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Comprehensive Physiology Apr 2014In the kidney, both anions, phosphate and sulfate, are almost freely filtered and afterwards reclaimed (reabsorbed) to a large extent from tubular fluid along the... (Review)
Review
In the kidney, both anions, phosphate and sulfate, are almost freely filtered and afterwards reclaimed (reabsorbed) to a large extent from tubular fluid along the proximal tubules. Under normal dietary conditions, fractional excretion of these anions is approximately 10%. Reabsorption of both anions occurs along the proximal tubules by active, saturable, and regulated transepithelial processes. Most of the transporters involved in renal handling of phosphate and sulfate have been identified and their transport functions as well as their cellular localizations have been described in detail. The role of these transporters in the renal handling of phosphate and sulfate has been investigated by the use of several mice knock out models and also by analysis of several inherited human diseases. Numerous hormonal and nonhormonal factors, have been described that alter renal excretion of phosphate or sulfate by mechanisms that alter the abundance of known phosphate/sulfate transporters and consequently renal excretion. These mechanisms contribute to the homeostasis of the extracellular concentrations of phosphate and sulfate.
Topics: Animals; Homeostasis; Humans; Kidney; Phosphates; Renal Reabsorption; Sulfates
PubMed: 24715567
DOI: 10.1002/cphy.c120031 -
International Journal of Molecular... Dec 2019The renal collecting duct fine-tunes urinary composition, and thereby, coordinates key physiological processes, such as volume/blood pressure regulation,... (Review)
Review
The renal collecting duct fine-tunes urinary composition, and thereby, coordinates key physiological processes, such as volume/blood pressure regulation, electrolyte-free water reabsorption, and acid-base homeostasis. The collecting duct epithelium is comprised of a tight epithelial barrier resulting in a strict separation of intraluminal urine and the interstitium. Tight junctions are key players in enforcing this barrier and in regulating paracellular transport of solutes across the epithelium. The features of tight junctions across different epithelia are strongly determined by their molecular composition. Claudins are particularly important structural components of tight junctions because they confer barrier and transport properties. In the collecting duct, a specific set of claudins (Cldn-3, Cldn-4, Cldn-7, Cldn-8) is expressed, and each of these claudins has been implicated in mediating aspects of the specific properties of its tight junction. The functional disruption of individual claudins or of the overall barrier function results in defects of blood pressure and water homeostasis. In this concise review, we provide an overview of the current knowledge on the role of the collecting duct epithelial barrier and of claudins in collecting duct function and pathophysiology.
Topics: Animals; Claudins; Epithelial Cells; Humans; Ion Transport; Kidney Tubules, Collecting; Renal Reabsorption
PubMed: 31905642
DOI: 10.3390/ijms21010221 -
Life Sciences Oct 2012Endothelin-1 (ET-1) is a multifunctional hormone which regulates the physiology of the cardiovascular and renal systems. ET-1 modulates cardiac contractility, systemic... (Review)
Review
Endothelin-1 (ET-1) is a multifunctional hormone which regulates the physiology of the cardiovascular and renal systems. ET-1 modulates cardiac contractility, systemic and renal vascular resistance, salt and water renal reabsorption, and glomerular function. ET-1 is responsible for a variety of cellular events: contraction, proliferation, apoptosis, etc. These effects take place after the activation of the two endothelin receptors ET(A) and ET(B), which are present - among others - on cardiomyocytes, fibroblasts, smooth muscle and endothelial cells, glomerular and tubular cells of the kidney. The complex and numerous intracellular pathways, which can be contradictory in term of functional response depending on the receptor type, cell type and physiological situation, are described in this review. Many diseases share an enhanced ET-1 expression as part of the pathophysiology. However, the use of endothelin blockers is currently restricted to pulmonary arterial hypertension, and more recently to digital ulcer. The complexity of the endothelin system does not facilitate the translation of the molecular knowledge to clinical applications. Endothelin antagonists can prevent disease development but secondary undesirable effects limit their usage. Nevertheless, the increasing understanding of the effects of ET-1 on the cardiac and renal physiology maintains the endothelin system as a promising therapeutic target.
Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Endothelin-1; Endothelins; Humans; Kidney; Kidney Diseases; Receptor, Endothelin A; Receptor, Endothelin B
PubMed: 22480517
DOI: 10.1016/j.lfs.2012.03.026 -
Pediatric Nephrology (Berlin, Germany) Jul 2017Magnesium is essential to the proper functioning of numerous cellular processes. Magnesium ion (Mg) deficits, as reflected in hypomagnesemia, can cause neuromuscular... (Review)
Review
Magnesium is essential to the proper functioning of numerous cellular processes. Magnesium ion (Mg) deficits, as reflected in hypomagnesemia, can cause neuromuscular irritability, seizures and cardiac arrhythmias. With normal Mg intake, homeostasis is maintained primarily through the regulated reabsorption of Mg by the thick ascending limb of Henle's loop and distal convoluted tubule of the kidney. Inadequate reabsorption results in renal Mg wasting, as evidenced by an inappropriately high fractional Mg excretion. Familial renal Mg wasting is suggestive of a genetic cause, and subsequent studies in these hypomagnesemic families have revealed over a dozen genes directly or indirectly involved in Mg transport. Those can be classified into four groups: hypercalciuric hypomagnesemias (encompassing mutations in CLDN16, CLDN19, CASR, CLCNKB), Gitelman-like hypomagnesemias (CLCNKB, SLC12A3, BSND, KCNJ10, FYXD2, HNF1B, PCBD1), mitochondrial hypomagnesemias (SARS2, MT-TI, Kearns-Sayre syndrome) and other hypomagnesemias (TRPM6, CNMM2, EGF, EGFR, KCNA1, FAM111A). Although identification of these genes has not yet changed treatment, which remains Mg supplementation, it has contributed enormously to our understanding of Mg transport and renal function. In this review, we discuss general mechanisms and symptoms of genetic causes of hypomagnesemia as well as the specific molecular mechanisms and clinical phenotypes associated with each syndrome.
Topics: Arrhythmias, Cardiac; Child; Epithelial Sodium Channel Blockers; Homeostasis; Humans; Hypercalciuria; Hypokalemia; Kidney Tubules, Distal; Loop of Henle; Magnesium; Magnesium Deficiency; Membrane Proteins; Mineralocorticoid Receptor Antagonists; Mitochondria; Mutation; Nephrocalcinosis; Phenotype; Recommended Dietary Allowances; Renal Elimination; Renal Reabsorption; Renal Tubular Transport, Inborn Errors; Seizures
PubMed: 27234911
DOI: 10.1007/s00467-016-3416-3 -
Pflugers Archiv : European Journal of... Mar 2015Dietary potassium (K(+)) intake has antihypertensive effects, prevents strokes, and improves cardiovascular outcomes. The underlying mechanism for these beneficial... (Review)
Review
Dietary potassium (K(+)) intake has antihypertensive effects, prevents strokes, and improves cardiovascular outcomes. The underlying mechanism for these beneficial effects of high K(+) diets may include vasodilation, enhanced urine flow, reduced renal renin release, and negative sodium (Na(+)) balance. Indeed, several studies demonstrate that dietary K(+) intake induces renal Na(+) loss despite elevated plasma aldosterone. This review briefly highlights the epidemiological and experimental evidences for the effects of dietary K(+) on arterial blood pressure. It discusses the pivotal role of the renal distal tubule for the regulation of urinary K(+) and Na(+) excretion and blood pressure and highlights that it depends on the coordinated interaction of different nephron portions, epithelial cell types, and various ion channels, transporters, and ATPases. Moreover, we discuss the relevance of aldosterone and aldosterone-independent factors in mediating the effects of an altered K(+) intake on renal K(+) and Na(+) handling. Particular focus is given to findings suggesting that an aldosterone-independent downregulation of the thiazide-sensitive NaCl cotransporter significantly contributes to the natriuretic and antihypertensive effect of a K(+)-rich diet. Last but not least, we refer to the complex signaling pathways enabling the kidney to adapt its function to the homeostatic needs in response to an altered K(+) intake. Future work will have to further address the underlying cellular and molecular mechanism and to elucidate, among others, how an altered dietary K(+) intake is sensed and how this signal is transmitted to the different epithelial cells lining the distal tubule.
Topics: Animals; Blood Pressure; Humans; Kidney; Potassium, Dietary; Renal Reabsorption; Water-Electrolyte Balance
PubMed: 25559844
DOI: 10.1007/s00424-014-1673-1 -
Frontiers in Bioscience (Landmark... Mar 2023Maintaining a balance between the supply and demand of oxygen is vital for proper organ function. Most types of acute kidney injury (AKI) are characterized by hypoxia, a... (Review)
Review
Maintaining a balance between the supply and demand of oxygen is vital for proper organ function. Most types of acute kidney injury (AKI) are characterized by hypoxia, a state where the supply of oxygen cannot match the demand for normal cellular activities. Hypoxia results from hypo perfusion and impaired microcirculation in the kidney. It inhibits mitochondrial oxidative phosphorylation, resulting in a decrease in production of adenosine triphosphate (ATP), which is essential to power tubular transport activities, especially reabsorption of Na+, and other vital cellular activities. To ameliorate AKI, the majority of studies have focused on increasing renal oxygen delivery by restoring renal blood flow and altering intra-renal hemodynamics. However, to date these approaches remain inadequate. In addition to augmenting oxygen supply, increasing renal blood flow also increases glomerular filtration rate, leading to increased solute deliver and workload for the renal tubules, causing an increase in oxygen consumption. The relationship between Na+ reabsorption and oxygen expenditure in the kidney is linear. Experimental models have demonstrated that inhibition of Na+ reabsorption can alleviate AKI. Since the proximal tubules reabsorb approximately 65% of filtered Na+, consuming the largest portion of oxygen, many studies focus on examining the effects of inhibiting Na+ reabsorption in this segment. Potential therapeutics that have been examined include acetazolamide, dopamine and its analog, inhibitors of the renin-angiotensin II system, atrial natriuretic peptide, and empagliflozin. The effectiveness of inhibition of Na+ reabsorption in the thick ascending limb of the Loop of Henle by furosemide has been also examined. While these approaches produced impressive results in animal models, their clinical benefits remain mixed. This review summarizes the progress in this area and argues that the combination of increasing oxygen supply with decreasing oxygen consumption or different approaches to reducing oxygen demand will be more efficacious.
