# HiLo

> **NIH NIH UH3** · DUKE UNIVERSITY · 2021 · $1,327,995

## Abstract

As the population ages and therapeutic advances improve life expectancies of chronic diseases, the prevalence
of end-stage renal disease (ESRD) inexorably increases. Kidney transplantation is the preferred treatment, but
an insufficient organ supply renders dialysis the only treatment option for most patients. Although dialysis
outcomes have improved modestly in recent years, annual rates of hospitalizations and mortality remain
unacceptably high and quality of life is poor. Starved for therapeutic advances to improve outcomes, the
nephrology community has adopted opinion-based clinical practice guidelines for many aspects of ESRD care,
including our approach to phosphate control. Current guidelines advocate aggressive treatment of
hyperphosphatemia to near normal levels (< 5.0 mg/dl) using dietary phosphate binders and highly restrictive
diets; however, because there have been no randomized clinical outcomes trials, the assumed benefits of this
approach are unproven, potential harms have not been identified, and the optimal serum phosphate target is
unknown. To address this important unmet need, we propose “HiLo”, a large, cluster-randomized pragmatic trial
to be conducted as one of the demonstration projects of the NIH Health Care Systems Research Collaboratory.
HiLo will evaluate the effects on important clinical outcomes of liberalizing serum phosphate target for patients
receiving treatment with maintenance hemodialysis. The trial will enroll 4400 patients and will be fully embedded
in the clinical care delivery of >100 dialysis facilities owned and operated by three dialysis provider organizations:
a large, national for-profit dialysis company, a mid-sized non-profit dialysis company, and an academically-owned
regional provider. HiLo will test the hypothesis that liberal control of serum phosphate to target 6–7 mg/dl will
yield non-inferior rates of hospitalization compared to the current standard approach of targeting phosphate
levels to <5.0 mg/dl. As a secondary objective, HiLo will test for superiority of the different arms on mortality.
The HiLo Data Coordinating Center will be based at the Duke Clinical Research Institute (DCRI), a highly
experienced academic research organization and the Coordinating Center for the Collaboratory. The project will
be implemented in two phases – a UG3 planning phase and a UH3 implementation phase – each of which has
specific milestones. In addition to addressing a question of high clinical relevance in ESRD, HiLo will advance
the field of pragmatic trials through several innovations: 1) answering a pressing clinical question rather than
evaluating strategies to enhance implementation of a proven therapy; 2) using a novel electronic approach for
patient-level consent to enable pragmatic evaluation of a “more than minimal risk” intervention for the first time in
ESRD; and 3) providing a precedent for a non-mortality primary endpoint in ESRD trials. Given the importance of
the trial question to patients, ...

## Key facts

- **NIH application ID:** 10229378
- **Project number:** 5UH3DK118748-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** MYLES S WOLF
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,327,995
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229378

## Citation

> US National Institutes of Health, RePORTER application 10229378, HiLo (5UH3DK118748-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10229378. Licensed CC0.

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