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International Journal of Molecular... Apr 2024To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This... (Review)
Review
To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in phosphate and composition of the renal filtrate and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long-held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully, this will raise questions and stimulate new ideas for further research.
Topics: Humans; Phosphates; Animals; Renal Reabsorption; Kidney; Kidney Tubules, Proximal
PubMed: 38731904
DOI: 10.3390/ijms25094684 -
Matrix Biology : Journal of the... Jun 2024Proteinuria, the presence of high molecular weight proteins in the urine, is a primary indicator of chronic kidney disease. Proteinuria results from increased molecular...
Proteinuria, the presence of high molecular weight proteins in the urine, is a primary indicator of chronic kidney disease. Proteinuria results from increased molecular permeability of the glomerular filtration barrier combined with saturation or defects in tubular protein reabsorption. Any solute that passes into the glomerular filtrate traverses the glomerular endothelium, the glomerular basement membrane, and the podocyte slit diaphragm. Damage to any layer of the filter has reciprocal effects on other layers to increase glomerular permeability. The GBM is thought to act as a compressible ultrafilter that has increased molecular selectivity with increased pressure due to compression that reduced the porosity of the GBM with increased pressure. In multiple forms of chronic kidney disease, crosslinking enzymes are upregulated and may act to increase GBM stiffness. Here we show that enzymatically crosslinking porcine GBM with transglutaminase increases the stiffness of the GBM and mitigates pressure-dependent reductions in molecular sieving coefficient. This was modeled mathematically using a modified membrane transport model accounting for GBM compression. Changes in the mechanical properties of the GBM may contribute to proteinuria through pressure-dependent effects on GBM porosity.
Topics: Animals; Transglutaminases; Glomerular Basement Membrane; Swine; Proteinuria; Pressure; Podocytes; Renal Insufficiency, Chronic; Humans; Porosity
PubMed: 38723871
DOI: 10.1016/j.matbio.2024.05.002 -
American Journal of Physiology. Renal... Jul 2024Pregnancy is associated with elevated demand of most nutrients, with many trace elements and minerals critical for the development of fetus. In particular, calcium (Ca)...
Pregnancy is associated with elevated demand of most nutrients, with many trace elements and minerals critical for the development of fetus. In particular, calcium (Ca) and magnesium (Mg) are essential for cellular function, and their deficiency can lead to impaired fetal growth. A key contributor to the homeostasis of these ions is the kidney, which in a pregnant rat undergoes major changes in morphology, hemodynamics, and molecular structure. The goal of this study is to unravel the functional implications of these pregnancy-induced changes in renal handling of Ca and Mg, two cations that are essential in a healthy pregnancy. To achieve that goal, we developed computational models of electrolyte and water transport along the nephrons of a rat in mid and late pregnancy. Model simulations reveal a substantial increase in the reabsorption of Mg along the proximal tubules and thick ascending limbs. In contrast, the reabsorption of Ca is increased in the proximal tubules but decreased in the thick ascending limbs, due to the lower transepithelial concentration gradient of Ca along the latter. Despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of Ca and Mg in pregnancy. Furthermore, we conducted simulations of hypocalcemia and hypomagnesemia. We found that hypocalcemia lowers Ca excretion substantially more than Mg excretion, with this effect being more pronounced in virgin rats than in pregnant ones. Conversely, hypomagnesemia reduces the excretion of Mg and Ca to more similar degrees. These differences can be explained by the greater sensitivity of the calcium-sensing receptor (CaSR) to Ca compared with Mg. A growing fetus' demands of minerals, notably calcium and magnesium, necessitate adaptations in pregnancy. In particular, the kidney undergoes major changes in morphology, hemodynamics, and molecular structure. This computational modeling study provides insights into how these pregnancy-induced renal adaptation impact calcium and magnesium transport along different nephron segments. Model simulations indicate that, despite the enhanced transport capacity, the marked increase in glomerular filtration rate results in elevated urinary excretions of calcium and magnesium in pregnancy.
Topics: Female; Pregnancy; Animals; Magnesium; Calcium; Kidney; Glomerular Filtration Rate; Rats; Computer Simulation; Renal Reabsorption; Models, Biological
PubMed: 38721663
DOI: 10.1152/ajprenal.00001.2024 -
Chemosphere Jul 2024Per- and polyfluoroalkyl substances (PFAS) are a large class of stable toxic chemicals which have ended up in the environment and in organisms in significant...
