Genetic determinants of hyperoxaluria and CaOx-nephrolithiasis in pa-tients after malabsorptive bariatric surgery (PD Dr. Jan Halbritter)
Prevalence of calcium oxalate nephrolithiasis (CaOx-NL) is markedly increased in obese patients after malab-sorptive bariatric surgery. Mechanistically, fat malabsorption is thought to lead to increased enteric oxalate absorption with secondary enteric hyperoxaluria (SEH) and potential CaOx-stone formation. Additionally, loss of enteric colonization with oxalate-digesting bacteria, e.g. Oxalobacter formigenes, may aggravate SEH. Conversely, in primary hyperoxaluria (PH) due to biallelic mutations of either AGXT, GRHPR, or HOGA1, en-dogenous hepatic oxalate overproduction is the underlying mechanism of stone formation. Therefore, the ques-tion arises whether genetic susceptibility predisposes certain patients to develop kidney stones after bariatric surgery.
We aim to investigate four specific aims:
i) to determine the prevalence of hyperoxaluria, CaOx-NL, and disturbed Oxalobacter formigenes colonization in the local bariatric cohort of (n=821).
ii) to investigate mutational status of known PH-genes in ≈ 100 cases (bariatric surgery with hyperoxaluria and/or CaOx-NL) and ≈ 300 matched controls (bariatric surgery without hyperoxaluria and/or CaOx-NL).
iii) to analyze additional candidate genes for CaOx-NL in aforementioned cases and controls.
iv) to functionally characterize identified gene variants in cell-culture and in vivo.
By determining patients at risk, initiation of adjusted prophylactic measures after bariatric surgery may be pos-sible, taking advantage of a growing armamentarium of drugs directed against hyperoxaluria.