# Kidney Tubular Damage and Dysfunction Identify a Novel Axis of Chronic Kidney Disease

> **NIH NIH R01** · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · 2023 · $591,938

## Abstract

PROJECT SUMMARY
 For over 50 years, clinicians have relied upon serum creatinine and albuminuria as the sole biomarkers to
measure and monitor kidney health. These measures primarily mark the glomerular filtration rate (GFR) and
glomerular damage, yet the kidney tubules are responsible for a myriad of functions critical to life, including
toxin secretion, nutrient reabsorption, acid/base control, and immune defense. Currently, clinicians cannot
evaluate tubule health except in rare instances when kidney biopsies are obtained. In our parent grant,
R01DK098234, an ancillary study in the landmark Systolic Blood Pressure Intervention Trial (SPRINT), we
found that non-invasive biomarkers that characterize health of the kidney tubules predict CKD progression and
cardiovascular disease events, independent of creatinine, albuminuria, and other risk factors. We also made
an important additional discovery that could challenge current paradigms, and will be a major focus of this
renewal application. SPRINT found that while intensive blood pressure lowering reduced cardiovascular events
and mortality, it also worsened serum creatinine. Yet, we found that participants in the intensive blood pressure
lowering arm appeared to have reduced tubule injury. These findings indicate that rising serum creatinine
levels in this setting typically reflect hemodynamic accommodation rather than intrinsic kidney injury; yet the
concern for kidney damage in clinical care prevents many individuals from receiving life-extending, optimal
hypertension treatment.
 Building on our successes in unlocking the prognostic potential of the kidney tubules in the parent grant,
this renewal has the objective of building a Kidney Tubule Health Panel (KTHP) that can be applied to
individual patients for eventual translation to clinical care. Our three major goals are: a) prediction of
progressive CKD; b) prediction of cardiovascular disease; and c) differentiation of intrinsic tubule damage from
benign hemodynamic accommodation within individuals who develop rising creatinine levels. To accomplish
these prediction goals, we must explore several additional critical functions of the kidney tubules, including
toxin secretion and ammonia production; and, we must explore more sensitive measures of kidney tubule
injury, including biomarkers measured in blood as well as urine. We will evaluate, compare, and combine these
new measures with existing measures from the parent award to identify a parsimonious set of measures that
maximally achieves each of the afore-mentioned prediction goals, utilizing latent variable approaches to
develop distinct and physiologically relevant axes of kidney tubule health that will comprise the KTHP. The
KTHP will then be measured, evaluated and validated in the community-based Nord-TrØndelag Health (HUNT)
Study and the Norwegian Kidney Biopsy Registry. This comprehensive work will allow us to advance the KTHP
as a novel and useful clinical tool to improve prediction ...

## Key facts

- **NIH application ID:** 10683087
- **Project number:** 5R01DK098234-09
- **Recipient organization:** VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
- **Principal Investigator:** Joachim H Ix
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $591,938
- **Award type:** 5
- **Project period:** 2019-09-20 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683087

## Citation

> US National Institutes of Health, RePORTER application 10683087, Kidney Tubular Damage and Dysfunction Identify a Novel Axis of Chronic Kidney Disease (5R01DK098234-09). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10683087. Licensed CC0.

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