MHH research team wants to find biomarkers for underlying diseases in interstitial nephritis and is being funded with half a million euros.
Want to separate the common "horses" from the rare "zebras" when researching the causes of kidney inflammation: Dr. Vega Gödecke and Prof. Dr. Dr. Christian Hinze. Copyright: Karin Kaiser/MHH
Our kidneys have a variety of functions, including detoxifying the body. Every day, many thousands of filter units in the two bean-shaped organs cleanse around 1,800 liters of blood and release waste and toxins via the urine. These so-called nephrons consist of a renal corpuscle and a connected renal tubule. If the kidney tissue between the fine renal tubules becomes inflamed, immune cells migrate into the kidneys. As a result, kidney function is impaired and chronic kidney failure can develop. The most common causes of the disease, known as interstitial nephritis (IN), are reactions to medication - such as antibiotics or painkillers - and infections. However, rare diseases can also trigger IN. The diagnosis can be made with the help of a kidney biopsy. In many cases, however, the tissue sample does not provide any information about the exact cause. This is an opportunity for early detection of a rare disease before further damage occurs. In their project "Rare Diseases with Interstitial Nephritis", Prof. Dr. Christian Hinze and Dr. Vega Gödecke from the Clinical Department of Nephrology and Hypertension at Hannover Medical School (MHH) are now looking for biomarkers to close this diagnostic gap. The project is being supported by the zukunft.niederachsen funding program with around half a million euros as part of the "Innovative diagnostics and therapeutic approaches to combat rare diseases" call for proposals.
Faster and more reliable typing
"Inflammation is often mistakenly attributed to drug-related causes as soon as an infection can be ruled out," says Professor Hinze, senior physician at the Clinical Department. However, it is also possible that an unknown rare disease is the cause, which should not be missed diagnostically. "It's a bit like automatically thinking of horses when you hear clattering hooves, even though a zebra could also be the cause." The researchers are now looking for a way to distinguish the more common "horses" from the rare "zebras". To do this, they want to find biomarkers that enable faster and more reliable typing of different forms of IN and the presence of rare diseases in order to prevent the loss of kidney function in affected patients.
They want to achieve this goal with the help of clinical data from IN patients, an extensive kidney biopsy program and molecular and bioinformatic methods. "We have extensive and unique patient cohorts and a large kidney biopsy program in our outpatient clinics for rare kidney diseases," says the nephrologist. "We want to use biopsies from 60 IN patients." The researchers hope to discover biomarkers that will make it possible in future to distinguish between common drug-induced causes and inflammation caused by rare diseases just by looking at the tissue sections under the microscope.
Biomarkers for systemic autoimmune diseases
In a second step, not only will the "horses" be distinguished from the "zebras", but the zebras themselves will also be differentiated more precisely. Although they look similar, their coat pattern is individually unique. The situation is similar with the rare diseases associated with IN. "There are currently around 8,000 known rare diseases, quite a few of which are associated with kidney problems," says senior physician Dr. Gödecke. "Considering rare systemic autoimmune diseases in particular as a cause of IN is important for a prediction, as these are the second most common cause of IN after infections and are treatable." These chronic inflammatory diseases are sometimes difficult to diagnose, as their course varies from person to person and the symptoms can occur at different times. What they have in common, however, is that the immune system mistakenly attacks the body's own healthy tissue. This can affect the kidneys, but also other organs. While some of the rare diseases can be identified by detecting antibodies, others must be confirmed with a tissue sample. In very rare cases, IN is caused by a congenital disease. Acquired autoimmune diseases that can trigger IN include sarcoidosis, an inflammatory disease with possible kidney involvement, and Sjögren's syndrome, a rheumatic disease of the salivary and lacrimal glands that can also affect the kidneys.
The project therefore focuses on these two autoimmune diseases as examples. The aim is to find specific biomarkers for the rare IN triggers so that rare diseases can be considered at an early stage, even in the case of non-specific findings. "The kidney is the window through which we can recognize a rare disease in IN," says Professor Hinze. "Now we want to use the biopsies to focus on the causes and thus enable faster access to suitable treatment."
Text: Kirsten Pötzke