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Renal biopsy interpretation, a crucial tool to diagnose diseases causing kidney malfunction, is a highly specialized science and art with only a handful of world-class practitioners. Columbia has two of them. They have helped the Department of Pathology more than quintuple the number of renal biopsy interpretations it has performed since 1984, becoming the East Coast's most in-demand renal pathology center. This huge volume has in turn fueled important research advances.

More than 200 nephrologists from hospitals in 13 states ship kidney tissue samples to Columbia for diagnoses of renal disorders. "The lab has grown tremendously," says Dr. Vivette D. D'Agati, director of the hospital's Renal Pathology Laboratory and professor of pathology. "When I took over in 1984, we were receiving 300 biopsies a year. Now it's 1,800. Ninety percent of our work comes from the outside."

Biopsy tissue allows for diagnoses of many kidney disorders such as acute renal failure or nephritic syndrome, which can stem from other diseases, such as congenital and hereditary disorders, infections, autoimmune diseases, drug toxicities, and vascular disease. The numerous conditions make the work difficult and specialized. "One disease can manifest many different morphological patterns and clinical presentations and the same morphological pattern or clinical presentation can be seen in many different diseases," Dr. D'Agati says.

"No single disease accounts for more than 7 percent of our biopsies," adds Dr. Glen S. Markowitz, associate professor of pathology and associate attending in pathology at the hospital. Dr. Markowitz joined the laboratory in 1997 as a fellow. Dr. D'Agati ran the laboratory alone since 1984, when she took over from Dr. Conrad Pirani, now professor emeritus of pathology, who founded it in 1973. She eventually needed help with the growing workload, leading to Dr. Markowitz's hiring.

A renal biopsy work-up and interpretation require at least two hours of professional time and about nine hours of technical time, including light microscopy with numerous special stains, immunofluorescence microscopy, and electron microscopy. Besides reading and interpreting the biopsy, a renal pathologist also integrates the patient's clinical history, serologies, and other laboratory findings.

Outside nephrologists using the Columbia service receive a phone consultation from Drs. Markowitz or D'Agati within 48 hours of shipping materials to the hospital. "The reason this practice is so successful is that we render a definitive diagnosis of the renal condition, discuss its possible causes, make prognostic forecasts and even make recommendation on treatment," Dr. Markowitz says. Quick turnaround is important, he adds, since doctors sometimes start incorrect treatments based on best guesses. Rapid and accurate biopsy results can prevent this.

Over time, Drs. Markowitz and D'Agati have forged close relationships with outside doctors, allowing the trust to translate into Columbia enrolling other doctors' patients in clinical studies. The large volume of material processed by the laboratory also has fostered research advances, including the identification of emerging diseases.

For instance, Dr. D'Agati, Dr. Markowitz, and colleagues identified a tenfold increase over 15 years in obesity-related glomerulopathy, a serious disease of the glomeruli, the kidneys' filtering units. The pattern "suggests a newly emerging epidemic," wrote the doctors in an April 2001 paper in the journal Kidney International.

Advances can occur when odd, unexplained conditions also begin to form a pattern. Such was the case when Drs. D'Agati and Markowitz noticed several mysterious cases of collapsing focal segmental glomerulosclerosis, a wrinkling of glomeruli membranes, associated with kidney failure. "It's generally seen in young African-American patients," Dr. Markowitz says. "But by having so many biopsies, we started to notice a pattern of cases in older, Caucasian patients."

Some detective work revealed all these patients had received higher-than-approved doses of a cancer drug, pamidronate. The findings appeared in the June 2001 Journal of the American Society of Nephrology.

These and other advances have enabled the laboratory to significantly reduce the percentage of inconclusive biopsies, Dr. D'Agati says. She estimates the percentage of inconclusive findings has dropped from approximately 20 percent in the mid-1980s to about 5 percent today.

Demand is huge for their expertise. "Vivette gets requests for second opinions from some of the top renal pathologists in the world," says Dr. Markowitz, speaking of Dr. D'Agati. The Renal Pathology Society has recognized both doctors for their achievements. Dr. D'Agati, a graduate of NYU School of Medicine, won its 2000 Jacob Churg Award for lifetime contributions to nephropathology. Dr. Markowitz—a graduate of Albert Einstein College of Medicine—won its 1998 Young Investigator Award.

The laboratory's reputation has spread largely by word of mouth. It hasn't advertised for 10 years. What does help the professional outreach, however, is Columbia's annual postgraduate course, Renal Biopsy in Medical Diseases of the Kidneys. "It's the largest renal pathology course of its type, now in its 25th year," Dr. D'Agati says. "This year the course was attended by more than 270 nephrologists and pathologists from all over the world." A lecture was given to honor Dr. Pirani, who attended the event.

Dr. Michael L. Shelanski, chairman of pathology and Delafield Professor of Pathology (in the Center for Neurobiology and Behavior), says the success boils down to the quality of the people. "It's hard to find people in any specialty that are that good," he said. "This type of outreach is common in academic medical centers. It's just that our people have been extremely successful at it."