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Trajectories of kidney function in diabetes: a clinicopathological update

Abstract

Diabetic nephropathy has been traditionally diagnosed based on persistently high albuminuria and a subsequent decline in glomerular filtration rate (GFR), which is widely recognized as the classical phenotype of diabetic kidney disease (DKD). Several studies have emphasized that trajectories of kidney function in patients with diabetes (specifically, changes in GFR and albuminuria over time) can differ from this classical DKD phenotype. Three alternative DKD phenotypes have been reported to date and are characterized by albuminuria regression, a rapid decline in GFR, or non-proteinuric or non-albuminuric DKD. Although kidney biopsies are not typically required for the diagnosis of DKD, a few studies of biopsy samples from patients with DKD have demonstrated that changes in kidney function associate with specific histopathological findings in diabetes. In addition, various clinical and biochemical parameters are related to trajectories of GFR and albuminuria. Collectively, pathological and clinical characteristics can be used to predict trajectories of GFR and albuminuria in diabetes. Furthermore, cohort studies have suggested that the risks of kidney and cardiovascular outcomes might vary among different phenotypes of DKD. A broader understanding of the clinical course of DKD is therefore crucial to improve risk stratification and enable early interventions that prevent adverse outcomes.

Key points

  • Diabetic kidney disease (DKD) is traditionally characterized by persistent high albuminuria and a subsequent decline in the glomerular filtration rate (GFR); this trajectory is widely recognized as the classical phenotype of DKD.

  • Three alternative, non-classical phenotypes of DKD have also been described, characterized by regression of albuminuria, rapid GFR decline, or the absence of proteinuria or albuminuria.

  • In diabetes, strong relationships exist between pathological kidney biopsy findings and clinical manifestations such as albuminuria and GFR decline.

  • Additional clinical parameters and treatments have been associated with trajectories of kidney function and might be used to predict DKD progression.

  • Risks of kidney and cardiovascular outcomes might also differ among phenotypes of DKD — understanding the trajectories of GFR and albuminuria is therefore important for risk stratification and early intervention.

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Fig. 1: Trajectories of kidney function in DKD.
Fig. 2: Pathological features of diabetic nephropathy.
Fig. 3: Clinicopathological factors associated with trajectories of kidney function in diabetes.

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M.O., M.S., M.Y. and T.W. researched data for the article. M.O., M.S., M.Y., T.T. and T.W. made substantial contributions to discussions of the content and wrote the manuscript. All authors reviewed or edited the manuscript before submission.

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Correspondence to Takashi Wada.

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Nature Reviews Nephrology thanks M. E. Jørgensen, D. Vistisen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Oshima, M., Shimizu, M., Yamanouchi, M. et al. Trajectories of kidney function in diabetes: a clinicopathological update. Nat Rev Nephrol 17, 740–750 (2021). https://doi.org/10.1038/s41581-021-00462-y

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