Thoughts on the silica hypothesis as a cause of Chronic kidney disease of unknown etiology (CKDu)
Chronic kidney disease of unknown etiology is a devastating form of kidney disease that strikes primarily young agricultural workers working in sugarcane and rice production. For a background on this I’d recommend this piece by Fletcher Reveley in Undark magazine and this article in the New England Journal of Medicine from Johnson et al. (2019). There are several competing hypotheses for the cause of the disease, including heat stress, exposure to agrochemicals or silica from pre-harvest burning, (done to reduce the biomass that needs to be transported to the mill). Silica exposure has been linked to kidney failure observationally (Vupputuri et al. 2011) and amorphous silica nanoparticles have been shown to cause kidney failure in a rat model (Sasai et al. 2022). We know that sugarcane workers are exposed to high levels of amorphous silica during burning (Schaeffer et al 2020).
My USDA-ARS research unit works with sugarcane breeders and so I wanted to offer some observations I have made from talking with them about this issue with them and hopefully be a connection to help medical and public health researchers find sugarcane breeders and agronomists who could help them get information on the biology and agronomic processes of the cropping system. I am not an expert on this at all but I’m posting these observations in the hope that I can help connect experts.
Changes in breeding and agronomic practice
One of the most perplexing things about this epidemic is its rapid rise starting in about the 1990’s. During this time there was an effort to breed for increased size and lodging resistance (resistance to being blown over). There is some evidence that cultivars of sugarcane do vary in their silica leaf content Deren et al. (1993) and by the silica content of the soils. The silica content of cultivars is not something that would have been recorded in most breeding records but there has been a lot of selection for plant morphology that could be changing the silica content of the plants over time. It is also possible that changes in the morphology of the phytoliths could be affecting the size and properties of the amorphous silica nanoparticles generated by burning.
Another change may be increased usage of calcium silicate and silicate-containing iron slag as a silicon fertilizer, particularly on land with tropical weathered soils (Camargo and Keeping 2021). Silica fertilization had been noted to improve yield, drought resistance and pest resistance. I do not have good data on the increased use of silica fertilizer in specific locations but there seems to be increased recommendation for its use. Silicate bioavailability may also be changes secondarily by management changed that alter the pH of the soil.
Amorphous silica nanoparticles
One of the criticisms of the silica hypotheses is that pulmonary silicosis does not cooccur with CKDu at high levels. There has been a large focus on crystalline silica, which causes silicosis. Some crystaline silica is present in sugarcane smoke and ash but for CKDu a bigger potential danger is pyrogenically formed amorphous silica nanoparticles. Croissant et al. (2020) have a helpful review article explaining how important the formation temperature size, shape, and impurities are to the toxicity of amorphous silica nanoparticles.
Alternatives to burning
Research is underway on green harvesting without burning and this practice is required in some countries. Burning reduces the amount of trash leaved transported to the mill by 4-8 tons per acre and makes it easier to manually harvest so it is the cheapest method of harvest. One alternative would be to make the “trash” more valuable by selling refined silica as a secondary, value-added product from milling. Research is ongoing to extract high grade silica from sugarcane bagasse Seroka et al. (2022) that would be profitable to sell.
If you are a researcher and want help connecting with sugarcane agronomists and breeders at USDA about this please reach out to me.
