# Theory of Solute and Water Transport Across Epithelia

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $211,875

## Abstract

PROJECT SUMMARY
The overall project objective has been mathematical modeling of renal fluid and electrolyte transport in
health and disease. Prior to the last period, this project had produced a model library of all kidney
tubule segments, and the first task of the last period was to concatenate these segmental models into a
nephron. The major effort of the last period was adding the medullary microcirculation, to advance the
nephron to a kidney model, in which medullary composition was calculated, rather than specified.
Simulation of major metabolic derangements (e.g. hyperglycemia, hyperkalemia, alkalosis), diuretic
use, and genetic transport defects require a model of this scope. While, the kidney model captured
overall solute excretion, interstitial concentration profiles and intratubular hydrostatic pressures need
additional work. Specifically, medullary Na+ and urea and NH4+ concentrations were lower than
expected; and changes in distal flow distorted pressures along the entire nephron. In the next period,
Aim 1 preserves current model structure, and addresses Na+ and urea and pressure. It is expected that
adjusting juxtamedullary nephron transport parameters will improve interstitial composition, and that
revising tubular compliance will mitigate pressure effects. Aim 2 addresses renal NH4+ concentrations
and partitioning of NH4+ flow between renal vein and urine. This cannot be done with parameter
adjustments, but requires cortical microvasculature. It is expected that countercurrent exchange within
cortical blood vessels can enhance ammonia excretion, while limiting renal venous ammonia (as seen
in acidosis and liver disease). Aim 3 will be introduce calcium as a new model solute. Renal calcium
concentration is a regulator of sodium transport, and of translational importance (e.g. hypercalciuric
disorders, stone formation). Aim 4 comprises model application in experimental collaborations. Work
continues with Dr. Tong Wang, examining the role of flow-dependent sodium reabsorption in renal
cystic disease. A polycystic kidney disease gene may mediate this flow-response, and we suspect that
failure to match fluxes to flows elevates tubule pressures, exacerbating cyst formation. In this regard,
attention in Aim 1 to tubule pressures and compliance will be foundational for this aim. Collaboration is
continuing with Dr. Larry Palmer to apply segmental and nephron models to K+ excretion in Na+-avid
states. These experiments typically document changes in specific transporter densities, and the models
provide a means of capturing these defects and estimating impact on other segments.

## Key facts

- **NIH application ID:** 9954077
- **Project number:** 5R01DK029857-34
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** ALAN M WEINSTEIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2018-06-19 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9954077

## Citation

> US National Institutes of Health, RePORTER application 9954077, Theory of Solute and Water Transport Across Epithelia (5R01DK029857-34). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9954077. Licensed CC0.

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