Normative urinary excretion parameters for early identification of primary hyperoxaluria or other kidney stone associated diseases in infants < 8 weeks of life

Abstract Background A thorough set of reference values for lithogenic and stone inhibitory substances in urine is of great relevance for diagnostic purposes in patients with kidney stones or nephrocalcinosis. This is especially important for the early detection of rare diseases, i.e. primary hyperoxaluria (PH) or cystinuria to rapidly treat and prevent major complications. Methods Multiple spot urines from 476 newborns and babies were collected during the first 8 weeks of life during a genetic newborn screening study on PH. The most prevalent variants in the PH1 (AGXT) and the PH3 (HOGA1) genes were screened. Urines were needed for further diagnostics in heterozygote participants. Molar urinary creatinine ratios for oxalate, glycolate, hydroxy- and dihydroxy-oxo-glutarate, 4-hydroxy-glutamate, citrate, calcium, magnesium, phosphate, sulphate and cystine were determined. Urine samples were divided into three groups: AGXT heterozygotes, HOGA1 heterozygotes and controls. Results Mean molar urinary oxalate-to-creatinine ratios were within published normative. Mean molar urinary glycolate-to-creatinine ratios were significantly lower in AGXT and HOGA1 heterozygotes compared to controls and to previously published data. Hydroxy-oxo-glutarate was only found in HOGA1 heterozygotes. The dihydroxy-oxo-glutarate-to-creatinine ratio was significantly higher in HOGA1 heterozygotes. Calcium excretion was significantly less in controls as compared to AGXT and HOGA1 heterozygotes. Conclusions We present new normative values for urinary lithogenic and stone inhibitory parameters in newborns and babies < 8 weeks of life. They will definitively play a significant role in the diagnosis of the primary hyperoxalurias with the lower normal glycolate- (PH1) and the elevated molar dihydroxy-oxo-glutarate-to-creatinine values (PH3). Clinical trial registration NCT05843851