Role of Monocytes and Macrophages in Kidney Stone Disease
Approximately 9% of the United States population will develop a kidney stone in their lifetime. Lifestyle factors, genetics, and diet all contribute to the development of kidney stones. The most common type of kidney stone is comprised of calcium oxalate (CaOx) crystals. Research on kidney stones is hampered by limited access to kidney cells and tissue from patients. Few studies have focused on circulating immune cells which may play a role in disease processes. Monocytes/macrophages are essential for crystal clearance and are recruited to the renal interstitium. We previously determined that monocytes but not lymphocytes or platelets have lower mitochondrial function in patients with CaOx kidney stones compared to healthy subjects. The objective of our current research is to evaluate changes in mitochondrial function, oxidative stress, and
inflammatory responses in circulating monocytes and plasma from patients with CaOx kidney stones and healthy subjects. This may identify specific responses associated with this disease. We hypothesize that circulating monocytes in patients with CaOx kidney stones develop mitochondrial dysfunction due to cellular events mediated by CaOx stones and/or exposure to CaOx crystals in the nephron. To test this hypothesis we are using an in vitro model as well as exposing healthy subjects to a dietary oxalate load to assess changes in monocyte metabolism and immune responses.
Crystalluria and Kidney Stone Disease
Urinary crystals are precursors to urinary stones. We recently developed a method to detect and quantify nanocrystalluria, which cannot be detected with conventional microscopy. This novel approach consists of fluorescently labeling crystals with a calcium binding dye and quantifying nanocrystals with NanoSight technology, a tool that assesses nanoparticles in biological samples based on Brownian motion. The advantage of this method is that it can accurately detect nanocrystals in the urine and may identify factors associated with crystal agglomeration and crystal toxicity. The ability to assess stone risk in patients with NanoSight Technology could be beneficial.
Role of Immune Cells in Interstitial Cystitis/Painful Bladder Syndrome
Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS) is a urological disorder that affects over 3.3 million women in the United States. It can also occur in men and children. IC/PBS results in recurring discomfort or pain in the bladder and surrounding pelvic region. Inflammation has been suggested to be a contributing factor to the etiology of IC/PBS. We are examining the significance of mitochondrial function and inflammation in immune cells during IC/PBS using clinical samples. Our preliminary data suggests that innate immune cells and inflammation may play an important role in IC/PBS.