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Glomerular hyperfiltration: definitions, mechanisms and clinical implications

Abstract

Glomerular hyperfiltration is a phenomenon that can occur in various clinical conditions including kidney disease. No single definition of glomerular hyperfiltration has been agreed upon, and the pathophysiological mechanisms, which are likely to vary with the underlying disease, are not well explored. Glomerular hyperfiltration can be caused by afferent arteriolar vasodilation as seen in patients with diabetes or after a high-protein meal, and/or by efferent arteriolar vasoconstriction owing to activation of the renin–angiotensin–aldosterone system, thus leading to glomerular hypertension. Glomerular hypertrophy and increased glomerular pressure might be both a cause and a consequence of renal injury; understanding the renal adaptations to injury is therefore important to prevent further damage. In this Review, we discuss the current concepts of glomerular hyperfiltration and the renal hemodynamic changes associated with this condition. A physiological state of glomerular hyperfiltration occurs during pregnancy and after consumption of high-protein meals. The various diseases that have been associated with glomerular hyperfiltration, either per nephron or per total kidney, include diabetes mellitus, polycystic kidney disease, secondary focal segmental glomerulosclerosis caused by a reduction in renal mass, sickle cell anemia, high altitude renal syndrome and obesity. A better understanding of the mechanisms involved in glomerular hyperfiltration could enable the development of new strategies to prevent progression of kidney disease.

Key Points

  • Glomerular hyperfiltration has been variably defined either as an abnormally high whole-kidney glomerular filtration rate (GFR), increased filtration fraction, or as increased filtration per nephron

  • An increased GFR occurs physiologically after consuming a high-protein meal and during pregnancy

  • Increased GFR can occur as an early manifestation of disease, for example in diabetes mellitus, but it remains to be proven whether glomerular hyperfiltration is a precursor of chronic kidney disease

  • Increased filtration per nephron occurs as an adaptive response to nephron loss, and leads to glomerular hypertension and subsequent glomerulosclerosis with progressive renal function decline

  • The mechanisms of glomerular hyperfiltration in disease conditions are variable and not entirely clear, although the renin–angiotensin–aldosterone system has been implicated as a contributing pathway

  • Longitudinal studies are needed to examine whether treatment of glomerular hyperfiltration will slow the progression of chronic kidney disease; this research requires uniform, pathophysiologically based definitions of glomerular hyperfiltration

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Figure 1: Mechanisms of glomerular hyperfiltration.

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Acknowledgements

I. Helal has received an International Society of Nephrology funded fellowship and support from the Laboratory of Kidney Pathology, Charles Nicolle Hospital, Tunis, Tunisia (LR00SP01, H. B. Maiz). This research was supported by the Zell Family Foundation.

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I. Helal and G. M. Fick-Brosnahan researched data to include in the manuscript. All authors contributed equally to discussion of content for the article. I. Helal, G. M. Fick-Brosnahan and R. W. Schrier wrote the manuscript and G. M. Fick-Brosnahan, B. Reed-Gitomer and R. W. Schrier reviewed and edited the manuscript before submission.

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Correspondence to Robert W. Schrier.

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R. W. Schrier has received honoraria from Otsuka Pharmaceutical. The other authors declare no competing interests.

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Helal, I., Fick-Brosnahan, G., Reed-Gitomer, B. et al. Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat Rev Nephrol 8, 293–300 (2012). https://doi.org/10.1038/nrneph.2012.19

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