Differences in renal ammonia metabolism in male and female kidney

Harris, Autumn N.; Lee, Hyun‐Wook; Osis, Gunars; Fang, Liangjuan; Webster, Kierstin L.; Verlander, Jill W.; Weiner, I. David

doi:10.1152/ajprenal.00084.2018

Cited by 40 publications

(79 citation statements)

References 66 publications

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“…NH 4 + excretion is predicted to be 19% higher in women ( Fig. 2E), consistent with the higher ammonia excretion reported in female mice, despite similar protein intake as males [26]. Urea is reabsorbed along most nephron segments, except the descending limbs of the loops of Henle, where urea enters due to the presumed higher interstitial urea concentration ( Fig.…”

Section: Sex Differences In Segmental Transport Under Baseline Conditsupporting

confidence: 85%

Sex Differences in Solute and Water Handling in the Human Kidney: Modeling and Functional Implications

McDonough

2021

Preprint

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Besides the excretion of metabolic wastes, the kidneys regulate homeostasis of electrolytes, pH, metabolites, volume and blood pressure. Sex differences in kidney function and blood pressure have been widely described across many species. Immunoblot analysis has revealed that the kidney of a female rat is not simply a smaller version of a male kidney. Rather, male and female rat kidneys exhibit dimorphic patterns of transporter expression and salt handling, the functional implications of which have been analyzed in a series of previously published modeling studies of rat kidney function. In the present study, we extend the analysis to the human kidney: we developed sex-specific models of solute and water transport in the human kidney, and identified epithelial transport parameters, consistent with patterns found in male and female rats, that yield urine output and excretion rates consistent with known human values. The model predicts that the lower sodium hydrogen exchanger 3 (NHE3) activity in women reduces the fractional reabsorption of Na+, K+, Cl-, and water along the proximal tubule, compared to men, and that the larger load on the distal nephron can be handled by enhanced activities in key Na+ transporter such as epithelial sodium channel (ENaC) and sodium chloride cotransporter (NCC) in women. Model simulations further indicate that the larger distal transport capacity and proximal transport reserve may better prepare women for elevated demands of pregnancy and lactation. The larger distal transport capacity may also contribute to reduced efficacy of angiotensin converting enzyme inhibitors to lower blood pressure in women.

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Section: Sex Differences In Segmental Transport Under Baseline Conditsupporting

confidence: 85%

Sex Differences in Solute and Water Handling in the Human Kidney: Modeling and Functional Implications

McDonough

2021

Preprint

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“…The idea evolved, in part, from observations from different transport profiles between sexes. Males are more proximal tubule-centric with more abundant proximal tubule sodium transporters, NHE3 and Napi2a, and aquaporin-1, associated with a greater sodium reabsorptive capacity and a longer tubular length than females (14,36) . Females have a more distal-centric transport compared to males (47,27), featuring more NCC, phospho-NCC and NCC activity (47,6).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, administration of loop diuretics, which increase sodium delivery to DCT, increases NCC abundance and activity, and also increase the length and volume of the DCT (2,8,15). Because female rodents have shorter proximal tubules with less sodium reabsorbing transporters compared to males, enhanced distal sodium delivery may stimulate a similar DCT adaptation (47,14,27). Here, we combine optical clearing methods, antibody labeling and 3D microscopy with volumetric imaging tools to explore potential sexual dimorphism of the DCT in the basal state, and in response to remodeling stimuli.…”

Section: Introductionmentioning

confidence: 99%

Distal convoluted tubule sexual dimorphism revealed by advanced 3D imaging

Tahaei

Coleman

Ellison

et al. 2020

American Journal of Physiology-Renal Physiology

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The thiazide-sensitive sodium chloride cotransporter (NCC) is more abundant in kidneys of females than of males. Because morphological remodeling of the distal convoluted tubule (DCT) is dependent on NCC activity, it has been generally assumed that there is a corresponding sexual dimorphism in the structure of the DCT, leading to a larger female DCT. Until now, this has never been directly examined. Here, optical clearing techniques were combined with antibody labeling of DCT segment markers, state-of-the-art high-speed volumetric imaging and analysis tools to visualize and quantify DCT morphology in male and female mice and study the DCT remodeling response to furosemide. We found an unexpected sex difference in the structure of the DCT. Compared to the males, females have a shorter DCT, a higher cellular density of NCC, and a greater capacity to elongate in response to loop-diuretics. Our study reveals a sexual dimorphism of the DCT. Females express a greater density of NCC transporters in a shorter structure to protect sodium balance in the face of greater basal distal sodium delivery yet have a larger reserve and structural remodeling capacity to adapt to unique physiological stresses. These observations provide insight into mechanisms that may drive sex differences in the therapeutic responses to diuretics.

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“…Another notable feature is the existence of sex differences in the metabolism of ammonia. Experiments in mice have shown that an increased level of basal NH 3 excretion in females is associated not only with differences in the proportion of proximal renal tubules compared to the kidneys of males, but also with higher expression of RhBG and RhCG (Harris et al 2018).…”

Section: General Mechanisms Underlying the Functionality Of Ammonia-cmentioning

confidence: 99%

Multifaceted ammonia transporters

et al. 2020

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Ammonia homeostasis is essential for the normal functioning of macro-and microorganisms. The change in concentration of ammonia derivatives in intracellular and extracellular environments is a marker of nitrogen metabolism imbalance. Transport of these molecules is now known to occur by both simple diffusion and special membrane-associated transporters belonging to the Amt/MEP/Rh family. This protein family is subdivided into two subfamilies: the ammonium transporter (AMT)methylammonium/ammonium permeases (MEP) and the rhesus (Rh) proteins. In this review, we systemize and generalize the long-established and some recent findings on the role of these proteins in nitrogen metabolism in general, and in the ammonia balance in particular. The similarities and differences of these systems in various living beings are discussed. The paper also focuses on the characteristics of several aspects of the classification and on the physiological importance of these proteins and their relationships to certain pathological processes. We also enumerate the prospects and unique challenges of research in this field of science. Deeper theoretical and practical research will provide a better understanding of the mechanisms underlying the structural-functional evolution of ammonia transport proteins, as well as the level of their involvement in the signaling pathways associated with the pathophysiology of nitrogen metabolism.

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Differences in renal ammonia metabolism in male and female kidney

Cited by 40 publications

References 66 publications

Sex Differences in Solute and Water Handling in the Human Kidney: Modeling and Functional Implications

Sex Differences in Solute and Water Handling in the Human Kidney: Modeling and Functional Implications

Distal convoluted tubule sexual dimorphism revealed by advanced 3D imaging

Multifaceted ammonia transporters

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