Adiponectin is a hormone produced by fat cells, which appears to protect blood vessels in diabetes and heart disease. In animal models of diabetes, adiponectin can protect from the development of diabetic kidney disease.

Blood vessels have a protective gel-like layer, the endothelial glycocalyx. This can be measured indirectly in humans using specialised microscopy imaging of blood vessels under the tongue, using a Glycocheck device. This has been shown to reflect changes to the endothelial glycocalyx on blood vessels elsewhere in the body, including the kidneys.Glycocheck parameters are being collected from individuals in ALSPAC (by Prof Abigail Fraser).

Damage to the endothelial glycocalyx in the filtering blood vessels of the kidney leads to protein, such as albumin, filtered into the urine (albuminuria), a hallmark of kidney disease. We have shown that adiponectin can protect the filtering blood vesssels in the kidney from glycocalyx damage and protect from the development of diabetic kidney disease.

We aim to show relevance to human disease by demonstrating that changes in adiponectin levels can cause albuminuria and kidney disease using Mendelian randomisation. We wish to use the ALSPAC data to explore the causal role of circulating levels of adiponectin and adiponectin receptor expression on glycocalyx depth (measured in ALSPAC- Glycocheck) and circulating levels of syndecan 4 (a marker of glycocalyx shedding). This will allow us to explore whether adiponectin signalling has a positive impact on kidney disease and function due to its effects on the glycocalyx.