Topics: Animals; Kidney; Acute Kidney Injury; Kidney Tubules, Proximal; Sodium; Oxygen; Hypoxia; Oxygen Consumption
PubMed: 37005768
DOI: 10.31083/j.fbl2803062 -
American Journal of Physiology. Renal... Aug 2017Salt-sensitive hypertension is associated with renal and vascular dysfunctions, which lead to impaired fluid excretion, increased cardiac output, and total peripheral... (Review)
Review
Salt-sensitive hypertension is associated with renal and vascular dysfunctions, which lead to impaired fluid excretion, increased cardiac output, and total peripheral resistance. It is commonly accepted that increased renal sodium handling and plasma volume expansion are necessary factors for the development of salt-induced hypertension. The epithelial sodium channel (ENaC) is a trimeric ion channel expressed in the distal nephron that plays a critical role in the regulation of sodium reabsorption in both normal and pathological conditions. In this mini-review, we summarize recent studies investigating the role of ENaC in the development of salt-sensitive hypertension. On the basis of experimental data obtained from the Dahl salt-sensitive rats, we and others have demonstrated that abnormal ENaC activation in response to a dietary NaCl load contributes to the development of high blood pressure in this model. The role of different humoral factors, such as the components of the renin-angiotensin-aldosterone system, members of the epidermal growth factors family, arginine vasopressin, and oxidative stress mediating the effects of dietary salt on ENaC are discussed in this review to highlight future research directions and to determine potential molecular targets for drug development.
Topics: Animals; Arginine Vasopressin; Blood Pressure; Disease Models, Animal; EGF Family of Proteins; Epithelial Cells; Epithelial Sodium Channels; Humans; Hypertension; Hypoglycemic Agents; Molecular Targeted Therapy; Nephrons; Oxidative Stress; Rats, Inbred Dahl; Renal Reabsorption; Renin-Angiotensin System; Signal Transduction; Sodium Chloride, Dietary
PubMed: 28003189
DOI: 10.1152/ajprenal.00427.2016 -
Comprehensive Physiology Dec 2015Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes.... (Review)
Review
Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function.
Topics: Animals; Apoptosis; Arachidonate Lipoxygenases; Cytochrome P-450 Enzyme System; Hemodynamics; Humans; Kidney; Renal Reabsorption
PubMed: 26756638
DOI: 10.1002/cphy.c150009 -
American Journal of Physiology. Renal... Jun 2017Calcium (Ca) and Magnesium (Mg) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular... (Review)
Review
Calcium (Ca) and Magnesium (Mg) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca and Mg reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation-permeable pores and channels, but also for generating the necessary driving forces for Ca and Mg transport. Alterations in these molecular constituents can have profound effects on tubular Ca and Mg handling. Diuretics are used to treat a large range of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na) transport, but also indirectly affect renal Ca and Mg handling, i.e., by establishing a prerequisite electrochemical gradient. It is therefore not surprising that substantial alterations in divalent cation handling can be observed following diuretic treatment. The effects of diuretics on renal Ca and Mg handling are reviewed in the context of the present understanding of basal molecular mechanisms of Ca and Mg transport. Acetazolamide, osmotic diuretics, Na/H exchanger (NHE3) inhibitors, and antidiabetic Na/glucose cotransporter type 2 (SGLT) blocking compounds, target the proximal tubule, where paracellular Ca transport predominates. Loop diuretics and renal outer medullary K (ROMK) inhibitors block thick ascending limb transport, a segment with significant paracellular Ca and Mg transport. Thiazides target the distal convoluted tubule; however, their effect on divalent cation transport is not limited to that segment. Finally, potassium-sparing diuretics, which inhibit electrogenic Na transport at distal sites, can also affect divalent cation transport.
Topics: Animals; Biological Transport; Calcium; Diuretics; Epithelial Cells; Humans; Kidney Tubules; Magnesium; Renal Reabsorption
PubMed: 28274923
DOI: 10.1152/ajprenal.00032.2017