Publications
Goal: Some people who have a sudden kidney injury never fully get better. Their kidneys keep getting worse, and they end up with long-term kidney disease. This study asked if a natural chemical called quinolinic acid helps cause that change.
Key results: The body makes quinolinic acid as it breaks down a protein building block. In mice, more of it led to worse kidney damage and signs of scarring, and mice that made less of it did better. It also built up in inflamed parts of kidney biopsies from people with sudden injury, and kids with long-term kidney disease had more of it in their urine.
Implications for patients: Quinolinic acid may be one reason a sudden kidney injury turns into lasting damage. Medicines that lower it could one day help protect the kidney after an injury. Most of this work was done in mice, so more research is needed in people.
Goal: To learn what goes wrong in kidney disease, scientists compare sick kidney tissue to healthy tissue. But healthy tissue can come from different places, such as kidney cancer surgery, living kidney donors, or healthy volunteers. This study asked whether the source of healthy tissue changes the results.
Key results: The team compared these three kinds of healthy tissue by reading gene activity in single cells. Each kind looked different, based on how it was collected and on the donor's age and sex. When the team adjusted for these differences, it changed which signs of diabetic kidney disease stood out.
Implications for patients: Choosing the right healthy tissue matters for kidney research. Researchers also need to account for age, sex, and how the tissue was collected. This helps make sure findings reflect the disease itself and not how the samples were gathered.
Goal: Sugar chains called glycans coat many proteins in the kidney. Changes in these sugars in certain parts of the kidney may help explain kidney disease, but they are hard to map. The team built a new way to see where these sugars sit in kidney biopsy tissue.
Key results: The method pairs a special imaging scan with AI that marks the kidney's main parts, like its filters and tubes. In healthy tissue, it could tell these parts apart by their sugars. One sugar type was higher in the filters and tubes in diabetic kidney disease, and in the tubes and blood vessels in sudden kidney injury.
Implications for patients: This is a new research tool, not a test or treatment yet. It may help scientists learn how kidney disease starts in each part of the kidney. More research is needed before it can help patients directly.
Goal: In a large study called SONAR, a drug named atrasentan helped protect the kidneys of people with type 2 diabetes and kidney disease. But it did not help everyone the same. Researchers looked for a sign in the urine that could show who was getting worse and who the drug was helping.
Key results: A protein in the urine called clusterin stood out. People with more clusterin were more likely to have their kidney disease get worse. The drug lowered clusterin by about 43% in six weeks, and people whose levels dropped early did better later on.
Implications for patients: A simple urine test could one day tell doctors early on if a kidney drug is working. That would help match each patient with the treatment most likely to help. This test is not yet used in clinics.
Goal: After a sudden kidney injury, the kidney's tiny tubes must regrow their lining to heal. Past work showed that a type of immune cell helps with this. This study asked how those immune cells send the signal to heal.
Key results: Working mostly in mice, the team found that the immune cells do not make the healing signal themselves. Instead, they tell nearby support cells to release a growth signal called IGF-1. IGF-1 then tells the tube cells that survived to grow and fix the damage.
Implications for patients: This helps explain how the kidney heals itself after a sudden injury. Knowing how these cells work together could one day lead to drugs that help the kidney heal. Because most of this work was done in mice, it is not ready for patient care yet.
Goal: Casts are small plugs of protein that can form inside the kidney's tiny tubes. Doctors have long seen them as a sign of kidney disease, but we know little about what is in them or what they mean. This study used KPMP kidney biopsies to find out.
Key results: The team looked at almost 500 casts from 42 people. Most casts held a protein called PROM1, which kidney cells make when they are hurt, and the tubes around these casts showed clear signs of damage. People with a sudden kidney injury also had more PROM1 in their urine than healthy people.
Implications for patients: Casts are not just waste. What is inside them can show how hurt the kidney is. In the future, a urine test for PROM1 might help doctors find sudden kidney injury early, but more research is needed first.
Goal: Many people have chronic kidney disease, often from diabetes or high blood pressure. Doctors rarely take a small piece of kidney tissue, called a biopsy, from these patients. This study looked at KPMP biopsies to see what the kidney really looks like in these common types of kidney disease.
Key results: Kidney experts studied biopsies from 39 adults and agreed together on what each one showed. Many people had the kidney damage doctors expected, but some had other kidney diseases no one suspected. About one in four doctors said the results were not what they expected.
Implications for patients: For 77% of people, the biopsy changed how doctors talked with them about what may happen next. This shows a biopsy can teach us a lot, even in common kidney disease. The study was small, so more research is needed.
Goal: Doctors and scientists now scan whole tissue slides into computers to study disease. Pulling useful details from these huge images can be very slow. The team built a new tool called PySpatial to speed this up.
Key results: PySpatial skips extra steps that older tools need, and the team tested it on two sets of images, including KPMP kidney slides. It was about 10 times faster for small objects and about twice as fast for larger kidney parts, like the filters and blood vessels. The team reports that it stayed highly accurate.
Implications for patients: This is a tool for researchers, not a test or treatment. Faster tools let scientists study many more kidney slides. That may help speed up kidney research over time.
Goal: Big computer programs, often called AI, are being built to read medical pictures. The team wanted to know how well three popular AI tools can find each cell in kidney biopsy pictures, and how to make them better.
Key results: On pictures from over 2,500 kidney slides, all three tools did a fair job but still made mistakes. The team then had experts fix only the hardest pictures instead of every cell. This extra training made all three tools better, with the best one going from 78% to 82% on an accuracy score.
Implications for patients: This does not change care today. It shows that AI tools need kidney-specific training to work well. It also shows a way to train them using less of experts' time, which can help researchers study kidney biopsies on a large scale.
Goal: Not all kidney disease in people with type 2 diabetes is caused by diabetes. Today, a kidney biopsy is often the only way to tell. The team looked for simple blood, urine and gene tests that could tell the difference without a biopsy.
Key results: The team studied 231 people whose kidney disease was confirmed by biopsy. They found that a common gene change lowers a small molecule in the urine. Putting together this gene change, the urine molecule and a blood sugar test told diabetes kidney disease apart from other kidney diseases very well.
Implications for patients: If larger studies agree, a few simple tests could help doctors find the cause of kidney damage in people with diabetes. Some patients might be able to skip a biopsy. That would help them get the right treatment sooner.
