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Glomerular hyperfiltration

Abstract

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.

Key points

  • ‘Absolute’ hyperfiltration is a supraphysiological elevation in glomerular filtration rate (GFR) that occurs when the single-nephron glomerular filtration rate (SNGFR) increases in a kidney with a normal number of functioning nephrons.

  • ‘Absolute’ hyperfiltration can occur in healthy people following consumption of a high protein meal and during pregnancy as well as in patients with obesity, diabetes mellitus or autosomal-dominant polycystic kidney disease.

  • ‘Relative’ hyperfiltration is an increase in SNGFR in the setting of a reduced number of functioning nephrons, which can result in a GFR that is within or below the normal range.

  • ‘Relative’ hyperfiltration can occur in patients with a congenitally reduced number of nephrons and in those with an acquired reduction in kidney mass as a result of surgery or kidney disease.

  • Independent of ‘absolute’ or ‘relative’ hyperfiltration, persistent increases in the SNGFR that are associated with glomerular hypertension can eventually lead to proteinuria, glomerulosclerosis and a decline in kidney function.

  • Improved understanding of the underlying mechanisms could lead to the development of novel therapeutic interventions to attenuate glomerular hyperfiltration and protect the kidney.

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Fig. 1: Changes in kidney function during feeding.
Fig. 2: Kidney function during pregnancy.
Fig. 3: Potential origins of obesity-related glomerular hyperfiltration.
Fig. 4: ‘Absolute’ glomerular hyperfiltration in diabetes mellitus.
Fig. 5: The effects of SGLT2 inhibition on ‘absolute’ glomerular hyperfiltration in diabetes mellitus.

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Acknowledgements

The authors wish to thank Kerstin Mierke (Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Italy) for her help with English language editing of the manuscript before submission.

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M.C. and N.P. researched the data for the article. M.C., N.P., P.R., A.R. and G.R. wrote the text and reviewed or edited the manuscript before submission. All authors made substantial contributions to discussions of the content.

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Correspondence to Giuseppe Remuzzi.

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Glossary

Microalbuminuria

A moderate increase in albuminuria indicating incipient nephropathy.

Macroalbuminuria

A severe increase in albuminuria characteristic of overt nephropathy.

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Cortinovis, M., Perico, N., Ruggenenti, P. et al. Glomerular hyperfiltration. Nat Rev Nephrol 18, 435–451 (2022). https://doi.org/10.1038/s41581-022-00559-y

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