Diabetic kidney disease, sometimes called diabetic nephropathy, is a condition in which diabetes damages the kidneys over time. The kidneys are the body's filters, removing waste and excess fluid from the blood; when the filters are injured, kidney function can decline gradually.
Not everyone with diabetes develops kidney disease, and among those who do, the course varies widely. Some people keep stable kidney function for many years; others progress more rapidly. Understanding why is the central question of TRIDENT.
Your kidneys filter your blood. Diabetes can slowly damage the tiny filters and the tubes around them, and this damage is usually silent for years. Blood and urine tests tell doctors that the kidney is injured, but not why, and not how fast it will get worse. Two people with the same test results can have very different futures.
TRIDENT is a research study for adults with diabetes whose own doctor has decided they need a kidney biopsy. During that same biopsy, one extra small piece of kidney is taken for research, together with a blood and a urine sample. The study team then follows your kidney function at visits about every six months, for years.
Scientists read the research tissue in great detail, down to the single cell and the single gene, and connect what they see to what later happens to each participant. The goal is to learn why some kidneys fail quickly and others do not, to find blood or urine tests that can tell the difference without a biopsy, and to find treatments matched to each kind of kidney damage.
Taking part is voluntary, does not change your care, and your name is never attached to the research data.
Two people with diabetes and the same laboratory values can have very different disease in the kidney itself. The biopsy, read at every molecular layer, tells which type.
TRIDENT follows every participant for years and ties the tissue to what happened afterward, so that the biopsy can say who is likely to progress and who is likely to stay stable.
Modern therapies help many patients but not all. TRIDENT 2.0 reads how these drugs change the kidney, toward the right treatment for the right patient.
High blood sugar, high blood pressure and chronic inflammation damage the small blood vessels and filtering units of the kidneys. Over time this leads to leakage of protein into the urine, gradual loss of kidney function, and a higher risk of kidney failure and cardiovascular disease. Because early damage often causes no symptoms, the disease may go unnoticed until it is advanced.
Even with modern treatments, some people continue to lose kidney function, because diabetic kidney disease is not a single condition but several biological processes that differ from person to person. Treatment decisions today rely on blood and urine tests, which do not capture what is happening inside the kidney tissue. That is why it is hard to predict who is at highest risk and which therapy will work for an individual.
ACE inhibitors and ARBs control blood pressure and reduce stress on the kidneys.
Diabetes medications that also protect the kidneys and heart by reducing kidney workload and inflammation.
Improve blood sugar control and provide additional cardiovascular and kidney benefits.
Reduce kidney inflammation and scarring in selected patients.
These therapies have improved outcomes substantially, but they do not work equally well for everyone.
By examining kidney tissue alongside blood and urine and following patients over time, TRIDENT links kidney biology to what happens to patients, in order to:
Living with diabetic kidney disease can be challenging, but treatment options and scientific understanding are advancing rapidly. If you are interested in research opportunities or in taking part in a study, speak with your healthcare provider or write to us.
TRIDENT enrolls at these sites. Your nephrologist can tell you whether your biopsy is being done at one of them, or write to the study team.
Sites whose enrollment is complete, and contributing sites, are listed on the consortium page. Study contact: TRIDENT@pennmedicine.upenn.edu, 215-898-2008.
Adults with diabetes who are undergoing a clinically indicated kidney biopsy at a participating site. The biopsy is ordered by your own nephrologist for your care; TRIDENT adds research to it.
One additional research core is taken during the same biopsy, blood and urine are collected, and the study team follows your kidney function at visits roughly every six months. Participation is voluntary and you may withdraw at any time.
TRIDENT measured this prospectively in 408 biopsies across 21 sites. Minor complications such as a small bruise were seen in about one in five biopsies; events needing a transfusion or procedure were uncommon (about 5 percent), and obtaining the additional research core did not significantly increase risk (Mohandes et al., CJASN 2026).
They are coded, stored securely, and studied with pathology, genomics, transcriptomics, spatial biology, proteomics and metabolomics. Results are linked to your coded clinical information, never to your name.
The clinical biopsy report goes to your nephrologist as usual. Research results are published for the whole cohort; individual research findings are not returned, because they are not yet validated for clinical use.
No. Your biopsy, diagnosis and treatment are decided by your own nephrologist exactly as they would be otherwise. TRIDENT adds research to the care you are already receiving.
Samples and data are labeled with a study code, not your name. The key linking the code to you is held securely at your site. Research data shared within the consortium and with partners are coded, and results are published only in aggregate.
TRIDENT is led from the Perelman School of Medicine at the University of Pennsylvania with academic sites across the United States and biopharmaceutical partners. It is registered at ClinicalTrials.gov as NCT02986984.
Participation is voluntary, and all research activities are conducted alongside standard clinical care.