Goal: Trillions of germs live in our gut, and they affect our health. The team wanted to know if people with long-term kidney disease or a sudden kidney injury have different gut germs than healthy people. They used stool samples from KPMP participants.
Key results: By reading the DNA in the stool, the team found that each group had its own mix of gut germs. Some germs were more common in long-term kidney disease, and one type was much more common after a sudden injury. Several 'good' gut germs were lower in people with a sudden injury.
Implications for patients: This does not change treatment yet. Because the gut germs look different in each kidney condition, they could one day help doctors diagnose kidney disease or lead to new treatments. The KPMP data are now available for other scientists to study.
Goal: This short article shares the authors' view on how scientists are building a detailed map of the kidney, cell by cell. Like a map of a city, it shows not only what each cell is, but also which cells live next to each other and how they work together. The authors explain why this matters and what still stands in the way.
Key results: The authors explain that a kidney cell can shift into different "states" as it heals or gets worse after an injury. KPMP has already used this kind of map to find a cell state linked to kidney disease getting worse. Looking at genes, proteins and other small chemicals in the same spot shows that two cells that look the same can do very different jobs.
Implications for patients: This article does not test a treatment. It explains how a cell-by-cell map of the kidney could help doctors find kidney disease earlier and choose treatments that fit each stage of the disease. The authors also note that ideas from these maps must be tested in the lab before they can lead to new medicines.
Goal: This article reviews a new lab method that maps where small chemicals sit inside a kidney biopsy. The authors explain how this map could help doctors pick the right treatment for each person.
Key results: The authors sum up what these maps have shown so far. For example, a chemical called adenine builds up in scarred parts of the kidney in people with diabetes. Mixing these maps with gene and protein data gives a fuller picture of the disease.
Implications for patients: There are more kidney treatments now, but doctors need better ways to know which one will work for each patient. Mapping chemicals inside a biopsy could help with that. This article sums up current research and does not test a new treatment.
Goal: New lab tools can show which genes and proteins are active in each tiny part of a tissue sample. The team wanted to make it easy to see this information right next to the normal microscope pictures that doctors use.
Key results: The team built FUSION, a free website that shows tissue pictures and lab data together. It works with many lab tools and with tissue from the kidney, gut, lung and skin. It helped tell healthy and hurt kidney filters apart and showed where scarring and immune cells were.
Implications for patients: This tool does not change patient care today. It helps kidney scientists link what they see under the microscope to what is going on inside cells. That can speed up the search for better ways to find and treat kidney disease.
Goal: The kidney has tiny tubes that clean the blood, and the first part is called the proximal tubule. When these tubes get hurt, some cells can heal and some cannot. The team wanted to see which cells in these tubes can repair themselves and how this changes with kidney disease.
Key results: The team used a new way to see many proteins at once in kidney tissue and matched them to gene activity. In healthy kidneys, many tube cells had a protein called THY1, which is linked to cell repair. In kidney disease, cells lost THY1 and began to make PROM1, a protein linked to failed repair.
Implications for patients: THY1 and PROM1 may show how well the kidney can heal and how far disease has gone. In the future, they might help doctors track kidney disease or find new treatments. More research is needed first.
Goal: People who stay in the hospital for a serious illness have a higher risk of losing kidney function later. Doctors do not fully know why. This study looked at proteins in urine to find clues.
Key results: The team tested urine from 174 people three months after they left the hospital. Then they followed them for about five years. They found about 400 urine proteins linked to how fast kidney function changed, and most of these proteins come from kidney cells. These proteins were tied to hurt kidney tubes, swelling, and scarring.
Implications for patients: A urine test could one day show who is most at risk of kidney decline after a hospital stay. This could help doctors watch these patients more closely. More research is needed before such a test is ready.
Goal: Glomeruli are the kidney's tiny filters. Doctors look at them under a microscope to find damage, but marking each part by hand is slow and experts do not always agree. The team wanted to teach a computer to do this job.
Key results: The team used more than 23,000 filters from human and mouse slides that experts had marked. They trained a computer program to find 14 things, including normal parts and types of damage. Training on mouse tissue first made the program better at finding damage in human tissue.
Implications for patients: This tool does not change care today. It helps scientists study large numbers of kidney biopsies faster and more evenly. Later on, it may help doctors read biopsies more quickly.
Goal: This is a review article, which sums up what other studies have found. It explains a tool called mass spectrometry, which can find and measure many kinds of molecules in a sample. Some versions can make a map that shows where each molecule sits in kidney tissue.
Key results: The review shows how researchers use these tools to study proteins, fats, drugs, and other molecules in the kidney. It explains how to prepare samples and how to study the kidney at many sizes, from urine to single cells. It also says these tools give information that gene tests alone cannot.
Implications for patients: This review does not test a treatment, so it does not change care today. These tools help researchers learn what is going on inside the kidney. Over time, this may lead to better ways to find and treat kidney disease.
Goal: Many proteins in the kidney are coated with sugars called glycans. A lab method called MALDI imaging can map where these sugars sit in a thin slice of tissue. This study asked if the type of machine and the thickness of the slice change the results.
Key results: The team tested two kinds of machines on stored human kidney tissue, and both found almost the same sugars, and the results were easy to repeat. One machine, called timsTOF, made sharper pictures and found a sugar that marks the kidney's tiny tubes. Very thin slices worked just as well as thicker ones.
Implications for patients: This study does not change patient care today. It helps researchers pick the best tools for mapping sugars in kidney tissue. Thin slices can also be checked under a microscope with more confidence, which may help future kidney studies.
Goal: Scientists can now read the genes that are active in single kidney cells. But sorting thousands of cells into types by hand takes experts a lot of time. This study tested whether computer programs that learn from examples could do this job.
Key results: The team used data from over 62,000 cells from 79 kidney biopsies. They tested five computer programs. All five sorted cells into the right type about 94% of the time. They did worse when trained on one kind of data and tested on another.
Implications for patients: This study does not change patient care directly. These programs can save time and help labs sort kidney cells the same way. That can speed up research on what goes wrong in kidney disease.
Goal: This is a review article, which sums up past research. It focuses on the proximal tubule, a part of the kidney's tiny tubes that does a lot of work. When these cells get hurt, they change, and these changes are called cell states.
