Evaluating N,N,N trimethyl-L-alanyl-L-proline betaine (TMAP) on progressive kidney disease
Co-Applicant(s): Andrew House, Matthew Lanktree, Matthew Weir
Lay Abstract
Chronic kidney disease is characterized by progressive decline in kidney function over time. When kidney function declines, the kidney becomes ineffective at clearing waste products from the body. This leads to build up of waste products in the blood that are normally eliminated in the urine. The accumulated products in the blood can be measured to quantify kidney disease. In addition, waste products that accumulate in the blood can be toxic to the kidney itself and other areas of the body such as the heart or blood vessels. This causes patients with kidney disease to suffer from greater risk of having a heart attack and stroke. Our team has recently identified a waste product that accumulates in the blood of patients with kidney disease called “TMAP”. Our studies suggest TMAP might be useful in diagnosing kidney disease and identifying patients who are more likely to develop kidney failure. Other than our studies indicating blood levels of TMAP reflect severity of kidney disease, there is nothing else known about TMAP including how it is produced in the body or what it does. Our studies seek to discover the biological source of TMAP and determine whether blood or urine concentrations of TMAP are related to how fast kidney function declines or whether its causes heart disease and/or stroke. We have unique access to over two thousand blood, urine and DNA samples from patients with kidney disease. These studies looked at over thousands of patients with kidney disease and collected detailed information about how fast their kidney function declined and what other medical events (e.g. heart attack, stroke) these patients suffered from. We will measure plasma and urinary TMAP in these patients to see how it influences the decline in kidney function and medical events such as heart attack and stroke. We’ll also study the genetic determinants of TMAP concentration to help identify its source. Our work will help determine new mechanisms for why patients with kidney disease suffer these other medical problems and may lead to new treatments to prevent problems like rapid decline of kidney function, heart attack and stroke, the leading causes of death in patients with kidney disease.
