Maria V. Irazabal Mira, M.D., Ph.D.

The purpose of this study is to determine whether patients with ADPKD present with abnormal levels of fumarate that correlates with disease severity and this increase in fumarate results in upregulation of Nrf2 signaling leading to increased cellular proliferation and contributing to cystogenesis.

The purpose of this study is to perform a comprehensive metabolic fingerprinting of pediatric-adolescents patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and healthy volunteers.

The primary objective of this study is to evaluate the use of Super-resolution ultrasound (SRU) to assess the intrarenal microvasculature in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD).

The purpose of this study is to assess homocysteine metabolism and endothelial function at early stages of ADPKD and how these influence microvascular function and renal disease severity and progression. 

The purpose of this study is to determine the value of oxidative stress and cAMP-PKA signaling-related biomarkers to assess disease severity and progression in patients with autosomal dominant polycystic kidney disease (ADPKD).

The purpose of this study is to determine whether patients with autosomal dominant polycystic kidney disease (ADPKD) present with abnormal endothelial function, increased levels of NOX4 activity and mitochondrial abnormalities, contributing to oxidative stress from early stages that correlate with disease severity.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a devastating genetic disorder that causes numerous cysts in the kidneys, and remains a leading cause of renal failure. However, the only FDA-approved therapy for ADPKD (tolvaptan) is limited to slowing-down disease progression, and has associated side effects. Furthermore, the mechanisms that contribute to cyst formation and further damage to the kidney are still uncertain. A better understanding of these processes may assist in development of new therapies with fewer adverse effects and improve the quality of life of these patients.

Another critical problem in the care of patients with ADPKD is that the rate of disease progression varies widely among individuals and markers of renal function don’t change until late stages, representing a major challenge for following these patients, identifying a treatment response or predicting the progression of the disease. Therefore, there is a pressing need for identifying early biomarkers of disease severity/progression and additional targets for therapeutic interventions.

Oxidative stress is the imbalance between the production of harmful free radicals and antioxidants and a major contributor of renal damage in other kidney diseases, but its role in ADPKD is unclear. This study will explore for the first time the role of oxidative stress damage in a preclinical model of ADPKD and related biomarkers at early stages of the disease. The findings resulting from this study are likely to have important clinical implications by: advancing the understanding of the mechanisms of renal damage in ADPKD, identifying novel early biomarkers, and highlighting additional processes that could be target for therapeutic intervention.