Healing Without Harm: Collaboration is Key in Clinical Pharmacist’s Quest to Safeguard Kidney Health

“It can happen to anyone, we're all susceptible.” she said.

While saving lives is the ICU’s top priority, a kidney injury can prevent these vital organs from functioning properly.

“As clinicians, we calculate the risk, and there will be instances where we have to use medications that are toxic to the kidneys,” said Awdishu. “For example, a patient who is admitted with sepsis is at high risk of developing acute kidney injury and requires antibiotics like vancomycin and piperacillin/tazobactam in the first 48 hours to reduce mortality. But these drugs may be harmful to the kidney.”

Witnessing the adverse effects of these therapies inspired Awdishu to focus her research on improving drug therapies for kidney disease and minimizing drug-induced kidney injury to improve patient outcomes.

Awdishu’s work is deeply personal. Earlier this year, she lost her father to kidney disease caused by irreversible kidney injury from surgical complications and medications to treat those complications.

“That really hit home as a pharmacist,” said Awdishu, who had many questions during her father’s treatment, which took place in Canada. “I was asking: Who is dosing these antibiotics? Who is monitoring kidney function? How can we mitigate the risk for my own family member?”

Deciphering acute kidney injury

Distinguishing drug-induced kidney injury from other causes is a challenge. Many patients have multiple health issues and are also taking a variety of medications, complicating diagnosis. Standard criteria for classifying the condition are currently lacking.

“We don’t have very great consensus even among expert nephrologists about how to differentiate,” said Awdishu.

She has been working with Ravindra Mehta, M.D., professor emeritus of medicine at UC San Diego School of Medicine, to develop better diagnostic tools for many years.

As part of the international Drug-Induced Renal Injury Consortium, Awdishu, Mehta and their colleagues analyzed hundreds of acute kidney injury cases to screen patients and identify risk factors.

Their research revealed that nearly 50% of enrolled acute kidney injury cases involved patients who had taken vancomycin. Drug-induced kidney injury was also much more common in patients who had taken nonsteroidal anti-inflammatory drugs (NSAIDS). Approximately 60% of patients still had persistent kidney injury when they were discharged from the hospital, highlighting the need for follow-up of kidney function after hospitalization.

The team developed a statistical model that took these and many other factors into account in order to understand which patients are susceptible to drug-induced kidney injury and whether the drug or other conditions led to the injury. Awdishu said the model did an excellent job of classifying the patients into one group or another.

“This helped us to understand the variables that might be associated with injury,” said Awdishu. “These types of findings are important because now we can start to apply them within a patient’s electronic health record — by screening patient labs looking for trajectories in kidney function and by recognizing patterns that correlate with drug exposures.”

The study could help clinicians reduce the risk of drug-induced kidney injury as well as intervene earlier, which can improve patient outcomes.

The researchers also collected patient blood samples to study how the genes of individual patients might affect their response to different medications.

“Genetic variation in drug-metabolizing enzymes and immune pathways can significantly increase the risk of drug-induced kidney injury in certain patients, making the same dose safe for some patients and harmful for others,” said Mehta. “Systematic genetic analyses can pinpoint high‑risk genotypes to inform drug selection, dosing and monitoring for developing precise therapies that reduce nephrotoxicity and improve patient safety.”

The team has identified several genes of interest, and is in the process of gathering data from more patients to replicate the findings.

Uncovering biological mechanisms

To better understand why and how certain drugs, like vancomycin, are toxic to the kidneys, Awdishu teamed up Mehta and colleagues from several other universities to study urinary exosomes — tiny messengers that help cells communicate.

“There had been a lot of controversy whether it was truly nephrotoxic or not,” said Awdishu.

The team identified 251 proteins involved in inflammatory and coagulation pathways in patients with vancomycin-induced kidney injury.

“Vancomycin upregulates inflammatory pathways, contributing to toxicity within the kidney,” said Awdishu.

These insights could improve diagnosis and treatment of kidney injuries.

Improving dialysis care for kidney injury

Many patients who experience acute kidney injury require dialysis after leaving the hospital because their kidneys can no longer remove waste products and excess fluid from the blood on their own. This puts them at high risk of adverse outcomes, including cardiovascular disease and death. Awdishu contributes to guidelines for how to best care for these patients.

