Hypocalcemic Tetany Transiently "Cured" by Pregnancy: A Case Report.

Hypocalcemia is an uncommon electrolyte abnormality. We evaluated a young woman with episodes of recurrent symptomatic hypocalcemia, which had started in her late teens. She was hypertensive and laboratory evaluation revealed elevated parathyroid hormone, elevated phosphate, and decreased renal phosphate excretion along with low ionized calcium levels.

The autonomic nervous system and bone health in chronic kidney disease.

Besides the well-known role of hormonal factors in mineral and bone metabolism, the sympathetic nervous system participates in this regulation by inhibiting bone formation and promoting bone resorption, primarily via β-adrenergic receptors expressed on osteoblasts. Conversely, the parasympathetic system, through cholinergic signalling, inhibits osteoclast activity, promoting bone formation and maintaining skeletal homeostasis. This review presents the role of the autonomic nervous system, with particular focus on the potential role of β-blockers, especially β1-selective blockers, in modulating bone health in people with normal kidney function and those with CKD.

Phosphorus: Chronicles of the epistemology of a vital element.

It was in the philosopher's stone quest that the alchemist Hennig Brand isolated chemiluminescent white phosphorus (P), Greek for "light bearer", from urine in 1669. By 1771 phosphorus was isolated from bone, and in 1777 it was identified by Antoine Lavoisier as a highly reactive element that exists predominantly in nature as ionic phosphate (PO) and in solution as phosphoric acid (HPO). Early 20 century studies revealed phosphorylated biomolecules as essential components of replicative nuclear material (RNA, DNA), a metabolic source of energy (ATP), and structural components of cellular membrane (phospholipid bilayer).

Kidney Stone Pathophysiology, Evaluation and Management: Core Curriculum 2023.

Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a disorder in which urinary solutes precipitate to form aggregates of crystalline material in the urinary space. The incidence of nephrolithiasis has been increasing, and the demographics have been evolving. Once viewed as a limited disease with intermittent exacerbations that are simply managed by urologists, nephrolithiasis is now recognized as a complex condition requiring thorough evaluation and multifaceted care.

Artificial intelligence-guided precision treatment of chronic kidney disease-mineral bone disorder.

Chronic kidney disease (CKD)-mineral bone disorder (MBD) is a complex clinical syndrome that begins early during CKD and evolves into one of the deadliest complications of CKD through its effects on the cardiovascular and skeletal systems. Achievement of treatment goals to decrease the risk of accelerated cardiovascular events and fractures has been challenging. We hypothesized that application of quantitative systems pharmacology (QSP) modeling combined with artificial intelligence techniques could improve the management of CKD-MBD with the goal of improving outcomes for patients with CKD.

Use of Artificial Intelligence to Identify New Mechanisms and Approaches to Therapy of Bone Disorders Associated With Chronic Kidney Disease.

Chronic kidney disease (CKD) leads to clinically severe bone loss, resulting from the deranged mineral metabolism that accompanies CKD. Each individual patient presents a unique combination of risk factors, pathologies, and complications of bone disease. The complexity of the disorder coupled with our incomplete understanding of the pathophysiology has significantly hampered the ability of nephrologists to prevent fractures, a leading comorbidity of CKD.

Development of a quantitative systems pharmacology model of chronic kidney disease: metabolic bone disorder.

Chronic kidney disease mineral bone disorder (CKD-MBD) is a virtually universal complication of kidney diseases, starting early in the course of disease and resulting in devastating clinical consequences ranging from bone fragility to accelerated atherosclerosis and early cardiovascular death. Guidelines for therapeutic goals for CKD-MBD have been published, and achievement of these guidelines is associated with improved survival. However, the incomplete understanding of CKD-MBD and the individual variability in the manifestations of CKD-MBD have made it difficult to achieve these guidelines.

Transcriptomes of Major Proximal Tubule Cell Culture Models.

Background: Cultured cell lines are widely used for research in the physiology, pathophysiology, toxicology, and pharmacology of the renal proximal tubule. The lines that are most appropriate for a given use depend upon the genes expressed. New tools for transcriptomic profiling using RNA sequencing (RNA-Seq) make it possible to catalog expressed genes in each cell line.

New roles of the Na/H exchange regulatory factor 1 scaffolding protein: a review.

Na/H exchange regulatory factor 1 (NHERF1), a member of a PDZ scaffolding protein family, was first identified as an organizer of membrane-bound protein complexes composed of hormone receptors, signal transduction pathways, and electrolyte and mineral transporters and channels. NHERF1 is involved in the regulation of Na/H exchanger 3, Na-dependent phosphate transporter 2a, and Na-K-ATPase through its ability to scaffold these transporters to the plasma membrane, allowing regulation of these protein complexes with their associated hormone receptors. Recently, NHERF1 has received increased interest in its involvement in a variety of functions, including cell structure and trafficking, tumorigenesis and tumor behavior, inflammatory responses, and tissue injury.

