Search

The glomerular filtration rate (GFR) is the outcome of glomerular hemodynamics, influenced by a series of parameters: renal plasma flow, resistances of afferent arterioles and efferent arterioles (EAs), hydrostatic pressures in the glomerular capillary and Bowman’s capsule, and plasma colloid osmotic pressure in the glomerular capillary. Although mathematical models have been proposed to predict the GFR at both the single-nephron level and the two-kidney system level using these parameters, mathematical equations governing glomerular filtration have not been well-established because of two major problems. First, the two-kidney system-level models are simply extended from the equations at the single-nephron level, which is inappropriate in epistemology and methodology. Second, the role of EAs in maintaining the normal GFR is underappreciated. In this article, these two problems are concretely elaborated, which collectively shows the need for a shift in epistemology toward a more holistic and evolving way of thinking, as reflected in the concept of the complex adaptive system (CAS). Then, we illustrate eight fundamental mathematical equations and four hypotheses governing glomerular hemodynamics at both the single-nephron and two-kidney levels as the theoretical foundation of glomerular hemodynamics. This illustration takes two steps. The first step is to modify the existing equations in the literature and establish a new equation within the conventional paradigm of epistemology. The second step is to formulate four hypotheses through logical reasoning from the perspective of the CAS (beyond the conventional paradigm). Finally, we apply the new equation and hypotheses to comprehensively analyze glomerular hemodynamics under different conditions and predict the GFR. By doing so, some concrete issues are eliminated. Unresolved issues are discussed from the perspective of the CAS and a desinger’s view. In summary, this article advances the theoretical study of glomerular dynamics by 1) clarifying the necessity of shifting to the CAS paradigm; 2) adding new knowledge/insights into the significant role of EAs in maintaining the normal GFR; 3) bridging the significant gap between research findings and physiology education; and 4) establishing a new and advanced foundation for physiology education.

The mechanisms responsible for glomerular hemodynamic regulation with sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney disease due to type 2 diabetes remain unclear. Therefore, we investigated changes in glomerular hemodynamic function using an animal model of type 2 diabetes, treated with an SGLT2 inhibitor alone or in combination with a renin-angiotensin-aldosterone system inhibitor using male Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats. Afferent and efferent arteriolar diameter and single-nephron glomerular filtration rate (SNGFR) were evaluated in ZDF rats measured at 0, 30, 60, 90, and 120 minutes after the administration of a SGLT2 inhibitor (luseogliflozin). Additionally, we assessed these changes under the administration of the adenosine A1 receptor (A1aR) antagonist (8-cyclopentyl-1,3-dipropylxanthine), along with coadministration of luseogliflozin and an angiotensin II receptor blocker (ARB), telmisartan. ZDF rats had significantly increased SNGFR, and afferent and efferent arteriolar diameters compared to ZL rats, indicating glomerular hyperfiltration. Administration of luseogliflozin significantly reduced afferent vasodilatation and glomerular hyperfiltration, with no impact on efferent arteriolar diameter. Urinary adenosine levels were increased significantly in the SGLT2 inhibitor group compared to the vehicle group. A1aR antagonism blocked the effect of luseogliflozin on kidney function. Co-administration of the SGLT2 inhibitor and ARB decreased the abnormal expansion of glomerular afferent arterioles, whereas the efferent arteriolar diameter was not affected. Thus, regulation of afferent arteriolar vascular tone via the A1aR pathway is associated with glomerular hyperfiltration in type 2 diabetic kidney disease., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The glomerular filtration rate (GFR) is the outcome of glomerular hemodynamics, influenced by a series of parameters: renal plasma flow, resistances of afferent arterioles and efferent arterioles (EAs), hydrostatic pressures in the glomerular capillary and Bowman's capsule, and plasma colloid osmotic pressure in the glomerular capillary. Although mathematical models have been proposed to predict the GFR at both the single-nephron level and the two-kidney system level using these parameters, mathematical equations governing glomerular filtration have not been well-established because of two major problems. First, the two-kidney system-level models are simply extended from the equations at the single-nephron level, which is inappropriate in epistemology and methodology. Second, the role of EAs in maintaining the normal GFR is underappreciated. In this article, these two problems are concretely elaborated, which collectively shows the need for a shift in epistemology toward a more holistic and evolving way of thinking, as reflected in the concept of the complex adaptive system (CAS). Then, we illustrate eight fundamental mathematical equations and four hypotheses governing glomerular hemodynamics at both the single-nephron and two-kidney levels as the theoretical foundation of glomerular hemodynamics. This illustration takes two steps. The first step is to modify the existing equations in the literature and establish a new equation within the conventional paradigm of epistemology. The second step is to formulate four hypotheses through logical reasoning from the perspective of the CAS (beyond the conventional paradigm). Finally, we apply the new equation and hypotheses to comprehensively analyze glomerular hemodynamics under different conditions and predict the GFR. By doing so, some concrete issues are eliminated. Unresolved issues are discussed from the perspective of the CAS and a desinger's view. In summary, this article advances the theoretical study of glomerular dynamics by 1) clarifying the necessity of shifting to the CAS paradigm; 2) adding new knowledge/insights into the significant role of EAs in maintaining the normal GFR; 3) bridging the significant gap between research findings and physiology education; and 4) establishing a new and advanced foundation for physiology education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kuang, Ahmetaj and Qu.)

Background: Increased renal sodium avidity is a hallmark feature of the heart failure syndrome., Summary: Increased renal sodium avidity refers to the inability of the kidneys to elicit potent natriuresis in response to sodium loading. This eventually causes congestion, which is a major contributor to hospital admissions and mortality in heart failure., Key Messages: Important novel concepts such as the renal tamponade hypothesis, accelerated nephron loss, and the role of hypochloremia, the sympathetic nervous system, inflammation, the lymphatic system, and interstitial sodium buffers are involved in the pathophysiology of renal sodium avidity. A good understanding of these concepts is crucially important with respect to treatment recommendations regarding dietary sodium restriction, fluid restriction, rapid up-titration of guideline-directed medical therapies, combination diuretic therapy, natriuresis-guided diuretic therapy, use of hypertonic saline, and ultrafiltration., (© 2024 The Author(s). Published by S. Karger AG, Basel.)