Glomerular Size and Glomerulosclerosis in Australian Aborigines Richard J. Young, BSc(Hons), Wendy E. Hoy, MD, Priscilla Kincaid-Smith, MD, Anthony E. Seymour, MD, and John F. Bertram, PhD ● We have previously described the prevalence of glomerulomegaly in biopsy specimens from Australian Aborigi- nes with renal disease, a phenomenon documented in a number of other indigenous populations. Many of the biopsy specimens showed variable degrees of focal and segmental glomerulosclerosis (FSGS). Correlations between glomerular size and FSGS have been described in various animal models, as well as studies of humans. The aim of this study is to determine whether a relation exists between glomerular volume and severity of FSGS in biopsy specimens from Australian Aboriginals in the Northern Territory and Aboriginal inhabitants of the Tiwi Islands (Bathurst Island and Melville Island, Northern Territory, Australia). Consecutive clinical biopsy specimens were obtained from 78 non-Tiwi and 72 Tiwi Aboriginals. Glomerular volume was estimated using the stereological method of Weibel and Gomez. FSGS was graded from 0 to 4; 0 indicates no sclerosis and 4 indicates severe sclerosis. A biphasic relationship between glomerular size and severity of FSGS was identified. As the severity of FSGS increased from grade 0 to grade 3, glomerular size also increased. For both populations studied, glomeruli scored as grades 1, 2, and 3 were approximately 50% (P < 0.001), 65% (P < 0.001), and 100% (P < 0.001) larger than normal glomeruli, respectively. However, in glomeruli with grade 4 FSGS, glomerular size decreased to the size of normal glomeruli. These results show a biphasic relationship between severity of FSGS and glomerular size in Australian Aborigines. © 2000 by the National Kidney Foundation, Inc. INDEX WORDS: Australian Aborigines; stereology; focal and segmental glomerulosclerosis (FSGS); glomerulo- megaly. A N INCREASED INCIDENCE of end-stage renal disease (ESRD) has been reported in a number of indigenous populations, including Australian Aborigines, 1 New Zealand Polyne- sians, 2 Navajo 3 and Zuni Indians 4 in the United States, and native Indians of Canada. 5 The aver- age annual number of Aboriginal people present- ing for renal failure treatment in the Top End of the Northern Territory of Australia currently doubles every 3.5 years. Aboriginal rates for ESRD are now 20 times those of non-Aboriginal people in the Northern Territory. For 1996, crude rates were 820 per million (pm) for Aboriginals compared with a rate of 40 pm for non-Aborigi- nals in the Northern Territory and approximately 78 pm for all Australian non-Aboriginals. The incidence of ESRD appears to be greatest in some of the island Aboriginal communities, in- cluding the Tiwi Islands (Melville and Bathurst Islands), where Aboriginal residents had an aver- age annual incidence (between 1993 and 1996) of ESRD of 2,607 pm. Glomerular enlargement has previously been reported in Australian Aborigines. Moore et al 6 found glomerular enlargement to be the major lesion in 11% of Aboriginal patients, signifi- cantly more than in non-Aboriginal patients, with glomerulomegaly particularly common in patients from Bathurst Island. We previously estimated glomerular tuft and renal corpuscle volume in clinical renal biopsy specimens from Australian non-Aboriginals, Aboriginals, and Ab- originals from the Tiwi Islands. 7 Mean glomeru- lar volume was significantly greater in the two Aboriginal cohorts than in the non-Aboriginals. Through comparing the histopathologic char- acteristics of renal biopsy specimens from Ab- original patients in South Australia and the North- ern Territory with data from non-Aboriginal Australians, Moore et al 6 also found that the distribution of glomerular lesions differed signifi- From the Department of Anatomy and Cell Biology, Monash University, Clayton; Department of Pathology, Uni- versity of Melbourne, Parkville, Victoria; Menzies School of Health Research, Darwin, Northern Territory; and the De- partment of Histopathology, The Queen Elizabeth Hospital, Woodville, South Australia, Australia. Received December 20, 1999; accepted in revised form April 14, 2000. Research contained in this study was conducted at the University of Melbourne, Parkville, and Monash University, Clayton, Victoria, Australia. Supported in part by grants from the National Health and Medical Research Council of Australia and from Janssen- Cilag Pty Ltd. Address reprint requests to John F. Bertram, PhD, Depart- ment of Anatomy and Cell Biology, Monash University, Clayton, Victoria 3800, Australia. E-mail: john.bertram@ med.monash.edu.au © 2000 by the National Kidney Foundation, Inc. 0272-6386/00/3603-0004$3.00/0 doi:10.1053/ajkd.2000.9788 American Journal of Kidney Diseases, Vol 36, No 3 (September), 2000: pp 481-489 481