) in all forms of PH, resulting in recurrent stone formation and/or nephrocalcinosis and in progressive kidney damage leading to systemic calcium oxalate deposition (systemic oxalosis), primarily in PH type I (100%), but also in PH II (50%). Systemic oxalosis in PH I is a catastrophic situation that must be prevented by all means. Yet, diagnosis is all too often missed or delayed until end-stage renal failure occurs (in more than one third of adult patients). This is particularly unfortunate because progressive renal damage can be delayed or even prevented by early intervention (Garrelfs et al. N Engl J Med. 2021;384(13):1216–26; Weigert et al. 2018;23(4):349–57). Secondary hyperoxaluria is due either to excessive oxalate or vitamin C intake (dietary hyperoxaluria), the latter being metabolized to oxalate, or to increased intestinal oxalate absorption (enteric, mostly based on chronic inflammatory bowel syndromes, Hoppe et al. Front Biosci. 2003;8:e437–43). Although the urinary oxalate excretion is usually <1 mmol/1.73 m² BSA/24 h, it may nevertheless lead to significant morbidity, i.e., to recurrent urolithiasis or progressive nephrocalcinosis with renal failure, especially in patients with Crohn's disease and ileocecal valve resections.