Per- and polyfluoroalkyl substances (PFAS) are a large class of stable toxic chemicals which have ended up in the environment and in organisms in significant concentrations. Toxicokinetic models are needed to facilitate extrapolation of bioaccumulation data across PFAS congeners and species. For the present study, we carried out an inventory of accumulation processes specific for PFAS, deviating from traditional Persistent Organic Pollutants (POPs). In addition, we reviewed toxicokinetic models on PFAS reported in literature, classifying them according to the number of compartments distinguished as a one-compartment model (1-CM), two-compartment model (2- CM) or a multi-compartment model, (multi-CM) as well as the accumulation processes included and the parameters used. As the inventory showed that simple 1-CMs were lacking, we developed a generic 1-CM of ourselves to include PFAS specific processes and validated the model for legacy perfluoroalkyl acids. Predicted summed elimination constants were accurate for long carbon chains (>C6), indicating that the model properly represented toxicokinetic processes for most congeners. Results for urinary elimination rate constants were mixed, which might be caused by the exclusion of reabsorption processes (renal reabsorption, enterohepatic circulation). The 1-CM needs to be improved further in order to better predict individual elimination pathways. Besides that, more data on PFAS-transporter specific processes are needed to extrapolate across PFAS congeners and species.
Topics: Fluorocarbons; Humans; Bioaccumulation; Toxicokinetics; Persistent Organic Pollutants; Environmental Monitoring; Environmental Pollutants; Models, Biological
PubMed: 38714250
DOI: 10.1016/j.chemosphere.2024.142253 -
Journal of Affective Disorders Aug 2024The association between magnesium status and sleep quality is unclear. The aim of this study was to determine the relationship between renal reabsorption-related...
BACKGROUND
The association between magnesium status and sleep quality is unclear. The aim of this study was to determine the relationship between renal reabsorption-related magnesium depletion score (MDS) and sleep quality.
METHODS
This study was conducted through a cross-sectional survey of adults aged ≥20 years who participated in NHANES 2005-2014. We used weighted logistic regression to examine the association between MDS and sleep quality and performed trend tests to analyze for the presence of a dose-response relationship. Subgroup analyses were performed based on various sleep outcomes and covariates.
RESULTS
A total of 20,585 participants were included in the study, with a mean age of 48.8 years and 50.7 % female. After adjusting for all covariates, we found a graded dose-response relationship between MDS and sleep trouble as well as sleep disorder. Further analyses revealed a significant positive association between MDS and sleep apnea (OR = 3.01; 95 % CI 1.37-6.62), but no association with restless legs, insomnia or insufficient sleep. In addition, subgroup analyses revealed that middle-aged, male, obese, low magnesium intake, and depressed patients were more prone to sleep trouble and sleep disorder; interestingly, MDS was positively associated with excessive sleep in subjects ≥60 years and without depression.
CONCLUSIONS
Our study found a significant association between MDS and sleep quality, particularly sleep apnea, but adequate magnesium intake may be beneficial in mitigating this association. MDS may be associated with excessive sleep in older adults, but not with insufficient sleep or insomnia.
Topics: Humans; Female; Male; Cross-Sectional Studies; Middle Aged; Magnesium Deficiency; Adult; Sleep Quality; Sleep Wake Disorders; Magnesium; Nutrition Surveys; Sleep Initiation and Maintenance Disorders; Aged; Young Adult; Sleep Apnea Syndromes
PubMed: 38703902
DOI: 10.1016/j.jad.2024.05.002 -
PeerJ 2024This review discusses the importance of homeostasis with a particular emphasis on the acid-base (AB) balance, a crucial aspect of pH regulation in living systems. Two... (Review)
Review
This review discusses the importance of homeostasis with a particular emphasis on the acid-base (AB) balance, a crucial aspect of pH regulation in living systems. Two primary organ systems correct deviations from the standard pH balance: the respiratory system gas exchange and the kidneys proton/bicarbonate secretion and reabsorption. Focusing on kidney functions, we describe the complexity of renal architecture and its challenges for experimental research. We address specific roles of different nephron segments (the proximal convoluted tubule, the loop of Henle and the distal convoluted tubule) in pH homeostasis, while explaining the physiological significance of ion exchange processes maintained by the kidneys, particularly the role of bicarbonate ions (HCO) as an essential buffer system of the body. The review will be of interest to researchers in the fields of physiology, biochemistry and molecular biology, which builds a strong foundation and critically evaluates existing studies. Our review helps identify the gaps of knowledge by thoroughly understanding the existing literature related to kidney acid-base homeostasis.