Key results: The review describes the main cell states found in the KPMP kidney cell atlas. It also shows how these states match ones found in other studies, which often use different names. This helps readers see which gene signals point to injury or repair.
Implications for patients: This review does not change patient care directly. It helps researchers speak the same language about hurt kidney cells. That makes it easier to compare studies and learn how the kidney heals.
Goal: Sudden kidney injury, called AKI, can lead to long-term kidney disease. Small molecules called miRNAs help turn genes up or down, but we know little about their role in AKI. This study looked at both genes and miRNAs in kidney tissue from people with AKI.
Key results: Kidneys with AKI showed changes linked to cell damage, swelling, and scarring. Four miRNAs were higher in AKI and were tied to calling in immune cells and swelling. Two of them were linked to lower levels of genes that may help the kidney recover.
Implications for patients: This study does not change patient care today. Its data are added to kidney atlases that researchers use, alongside other KPMP data. This may help explain why some people recover from AKI and others do not, but more research is needed.
What Was Studied
Researchers tested blood samples from people with kidney disease to find proteins signaling kidney cell damage. This type of damage is called acute tubular injury (ATI). ATI can happen in many kidney diseases and may lead to kidney failure.
Scientists found 156 blood proteins linked to ATI. Three stood out: osteopontin, mannose receptor, and tenascin C. Kidney cells may release some of these when they are stressed or hurt.
Key Findings
The team used tissue and cell data from the Kidney Precision Medicine Project (KPMP) to confirm these proteins come from damaged kidney cells. Other large kidney studies backed up the results.
What This Means for Patients
These findings may lead to blood tests that catch kidney injury early without a biopsy. Blood tests are safer, simpler, and can be done more often. They may also help doctors find new treatments to protect kidney tissue.
Big Picture Takeaway
This research brings us closer to catching kidney injury early — with just a blood test.
This summary was created by the KPMP community engagement committee including patient partners to make the research easy for everyone to understand.
Goal: Many proteins in the body have small sugar chains, called glycans, stuck to them. These sugars help proteins do their jobs. This study asked how these sugars change in the kidney's tiny filters, called glomeruli, in people with diabetic kidney disease.
Key results: The team studied biopsies from five people with diabetic kidney disease and three healthy kidney samples. Five sugar patterns were clearly different in scarred filters than in healthy ones. Other tests found that scarred filters also had less of the genes and proteins that build some of these sugars.
Implications for patients: This study does not change care today. These sugar changes might one day help spot kidney damage from diabetes. More research is needed to find out.
Goal: Proteins and other small chemicals in the blood work together in the body. Researchers wanted to see if studying them together could show which ones are linked to kidney disease getting worse.
Key results: The team tested blood from about 1,700 people with kidney disease who were followed for about 9 years. They sorted thousands of proteins and chemicals into groups that rise and fall together. Two groups were strongly linked to kidney disease getting worse and to kidney failure, and this held true in a second set of people.
Implications for patients: These groups point to body processes that may push kidney disease forward. One day they could help doctors spot people at high risk of kidney failure sooner. They also give scientists new targets for treatment.
Goal: Proteins and other small molecules in the blood often work together. The team wanted to see if groups of these could show who is more likely to have kidney disease get worse. They used blood data from about 1,700 people in a large kidney study called CRIC.
Key results: The team found 139 groups of linked proteins and small molecules. Two groups were strongly tied to kidney disease getting worse and to kidney failure. One of these groups held proteins made by podocytes, special cells in the kidney's filters.
Implications for patients: This study does not change care today. It points to new proteins that may help explain why kidney disease gets worse. More research is needed to see if they could lead to new tests or treatments.
Goal: Fructose is a type of sugar found in many foods. Eating too much of it can raise blood pressure, partly because the kidney takes fructose back from the urine it is making. This study asked where in the kidney's tubes this happens.
Key results: The team used shared data on rat kidney cells and tiny tube pieces. All four known fructose carriers were found along the first part of the tube. Two key carriers were highest at the end of that part, and human kidneys showed the same pattern.
Implications for patients: This tells us where the kidney takes back most of its fructose. It may help explain how diets high in fructose raise blood pressure. More research is needed before it changes care.
Goal: Genes work like light switches inside each cell. They can be on, off, or ready to turn on. The team wanted to map these switches in kidney cells that are healthy, hurt, or healing.
Key results: The team built a map of these switches and found that each kind of kidney cell handles injury in its own way. In cells that line the kidney's tiny tubes, three proteins (ELF3, KLF6, and KLF10) helped decide if a cell stayed healthy or became hurt. When the team turned these three off in lab-grown cells, the cells showed signs of healing.
Implications for patients: Damage to kidney cells is linked to kidney disease getting worse. This map shows which genes help push cells from healthy to hurt. In the future, it may help researchers find treatments that help kidney cells heal.
Goal: A kidney biopsy takes a tiny piece of kidney with a needle. KPMP asks people to have a biopsy for research. The team wanted to learn how these people felt about it and why they took part.
Key results: A total of 111 people filled out a survey about a month after their biopsy, and most joined to help future patients, and almost all understood the consent form. About half felt some pain and about two out of three felt some worry, but most rated it low. More than half said taking part changed how they eat, exercise, or think about kidney disease.
Implications for patients: People who join KPMP do it mostly to help others. Their feedback can help doctors make research biopsies more comfortable. It also shows that clear, simple consent forms work.
Goal: Long-term kidney disease and sudden kidney injury can look the same in tests but act very differently. People with the same diagnosis may do well or poorly, and may respond to treatment in different ways. This paper explains how KPMP plans to find out why.
Key results: KPMP is building a map of the kidney's cells in health and disease. It uses kidney biopsies and many kinds of lab tests, such as looking at genes and proteins. This paper describes how KPMP is set up and how it brings all this data together.
Implications for patients: This map may help doctors sort kidney disease into new groups that today's tests cannot see. In the future, that could help match each patient to the right care. More research is needed to get there.
Goal: People in the hospital with COVID-19 have a higher risk of serious kidney problems. But not everyone gets them. The team wanted to find blood tests that could show who is most at risk.