Sodium-hydrogen exchanger regulatory factor-1 (NHERF1) confers salt sensitivity in both male and female models of hypertension in aging.

Hypertension is a risk factor for premature death and roughly 50% of hypertensive patients are salt-sensitive. The incidence of salt-sensitive hypertension increases with age. However, the mechanisms of salt-sensitive hypertension are not well understood.

Loss of the Na/H Exchange Regulatory Factor 1 Increases Susceptibility to Cisplatin-Induced Acute Kidney Injury.

Na/H exchange regulatory cofactor (NHERF)-1, a scaffolding protein, anchors multiple membrane proteins in renal proximal tubules. Cultured proximal tubule cells deficient in Nherf1 and proximal tubules from Nherf1-deficient mice exhibit aberrant trafficking. Nherf1-deficient cells also exhibit an altered transcription pattern and worse survival.

Loss of NHERF-1 expression prevents dopamine-mediated Na-K-ATPase regulation in renal proximal tubule cells from rat models of hypertension: aged F344 rats and spontaneously hypertensive rats.

Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R).

Low dose ouabain stimulates NaK ATPase α1 subunit association with angiotensin II type 1 receptor in renal proximal tubule cells.

Our laboratory has recently demonstrated that low concentrations of ouabain increase blood pressure in rats associated with stimulation of NaK ATPase activity and activation of the Src signaling cascade in NHE1-dependent manner. Proteomic analysis of human kidney proximal tubule cells (HKC11) suggested that the Angiotensin II type 1 receptor (AT1R) as an ouabain-associating protein. We hypothesize that ouabain-induced stimulation of NaK ATPase activity is mediated through AT1R.

Protein-DNA Interactions at the Opossum Npt2a Promoter are Dependent upon NHERF-1.

Background/aims: Phosphate homeostasis is controlled by the renal reabsorption of Pi by the type IIa sodium phosphate cotransporter, Npt2a, which is localized in the proximal tubule brush border membrane. Regulation of Npt2a expression is a key control point to maintain phosphate homeostasis with most studies focused on regulating protein levels in the brush border membrane. Molecular mechanisms that control Npt2a mRNA, however, remain to be defined.

Identification of an RNA-binding protein that is phosphorylated by PTH and potentially mediates PTH-induced destabilization of Npt2a mRNA.

Parathyroid hormone (PTH) is a key regulator of the expression and function of the type IIa sodium-phosphate cotransporter (Npt2a), the protein responsible for regulated renal phosphate reabsorption. We previously showed that PTH induces rapid decay of Npt2a mRNA through posttranscriptional mechanisms. We hypothesized that PTH-induced changes in RNA-binding protein (RBP) activity mediate the degradation of Npt2a mRNA.

Role of Na+/H+ exchanger regulatory factor 1 in forward trafficking of the type IIa Na+-Pi cotransporter.

Na+/H+ exchanger regulatory factor (NHERF1) plays a critical role in the renal transport of phosphate by binding to Na+-Pi cotransporter (NpT2a) in the proximal tubule. While the association between NpT2a and NHERF1 in the apical membrane is known, the role of NHERF1 to regulate the trafficking of NpT2a has not been studied. To address this question, we performed cell fractionation by sucrose gradient centrifugation in opossum kidney (OK) cells placed in low-Pi medium to stimulate forward trafficking of NpT2a.

Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils.

Structural determinants for the ouabain-stimulated increase in Na-K ATPase activity.

Recent studies suggest that at low concentrations, ouabain increases Na-K ATPase and NHE1 activity and activates the Src signaling cascade in proximal tubule cells. Our laboratory demonstrated that low concentrations of ouabain increase blood pressure in rats. We hypothesize that ouabain-induced increase in blood pressure and Na-K ATPase activity requires NHE1 activity and association.

Aldosterone regulates Na(+), K(+) ATPase activity in human renal proximal tubule cells through mineralocorticoid receptor.

The mechanisms by which aldosterone increases Na(+), K(+) ATPase and sodium channel activity in cortical collecting duct and distal nephron have been extensively studied. Recent investigations demonstrate that aldosterone increases Na-H exchanger-3 (NHE-3) activity, bicarbonate transport, and H(+) ATPase in proximal tubules. However, the role of aldosterone in regulation of Na(+), K(+) ATPase in proximal tubules is unknown.

Vacuolar ATPase driven potassium transport in highly metastatic breast cancer cells.

Breast cancer is the second leading cause of death in women and thus has received a great deal of attention by researchers. Recent studies suggested decreased occurrence of cancer in patients treated with cardiac glycosides (CGs) for heart conditions. Because CGs induce their cellular effects via the Na(+), K(+) ATPase (Na-K), we treated four breast cancer cell lines (MCF-7, T47D, MDA-MB453, and MDA-MB231) and a non-cancerous breast ductal epithelial cell line (MCF-10A) with ouabain, a well-characterized CG, and measured cell proliferation by measuring bromodeoxyuridine incorporation.