-
Vitamins and Hormones 2020In mammals, three subtypes of V-receptors have been identified in the kidney. The effects of vasopressin, a hormone synthesized in the hypothalamus, are triggered by... (Review)
Review
In mammals, three subtypes of V-receptors have been identified in the kidney. The effects of vasopressin, a hormone synthesized in the hypothalamus, are triggered by three distinct receptor isoforms: V2, V1a, and V1b. Stimulation of V2-receptors regulates urine osmotic concentration by increasing sodium reabsorption in the thick ascending limb of the loop of Henle and enhancing osmotic permeability of the epithelium cells in the collecting duct. Stimulation of V1a-receptors inhibits renal sodium reabsorption and induces natriuresis, comparable to the effect of the diuretic furosemide, in the thick ascending limb of the loop of Henle. Stimulation of V1b-receptors induces potassium secretion in the final parts of the distal segments and initial parts of the collecting ducts. In this review, we discuss the role of vasopressin and its interaction with V-receptor subtypes in natriuresis and for stabilizing the physicochemical parameters of the internal environment and water-salt homeostasis in humans. A better understanding of these systems and their regulation is necessary to facilitate identification of additional system components and mechanisms, clarify their contribution during various normal and pathological functional states, and suggest novel strategies for the development of therapeutic interventions.
Topics: Humans; Kidney; Receptors, Vasopressin; Renal Elimination; Renal Reabsorption; Sodium
PubMed: 32138950
DOI: 10.1016/bs.vh.2019.08.013 -
Nutrients Aug 2020Vitamin D is well known for its important roles in maintaining calcium homeostasis and bone mineralization via the regulation of calcium mobilization and renal...
Vitamin D is well known for its important roles in maintaining calcium homeostasis and bone mineralization via the regulation of calcium mobilization and renal reabsorption, and the intestinal absorption of both calcium and phosphorus [...].
Topics: Bone and Bones; Calcification, Physiologic; Calcium; Epigenesis, Genetic; Homeostasis; Humans; Intestinal Absorption; Nutrigenomics; Nutritional Physiological Phenomena; Receptors, Calcitriol; Renal Reabsorption; Vitamin D; Vitamin D Response Element
PubMed: 32785003
DOI: 10.3390/nu12082388 -
Frontiers in Cell and Developmental... 2023Protein reabsorption in renal proximal tubules is essential for maintaining nutrient homeostasis. Renal proximal tubule-specific gene knockout is a powerful method to...
Protein reabsorption in renal proximal tubules is essential for maintaining nutrient homeostasis. Renal proximal tubule-specific gene knockout is a powerful method to assess the function of genes involved in renal proximal tubule protein reabsorption. However, the lack of inducible renal proximal tubule-specific Cre recombinase-expressing mouse strains hinders the study of gene function in renal proximal tubules. To facilitate the functional study of genes in renal proximal tubules, we developed an knock-in mouse strain expressing a Cre recombinase-estrogen receptor fusion protein under the control of the promoter of the gene, a protein reabsorption receptor in renal proximal tubules. knock-in mice were generated using the CRISPR/Cas9 strategy, and the tissue specificity of Cre activity was investigated using the Cre/loxP reporter system. We showed that the expression pattern of CreERT2-mEGFP in mice was consistent with that of the endogenous gene. Furthermore, we showed that the Cre activity in knock-in mice was only detected in renal proximal tubules with high tamoxifen induction efficiency. As a proof-of-principle study, we demonstrated that renal proximal tubule-specific knockout of using AMN led to albumin accumulation in renal proximal tubular epithelial cells. The mouse is a powerful tool for conditional gene knockout in renal proximal tubules and should offer useful insight into the physiological function of genes expressed in renal proximal tubules.
