4.6 Review

Glomerular hyperfiltration

Journal

NATURE REVIEWS NEPHROLOGY
Volume 18, Issue 7, Pages 435-451

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41581-022-00559-y

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Glomerular hyperfiltration can be categorized as 'absolute' hyperfiltration and 'relative' hyperfiltration. 'Absolute' hyperfiltration occurs in the context of a normal number of functioning nephrons and can be seen in high protein intake, pregnancy, diabetes, obesity, or polycystic kidney disease. 'Relative' hyperfiltration occurs when the number of functioning nephrons is reduced and can be seen in patients with a congenitally reduced nephron number or acquired reduction in nephron mass due to surgery or kidney disease.
Circulating blood is filtered across the glomerular barrier to form an ultrafiltrate of plasma in the Bowman's space. The volume of glomerular filtration adjusted by time is defined as the glomerular filtration rate (GFR), and the total GFR is the sum of all single-nephron GFRs. Thus, when the single-nephron GFR is increased in the context of a normal number of functioning nephrons, single glomerular hyperfiltration results in 'absolute' hyperfiltration in the kidney. 'Absolute' hyperfiltration can occur in healthy people after high protein intake, during pregnancy and in patients with diabetes, obesity or autosomal-dominant polycystic kidney disease. When the number of functioning nephrons is reduced, single-nephron glomerular hyperfiltration can result in a GFR that is within or below the normal range. This 'relative' hyperfiltration can occur in patients with a congenitally reduced nephron number or with an acquired reduction in nephron mass consequent to surgery or kidney disease. Improved understanding of the mechanisms that underlie 'absolute' and 'relative' glomerular hyperfiltration in different clinical settings, and of whether and how the single-nephron haemodynamic and related biomechanical forces that underlie glomerular hyperfiltration promote glomerular injury, will pave the way toward the development of novel therapeutic interventions that attenuate glomerular hyperfiltration and potentially prevent or limit consequent progressive kidney injury and loss of function.

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