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Hypertension-attributed nephropathy: what's in a name?

Key Points

  • 'Hypertensive nephrosclerosis' is a non-specific clinical diagnosis applied to non-diabetic patients, often those with recent African ancestry, who present with chronic kidney disease, low-level proteinuria and elevated blood pressure

  • Poorly controlled mild-to-moderate hypertension can contribute to arteriolar nephrosclerosis, a vascular lesion in the preglomerular arterioles that leads to glomerular ischaemia

  • Non-diabetic aetiologies of end-stage renal disease (ESRD), including those typically ascribed to essential hypertension, lupus nephritis, focal segmental glomerulosclerosis or HIV-associated nephropathy, aggregate in African American families

  • Patients in such multiplex families who lack an obvious initiating cause of nephropathy are often labelled as having 'hypertensive nephrosclerosis' after a cursory evaluation

  • Genetic breakthroughs demonstrate that inherited forms of glomerulosclerosis can present in a similar fashion to arteriolar nephrosclerosis; these renal-limited disorders secondarily elevate blood pressure

  • The presence of two apolipoprotein L1 gene (APOL1) renal-risk variants is powerfully associated with approximately 70% of non-diabetic glomerulosclerosis and up to 40% of all cases of ESRD in African Americans

Abstract

Unrelated disease processes commonly occur in non-diabetic individuals with mild-to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease. Although nephropathies that are associated with variants in the apolipoprotein L1 gene (APOL1) often cause secondarily elevated blood pressure, they belong to the spectrum of focal segmental glomerulosclerosis and are not initiated by systemic hypertension. Because genetic testing for APOL1 variants and other glomerulosclerosis-associated gene variants is available and can provide a precise definition of disease pathogenesis, we believe that the term 'hypertensive nephrosclerosis' should now be abandoned and replaced with either gene-based (for example, APOL1-associated) glomerulosclerosis or arteriolar nephrosclerosis. Precision medicine will be key to improving diagnostic accuracy in this field. Discrimination of these disparate disorders has the potential to eradicate primary forms of glomerulosclerosis that are associated with APOL1 renal-risk variants.

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Figure 1: Schematic representation of vascular and glomerular lesions in hypertension-attributed nephropathy.
Figure 2: Histologic features of arteriolar nephrosclerosis.
Figure 3: Histologic features of APOL1-associated glomerulosclerosis.

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Acknowledgements

The authors thank Dr Todd W. Robinson, Wake Forest School of Medicine, NC, USA, for his expert review of this manuscript before submission. The authors' work described in this Review was supported by grants from the NIH (R01 DK070941, R01 DK084149 and R01 HL56266).

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B.I.F. and A.H.C. contributed equally to researching the data, writing the article and reviewing and/or editing of the manuscript before submission.

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Correspondence to Barry I. Freedman.

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The authors declare no competing financial interests.

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Freedman, B., Cohen, A. Hypertension-attributed nephropathy: what's in a name?. Nat Rev Nephrol 12, 27–36 (2016). https://doi.org/10.1038/nrneph.2015.172

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