Key results: The team tested 26 markers in the blood of 576 people in the hospital with COVID-19. About 1 in 6 had a serious kidney problem or died within 60 days. Higher levels of two markers, called sTNFR1 and sTNFR2, were linked to a much higher risk.
Implications for patients: These blood tests could one day help doctors spot who needs closer kidney care after COVID-19. That could guide follow-up visits and talks with patients. More research is needed before they are used in care.
Goal: Kidney disease from diabetes can lead to kidney failure and death, and doctors need better ways to tell who is at high risk. This is hard in people who do not have much protein in their urine. The team asked if adenine, a substance the body makes, could be a warning sign.
Key results: The team checked urine adenine in people with diabetes from three large studies. Those with the most adenine were more likely to reach kidney failure, even with little protein in their urine. A diabetes drug called empagliflozin lowered urine adenine in some people, and in diabetic mice, blocking the body's adenine production reduced kidney injury.
Implications for patients: Adenine may not just be a warning sign. It may help cause kidney damage in diabetes. Someday a urine test for adenine could help find people at risk, but more research is needed first.
Goal: Doctors do not agree on how useful a kidney biopsy is. We know even less about what patients think. This study asked both KPMP patients and their doctors.
Key results: The study included 167 patients and 58 doctors. Most patients who answered said the biopsy helped them understand their illness, and some said it changed their medicines. After the biopsy, doctors felt it helped more with treatment but told them less about the future.
Implications for patients: Patients and doctors can see the value of a biopsy in different ways. Talking openly can help them decide together whether a biopsy is right. Clearer biopsy reports could also make results more useful.
Goal: KPMP studies kidney biopsies to learn what drives kidney disease. This report looked at one 66-year-old woman with kidney disease caused by diabetes. The goal was to see what new lab methods could add to a standard biopsy exam.
Key results: Under a regular microscope, her biopsy showed typical kidney damage from diabetes. But 3D imaging showed many new blood vessels growing around the kidney's filters, which standard methods had mostly missed. Genes in these areas were busy building new blood vessels and keeping them stable.
Implications for patients: This case shows that new lab tools can find kidney changes a regular exam might miss. That may help researchers better understand how diabetes harms the kidney. It is only one case, so more research is needed.
Goal: Kidney stones are painful and send many people to the doctor. The team wanted to learn what happens in the cells of the kidney part where stones often form. They compared people with the most common type of stone to healthy people.
Key results: The team made a map of the cells and genes in this part of the kidney. In people with stones, the whole area showed signs of injury, not just the spots with stones. Two proteins, MMP7 and MMP9, were higher in their urine and tracked with how active the stone disease was.
Implications for patients: Stones may harm more of the kidney than we thought. In the future, a urine test for MMP7 and MMP9 might help doctors track stone disease. More research is needed first.
Goal: The kidney is made of many kinds of cells. To understand kidney disease, scientists need a clear map of these cells, both when healthy and when hurt. This study set out to build that map.
Key results: The team studied over 400,000 cells from 45 healthy kidneys and 48 diseased kidneys. They found 51 main cell types, including some rare ones never described before, and 28 cell states that change when the kidney is hurt, such as cells trying to repair. Some repair patterns were linked to a drop in kidney function.
Implications for patients: This map is open to the public online. It gives researchers a guide to how kidney cells respond to injury. Over time, it may help find new ways to spot and treat kidney disease, but more research is needed.
Goal: Sudden kidney injury is common in people in the hospital. We know some genes raise the risk of long-term kidney disease, but little about genes and sudden injury. This study looked for gene changes linked to sudden kidney injury.
Key results: The team studied the genes of 1,369 people in the hospital, with and without sudden kidney injury. No gene change met the strict bar for a firm link, but the two strongest leads were near two genes called DISP1 and TLR5. KPMP biopsies showed these genes acted differently in injured kidneys.
Implications for patients: This area of our genes may play a part in who gets sudden kidney injury. It gives researchers a new place to look. More research is needed to confirm it.
Goal: Some common pain medicines, called NSAIDs, can hurt the kidneys. This report looked at a 38-year-old woman who had a sudden kidney injury after giving birth by C-section. Doctors thought NSAIDs caused it, and she had a research kidney biopsy through KPMP.
Key results: Under the microscope, her kidney showed only mild injury and no lasting scars. A study of the proteins in her kidney agreed, and it also showed changes in natural chemicals called prostaglandins, which may be a response to the NSAIDs. It also found early signs of inflammation and scarring that the microscope did not show.
Implications for patients: Protein testing can show kidney changes that a microscope alone may miss. This may help doctors better understand kidney injury from medicines in the future. This is only one case, so more research is needed.
Goal: A protein called FGL2 was recently linked to kidney scarring in mice. Scientists thought it might be a target for treating chronic kidney disease (CKD). This study asked if FGL2 plays a role in people with CKD too.
Key results: The team studied kidney biopsy data from people with CKD and from healthy people, including KPMP data. The FGL2 gene was more active in CKD kidneys, and people with higher levels had more scarring and lower kidney function, and their disease got worse faster.
Implications for patients: FGL2 may be a useful sign of how kidney disease will progress. It may also be a target for new medicines someday. More research is needed to test this.
Goal: Kidney disease from diabetes is the leading cause of kidney failure. Doctors need better blood tests to predict who will get worse. This study looked for blood proteins that could help and that also reflect what goes wrong in the kidney.
Key results: The team found a set of three blood proteins that, added to standard tests, better predicted kidney decline. One of them, called ANGPT2, was linked to worse kidney outcomes in two other large groups of people. Higher ANGPT2 in the blood also matched more activity of related genes in the kidney's filters.
Implications for patients: ANGPT2 could become a blood test to help predict how diabetic kidney disease will progress. It may also play a part in how the disease harms the kidney's filters. More research is needed before it is used in care.
Goal: Computers can learn to find parts of tissue in microscope images. This can speed up the study of kidney samples. But these tools are often hard to set up and use without computer coding skills.
Key results: The team made a free, easy-to-use tool that runs over the internet. It uses a type of artificial intelligence to outline parts of tissue, like the kidney's filters, scarring, and blood vessels. The team showed it works on kidney and other tissue, and in mouse studies.
Implications for patients: This tool makes it easier for kidney experts to study tissue images. It may help speed up kidney research. Over time, tools like this could also support how doctors read biopsies.
