# Dissecting the role of soluble a-Klotho in cardiovascular aging

> **NIH NIH K23** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $51,810

## Abstract

PROJECT SUMMARY/ABSTRACT
The proposed career development award will foster and promote the candidate’s training and evolution toward
independent investigator. Candidate: Dr. Kenneth Lim is Assistant Professor of Medicine in the Division of
Nephrology at Indiana University. The proposed study integrates patient-oriented research, cardiopulmonary
exercise testing (CPET) technology, proteomics and computational biology embedded in a rigorous training
plan. Mentorship: Dr. Sharon Moe (Primary Mentor) is Past President of the American Society of Nephrology
(ASN), Associate Dean of Clinical and Translational Research and Director of the Division of Nephrology at
Indiana University. Dr. Ravi Thadhani (Secondary Mentor) is Chief Academic Officer at MassGeneralBrigham
and Faculty Dean at Harvard Medical School. Research: Age-associated changes of the cardiovascular
system and its complications are the leading cause of death in patients with chronic kidney disease (CKD).
Despite this, there are currently no direct therapies available to treat this condition today. Klotho is a protein
present in circulation that exerts highly pleiotropic aging suppressive effects. Animal studies have
demonstrated promising therapeutic properties of Klotho that could be used for the treatment of cardiovascular
disease in CKD. However, several fundamental problems must first be overcome before future human
interventional studies can proceed: Firstly, published studies examining circulating Klotho with cardiovascular
outcomes to-date have focused mainly on morphological alterations, while clear evidence has shown that
aging is tightly associated with reduced cardiovascular functional reserve. Secondly, the precise levels of the
various circulating isoforms of Klotho and the nature of their specific roles in cardiovascular health are still
undefined. The overall aim of the proposed study is therefore to bridge a critical gap in our understanding of
the role of circulating Klotho in the regulation of the cardiovascular aging response in CKD. We hypothesize
that circulating Klotho deficiency is a major determinant of premature cardiovascular aging in CKD.
In specific aim 1, we will characterize the relationship of the various Klotho isoforms with cardiovascular
structure and functional reserve using state-of-the-art CPET technology. We will define levels of circulating
Klotho isoforms in health and advanced CKD (cross-sectional), and after kidney transplantation (prospectively).
Circulating Klotho isoform levels will be assessed using an established immunoprecipitation and western
blotting method.
In specific aim 2, we will conduct a cross-section study to characterize the relationship of circulating Klotho
with premature vascular changes using human arteries from healthy and CKD patients. To further determine
therapeutic properties of Klotho, we will conduct an interventional study using arterial explant organ cultures.

## Key facts

- **NIH application ID:** 10630417
- **Project number:** 3K23DK115683-05S1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Kenneth Lim
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,810
- **Award type:** 3
- **Project period:** 2022-05-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10630417

## Citation

> US National Institutes of Health, RePORTER application 10630417, Dissecting the role of soluble a-Klotho in cardiovascular aging (3K23DK115683-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10630417. Licensed CC0.

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