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NDT Advance Access originally published online on September 22, 2007
Nephrology Dialysis Transplantation 2008 23(1):213-222; doi:10.1093/ndt/gfm560
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org


Prediction of early progression in recently diagnosed IgA nephropathy

Kevin V. Lemley1, Richard A. Lafayette1, Geraldine Derby1, Kristina L. Blouch1, Linda Anderson2, Bradley Efron3 and Bryan D. Myers1

1Division of Nephrology, 2Department of Pathology, Stanford University School of Medicine and 3Department of Statistics, Stanford University, Stanford, CA 94305, USA

Correspondence to: Kevin V. Lemley, MD, PhD, Division of Nephrology, MS#40, Childrens Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027, USA. Email: klemley{at}chla.usc.edu



  Abstract

Background. Most studies of prognosis in IgA nephropathy (IgAN) have tried to predict dichotomous outcomes based on a small number of clinical or semi-quantitative histological variables in large numbers of patients.

Methods. We pursued a quite different approach. We measured GFR annually for 4–5 years in 22 adult patients with recently diagnosed IgAN. Quantitative morphology was performed on the diagnostic biopsy specimens and baseline glomerular filtration dynamics were performed at study entry. An initial set of 30 plausible predictor variables (half demographic or physiological, half structural) was reduced to 22 using phylogenetic trees. Least-angle regression (LARS) was used to predict the rate of GFR change from these variables

Results. The rate of GFR change ranged from a loss of 41 ml/min/year to a gain of 8.6 ml/min/year. We found an optimum predictor set of five baseline variables: the percentage of glomeruli with global sclerosis, the fractional interstitial area, the serum creatinine, the average tuft volume of non-sclerotic glomeruli and the renal plasma flow.

Conclusions. The strong predictive relationship of the three structural variables with the slope of GFR in our subjects suggests that even at the time of their initial diagnosis many patients with IgAN already manifest a ‘remnant kidney’ phenomenon. The distinctive pathophysiological insights derived from this study suggest some of the advantages of intense quantitative investigations applied to a small number of subjects.

Keywords: GFR; glomerular sclerosis; IgA nephropathy; least-angle regression; morphometry; progression

Received for publication: 1. 3.07
Accepted in revised form: 24. 7.07


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