# Silica Nephropathy and Chronic Kidney Disease of Unknown Etiology

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $629,682

## Abstract

Project Summary
 Epidemics of chronic kidney disease of unknown etiology (CKDu) have emerged along the Pacific Coast
of Central America (Mesoamerican Nephropathy), in northern Sri Lanka (Sri Lankan nephropathy), in Andhra
Pradesh and other regions of India (Uddanam Nephropathy), and in Veracruz, Mexico. In all cases, the primary
histologic finding is chronic interstitial nephritis with variable degrees of glomerulosclerosis. To date a variety of
causes have been considered, including heavy metals, agrochemicals, infectious diseases, and recurrent heat
stress and dehydration. Here we evaluate the novel hypothesis that amorphous silica, released into the air during
the burning of sugarcane and rice, may be a primary cause. The evidence supporting this hypothesis consists
of the following: 1. Amorphous silica is present in sugarcane and rice and is released when sugarcane is burned
or rice husks are burned each season. 2. The particular matter fraction (PM2.5) of burned sugarcane and rice
contains 80-90 percent amorphous, nanoparticle sized silica. 3. Both PM2.5 and exposure to silica is associated
with risk for CKD, and records show that the amount of burning of sugarcane in Central America and of rice in
Sri Lanka parallel the epidemics in these countries. 4. Rats administered amorphous nanoparticle sized silica
develop CKD with minimal respiratory signs and the biopsies show chronic interstitial nephritis with silica particles
in tubules. 5. Human biopsies of subjects with Mesoamerican Nephropathy, Sri Lankan Nephropathy, and
Uddanam nephropathy show dramatic presence of amorphous nano-sized silica particles in tubules compared
to controls by darkfield spectral microscopy and confirmed by ICP-mass spectrometry of the kidney tissues.
Given these findings, we propose to 1) Identify the Route(s) and Mechanisms by which nanoparticle silica may
cause kidney injury in a rat model, evaluating both oral and intranasal approaches; varying the nanoparticle size,
and doing both a time and dose response; evaluating the potentially synergistic effect of heat; determining if the
mechanism involves lysosomal uptake and inflammasome activation; evaluating if other organs (such as the
lung) are involved, and testing the therapeutic potential of mycophenolate and allopurinol. 2) To characterize the
silica in the kidney biopsy tissue and urine using ICP-MS, Raman spectroscopy, electron microscopy and
enhanced darkfield hyperspectral imaging. 3) To identify the Impact of Silica Nephropathy in both Epidemic
CKDu and Other Renal Diseases by better characterizing silica nephropathy in kidney biopsies from known
epidemic areas, predicting and testing for silica nephropathy in other regions where sugarcane is burned (or
not); and 4) Evaluating previously collected kidney biopsies in Denver and Stockholm, and other areas of the
world to determine if silica is increased in CKDu compared to other renal diseases. These studies will
characterize silica nephropathy, possibly o...

## Key facts

- **NIH application ID:** 10682599
- **Project number:** 5R01DK125351-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Jared Michael Brown
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $629,682
- **Award type:** 5
- **Project period:** 2020-07-07 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10682599

## Citation

> US National Institutes of Health, RePORTER application 10682599, Silica Nephropathy and Chronic Kidney Disease of Unknown Etiology (5R01DK125351-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10682599. Licensed CC0.

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