Kidney Disease

Nephron Number and Associations in Australian, American and African Kidneys

We are determining nephron number in human kidneys and correlating our findings with birth weight, body mass index, body surface area, race, gender, age, glomerular size, glomerulosclerosis, cortical interstitial fibrosis, renal vessel hypertrophy, heart weight, albuminuria, blood pressure and other clinical parameters. There is increasing evidence that low nephron number is an important determinant of kidney and cardiovascular disease in adulthood. We are determining nephron number in white and Aboriginal Australians, white and African Americans and Senegalese Africans. We recently published two reports of a correlation between low nephron number in humans and increased blood pressure. We found this relationship in whites from the Southeastern US, but interestingly this relationship was not observed in African Americans from the same geographic region (LINK to PUB). We have also shown that Aboriginals with low nephron number have higher blood pressure than Aboriginals with high nephron number (LINK to PUB).

A major focus in these studies is glomerular size. In part this is because the single consistent finding in renal biopsies from Aborigines is glomerulomegaly (abnormally enlarged glomeruli). It is not clear whether this glomerulomegaly represents compensatory hypertrophy in response to decreased glomerular endowment (decreased nephrogenesis during development) and/or whether it is secondary to haemodynamic/metabolic and other influences, including chronic and repeated infections. Photomicrographs of glomeruli from white and Aboriginal Australians are shown below.

Photographs of glomeruli from: (A) a Caucasian Australian biopsy, and (B, C) an Australian Aboriginal biopsy. (A) shows a 'normal' glomerulus, while (B, C) show severe sclerosis (scarring) of the glomeruli, which leads to capillary collapse and loss of glomerular function.

The National Audit of Aboriginal Renal Biopsies (The NAARB Study)

The incidence of end stage renal disease in Australian Aborigines nationwide is more than 13 times the national average. In the Northern Territory, renal deaths are greatly increased; the age-adjusted rate of entry into the end stage renal disease program in the Top End is 21 times higher in Aborigines than the Australian aggregate rates and the rate is doubling every 3 to 4 years.

The single consistent finding in renal biopsies from Aborigines is glomerulomegaly (abnormally enlarged glomeruli), but remarkably, the incidence and associations of kidney disease in these populations is not clear. It is important to define the types of renal disease and pathology present in Aborigines, and to identify the correlations between renal pathology and clinical records. Only with a clear understanding of the nature of the kidney disease in Aborigines, will we be in a strong position to develop optimal preventative and therapeutic strategies.

We have therefore established the The National Audit of Aboriginal Renal Biopsies (The NAARB Study). Headed by Professor Wendy Hoy of the University of Queensland, we have brought together an expert panel of renal pathologists from the USA and Australia to evaluate the majority of Aboriginal renal biopsies performed in Australia in recent years. At the end of the study, we will have examined the light microscopic pathology, immunofluorescence, electron microscopy, and clinical records, of approximately 1,000 biopsies.