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Elaine Worcester, MD

Dr. Elaine Worcester received her undergraduate degree from Augustana College in Rock Island, IL and her medical degree from the University of Illinois. She completed a residency in internal medicine at Loyola University Medical Center, and a nephrology fellowship at the University of Chicago, where she worked with Dr. Fredric Coe on calcium oxalate crystallization. She spent her early faculty years at the Medical College of Wisconsin but later came to the University of Chicago in 2000, where she is currently a Professor of Medicine in the Section of Nephrology. Here, her clinical research focuses on idiopathic hypercalciuria, a major metabolic abnormality leading to kidney stones and bone disease. In 2014, she became the primary investigator of the NIH funded PO1 in Calcium Nephrolithiasis (previously led by Dr. Coe) and in 2017, she successfully secured funding renewal for this program project grant (PPG) for another five years.

Dr. Worcester’s research into hypercalciuria began with a question that challenged the long-accepted theory then that dietary calcium overabsorption was the cause – could the kidneys themselves be the reason for urinary calcium loss and subsequent bone loss? Studying normal subjects and patients with calcium kidney stones who were fed identical diets, she proved that reduced kidney calcium conservation caused the high urine calcium in the study population, thus ending the misconception and profoundly altering patient care by eliminating low calcium diet from clinical practice.

To determine where in the nephron the defect lies, she used endogenous lithium clearance to demonstrate marked alterations in sodium and calcium transport in the proximal tubule that lead to less reabsorption. Both minerals then must be reabsorbed at more distal nephron segments. In hypercalciuria, sodium is reabsorbed completely, but calcium is not. In addition, men have more marked proximal defects than women, although both sexes are equally hypercalciuric. The proximal tubule alteration can be partially corrected by use of thiazide diuretics, a treatment commonly used to lower urine calcium, prevent kidney stones, and improve bone mineral balance.

Ingestion of nutrients is known to be the stimulus for the altered proximal tubule reabsorption, and this change is magnified in hypercalciuric stone formers. In the course of her work, she noticed that hypercalciuric people have abnormal glucose metabolism, leading her to hypothesize that the complex glucose regulatory system somehow alters renal Na and calcium transport, although not simply via insulin or glucagon. Together with a colleague, Dr. Benjamin Ko, she discovered that the rise of urine calcium after eating is associated with changes in key proximal and distal transporter membrane abundances to favor reduced calcium reabsorption. Working with another colleague, Dr. Anna Zisman, she is now studying the effects of oral glucose on lithium clearance and urine exosomes to uncover the molecular basis of the sugar hypercalciuria, which can in turn open exciting new avenues to explore human renal transport physiology.

Her PPG group has two projects (at Indiana University) that investigated the sites where kidney stones begin to form in kidney papillary tissue, using surgical and state-of-the-art histopathological techniques. These studies found that idiopathic calcium oxalate stones form as overgrowths on interstitial calcium phosphate deposits found at the tip of the renal papillae, which are most commonly present in patients with hypercalciuria. Furthermore, the initial crystal deposits in the ascending thin limb of Henle’s loop, the site predicted by the accelerated delivery of calcium out of the proximal tubule. Utilizing modern digital endoscopes, the group is developing a grading scale that can change the surgical approach to the treatment of stone disease, allowing identification patients at highest risk of recurrence. Treatment of hypercalciuria can prevent both urine calcium loss as well as deposition of mineral in the papillae of stone formers, greatly decreasing the long term risk of stones