Goal: KPMP is building a detailed map of the human kidney, down to single cells. To understand disease, researchers first need to know what a healthy kidney looks like. This study built that healthy reference map.
Key results: The team used healthy kidney tissue from 56 adults. They used many lab methods to study genes, proteins, and other small molecules, and where each is in the kidney. Together, the results matched cell types to their jobs in different parts of the kidney.
Implications for patients: This map is a starting point for comparing healthy and sick kidneys. It may help researchers sort kidney disease into types, even when patients look alike. More research is needed before it changes care.
Goal: KPMP studies tiny bits of kidney tissue taken in a biopsy. This report looked at one woman with long-term kidney disease. The team wanted to see if lab tests on her kidney's genes could add to what doctors see under a microscope.
Key results: Under the microscope, her kidney showed mild damage from high blood pressure. It did not show clear signs of kidney damage from diabetes. But gene tests found early signs of diabetes damage all through her kidney, which fit with her known diabetes.
Implications for patients: Some kidney damage may not show up under a microscope yet. Gene tests on a biopsy can add to what doctors learn from it. This was KPMP's first report to use this approach for one person's kidney disease.
Goal: Some people with type 1 diabetes lose kidney function much faster than others. Doctors need better ways to spot who is at risk. This study looked for proteins in urine that could warn of fast kidney decline.
Key results: The team studied 1,270 people with type 1 diabetes for about 8 years. They tested 20 proteins and found that one, called cathepsin D, was linked to faster loss of kidney function. In other groups of people, more cathepsin D in urine went along with damage to the kidney's tiny tubes and the tissue around them.
Implications for patients: A urine test for cathepsin D may one day help doctors find people with diabetes whose kidneys are at higher risk. It may also point to a way kidney damage happens. More research is needed before it can be used in care.
Goal: After a kidney transplant, some special filter cells called podocytes start to come loose. Losing these cells is linked to the new kidney failing years later. This study asked what changes inside filter cells early on, even when the new kidney looks healthy.
Key results: The team studied first-year biopsies from 14 transplant patients whose kidneys looked normal. They compared them with 20 healthy kidney donors. Cells lining the tiny blood vessels showed signs of stress from blood flow, and podocytes made less of the proteins that help them stay attached. The same kind of changes showed up in rats under similar strain.
Implications for patients: Even a transplanted kidney that looks healthy may already be under stress. These early changes could lead to kidney damage over time. Knowing this may help researchers find ways to protect new kidneys, but more research is needed.
Goal: Sudden kidney injury, or AKI, happens when the kidneys stop working well over a short time. The team studied a kidney biopsy from one person with AKI. They wanted to learn how kidney cells get hurt and how they heal.
Key results: The team looked at genes in single cells and also studied the tissue under a microscope. They found many kinds of cells that were hurt or healing, including in the kidney's tubes, blood vessels, and immune cells. They also found signs linked to common pain pills called NSAIDs, even after the person stopped taking them.
Implications for patients: Studies like this can show how a kidney is hurt and whether it is healing. In the future, this may help doctors guess who will get better and who may get worse. More research with more people is needed first.
Goal: People who join KPMP agree to have a kidney biopsy, which means a doctor removes a tiny piece of kidney. This carries some risk and may not help their own health directly. This paper asked how research like this can still be fair and good for the people who join.
Key results: The team used their work planning KPMP as an example. They found that people may gain from research in more ways than just better health. These include having their values respected, the chance to help others, and benefits to their community.
Implications for patients: This paper may guide researchers to better respect and support the people who take part in studies. It may also help make kidney research better for everyone with kidney disease.
Goal: Scientists are building a 3D map of the human body, cell by cell. To do this, they must record exactly where each tissue sample came from inside an organ. This study compared a regular computer screen with two virtual reality, or VR, setups for doing this.
Key results: The team tested the three setups with 42 people. VR users were about three times faster and placed the angle of samples more accurately. But all three setups were just as good at placing samples in the right spot.
Implications for patients: The regular computer screen works well enough, and it is cheaper and easier to use than VR. This helps scientists build the body map faster. This work helps research, not patient care directly.
Goal: Sugar chains called N-glycans are attached to many proteins in our cells. A method called mass spectrometry imaging can map where these sugars sit in a slice of tissue. But there was no fast tool to sort and name them in this kind of data, which slowed research down.
Key results: The team built a free public list of N-glycans called NGlycDB. They added it to METASPACE, a free online tool that names molecules in imaging data. They showed it works on stored slices of human kidney and mouse lung.
Implications for patients: This study does not change patient care directly. It gives researchers a faster, free way to map sugars in tissue such as kidney. That may help them learn more about health and disease in the future.
Goal: A kidney biopsy is when a doctor takes a tiny piece of kidney to study. Kidney doctors do not all agree on when to do one, and there are no clear rules. This study asked kidney doctors how they decide.
Key results: The team talked with 20 kidney doctors from across the United States. The doctors made very different choices about biopsies. Their choices depended on their training and comfort with the test, worry about harm, how much the result might change treatment, and the patient's own wishes.
Implications for patients: Whether you get a biopsy may depend partly on which doctor you see. This study shows a need for shared rules so biopsy choices are more consistent. The study was small, so more research is needed.
Goal: Many people with chronic kidney disease (CKD) lose muscle, which can make them sicker and raises the risk of death. It is not well known how the kidneys and muscles are linked. This study looked for signals that pass from sick kidneys to muscles.
Key results: The team found that CKD raises blood levels of factors that cause muscle wasting, including one called activin A. In the kidney, activin A came from certain cell types. In mice with kidney disease, blocking activin A or its receptor on muscle stopped the muscle loss.
Implications for patients: Activin A may be a key reason people with CKD lose muscle. Drugs that block this signal could one day help protect muscle. These treatments were tested only in mice, so more research is needed in people.
Goal: Kidney fibrosis is scarring in the kidney that can harm how well it works. Right now, doctors need a biopsy to measure it. This study looked for proteins in blood or urine that could show scarring without a biopsy.
Key results: The team tested five proteins in two groups of people with kidney disease. Three proteins, called CDH11, SMOC2, and PEDF, were higher in people with more kidney scarring. Some of these were also higher in people whose kidneys later failed.
