Kidney Week

Abstract: FR-PO1179

Urine Ammonium-pH Index: A Sensitive Measure of Renal Tubular Function

Session Information

• CKD: Mechanisms, AKI, and Beyond - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Berg, Peder, Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Peder Berg, MD, PhD

• Andersen, Jesper Frank, Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Jesper Frank Andersen, MD

• Chrysopoulou, Maria, Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Maria Chrysopoulou, MS, MSc

• Hummelgaard, Sandra, Novo Nordisk A/S, Bagsværd, Capital Region of Denmark, Denmark

Sandra Hummelgaard, MS, MSc

• Ayasse, Niklas, Universitat Heidelberg Medizinische Fakultat Mannheim, Mannheim, BW, Germany

Niklas Ayasse, MD

• Jensen, Iben Skov, Syddansk Universitet Det Sundhedsvidenskabelige Fakultet, Odense, Region Syddanmark, Denmark

Iben Skov Jensen, MD

• Weyer, Kathrin, Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Kathrin Weyer, PhD

• Svendsen, Samuel L.C., Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Samuel L.C. Svendsen, MD, PhD

• Weinstein, Alan Mark, Weill Cornell Medicine, New York, New York, United States

Alan Mark Weinstein, MD

• Buus, Niels Henrik, Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Niels Henrik Buus

• Sorensen, Mads Vaarby, Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Mads Vaarby Sorensen, PhD

• Birn, Henrik, Aarhus Universitetshospital Afdeling Nyresygdomme, Aarhus, Central Denmark Region , Denmark

Henrik Birn, MD, DrMed, PhD

• Weiner, I. David, University of Florida Division of Nephrology Hypertension & Renal Transplantation, Gainesville, Florida, United States

I. David Weiner, MD, FASN

• Rinschen, Markus M., Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Markus M. Rinschen, MD

• Leipziger, Jens G., Aarhus Universitet Institut for Biomedicin, Aarhus, Central Denmark Region , Denmark

Jens G. Leipziger, DrMed, MD

Background

Kidney function is typically assessed by eGFR and albumin-creatinine ratio (ACR), reflecting filtration capacity and filtration barrier integrity. However, the majority of kidney tissue is comprised of the tubular and interstitial compartments, for which no clinically available biomarkers exist. We recently developed a urine ammonium-pH index (API) to evaluate the renal capacity for ammonium excretion. A low API is strongly associated with adverse outcomes in CKD. Here, we investigated the underlying physiology of the API and its potential as a marker of tubular function.

Methods

As urine ammonium excretion is substantially modulated by acid-base and potassium status, the API was calculated in mice subjected to acid/base loading or potassium restriction/loading. The index was also assessed in genetic mouse models with impaired ammoniagenesis or ammonium transport along the tubular system, and in rodent kidney disease models. Using data from the literature, the API was assessed in patients with isolated proximal tubular acidosis or Fanconi syndrome. A mathematical model of whole-kidney function explored the relationship between proximal tubule ammoniagenesis and the API.

Results

In healthy mice, the API remained stable across large graded acid-base or potassium conditions. Genetic knockouts affecting ammonium production or transport, especially in the proximal tubule, severely reduced the API. In rodent kidney disease models, the API declined independently of GFR and ACR. Proteomic analysis pointed to disrupted proximal tubule ammoniagenesis and acid-base transport as primary contributing factors. Patients with isolated proximal renal tubular acidosis or Fanconi syndrome (with normal GFR), had a markedly reduced API. Mathematical modeling confirmed that proximal tubule ammoniagenesis is a primary driver of the API.

Conclusion

The API is unaffected by systemic acid-base or potassium levels when kidney function is intact but decreases with tubular dysfunction independent of established markers of kidney function. It is consistently diminished in rodent kidney disease models and patients with proximal tubular dysfunction and could serve as a non-invasive biomarker of tubular health.

Funding

• Private Foundation Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025mmq4fqc0