The discovery of anti-brush border antibody (ABBA) disease was made in the UofL Core Proteomics Laboratory, led by Director , MD, PhD, UofL School of Medicine vice dean for research and professor of medicine, and James Graham Brown Foundation Chair in Proteomics. Klein worked with the laboratory’s Co-Director Michael Merchant, PhD, associate professor in the Division of Nephrology & Hypertension in the Department of Medicine at UofL.

Klein and co-investigators presented their findings Nov. 3 at the American Society of Nephrology’s annual meeting in New Orleans.

“It’s the first time in my career that I’ve described a new disease, and truthfully, most people in their career don’t stumble on this,” said Klein, who is internationally recognized for his expertise in biomarker discovery related to kidney disease and practices with . “We don’t know yet whether this causes kidney failure in a lot of people. It’s early in the story.”

The UofL lab identified ABBA after analyzing biopsied kidney tissue from 10 patients who had developed acute kidney injury, a sudden episode of kidney failure or damage that happens within a few hours or days. The condition causes a build-up of waste products in the blood and makes it difficult for kidneys to maintain adequate balance of fluid in the body.

For the first time, researchers discovered that in the nephrons, the functional units of the kidneys, antibodies had coated a specialized part of cells called brush borders, which help reabsorb and process proteins.

“The disease is rather insidious,” Klein said. “It was documented in a group of older men who simply turned up with abnormal kidney function, and there were no symptoms until they had very advanced kidney failure.”

Since it is an autoimmune disease, different approaches to suppress the immune system were used to treat the patients, but those efforts were unsuccessful, Klein said.

Further research will focus on defining demographics of patients with ABBA and the disease’s prevalence. Also, determining where on the protein megalin – which acts as a sponge to absorb proteins and other compounds that enter the nephron – the antibody binds is key to treating the disease, Klein said.

It’s unknown what stimulates the antibody formation.

“Antibodies have very specific targets; they bind to only certain proteins in autoimmune kidney diseases, and then to only certain portions of that protein,” Klein said. “That’s where you learn how to begin to block the antibody binding.”

Klein said the disease had gone undetected because most people with abrupt kidney failure recover and do not get biopsies. In cases of ABBA, however, kidneys do not improve.

Lead investigators of the study are Laurence H. Beck, MD, PhD, of Boston University School of Medicine, and Christopher P. Larsen, MD, a nephropathologist at Arkana Laboratories in Little Rock, Arkansas. 

Lederer also is chief of the Division of Nephrology and Hypertension, associate training program director and associate ombudsman for the UofL School of Medicine. Additionally, she serves as director of the UofL Physicians Metabolic Stone Clinic as well as the associate chief of staff for research and development at the Robley Rex VA Medical Center. Board certified in internal medicine and nephrology, Lederer is an UNOS-certified transplant physician.

Her research focuses on divalent ion metabolism, the minerals important for bone health. She oversees a basic science research laboratory funded by the Department of Veterans Affairs Merit Review Board, studying the mechanisms of regulation of the sodium phosphate transporter in a part of the kidney’s nephron known as the proximal renal tubule. She also has clinical interests in stone disease, and since starting the Metabolic Stone Clinic at UofL, has initiated research into the protein components of stones and their potential role in the pathogenesis of stone formation.

Lederer has a history of close involvement with ASN. She is a Fellow of the ASN and has served the organization in numerous roles including membership on the Communications Committee, Program Committee, Nominating Committee, Abstract Selection Committee, Training Program Directors Executive Committee, Women in Nephrology Professional Development Seminar Organizing Committee and In-Training Examination Writing Committee. She is a section editor for Clinical Nephrology and eMedicine Nephrology.

“Being on the ASN Council for the past few years has given me significant insight into the many different challenges and tasks facing medical societies – policy and advocacy issues, development of quality educational tools, promotion of research – for an extraordinarily diverse group of individuals,” Lederer said. “As president, I will be in a position to respond to the voice of the membership and the voice of the patients, our charges.”

Although Lederer sees several substantive nephrology-related issues to be addressed within the following year, she said the most challenging are the implications of the exploding population of patients with kidney failure worldwide.

“Kidney diseases are a global issue, and the challenges of developing and developed nations are similar – too many patients, too few resources,” she said.

Lederer said she hopes that by working with other national and international societies, kidney care can be improved on a global scale.