Implications for patients: In the future, a blood or urine test might show how scarred a kidney is. It might also help find people at high risk of kidney failure. These proteins could help test new treatments for scarring, but more research is needed.
Goal: When a doctor looks at a kidney biopsy, they score how much scarring and damage it has. This score helps show how serious the disease is. But different doctors can give the same sample different scores, so the team built a computer tool to help.
Key results: The team taught a computer program to score kidney scarring from images of biopsy slides. They checked its scores against those from expert doctors. The program agreed with the experts about two out of three times, including on KPMP samples.
Implications for patients: Tools like this could one day give doctors a second opinion when they score a biopsy. This may make scores more consistent and save time. More work is needed before it is used in the clinic.
Goal: Heart surgery can sometimes injure the kidneys. Doctors need better ways to tell who will go on to have chronic kidney disease (CKD) later. This study tested two urine proteins, EGF and MCP-1, as warning signs.
Key results: The team checked urine from 865 adults after heart surgery and followed them for about 6 years. About 3 in 10 developed CKD or got worse. Higher EGF, a sign of healthy kidney cells, was linked to lower risk. Higher MCP-1, a sign of swelling and irritation, was linked to higher risk.
Implications for patients: A simple urine test after heart surgery might one day help doctors see whose kidneys are at risk. It may also point to new ways to protect the kidney. More research is needed before these tests are used in care.
Goal: Long-term kidney disease and sudden kidney injury are common and serious. This paper describes the goals and plan of KPMP. The aim is to better understand these diseases so care can fit each person.
Key results: KPMP takes kidney biopsies from adults with these diseases, done safely for research. It focuses on the most common causes, such as diabetes and high blood pressure. The team will study the tissue in many ways and follow people for 10 years.
Implications for patients: KPMP will build an online map of the kidney that anyone can search. All of its data will be shared with scientists, doctors, and patients. The goal is to find new ways to prevent and treat kidney disease.
Goal: KPMP wants its research to bring real benefits to people with kidney disease. To do that, it treats patients as equal partners. Patients help decide what to study, how to run the study, and how to share results.
Key results: Patients sit on KPMP's Community Engagement Committee with scientists. Patient partners led work on how people agree to join the study and how results are shared back. They also wrote a guide to help scientists understand patients.
Implications for patients: Patients' views have helped shape what KPMP studies and how. This makes it more likely that the research will matter to patients. It sets a new standard for including patients in research.
Goal: The interstitium is the space and tissue between the kidney's tubes, filters and blood vessels. Scientists still know little about which genes are active there. This study mapped those genes in healthy kidneys and in kidneys with diabetes damage.
Key results: The team cut out the interstitium from 9 healthy kidney samples and 6 samples from people with diabetic kidney disease. They read the genes that were turned on and checked them against data from single cells. They found new marker genes for this area. In diabetes, genes that build the tissue framework were more active.
Implications for patients: This study does not change patient care directly. It gives researchers a clearer map of a part of the kidney that is often missed. That may help them understand how kidney disease, including diabetic kidney disease, develops.
Goal: Some people get small lumps of scar tissue in the kidney's filters, which can happen in diabetes. A rare form of this happens in people who do not have diabetes. Its cause is unknown, so the team compared it with the diabetes form.
Key results: The team found 48 people with the rare form. Most had high blood pressure and many had smoked. Their kidney filters looked like the diabetes form under a microscope. But gene tests showed real differences, including one gene that was much more active.
Implications for patients: The rare form may not be the same disease as the diabetes form, even though they look alike. This could one day lead to better ways to tell them apart and treat them. More research is needed.
Goal: Many people in the hospital have kidney damage. Doctors need a better way to know whose kidneys will keep getting worse over time. This study asked if three proteins in urine could help predict that.
Key results: The team tested urine from over 1,500 people three months after a hospital stay, then followed them for about four years. People with more of two proteins, MCP-1 and YKL-40, lost kidney function faster, while people with more UMOD did better. Using all three proteins predicted risk better than the usual health facts alone.
Implications for patients: A simple urine test after a hospital stay might one day show who is at risk for kidney disease that gets worse. Those people could get closer follow-up care. More research is needed before this test is used by doctors.
Goal: KPMP is building detailed 3D maps of healthy and diseased kidneys using many lab tools at many sites. Getting the same reliable results across different labs is hard. This paper sets out rules to make sure the work is careful and can be repeated.
Key results: The team made a "follow the tissue" plan that checks quality at every step. It covers collecting, storing and shipping tissue, then making, studying and sharing data. Labs first tested the same tissue and had their results reviewed before they could study patient biopsies.
Implications for patients: Kidney biopsies are precious, and these rules help make the most of each one. They also make KPMP results more trustworthy. Other large research projects can use this plan as a model.
Goal: Tissue cytometry is a way to count and describe every cell in a piece of tissue. It keeps each cell in its place, which helps show how cells work together. But past methods needed special tools that most labs do not have.
Key results: The team built a full step-by-step method to image and study human kidney tissue in 3D. It uses common lab tools and free software called VTEA. They used it on kidney samples, including from people with diabetic kidney disease. They counted tens of thousands of cells in each sample.
Implications for patients: This study does not change patient care directly. It gives more labs a way to study kidney tissue in great detail. That may help researchers link cell changes to kidney disease.
Goal: Few patients get a say in how medical research is planned. KPMP wanted patients to be equal partners from the start. This report describes how patients help guide KPMP and why it matters.
Key results: Patients with kidney disease and doctors lead KPMP's Community Engagement Committee and serve on other KPMP groups. Patients helped create key parts of the study, like the consent process and insurance in case of harm. They also made a plan to share results with participants and wrote a guide for scientists and the public.
Implications for patients: Patients helped shape KPMP so its research matches what matters most to them. This sets a new standard for patient leaders in kidney research. It can help make study results more useful to people living with kidney disease.
Goal: People with diabetes and kidney disease get sicker from COVID-19, but no one knows why. The virus enters cells through a doorway protein called ACE2. The team asked where ACE2 sits in the kidney, and whether kidney disease or common blood pressure drugs change it.
Key results: ACE2 was found mostly in one kind of cell in the kidney's tiny tubes. Common blood pressure drugs did not change ACE2 levels. In people with diabetic kidney disease, these cells turned on genes like those in virus-infected cells, and cells in the urine of 13 people in the hospital with COVID-19 did the same.
