medRxiv : the preprint server for health sciences · 2026
The Urine Ammonium-pH Index is a Measure of Kidney Tubular Function.
СтатьяПрепринтНазвание и аннотация: Перевод пока не подготовлен
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Andersen Jesper Frank, Sørensen Mads Vaarby, Chrysopoulou Maria, Gullaksen Søren, Nielsen Steffen Flindt, Hummelgaard Sandra, Ayasse Niklas, Jensen Iben Skov, Salomo Louise, Simonsen Natasja P, Atay Jasmine Cl, Poulsen Per Løgstrup, Nørregaard Rikke, Vernstrøm Liv, Weyer Kathrin, Demir Fatih, Svendsen Samuel Levi, Weinstein Alan M, Nielsen Sebastian, Nielsen Marie Bodilsen, Buus Niels Henrik, Birn Henrik, Weiner I David, Rinschen Markus, Leipziger Jens, Berg Peder
Аннотация
Dysfunction of the tubulointerstitial compartment is a key driver of chronic kidney disease (CKD) progression. However, tubular function remains largely unaddressed by routine clinical assessment. Here, we show that the urine ammonium-pH index (uAPI), a composite of urinary ammonium and pH, reflects kidney tubular function and predicts kidney function decline. Using acid/base, dietary, and potassium perturbations, segmental disruption of tubular ammonium handling, mathematical modelling, and data from patients with renal tubular acidosis, we identified defective ammoniagenesis as the main uAPI determinant. The uAPI was suppressed across four kidney disease models and dissociated from GFR. Kidney proteomics and single-nucleus RNA sequencing indicated downregulation of ammoniagenesis in proteinuric and diabetic kidney disease. In type 2 diabetes patients with preserved GFR, a reduced uAPI was associated with faster kidney function decline. In three CKD cohorts, low uAPI predicted CKD progression and significantly improved risk prediction. Together, this positions the uAPI as a scalable, non-invasive measure of kidney tubular function.