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Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes

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Abstract

Despite almost universal implementation of renoprotective therapies over the past 25 years, the risk of end-stage renal disease (ESRD) in type 1 diabetes (T1D) is not decreasing, and ESRD remains the major cause of excess morbidity and premature mortality [1]. Such a state of affairs prompts a call to action. In this review we re-evaluated the proteinuria-centric model of diabetic nephropathy and showed its deficiencies. On the basis of extensive studies that we have been conducting on the patients attending the Joslin Clinic, we propose that progressive renal decline, not abnormalities in urinary albumin excretion, should be considered as the major feature of disease processes leading to ESRD in T1D. The etiology of diabetic nephropathy should be reconsidered in light of our new findings so our perspective can be broadened regarding new therapeutic targets available for interrupting the progressive renal decline in T1D. Reduction in the loss of glomerular filtration rate, not reduction of albumin excretion rate, should become the measure for evaluating the effectiveness of new therapeutic interventions. We need new accurate methods for early diagnosis of patients at risk of progressive renal decline or, better still, for detecting in advance which patients will have rapid, moderate or minimal rate of progression to ESRD.

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Acknowledgments

This study was supported by the following grants: NIH grants DK-41526 and DK676381 and JDRF grants 1-2008-1018 and 17-2013-8 to A.S. Krolewski; and Diabetes Research Center—Joslin, Pilot and Feasibility Grant, P30DK036836 to M.A. Niewczas.

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The authors have declared that no conflict of interest exists.

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Authors and Affiliations

  1. Section on Genetics and Epidemiology, Research Division of Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215, USA

    Andrzej S. Krolewski, Tomohito Gohda & Monika A. Niewczas

  2. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Andrzej S. Krolewski, Tomohito Gohda & Monika A. Niewczas

  3. Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan

    Tomohito Gohda

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  1. Andrzej S. Krolewski
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  2. Tomohito Gohda
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Correspondence to Andrzej S. Krolewski.

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Krolewski, A.S., Gohda, T. & Niewczas, M.A. Progressive renal decline as the major feature of diabetic nephropathy in type 1 diabetes. Clin Exp Nephrol 18, 571–583 (2014). https://doi.org/10.1007/s10157-013-0900-y

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