- Dr. Alvaro Pacheco-Silva, Principal Investigator
- Dr. Aparecido B. Pereira, Co-Investigator
- Dr. Niels O. Câmara, Co-Investigator
- Dr. Kikumi S. Ozaki, Collaborator
- Dr. Rogério Chinene, Research Associate
- Dr. Georgia D. Marques, Research Associate
- Dr. Marcos A. Cenedeze, Research Associate
- Universidade Federal de São Paulo, São Paulo, Brazil
- Detection and Prevention of Patients with Chronic Allograft Nephropathy
Renal transplantation is the best therapeutic option for patients with chronic renal disease. It contributes to improve life quality and decreases the relative risk of cardiovascular death when compared to patients kept on dialysis. One-year graft survival has improved a lot during the last 20 years, and currently is around 90% in recipients of kidneys from deceased donors. However, only 50% of kidney transplant patients will still have functioning organs after 10 years of transplantation. The main cause of graft loss after the first year is an entity denominated chronic allograft nephropathy (CAN).
Thus, CAN is currently the greatest barrier to long-term success of a renal transplantation. Many factors are known to be associated with CAN development and its progression but our understanding of these are still incomplete. CAN is characterized by a progressive diminution of renal function, and the histological analyses show evidence of progressive tubulointerstitial fibrosis and tubular atrophy. There is currently no clinical or invasive test that favors its early detection. Therefore, CAN can only be confirmed by graft biopsy when usually clinical alterations are already present. This late diagnosis makes it very difficult to establish any clinical maneuver to halt this process.
At early time points, CAN can be associated with tubulointerstitial injury, manifested by dysfunction of renal proximal tubular cells. We are proposing to use a new tool, the evaluation of proximal tubular function, for an early diagnosis and a better comprehension of CAN. Proximal tubular function can be assessed by the determination of urinary tubular proteins, especially retinol binding protein (RBP). We intend to reverse the tubular dysfunction by modifying immunosuppressive drugs, toward a less toxic schema. Genes and proteins involved in the initiation process of proximal tubular dysfunction and those related to CAN will also be investigated.