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New Kidney-on-a-Chip Platform Developed for Drug Screening and Testing


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A team of engineers developed kidneys grown in the lab designed for testing new drugs. The platform will allow pharmaceutical companies, scientists, and clinicians to develop new medications without the need for animal models. It will also enable medical experts and researchers to better understand the interaction of new meds to the kidneys.

 

 

Nephrotoxicity is one of many scenarios patients in the intensive care unit may suffer while under treatment. It is because drugs are extensively used in ICU patients that can cause kidney damage or injury. Medications, chemicals, and substances can cause toxicity in the kidneys that may lead to organ failure if left untreated. A patient's risk of developing nephrotoxicity increases substantially due to their underlying health problem. According to a study by Kidney International, one out of three patients is affected by nephrotoxicity. 

"One such complication is acute kidney injury, a relatively common problem in the ICU, which results from multiple insults. Importantly, potentially nephrotoxic medications contribute significantly to the development of AKI," researchers noted. 

Acute kidney injury is a sudden episode of kidney damage that happens within a few hours or a few days. When a patient suffers AKI, waste products pile up in the bloodstream that stresses the kidneys to keep the balance of fluids in the body. AKI can affect other internal organs, including the brain, heart, and the lungs, because of the fluid imbalance. 

 

 

Symptoms of AKI include too little urine, fatigue, shortness of breath, confusion, chest pain, and swelling in the ankles and legs. The symptoms, however, vary based on what caused the AKI, such as: 

- Hypotension or low blood pressure. A sudden drop in the blood pressure or major blood loss will damage the kidneys. 

- A trauma or injury that directly impacts the kidneys can damage the organs, affecting their functionality. 

- Heart conditions, such as heart attack or decreased cardiac function, affect the ability of the kidneys to balance fluids and filter waste products. 

- Medications, such as pain relievers, can cause kidney damage depending on the dosage and duration. 

- Burns can cause acute renal failure. This is because of the reduced output of the heart caused by fluid loss from burns. 

Engineers at Draper developed a kidney-on-a-chip platform to address the issue of AKI caused by medications. The platform is a tiny 3D structure that replicates many features of a full-sized human kidney. The main objective of the platform is to allow a better understanding how diseases affect the kidneys and the kind of therapeutic methods that may be applied. The engineers can reproduce the kidney platform in a microfluidic device called PREDICT-96, which holds 96 of such kidneys. 

"Given that the kidneys play a major role in how drugs interact with the body, these organs take on a particular relevance for drug R&D. Nephrotoxicity is a major cause of attrition during pre-clinical, clinical and post-approval states in pharmaceutical drug development," said Dr. Joseph Charest at Draper Laboratory. 

 

 

There are several medications that can damage the kidneys, especially in high doses and on longer durations, according to the National Kidney Foundation: 

1. Antibiotics: People with kidney disease usually receive a few antibiotics to reduce the risk of kidney damage. Antibiotics, such as aminoglycosides, cephalosporins, and vancomycin, can cause acute kidney failure. 

2. Pain relievers: People normally take painkillers, such as aspirin, ibuprofen, and naproxen, to treat mild to moderate pain. However, chronic intake of pain relievers can damage the kidneys, which is why people who suffer from chronic pain must discuss it with a clinician. The National Kidney Foundation recommends the use of over-the-counter medications no more than 10 days for pain or more than three days of fever. 

3. Prescription laxatives: Laxatives can be purchased as an over-the-counter medication and considered safe for most people. But some laxatives, such as prescription kinds used for cleaning the bowel before colonoscopy, can damage the kidneys. The National Kidney Foundation advises patients with chronic kidney disease to take oral sodium phosphate bowel cleansing agents with extreme caution. Phosphate crystals may accumulate in the kidneys that may lead to kidney function loss or acute kidney injury. 

Aside from understanding diseases and therapies on kidneys, the platform may also be used to reconstruct the physiological function of the organ at cellular and tissue level. In these levels, scientists can measure and analyze the interaction between drugs and the kidneys in real time. The platform can also be used for screening and testing of new drugs to determine kidney toxicity, mechanism of action, and other clinically-relevant tests without the need of animal models. 

"Used early in the drug discovery process, PREDICT-96 should allow developers to refocus resources on the strong candidates earlier and end unproductive research earlier, minimizing losses. What researchers want in a platform is to recreate human physiology in an accurate, reproducible, scalable, high-throughput, cost-effective and predictive format for testing candidate therapies for safety and efficacy," said David O'Dowd, an assistant director of Biomedical Solutions at Draper. 


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