Implications for patients: This study does not mean people should stop or start any drug. It points to kidney cells that may be at risk when the virus strikes. The findings give researchers a place to start to learn who is at most risk and how to protect the kidney, but more research is needed.
Goal: A kidney biopsy takes a tiny piece of the kidney with a needle so doctors can study it. Everyone who joins KPMP has a biopsy, so it is key to know how safe it is. The team pulled together many past studies to see how often problems happen.
Key results: The team looked at 87 studies with more than 118,000 biopsies. Pain at the needle site happened in about 4 in 100 people, and bleeding that needed a blood transfusion in fewer than 2 in 100. Death was very rare, about 6 in 10,000, and problems were more common in people in the hospital or with a sudden kidney injury.
Implications for patients: A kidney biopsy is a procedure with some risk, but serious bleeding is uncommon. People thinking about a biopsy can use these numbers to talk with their doctor. The results also help KPMP keep its research biopsies as safe as they can be.
Goal: Proteins do most of the work inside our cells. The team wanted to study proteins in very small parts of a healthy human kidney. They looked at two parts: the filters that clean the blood and the first tubes that the fluid flows through.
Key results: The team used a laser to cut out tiny groups of about 30 to 40 kidney cells. In these small samples, they found more than 2,500 proteins. Some proteins were found only in the tubes, and others only in the filters.
Implications for patients: This study does not change care for patients today. It gives researchers a new way to study very small parts of the kidney. Later, this method may help show how proteins change in sudden and long-term kidney disease.
Goal: KPMP collects many kinds of data from people with kidney disease, like health records, images, and biopsy results. To use all this data together, researchers need a shared way to name and sort it. This paper explains how tools called ontologies can help.
Key results: An ontology is like a shared dictionary that names each piece of data and shows how the pieces link. The team built two new ontologies for kidney research. They will help build the Kidney Tissue Atlas, a detailed map of the kidney's cells and molecules.
Implications for patients: These tools help researchers combine data from many places in the same way. Over time, this may lead to new ways to define kidney disease. That could help doctors pick the right treatment for each person.
Goal: Fats in the body, called lipids, can break down quickly once tissue is removed. KPMP often shares thin slices of kidney tissue between labs. The team wanted to find the best way to store these slices so the fats stay intact.
Key results: The team stored slices in five ways for a week and compared them to freshly cut tissue. Slices at room temperature lost the most fats, while slices kept very cold under nitrogen gas stayed closest to fresh. Some breakdown happened no matter how the slices were stored.
Implications for patients: Kidney biopsies are precious, so each one should give as much information as possible. Storing slices cold and under nitrogen helps protect the data researchers can get from them. This helps make KPMP research more reliable.
Goal: Precision medicine means choosing care based on what is causing each person's disease. To do this, researchers need to learn what drives the many causes of kidney failure. This article asked people with kidney failure what this research means to them.
Key results: Three people affected by kidney failure shared their views. They talked about why it matters to learn what causes kidney disease. They also shared what they hope this knowledge can do for them and others.
Implications for patients: Patients' voices can help guide what kidney research focuses on. Hearing their hopes reminds researchers who the work is for. This kind of input can help keep research focused on what matters to patients.
Goal: Studying which genes are turned on in kidney tissue helps researchers understand health and disease. Newer tools can read genes in single cells, but they lose track of where each cell was in the tissue. The team wanted a way to read genes while keeping that location.
Key results: The team used a laser to cut out small, chosen parts of thin kidney slices. A quick glowing stain helped them find five different areas of the kidney to cut out. They then read the genes in each area and shared checks to tell if each sample was good enough to use.
Implications for patients: This is a lab method, so it does not change patient care right now. It lets researchers learn which genes are active in each part of the kidney while making the most of rare tissue samples. The same method may also work for other organs.
Goal: KPMP studies kidney biopsies to map how each kind of kidney cell works and fails. This study set up a way to read the genes in single cells from biopsies. The team then used it to look for differences between kinds of disease in the kidney's filters.
Key results: The team read the genes of more than 22,000 single cells and sorted them into 31 groups. They found three kinds of cells that line the kidney's blood vessels, and the cells lining the filters were most active in people with a disease called FSGS, which scars the filters. A gene called A2M split people with FSGS into two groups, and higher A2M was linked to lower odds that protein in the urine would go away.
Implications for patients: This work may one day help doctors tell which people with FSGS are less likely to get better. A2M could become a sign to guide care. More research is needed before it can be used in the clinic.
Goal: Some labs make picture maps of the molecules in a thin slice of tissue. First, a machine sprays a coating on the slice, and the spray settings must be just right. This study looked for a faster, better way to choose those settings.
Key results: Most labs change one setting at a time, which is slow and may miss the best mix. The team tested five settings at once and used math to see how they worked together. They found the mix that gave the sharpest and strongest results.
Implications for patients: This method helps get the best data from each kidney biopsy, which is hard to get. It saves time and tissue. Other labs may also use it for other tissues and molecules.
Goal: Doctors find a sudden kidney injury, called AKI, with a blood test for creatinine. Creatinine is a waste product from muscle, and it is not a very exact sign of kidney damage. This review looks at newer tools that can show what is really happening in the kidney.
Key results: New tools can measure genes and proteins in the kidney, urine, and blood. They can even look inside single cells, but signs of kidney damage often do not match creatinine levels. The authors explain this by showing that AKI is not one disease but many types, each with its own pattern of signs.
Implications for patients: This review does not change care right away. It suggests that sorting AKI into types could lead to better tests and care in the future. The authors also offer a model of how injury moves from hurt cells to kidney failure over time.
Goal: The kidney is made of many kinds of cells. To understand kidney disease, we first need to know each cell type and what it does. The team built a reliable method to read which genes are turned on in single cells from human kidneys.
Key results: The method found 30 different groups of cells in the adult kidney and showed how cells change along its tiny tubes. The team also found where genes linked to kidney disease, diabetes, and high blood pressure are active. Some cells in the tubes showed signs linked to disease.
Implications for patients: This method gives researchers a tool to map healthy and sick kidneys in detail. Knowing which cells are involved in disease may point to new targeted treatments. More research is needed before this helps patients directly.
