# Thiamine as a Renal Protective Agent in Septic Shock

> **NIH NIH K23** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $46,613

## Abstract

Project Summary/Abstract:
Septic shock is a common and highly morbid clinical syndrome that affects over 200,000 patients in the United
States annually and results in over 40,000 deaths. Kidney failure is a frequent complication of sepsis and
septic shock that is associated with worse outcomes. To date, the understanding of kidney injury in sepsis and
septic shock has traditionally focused on decreased blood pressure leading to kidney hypoperfusion. Recent
studies have challenged this paradigm, however, illustrating that sepsis associated kidney injury often occurs
even when perfusion is adequate. These findings suggest that alternative pathophysiologic mechanisms may
have a role in sepsis related kidney injury. The mechanisms remain poorly understood and as yet there are no
proven interventions aimed at mitigating sepsis-induced kidney injury.
Thiamine (vitamin B1), a key cofactor of pyruvate dehydrogenase, is a critical component of oxidative
phosphorylation (i.e. aerobic mitochondrial respiration). In the absence of thiamine, mitochondrial metabolism
shifts towards anaerobic energy production, which is inefficient and results in lactate production. Thiamine
deficiency has also been linked to increased levels of reactive oxygen species. Our research group has
previously demonstrated that thiamine deficiency is common in critical illness and inversely associated with
lactate levels. We hypothesize that thiamine deficiency during critical illness may occur due to increased
metabolic demand which rapidly consumes available thiamine stores.
In a randomized trial, our research group has found that the administration of thiamine to thiamine deficient
patients with septic shock leads to reduced lactate at 24-hours. In a post-hoc analysis of that study, my work
has shown that patients (including both thiamine replete and thiamine deficient patients) who received thiamine
had lower creatinine values at 24-hours and were less likely to require kidney replacement therapy (e.g.
dialysis). Our research group has also shown improved cellular oxygen consumption in septic patients and
cardiac surgery patients who receive thiamine.
Given the above, we hypothesize that thiamine attenuates kidney injury during septic shock by supporting
aerobic mitochondrial metabolism. To test this hypothesis, we have planned a randomized, double-blind
placebo-controlled trial of thiamine to improve in kidney function in patients with septic shock. This award will
allow me to further develop as a physician-investigator and to test important hypotheses with potentially
significant therapeutic benefits for patients with sepsis and septic shock.

## Key facts

- **NIH application ID:** 10369886
- **Project number:** 7K23GM128005-04
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Ari Moskowitz
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $46,613
- **Award type:** 7
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369886

## Citation

> US National Institutes of Health, RePORTER application 10369886, Thiamine as a Renal Protective Agent in Septic Shock (7K23GM128005-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10369886. Licensed CC0.

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