“This group of patients is mixed into the dialysis unit with patients who have end-stage kidney disease,” she said. Standard protocols don't apply to caring for these patients, and other factors need to be taken into account after the stress of being hospitalized. “My research brings to light the importance of a pharmacist in the clinical care of these patients,  to partner with the physician on complex issues in a critical period of recovery.”

Team Science

In addition to working with other pharmacists and experts in kidney care, Awdishu collaborates with researchers across UC San Diego and beyond, including surgeons, bioinformatics experts, engineers and computer scientists. She and her colleagues increasingly turn to artificial intelligence (AI) to tease apart the variables that influence a patient’s response to various treatment regimens.

“We're studying how to use AI in prediction models and it's probably going to be a really big area for clinician-guided precision therapy,” said Awdishu.

For example, when surgeons perform kidney transplants, they use drugs that suppress the immune system so that patients are less likely to reject a donor kidney. Awdishu collaborated with computer scientist Shamim Nemati, Ph.D., associate professor of medicine at UC San Diego School of Medicine and colleagues in other departments to develop a deep learning AI model to predict responses to tacrolimus, a powerful immunosuppressant drug. Deep learning models are used to uncover complex patterns from large amounts of raw patient data.

Tacrolimus prevents organ rejection in transplant recipients. However, the drug has a narrow therapeutic index, meaning that the difference between an effective dose and a toxic one is very small and varies from patient to patient.

“Unfortunately, one of the adverse effects of this drug is kidney injury, so precision dosing becomes very important.” Awdishu said.

Overall, the model achieved 73% accuracy in predicting patients’ tacrolimus levels the day after treatment with the drug for kidney — and also liver — transplants.

The ultimate goal is to guide clinicians in choosing the right tacrolimus dosages for individual patients to prevent over- or under-dosing.

“The next step in the project is to study the impact of the model to see if it's working as well as, or superior to clinician judgment,” said Awdishu.

The tacrolimus project exemplified the importance of multidisciplinary collaboration in kidney research, according to Awdishu, who developed clinical pharmacy transplant services at Jacobs Medical Center at UC San Diego Health. “It was the epitome of team science. Expertise was needed from everyone from engineering grad students to transplant surgeons to tackle this complex problem.”

“One of UC San Diego’s greatest strengths is its interdisciplinary environment, where collaboration across clinical and computational domains enables us to build AI systems that are not merely theoretical constructs, but clinically actionable tools designed to transform patient care in real time,” said Nemati. “Linda Awdishu is one of those rare collaborators who engages deeply with the underlying computational methods, often challenging us to think more critically and refine our AI systems with clinical nuance.

Tackling chronic kidney disease

Diabetes, hypertension and cardiovascular disease are major risk factors for chronic kidney disease, but genetics, certain medications, smoking and other factors can also play a role.

Awdishu’s chronic kidney disease research aims to improve drug therapies for chronic kidney disease by accounting for patients’ demographics, vital signs, medical conditions, prior dosing history, diet, medications and lab results.

Doing so allows clinicians to tailor therapy to the patient in front of them using precision dosing of the correct drug for them. Awdishu also advocates for stronger collaboration between physicians and pharmacists. At UC San Diego Health, Awdishu spearheaded the formation of the multidisciplinary Chronic Kidney Disease Program.

“The work that we're doing in optimizing therapy for patients with kidney disease has highlighted the role of the pharmacist in the care of these patients in general,” she said.

The future of kidney care

Chronic kidney disease is a growing global public health issue that disproportionately affects older people, like Awdishu’s father, as well as people experiencing poverty, people of color, and other marginalized communities.

With more than 37 million people in the U.S. and 850 million across the globe experiencing some form of the disease — with numbers rising every day — research into improving kidney care for patients is more vital than ever. Yet, kidney disease research remains underfunded even as health care costs to treat it soar.

Though non-profit research organizations like the International Serious Adverse Event Consortium provide some support for kidney injury research, finding innovative solutions to the complexity of kidney disease in the U.S. largely depends on federal funding from the National Institutes of Health (NIH).

For example, Awdishu is a co-investigator of the O'Brien Center for Acute Kidney Injury, a collaboration between UC San Diego and the University of Alabama.

Proposed cuts to the NIH in recent months put this research in jeopardy.

“If the O'Brien Center is impacted by the NIH cuts,  it has a huge effect on scientists across the country and internationally,” she said. “The research would be very difficult to continue without the funding.”

Learn more about why federal funding matters and how you can support UC San Diego Health Sciences research into chronic kidney disease and other conditions.