PubMed: 37215091
DOI: 10.3389/fcell.2023.1171637 -
Comprehensive Physiology Jun 2018States of hypo- and hyperphosphatemia have deleterious consequences including rickets/osteomalacia and renal/cardiovascular disease, respectively. Therefore, the... (Review)
Review
States of hypo- and hyperphosphatemia have deleterious consequences including rickets/osteomalacia and renal/cardiovascular disease, respectively. Therefore, the maintenance of appropriate plasma levels of phosphate is an essential requirement for health. This control is executed by the collaborative action of intestine and kidney whose capacities to (re)absorb phosphate are regulated by a number of hormonal and metabolic factors, among them parathyroid hormone, fibroblast growth factor 23, 1,25(OH) vitamin D , and dietary phosphate. The molecular mechanisms responsible for the transepithelial transport of phosphate across enterocytes are only partially understood. Indeed, whereas renal reabsorption entirely relies on well-characterized active transport mechanisms of phosphate across the renal proximal epithelia, intestinal absorption proceeds via active and passive mechanisms, with the molecular identity of the passive component still unknown. The active absorption of phosphate depends mostly on the activity and expression of the sodium-dependent phosphate cotransporter NaPi-IIb (SLC34A2), which is highly regulated by many of the factors, mentioned earlier. Physiologically, the contribution of NaPi-IIb to the maintenance of phosphate balance appears to be mostly relevant during periods of low phosphate availability. Therefore, its role in individuals living in industrialized societies with high phosphate intake is probably less relevant. Importantly, small increases in plasma phosphate, even within normal range, associate with higher risk of cardiovascular disease. Therefore, therapeutic approaches to treat hyperphosphatemia, including dietary phosphate restriction and phosphate binders, aim at reducing intestinal absorption. Here we review the current state of research in the field. © 2017 American Physiological Society. Compr Physiol 8:1065-1090, 2018.
Topics: Animals; Biological Transport; Gene Expression Regulation; Homeostasis; Humans; Intestines; Phosphate Transport Proteins; Phosphates
PubMed: 29978897
DOI: 10.1002/cphy.c170024 -
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 -
Nature Reviews. Nephrology Jan 2017The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing... (Review)
Review
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (Tm) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the Tm and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, however, with new studies demonstrating that inhibition of renal glucose reabsorption reduces blood pressure, ameliorates glucotoxicity and induces haemodynamic effects that lead to improved cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. In this Review we examine the role of SGLT2 and SGLT1 in the regulation of renal glucose reabsorption in health and disease and the effect of SGLT2 inhibition on renal function, glucose homeostasis, and cardiovascular disease.
Topics: Animals; Blood Glucose; Cardiovascular Diseases; Glucose; Homeostasis; Humans; Kidney; Renal Reabsorption; Sodium-Glucose Transporter 1; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 27941935
DOI: 10.1038/nrneph.2016.170 -
Drugs Sep 2017Canagliflozin (Invokana) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2... (Review)
Review
Canagliflozin (Invokana) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2 diabetes (T2D). Canagliflozin lowers blood glucose levels independently of insulin, with the inhibition of SGLT2 reducing renal reabsorption of glucose and increasing excretion of glucose in the urine. In well-designed clinical trials, canagliflozin (as first-line monotherapy or add-on therapy to other antihyperglycaemic agents) improved glycaemic control in adults with T2D, including those of older age and/or at high cardiovascular (CV) risk, and also had beneficial effects on their bodyweight and blood pressure (BP). CV risk reduction, as well as possible renal benefits, were also seen with canagliflozin in T2D patients at high CV risk in the CANVAS Program, an integrated analysis of two large CV outcomes studies. Canagliflozin was generally well tolerated, had a low risk of hypoglycaemia and was most commonly associated with adverse events such as genital and urinary tract infections and increased urination, consistent with its mechanism of action. Although the amputation and fracture risk observed among recipients of the drug require further investigation, canagliflozin is an important option for T2D management in adults.
Topics: Blood Glucose; Canagliflozin; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Renal Reabsorption; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 28836175
DOI: 10.1007/s40265-017-0801-6 -
Physiological Reports Apr 2018Inorganic sulfate is essential for normal cellular function and its homeostasis is primarily regulated in the kidneys. However, little is known about renal sulfate...
