CINAC, a major globally emerging chronic renal disease of unknown origin: unraveling the molecular mechanism and etiology to allow diagnostic tool development.

In the last two decades, an increase is observed in the prevalence of a new form of chronic kidney disease in various countries around the world. A notable feature here is that it cannot be attributed to the common causes of CKD and is only diagnosed through aspecific criteria. The disease is primarily affecting young, male agricultural workers working in harsh conditions in hot tropical climates. Considering the epidemiological and histopathological findings in human biopsy material, this disease was named Chronic Interstitial Nephritis in Agricultural Communities (CINAC). The cause of CINAC remains unclear as there is no scientific consensus on a main causative agent. The histopathological phenotype is indistinguishable to that of patients' biopsies, treated with calcineurin inhibitors, suggesting CINAC might have a toxicological cause. In a preliminary study in our lab, biopsies from CINAC patients from Sri Lanka, El Salvador, and Portugal have been examined and they all showed an increase in the number of dysmorphic lysosomes and the shedding of cell fragments of affected cells. This histopathological phenotype suggests that the cellular fragments can be retrieved in, and isolated from, urine. From these isolated fragments, a protein analysis will be performed, possibly revealing the involvement of certain molecular pathways. Subsequently, a non-invasive diagnostic screening method can be developed. This can provide a first positive discriminator to diagnose this disease.

Keywords:KIDNEY DISEASE

Disciplines:Morphological sciences

Project type:Collaboration project