Topics: Humans; Acid-Base Equilibrium; Kidney; Homeostasis; Hydrogen-Ion Concentration; Animals; Bicarbonates
PubMed: 38699185
DOI: 10.7717/peerj.17316 -
Cureus Mar 2024Introduction Dotinurad is being developed as a selective uric acid reabsorption inhibitor. However, its effect on lowering serum uric acid (UA) levels in chronic kidney...
Introduction Dotinurad is being developed as a selective uric acid reabsorption inhibitor. However, its effect on lowering serum uric acid (UA) levels in chronic kidney disease (CKD) patients with severe renal dysfunction is unknown. Therefore, the purpose of this study was to determine the effect of dotinurad on renal function in CKD patients with an estimated glomerular filtration rate (eGFR) below 25 mL/min/1.73 m. Methods Seven patients with CKD who received dotinurad 0.5 mg to 4 mg per day were studied retrospectively. Changes in UA, eGFR, and urine protein-to-creatinine ratio (UPCR) were analyzed. The observation period was 10.9±2.1 months. Results Serum UA levels were decreased and maintained with dotinurad administration. Nevertheless, there were no improvements noted in renal function. Additionally, no serious adverse effects were identified in any of the patients throughout the observation period. Conclusion Although the sample size in this study was small, our findings demonstrate the efficacy of dotinurad in individuals with advanced CKD who have an eGFR lower than 25 mL/min/1.73 m.
PubMed: 38694413
DOI: 10.7759/cureus.57362 -
Indian Journal of Thoracic and... May 2024Bartter syndrome is a rare, renal tubulopathy caused by defective salt reabsorption in the thick ascending limb of the loop of Henle which results in salt wasting,...
Bartter syndrome is a rare, renal tubulopathy caused by defective salt reabsorption in the thick ascending limb of the loop of Henle which results in salt wasting, hypokalemia, and metabolic disturbances. The electrolyte disturbances associated with this condition can be difficult to manage in the postoperative setting, especially in patients undergoing cardiac surgery. We report a case of a 62-year-old male with a history of diabetes, hypertension, coronary artery disease, and Bartter syndrome who underwent coronary artery bypass grafting and who developed severe lactic acidemia and severe electrolyte abnormalities postoperatively. Treatment consisted of aggressive resuscitation with crystalloid and intravenous (IV) electrolyte replacement.
PubMed: 38681720
DOI: 10.1007/s12055-023-01658-6 -
Asian Journal of Urology Apr 2024Urolithiasis formation has been attributed to environmental and dietary factors. However, evidence is accumulating that genetic background can contribute to urolithiasis... (Review)
Review
OBJECTIVE
Urolithiasis formation has been attributed to environmental and dietary factors. However, evidence is accumulating that genetic background can contribute to urolithiasis formation. Advancements in the identification of monogenic causes using high-throughput sequencing technologies have shown that urolithiasis has a strong heritable component.
METHODS
This review describes monogenic factors implicated in a genetic predisposition to urolithiasis. Peer-reviewed journals were evaluated by a PubMed search until July 2023 to summarize disorders associated with monogenic traits, and discuss clinical implications of identification of patients genetically susceptible to urolithiasis formation.
RESULTS
Given that more than 80% of urolithiases cases are associated with calcium accumulation, studies have focused mainly on monogenetic contributors to hypercalciuric urolithiases, leading to the identification of receptors, channels, and transporters involved in the regulation of calcium renal tubular reabsorption. Nevertheless, available candidate genes and linkage methods have a low resolution for evaluation of the effects of genetic components versus those of environmental, dietary, and hormonal factors, and genotypes remain undetermined in the majority of urolithiasis formers.
CONCLUSION
The pathophysiology underlying urolithiasis formation is complex and multifactorial, but evidence strongly suggests the existence of numerous monogenic causes of urolithiasis in humans.
PubMed: 38680588
DOI: 10.1016/j.ajur.2023.03.004