Dr. Jonathan Himmelfarb on Personalizing Treatments for Chronic Kidney Disease

Excerpts from our conversation with Dr. Jonathan Himmelfarb, a kidney-health researcher at Mount Sinai in New York City.

Read the story Curbing Chronic Kidney Disease in NIH News in Health.

NIHNiH: How can diabetes, obesity, or heart disease lead to kidney damage in some people?

Himmelfarb: The kidneys get exposed 24/7 to whatever is in the blood, and some of that can be damaging to the kidneys.

In diabetes, people have high blood sugar. There are changes in the amount of fats in the blood, and other Related to metabolism, the chemical changes in the body that create the energy and substances you need to grow, move, and stay healthy. metabolic changes as well. All this creates added work for the kidneys, and over time that can cause damage.

It takes around 10 to 15 years for this to happen, but you can eventually get irreparable damage to the kidneys, which can ultimately lead to kidney failure. That’s also true for obesity. Even if your blood sugar is normal, in obesity there are other metabolic changes in the body that can impact the kidneys.

High blood pressure is another common condition that directly affects the kidneys. Because the kidneys have so much blood flow through them, a high proportion of their structure is blood vessels. And those blood vessels can be damaged by constant pressure and stress.

NIHNiH: Why is developing more personalized therapies for chronic kidney disease important?

Himmelfarb: Chronic kidney disease is really a syndrome more than it is a specific disease. It’s a syndrome that’s defined by how well the kidneys are functioning. If there’s a loss of the ability of the kidneys to filter the blood or to prevent leakage of proteins from the blood, that’s chronic kidney disease.

But there are many, many different causes that can lead to that syndrome. Even for people with a specific risk factor, like diabetes or obesity, their kidneys can be affected differently.

Different cell types in the kidney can be injured in different ways. And the response to injury can vary by the cell type, what’s causing the injury, and your genetic background as well.

We’re in an exciting era where, for the first time, we have some very effective drugs for chronic kidney disease. But say you have diabetes and chronic kidney disease, you may improve with drug A. Or your disease may stay stable. But some people will continue to have loss of kidney function on drug A, and might have done better with drug B.

Right now, we have no way to know that up front. What the Kidney Precision Medicine Project is designed to do is eventually help doctors pick the right drug or drug combination at the beginning of treatment, rather than through trial and error.

NIHNiH: Your team is also building ‘kidney-on-a-chip’ models with human cells. What are the potential advantages over this approach compared to using animals to test new drugs?

Himmelfarb: We’ve cured a lot of diseases in animals, but that hasn’t translated to the same benefits when you use those treatments in people. Most drugs still fail when they go into clinical trials. They either turn out to be too toxic, or they’re just not effective.

If we can improve that by working with human models from the beginning, and we can shorten the period of time it takes to bring new drugs to patients, that would be a win not just for treating kidney diseases, but other diseases as well.

And with organ-on-a-chip models, we can take into account the genetic variation you have in people. Genes can also contribute to what would be the best treatment for an individual, or even for their risk of getting a certain disease in the first place.