# Clinical Pathophysiology of Nephrolithiasis

> **NIH NIH P01** · UNIVERSITY OF CHICAGO · 2021 · $261,314

## Abstract

Summary 
The project's broad objective is an understanding of the impact of two common treatments for stone disease 
on renal calcium (Ca) handling, and the links between renal physiology and tissue calcifications in stone 
formers (SF). Stone formation requires urine supersaturation (SS) with calcium oxalate (CaOx) and calcium 
phosphate (CaP); idiopathic hypercalciuria (IH) is a common cause of increased SS. Prevention of stone 
recurrence relies on decreasing SS, but the optimal means of doing this in a given patient is not clear. 
Decreased tubular Ca reabsorption (rCa), in both proximal and distal nephron, is characteristic of IH. We 
hypothesize that renal tubule transport alterations are linked to pathogenesis of the tissue calcifications found 
in SF, as well as to their stones, and propose to study Ca SF with IH (IHSF) who have undergone papillary 
mapping during endoscopy who will be selected for one of two papillary appearances: 1) papillae with 
abundant plaque but no plugging (typical of many CaOx SF) or 2) plugs with modest plaque (typical of apatite 
SF). We will test the hypothesis that plaque surface area correlates with decreased proximal tubule rCa, and 
plug area correlates with increased CaP SS (Aim 1.1a,b). Having demonstrated differences between IHSF and 
normals (N) in rCa on a stable diet, both fasting and fed, we propose to explore these findings using high and 
low Na intake, with or without Kcitrate. We will study the effects on rCa, fasting, fed and overnight (a high risk 
period for stone formation), using lithium clearance and urine stone risk factors (Aims 1.2a, 1.4a, 1.5). To 
understand the mechanisms of the changes in rCa that we expect with low Na diet and K citrate, we will 
measure urine exosomes for both proximal and distal nephron transporters (Aims 1.2b, 1.4, and 1.5). SS and 
upper limit of metastability will be measured to gain a better understanding of how K citrate and low Na diet 
affects these important treatment parameters (Aim 1.5, 1.6). To gain further insight into plaque and plug 
formation the role of inflammation (Aim 1.3).

## Key facts

- **NIH application ID:** 10246876
- **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:** $261,314
- **Award type:** 5
- **Project period:** 2000-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246876

## Citation

> US National Institutes of Health, RePORTER application 10246876, Clinical Pathophysiology of Nephrolithiasis (5P01DK056788-20). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246876. Licensed CC0.

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