Elevated Levels of Renalase, the β-NAD(P)H Isomerase, Can Be Used as Risk Factors of Major Adverse Cardiovascular Events and All-Cause Death in Patients with Chronic Kidney Disease.

Wojciech Knop,Barbara Dołęgowska,Magda Wiśniewska,Aleksandra Gomółka,Bartłomiej Grygorcewicz,Elżbieta Cecerska-Heryć,Natalia Maria Serwin,Kazimierz Ciechanowski

doi:10.3390/biom11101514

Abstract

Background: Renalase is an enzyme and a cytokine involved in cell survival. Since its discovery, associations between it and both cardiovascular and kidney disease have been noted. Recognizing this, we conducted a study in which we followed patients with chronic kidney disease. Material and methods: The study involved 90 CKD patients with varying stages of the disease and 30 healthy controls. Renalase was measured with an ELISA kit, and patients were followed-up after a median of 18 months. During the follow-up, we asked about the occurrence of MACE, all-cause mortality and the need for dialysis initiation. Results: In CKD subgroups, RNSL correlated with all-cause death only in the HD group (Rs = 0.49, p < 0.01). In the whole CKD population, we found a positive correlation of RNSL concentration and both MACE occurrence (Rs = 0.38, p < 0.001) and all-cause death (Rs = 0.34, p < 0.005). There was a significant increase in MACE occurrence probability in patients with elevated renalase levels (>25 μg/mL). Conclusions: Elevated renalase levels can be used as a risk factor of MACE in patients with CKD, but its long-term utility needs further research. High renalase levels are a risk factor of death among CKD patients. In HD patients, all deaths were observed among patients with >30 μg/mL; this level could be used as a “red flag” marker in future studies.

Highlights

Renalase (RNLS) is a small flavoprotein produced mainly by the kidney
chronic kidney disease (CKD) patients into subgroups, each consisting of 30 participants: CKD stage III (CKD III), CKD stage IV (CKD IV), CKD stage 5D who were hemodialyzed (HD) and 30 adults
We looked for all-cause mortality and a need to start renal replacement therapy (RRT)

Summary

Introduction

Renalase (RNLS) is a small flavoprotein produced mainly by the kidney. the latest investigations show that RNLS might be an “organolase”, as the RNLS gene is expressed in many other cells and tissues, including the nervous system, endocrinal and digestive tract organs, lungs or heart in humans and some other mammals [1]. Intracellular RNLS acts as an enzyme that, in the presence of a FAD cofactor, oxidizes 2- and 6- DHNAD(P) to β-NAD(P)+, its biologically active form. This action prevents toxicity resulting from the inhibition of many β-NAD(P)+ dependent enzymes and reactions. Extracellular renalase and RP-200 and RP-220 peptides, which are fragments of the protein, activate some signaling pathways, including Akt and MAP kinases, promoting cell survival. This activity is mediated by the binding of renalase to its recently discovered receptor–plasma membrane

Methods

Discussion

Conclusion