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Review
. 2023 Feb;46(2):299-310.
doi: 10.1038/s41440-022-01061-5. Epub 2022 Oct 12.

Nephrons, podocytes and chronic kidney disease: Strategic antihypertensive therapy for renoprotection

Kotaro Haruhara  1 , Go Kanzaki  1 , Nobuo Tsuboi  2
Affiliations
Review

Nephrons, podocytes and chronic kidney disease: Strategic antihypertensive therapy for renoprotection

Kotaro Haruhara et al. Hypertens Res. 2023 Feb.

Abstract

Chronic kidney disease (CKD) is one of the strongest risk factors for hypertension, and hypertension can exacerbate the progression of CKD. Thus, the management of CKD and antihypertensive therapy are inextricably linked. Research over the past decades has shown that the human kidney is more diverse than initially thought. Subjects with low nephron endowment are at increased risk of developing CKD and hypertension, which is consistent with the theory of the developmental origins of health and disease. Combined with other lifetime risks of CKD, hypertension may lead to a vicious cycle consisting of podocyte injury, glomerulosclerosis and further loss of nephrons. Of note, recent studies have shown that the number of nephrons correlates well with the number of podocytes, suggesting that these two components are intrinsically linked and may influence each other. Both nephrons and podocytes have no or very limited regenerative capacity and are destined to decrease throughout life. Therefore, one of the best strategies to slow the progression of CKD is to maintain the "numbers" of these essential components necessary to preserve renal function. To this end, both the achievement of an optimal blood pressure and a maximum reduction in urinary protein excretion are essential. Lifestyle modifications and antihypertensive drug therapy must be carefully individualized to address the potential diversity of the kidneys.

Keywords: Chronic kidney disease; Hypertension; Nephron; Podocyte; Salt handling.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Estimating the total nephron number in humans using the physical disector/fractionator combination. A The area of the section is estimated using point counting. B Glomeruli are counted using physical dissectors. A known fraction of the area of the sections is used for glomerular counting. Then, simple algebra is used to estimate the number of glomeruli in the whole kidney. Photographs were taken at the Department of Anatomy and Developmental Biology, Monash University
Fig. 2
Fig. 2
Vicious cycle involving nephron/podocyte loss, hypertension and chronic kidney disease. The decrease in nephron number in humans is influenced by the immaturity of kidney development due to the fetal-maternal environment and aging changes and maladaptation after birth. Podocyte loss and increased salt sensitivity lead to further nephron loss, resulting in a vicious cycle of reduced nephron numbers, hypertension, and chronic kidney disease
Fig. 3
Fig. 3
The concept of podometrics. In cases of glomerular hypertrophy due to a reduced total nephron mass, podocytes adapt by enlarging their bodies to maintain glomerular structure and filtration function. Podometrics evaluates the number, density, and volume of the “remaining” podocytes in situ in healthy and diseased glomeruli. p Podocyte, p’ Injured podocyte
See this image and copyright information in PMC

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