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Curr Opin Nephrol Hypertens. 2013 May;22(3):266-72. doi: 10.1097/MNH.0b013e3283600f8c.

Rethinking hypertensive kidney disease: arterionephrosclerosis as a genetic, metabolic, and inflammatory disorder.

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Kidney Disease Section, NIDDK, NIH, Bethesda, Maryland, USA.



Hypertension is the attributed cause of approximately 30% of end-stage kidney disease cases in the United States, but there has been controversy as to whether benign hypertension is a cause of chronic kidney disease.


The histology of chronic kidney disease attributed to nonmalignant hypertension is arterionephrosclerosis, with pathology in the terminal branches of the interlobular arteries, together with global glomerulosclerosis. The identification of coding region variants in APOL1, encoding apolipoprotein L1, has opened a new perspective on this debate. These variants are restricted to populations of recent African descent and are strongly associated with clinically diagnosed arterionephrosclerosis, particularly when there is moderate-grade or high-grade proteinuria or progression to more advanced levels of kidney dysfunction. Nevertheless, not all African Americans with hypertension who progress to end-stage kidney disease have two APOL1 risk variants, and individuals of European and Asian descent also manifest arterionephrosclerosis. Further, we do not understand the mechanisms by which APOL1 initiates pathology in the renal microcirculation.


APOL1 nephropathy comprises a disease spectrum (perhaps with distinct endophenotypes), including focal segmental glomerulosclerosis, collapsing glomerulopathy, and arterionephrosclerosis. The terms hypertensive kidney disease and hypertensive nephrosclerosis have outlived their usefulness. It may be time to use the established, etiologically neutral term, arterionephrosclerosis, to consider whether this is a disease rather than a pathologic description, and to determine the causal role of various clinical correlates including aging, obesity, hyperlipidemia, smoking, chronic inflammation, and oxidative stress.

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