# High Concentrations of Circulating 2PY and 4PY—Potential Risk Factor of Cardiovascular Disease in Patients with Chronic Kidney Disease

## TL;DR

High levels of 2PY and 4PY, byproducts of NAD+, may increase heart disease risk in patients with advanced kidney disease.

## Contribution

The paper proposes that elevated 2PY and 4PY concentrations may be a novel risk factor for cardiovascular disease in chronic kidney disease patients.

## Key findings

- Advanced CKD patients have significantly higher circulating 2PY and 4PY concentrations than healthy individuals.
- High 2PY and 4PY levels may contribute to cardiovascular events and premature death in CKD patients.
- NAD+ boosters may raise 2PY and 4PY levels, suggesting caution in their use for CKD patients at high CVD risk.

## Abstract

Recently published data indicate that elevated circulating concentrations of N1-methyl-2-pyridone-5-carboxamide (2PY, also described as Met2PY) and N1-methyl-4-pyridone-5-carboxamide (4PY, also described as Met4PY), terminal catabolites of nicotinamide adenine dinucleotide (NAD+), are associated with cardiovascular disease (CVD) risk in humans. Previously, we and the others have shown that patients with advanced stages of chronic kidney disease (CKD) exhibit several-fold higher circulating 2PY and 4PY concentrations compared to healthy subjects or patients in the early stages of the disease. It is also well documented that patients with advanced CKD stages exhibit markedly elevated CVD risk, which is the main cause of premature death (in these patients). Therefore, we hypothesize that high concentrations of circulating 2PY and 4PY are important factors that may contribute to cardiovascular events and, ultimately, premature death in CKD patients. However, further, accurately controlled clinical research is needed to provide definitive answers concerning the role of 2PY and 4PY in CVD risk in CKD patients. Moreover, we are dealing with some issues related to the use of NAD+ precursors (NAD+ boosters) as drugs (also in CKD patients) and/or supplements. Due to the increase in circulating 2PY and 4PY levels during treatment with NAD+ boosters, these precursors should be used with caution, especially in patients with increased CVD risk.