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Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage

Journal of Human Hypertension volume 28, pages 74–79 (2014)Cite this article

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Abstract

Kidney damage represents a frequent event in the course of hypertension, ranging from a benign to a malignant form of nephropathy depending on several factors, that is, individual susceptibility, degree of hypertension, type of etiology and underlying kidney disease. Multiple mechanisms are involved in determination of kidney glomerular, tubular and interstitial injuries in hypertension. The present review article discusses relevant contributory molecular mechanisms underpinning the promotion of hypertensive renal damage, such as the renin–angiotensin–aldosterone system (RAAS), oxidative stress, endothelial dysfunction, and genetic and epigenetic determinants. We highlighted major pathways involved in the progression of inflammation and fibrosis leading to glomerular sclerosis, tubular atrophy and interstitial fibrosis, thus providing a state of the art review of the pathogenetic background useful for a better understanding of current and future therapeutic strategies toward hypertensive nephropathy. An adequate control of high blood pressure, obtained through an appropriate therapeutic intervention, still represents the key strategy to achieve a satisfactory control of renal damage in hypertension. In this regard, we reviewed the impact of currently available antihypertensive pharmacological treatment on kidney damage, with particular regard to RAAS inhibitors. Notably, recent findings underscored the ability of the kidneys to regenerate and to repair tissue injuries through the differentiation of resident embryonic stem cells. Pharmacological modulation of the renal endogenous reparative process (that is, with angiotensin-converting enzyme inhibitors and AT1 angiotensin II receptor blockers), as well as future therapeutic strategies targeted to the renopoietic system, offers interesting perspectives for the management of hypertensive nephropathy.

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Acknowledgements

The present work was supported by a grant (Ricerca Corrente) from the Italian Ministry of Health to MV and SR; by the 5‰ grant to MV and SR; by PRIN 2009 to SR; and by InGenious Hypercare European project to MV.

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Authors and Affiliations

  1. Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome, Italy

    S Mennuni, S Rubattu, G Pierelli & M Volpe

  2. IRCCS Neuromed, Pozzilli, Italy

    S Rubattu, G Tocci & M Volpe

  3. Nephrology and Dialysis Unit, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome, Italy

    C Fofi

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  1. S Mennuni
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Correspondence to S Rubattu or M Volpe.

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Mennuni, S., Rubattu, S., Pierelli, G. et al. Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage. J Hum Hypertens 28, 74–79 (2014). https://doi.org/10.1038/jhh.2013.55

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