# Pathogenesis of Calcium Nephrolithiasis

> **NIH NIH P01** · UNIVERSITY OF CHICAGO · 2021 · $1,364,869

## Abstract

Idiopathic calcium (Ca) stone formers (ICSF) have papillary calcifications: interstitial plaque or ductal plugging
(DP), which may anchor stone growth. Ca oxalate (CaOx) stones associate with plaque, apatite (AP) stones
with DP. Decreased renal Ca reabsorption (rCa) is characteristic of idiopathic hypercalciuria (IH); how
decreased rCa promotes plaque and DP, as well as stones, is a theme of the PPG. In Project 2 a papillary
grading scale (PGS) will be used to quantify plaque and DP during endoscopic stone surgery, and to select
ICSF with IH as subjects for Projects 1 and 3, so that physiology (Project 1) and tissue studies (Project 3) will
be done on similar ICSF, chosen for high scores for either plaque or DP. The ability of the PGS to correlate
with clinical and histopathologic features of stone formation, and with risk of stone recurrence will be tested in
aims 2.1 and 2.5. Whether papillary appearance in pediatric stone formers is similar to adults will be tested in
aim 2.2. Aims 1.1a and 3.1a-b will test whether plaque is caused by decreased rCa in proximal tubule. Animal
models suggest that inflammatory mediators or reactive oxygen species play a role in stone formation, and we
will test this in urine (aim 1.3) and tissue (3.2.1a-c, 3.2.2, 3.3a-b) of ICSF with plaque or DP. Whether DP can
propagate via an inflammatory "field effect" will be tested in aim 3.3c. We predict DP will associate with Ca
phosphate supersaturation in urine (aim 1.1b), with presence of AP in stones (aim 2.3), and with renal
impairment (aim 2.4). The possibility that DP-induced inflammation causes pain will be explored in aim 2.6. We
will compare the effects of 2 common stone treatments, low Na diet with or without Kcitrate, on segmental rCa
in controls and ICSF, using endogenous lithium clearance and urine exosomal markers to study effects on both
proximal (aim 1.2) and distal (aim 1.4) nephron rCa, as well as effects on overnight urine Ca (aim 1.5), and on
urine SS and upper limit of metastability (aim 1.6).

## Key facts

- **NIH application ID:** 10246872
- **Project number:** 5P01DK056788-20
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** ELAINE M WORCESTER
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,364,869
- **Award type:** 5
- **Project period:** 2000-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246872

## Citation

> US National Institutes of Health, RePORTER application 10246872, Pathogenesis of Calcium Nephrolithiasis (5P01DK056788-20). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246872. Licensed CC0.

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