Glomerular Disease Differs Globally

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International survey finds geographic variation in the subtype frequencies in biopsied patients.
International survey finds geographic variation in the subtype frequencies in biopsied patients.

Glomerular disease subtype frequencies vary markedly by continent, even among patients of similar race or ethnicity, according to a new study.

In North America, the predominant subtypes are diabetic glomerulosclerosis (GS) and focal segmental glomerulosclerosis (FSGS), each making up 19.1% of patients with biopsy-proven glomerular disease. Lupus nephritis (38.1%) and FSGS (15.8%) were the most common subtypes in Latin America, whereas IgA nephropathy (IgAN, 22.1%) and FSGS (14.9%) predominated in Europe. IgAN (39.5%) and lupus nephritis (16.8%) predominated in Asia.

As part of the International Kidney Biopsy Survey, a team led by Michelle M. O'Shaughnessy, MD, of Stanford University School of Medicine in Palo Alto, California, sent standardized data collection forms to 29 nephropathology laboratories on 4 continents. They obtained recent consecutive kidney biopsy diagnosis frequencies at each center and summary demographics for each diagnosis. The study included 42,603 patients diagnosed with glomerular disease. They had a median age of 47 years.

“This study represents an exciting step toward studying glomerular disease at the global level, and demonstrates the feasibility of engaging multiple stakeholders from diverse geographic, economic and cultural regions in a collaborative research effort,” the authors concluded in a paper published online ahead of print in Nephrology Dialysis Transplantation.

Also part of the research team were Agnes Fogo, MD, of Vanderbilt University in Nashville, Tennessee; Rosanna Coppo, MD, of Regina Margherita Hospital in Turin, Italy; and Susan Hogan, PhD, Bawana Thompson, BS, and Charles Jennette, MD, of the University of North Carolina at Chapel Hill.

Across racial and ethnic groups, the study also found intercontinental variation in glomerular disease subtype frequencies. For example, among whites, those in North America had a significantly higher frequency of FSGS and diabetic GS compared with those in Europe (18.9% vs 13.5% and 18.7% vs 6.5%, respectively), whereas IgAN occurred significantly less frequently among whites in North America than in Europe (14.4% vs 25.4%). Among Latinos, diabetic GS occurred significantly more frequently in North America than in Latin America (17.4% vs 4.3%), as did FSGS (17.3% vs 11.8%), whereas lupus nephritis occurred significantly less frequently among Latinos in North America than in Latin America (15.8% vs 45.6%). FSGS had a significantly greater frequency among Asians in North America than in Asia (13.1% vs 7.1%), whereas the frequency of IgAN was significantly lower (27.4% vs 40.5%).

“The reasons for the generally higher frequencies of diabetic GS and FSGS among biopsied patients in North America, even when compared with patients of a similar racial/ethnic background residing in their country of ancestral origin, cannot directly be determined from this study,” Dr. O'Shaughnessy and her colleagues stated.

The investigators noted, however, that given that diabetic GS and obesity-related secondary forms of FSGS are heavily influenced by lifestyle factors, and that the incidences of diabetes and obesity are rising steadily in the United States, “we suspect that an absolute increase in the biopsy frequencies of diabetic GS and FSGS (as opposed to a major reduction in the incidences of other subtypes) when patients migrate to North America is the most important contributor to this finding.” The investigators pointed out that biopsy-derived data can underestimate disease frequencies, particularly where the diagnosis is often clinically evident, such as for diabetic nephropathy, and can be affected by regional biopsy practices.

“This study looking at a vast and diverse population across 17 countries and 4 continents provide further insights into the epidemiology of glomerular disease and also underscore the complexity behind the etiology of glomerulonephropathies,” said John J. Sim, MD, who has conducted epidemiologic studies of glomerular diseases but was not involved in the new study. “The findings suggest the interplay and importance of both nature and nurture on glomerular disease.”

Dr Sim is an assistant clinical professor at David Geffen UCLA School of Medicine in Los Angeles and Area Research Chair at Kaiser Permanente Los Angeles Medical Center.

In the past, Dr Sim told Renal & Urology News, researchers assumed certain racial and ethnic groups are more predisposed to specific glomerulonephropathies. This may be the case with Asians, who are believed to be at genetically higher risk for IgAN, he said. The new study showed that IgAN was most prevalent among Asians living in Asia, but FSGS superseded IgAN among Asians in North America. Although genetic or epigenetic factors are likely strong contributors to IgAN, Dr Sim said, the environment and patient behaviors appear to exert an equal or greater influence on the development of certain glomerulonephropathies.

“While there may be heterogenous practice patterns across the world that may confound the interpretation of some of these [new study's] findings,” Dr Sim said, “this study further supports previous work and emphasizes the need to consider the multifactorial mechanisms underlying the pathophysiology of glomerular diseases.”

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