Inorganic sulfate is essential for normal cellular function and its homeostasis is primarily regulated in the kidneys. However, little is known about renal sulfate handling in humans and particularly in populations with impaired kidney function such as renal transplant recipients (RTR). Hence, we aimed to assess sulfate reabsorption in kidney donors and RTR. Plasma and urinary sulfate were determined in 671 RTR and in 251 kidney donors. Tubular sulfate reabsorption (TSR) was defined as filtered load minus sulfate excretion and fractional sulfate reabsorption (FSR) was defined as 1-fractional excretion. Linear regression analyses were employed to explore associations of FSR with baseline parameters and to identify the determinants of FSR in RTR. Compared to kidney donors, RTR had significantly lower TSR (15.2 [11.2-19.5] vs. 20.3 [16.7-26.3] μmol/min), and lower FSR (0.56 [0.48-0.64] vs. 0.64 [0.57-0.69]) (all P < 0.001). Kidney donation reduced both TSR and FSR by circa 50% and 25% respectively (both P < 0.001). In RTR and donors, both TSR and FSR associated positively with renal function. In RTR, FSR was independently associated with urinary thiosulfate (β = -0.18; P = 0.002), growth hormone (β = 0.12; P = 0.007), the intakes of alcohol (β = -0.14; P = 0.002), methionine (β = -0.34; P < 0.001), cysteine (β = -0.41; P < 0.001), and vitamin D (β = -0.14; P = 0.009). In conclusion, TSR and FSR are lower in RTR compared to kidney donors and both associated with renal function. Additionally, FSR is determined by various dietary and metabolic factors. Future research should determine the mechanisms behind sulfate handling in humans and the prognostic value of renal sulfate reabsorption in RTR.
Topics: Adult; Aged; Cross-Sectional Studies; Female; Healthy Volunteers; Humans; Kidney; Kidney Transplantation; Male; Middle Aged; Renal Reabsorption; Sulfates; Transplant Recipients
PubMed: 29671959
DOI: 10.14814/phy2.13670 -
The Veterinary Clinics of North... Mar 2017Respiratory alkalosis, or primary hypocapnia, occurs when alveolar ventilation exceeds that required to eliminate the carbon dioxide produced by tissues. Concurrent... (Review)
Review
Respiratory alkalosis, or primary hypocapnia, occurs when alveolar ventilation exceeds that required to eliminate the carbon dioxide produced by tissues. Concurrent decreases in Paco, increases in pH, and compensatory decreases in blood HCO levels are associated with respiratory alkalosis. Respiratory alkalosis can be acute or chronic, with metabolic compensation initially consisting of cellular uptake of HCO and buffering by intracellular phosphates and proteins. Chronic respiratory alkalosis results in longer-lasting decreases in renal reabsorption of HCO; the arterial pH can approach near-normal values.
Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Algorithms; Alkalosis, Respiratory; Animals
PubMed: 27939863
DOI: 10.1016/j.cvsm.2016.10.005 -
Current Opinion in Nephrology and... Sep 2017Antenatal Bartter syndrome (aBS) is a heterogenous disease resulting from defective ion transport in the thick ascending limb of the loop of Henle. Novel insights into... (Review)
Review
PURPOSE OF REVIEW
Antenatal Bartter syndrome (aBS) is a heterogenous disease resulting from defective ion transport in the thick ascending limb of the loop of Henle. Novel insights into the pathophysiology, as well as the recent identification of a novel genetic cause of aBS, merit an update on this topic.
RECENT FINDINGS
In aBS, severe salt losing is further aggravated by defective salt sensing in the macula densa, where a reduced tubular salt concentration is perceived and glomerular filtration is increased instead of decreased. As patients with aBS come of age, there is an increased incidence of proteinuria and impaired renal function.Moreover, we recently reported a new form of aBS. Indeed, we described a series of nine families in whom pregnancies with male fetuses where complicated by acute polyhydramnios, preterm delivery and with severe but transient polyuria. We identified mutations in melanoma-associated antigen D2 in all study participants and showed, in vivo and in vitro, reduced expression of the furosemide and thiazide sensitive transporters sodium-potassium-2-chloride cotransporter and sodium chloride cotransporter, respectively.
SUMMARY
Genetic studies revealed the complexity of ion transport in the thick ascending limb of the loop of Henle and will help to clarify the pathophysiology, which is essential to design new therapies.
Topics: Adaptor Proteins, Signal Transducing; Antigens, Neoplasm; Bartter Syndrome; Female; Fetal Diseases; Humans; Male; Mutation; Polyhydramnios; Polyuria; Pregnancy; Premature Birth; Renal Reabsorption; Sodium Chloride; Sodium Chloride Symporters; Sodium-Potassium-Chloride Symporters
PubMed: 28598867
DOI: 10.1097/MNH.0000000000000346