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Diabetes and chronic kidney disease: lessons from the Pima Indians

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Abstract

Although diabetic nephropathy is a very rare cause of kidney failure during childhood, the underlying events leading to progressive kidney injury begin during childhood in many patients with type 1 diabetes mellitus (T1DM) and in increasing numbers of children with type 2 diabetes mellitus (T2DM). The Pima Indians of Arizona represent an exceptionally thoroughly studied population suffering from very high rates of T2DM and diabetic nephropathy (T2DN). This population well illustrates the often inexorable progression from glomerular hyperfiltration to microalbuminuria to overt proteinuria and loss of glomerular filtration rate (GFR), paralleled by the accumulation of mesangial matrix and basement membrane, glomerular hypertrophy, loss of podocytes and eventual glomerular sclerosis and interstitial fibrosis. Structural changes quantitatively account for the loss of GFR in T2DN. The mechanism of albuminuria (and its relationship to GFR loss) is much less clear. There is strong functional and structural evidence for defects in glomerular size-selectivity (shunts) due to podocyte pathology, but only beginning at relatively high levels of proteinuria (albumin/creatinine ratios > 3000 mg/g). Podocyte loss accompanies, and may underlie, the loss of glomeruli to sclerosis. At this point, most evidence in humans suggests detachment of intact podocytes from the glomerular basement membrane, rather than apoptosis, as the predominant mechanism of podocyte loss.

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Notes

  1. The NIH study has included Pima Indians and Tohono O’odham (Papago) Indians from the Gila River Indian Community.

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Acknowledgments

Many of the studies reported here represent the collaborative work of groups at Stanford University and the Phoenix Epidemiology and Clinical Research Branch of the NIDDK. Drs. Bryan D. Myers, Timothy W. Meyer, Peter H. Bennett and Robert G. Nelson and Ms. Kristina L. Blouch, Linda Anderson and Lois I. Jones have been principal colleagues in these investigations. Support for some of this work was provided by NIH DK 54600, the Juvenile Diabetes Foundation (#195080) and a Faculty Scholar Award from Satellite Dialysis Corporation, Inc.

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  1. Division of Nephrology, MS#40, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA, 90027, USA

    Kevin V. Lemley

  2. Division of Nephrology, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Kevin V. Lemley

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Correspondence to Kevin V. Lemley.

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Lemley, K.V. Diabetes and chronic kidney disease: lessons from the Pima Indians. Pediatr Nephrol 23, 1933–1940 (2008). https://doi.org/10.1007/s00467-008-0763-8

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