Goal: NIDDK is a part of the National Institutes of Health that funds kidney research. This article looks at two NIDDK research groups that work closely with patients and communities. It asks how this teamwork helps kidney research.
Key results: Putting patients first and treating them as full partners may make research more useful. It may also make research run more smoothly. This may help most in studies of groups that are often left out of research.
Implications for patients: When patients and communities have a voice, research is more likely to meet their needs. This can help patients, researchers, and the whole kidney field.
Goal: Diabetes is the top cause of kidney disease and kidney failure around the world. Few new drugs for diabetic kidney disease have been approved in about 30 years. This review looks at a newer type of diabetes drug, called GLP-1 receptor agonists, and how it may protect the kidneys.
Key results: The review brings together findings from patient studies and lab research. These drugs show promise for keeping kidney disease from starting or getting worse. Beyond lowering blood sugar, they may help the body get rid of extra salt and calm swelling.
Implications for patients: These drugs may become another way to protect the kidneys in people with diabetes. Learning how they work can help show who is most likely to benefit. More research is needed to confirm this.
Goal: Doctors find a sudden kidney injury, called AKI, by watching a blood test called creatinine over time. This test is not very exact and does not show what kind of injury it is. This review looks at new ways to study kidney tissue to better define AKI.
Key results: Newer urine and blood markers, such as NGAL and KIM-1, can spot AKI sooner. They can also tell short-lived problems from longer ones, but they cannot tell the cause, such as infection, low blood flow, or harm from drugs. The authors describe tools that read genes in single cells to fill these gaps.
Implications for patients: This review does not change care today. These tools may help doctors sort AKI by cause and stage in the future. This is a step toward precision medicine, which means care fitted to each person, but more research is needed.
Goal: Sudden kidney injury and long-term kidney disease are closely linked. But they can play out very differently from one person to the next. This study asked whether the two share the same damage patterns inside kidney cells.
Key results: The team studied kidney biopsies from over 150 KPMP participants and found two patterns of cell activity, one tied to new injury and one to lasting damage. Both patterns showed up in people with either sudden or long-term kidney disease. Matching protein signs in blood and urine helped predict later kidney health in a group of 44,000 people in the UK.
Implications for patients: Kidney damage may work in similar ways no matter what the disease is called. In the future, a blood or urine test might show what is going on in a person's kidney without a biopsy. This study is not yet peer reviewed, and more research is needed first.
Goal: Uromodulin is a protein made only by the kidney. It helps protect the kidney from sudden injury. This study in mice asked how it protects the kidney in the first hours after blood flow is cut off and then comes back.
Key results: Six hours after injury, every part of the kidney's tiny tubes reacted, and uromodulin helped keep immune cells in one safe zone. Mice without it had worse injury and swelling, and their immune cells spread into weak areas. Some collecting tube cells in these mice began to act like immune cells, and the team found such cells in human biopsies too.
Implications for patients: This study helps explain how the kidney's own protein keeps early injury in check. It may point to new ways to limit damage after a sudden kidney injury. Most of this work was done in mice and is not yet peer reviewed, so more research is needed.
Goal: Many people with diabetes or high blood pressure get chronic kidney disease. Doctors often guess the cause without a kidney biopsy. This KPMP study asked what biopsies show about the true cause of disease and what lies ahead.
Key results: Experts reviewed biopsies from 258 people, and only about half of those with diabetes or high blood pressure had damage mainly from that cause. Damage from diabetes looked more severe and showed more signs of swelling and stress in cells. A score built from age, blood sugar, and blood and urine tests could predict this damage, and in another group a higher score was linked to kidney disease getting worse.
Implications for patients: The cause of kidney disease is not always what doctors expect. A biopsy can show the real cause, which may change treatment choices. This study is not yet peer reviewed, and more research is needed.
Goal: After an injury, the kidney sometimes heals and sometimes does not. When healing fails, scarring and lasting disease can follow. This study built a detailed map to learn why some kidneys heal and others do not.
Key results: The team studied about 1.7 million cells from more than 350 patients, along with mouse data and maps of where cells sit in the tissue. They found cell types tied to healing and others tied to failed healing and scarring, gathered in certain spots in the kidney. They also found signs in the body that predicted which sudden injuries would turn into long-term disease.
Implications for patients: This map is a large resource for kidney research. It points to possible drug targets and signs that could show who is at risk. This study is not yet peer reviewed, and more research is needed before it helps patients directly.
Goal: Arteriolar hyalinosis is a buildup of protein in the walls of the kidney's small blood vessels. It is linked to heart disease, the main cause of death in people with chronic kidney disease. Little is known about why it happens, so this study looked for clues in KPMP kidney biopsies.
Key results: The team compared gene activity in single cells with images of the same biopsies. In the cells lining the blood vessels, they found three groups of genes tied to the buildup. In a separate group of patients, one of these gene groups was linked to a faster loss of kidney function.
Implications for patients: This work points to signals that may drive damage in the kidney's small blood vessels. These signals could become targets for new treatments someday. More research is needed to confirm the results.
Goal: HuBMAP is a large research program that aims to map all the cells in the healthy human body. Tissue samples come from many labs, so it is hard to fit all the data into one shared 3D map. This paper describes a common map system to solve that problem.
Key results: The team built a Common Coordinate Framework, a shared 3D map of the whole body. Each sample gets labels that say who the donor was, what body part and cell types the sample holds, and where in the body it came from. Research centers used it to label and place 48 kidney and spleen tissue samples, which people can explore online in the HuBMAP Portal.
Implications for patients: This work does not change patient care right now. It gives researchers one shared way to label and line up tissue samples from many places. That makes it easier to compare data and build a better map of the healthy body, including the kidney.
Goal: The kidney has many kinds of cells, and each does a different job. Older tools only showed the average of thousands of cells at once. The team wanted a better way to study single cells, even from the small samples a needle biopsy gives.
Key results: After improving how they break tissue into single cells, the team read the genes of over 45,000 kidney cells and found 37 main cell groups, with almost 100 smaller groups. They also tested a method called Mux-Seq, which mixes samples from several people and then sorts the cells back by computer. This cut costs and unwanted differences between batches.
Implications for patients: This work does not change patient care right now. It shows that small biopsy samples can be studied cell by cell. That can help researchers learn more about kidney disease from the samples patients give.