Low-dose Spironolactone Combined with ACEIs/ARBs May Reduce Cardiovascular Events in Patients with CKD Stages 3b-5: A Nationwide Population-Based Cohort Study in Taiwan.

ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly prescribed for hypertension and chronic kidney disease (CKD) management, but they can increase the risk of renal function deterioration and hyperkalaemia. Spironolactone, known for reducing cardiovascular events in CKD patients, faces limited use due to the risk of hyperkalaemia. This study evaluates the potential efficacy and complications of low-dose spironolactone as an adjunct therapy in patients with CKD stages 3b to 5 who are maintained on ACEIs or ARBs.

Transport activity regulates mitochondrial bioenergetics and biogenesis in renal tubules.

Renal tubules are featured with copious mitochondria and robust transport activity. Mutations in mitochondrial genes cause congenital renal tubulopathies, and changes in transport activity affect mitochondrial morphology, suggesting mitochondrial function and transport activity are tightly coupled. Current methods of using bulk kidney tissues or cultured cells to study mitochondrial bioenergetics are limited.

Mitochondrial bioenergetics: coupling of transport to tubular mitochondrial metabolism.

Purpose Of Review: Renal tubules have robust active transport and mitochondrial metabolism, which are functionally coupled to maintain energy homeostasis. Here, I review the current literature and our recent efforts to examine mitochondrial adaptation to different transport activities in renal tubules.

Recent Findings: The advance of extracellular flux analysis (EFA) allows real-time assessments of mitochondrial respiration, glycolysis, and oxidation of energy substrates.

Transport activity regulates mitochondrial bioenergetics and biogenesis in renal tubules.

Unlabelled: Renal tubules are featured with copious mitochondria and robust transport activity. Mutations in mitochondrial genes cause congenital renal tubulopathies, and changes in transport activity affect mitochondrial morphology, suggesting mitochondrial function and transport activity are tightly coupled. Current methods of using bulk kidney tissues or cultured cells to study mitochondrial bioenergetics are limited.

WNK1 promotes water homeostasis by acting as a central osmolality sensor for arginine vasopressin release.

Maintaining internal osmolality constancy is essential for life. Release of arginine vasopressin (AVP) in response to hyperosmolality is critical. Current hypotheses for osmolality sensors in circumventricular organs (CVOs) of the brain focus on mechanosensitive membrane proteins.

Impairment in renal medulla development underlies salt wasting in Clc-k2 channel deficiency.

The prevailing view is that the ClC-Ka chloride channel (mouse Clc-k1) functions in the thin ascending limb to control urine concentration, whereas the ClC-Kb channel (mouse Clc-k2) functions in the thick ascending limb (TAL) to control salt reabsorption. Mutations of ClC-Kb cause classic Bartter syndrome, characterized by renal salt wasting, with perinatal to adolescent onset. We studied the roles of Clc-k channels in perinatal mouse kidneys using constitutive or inducible kidney-specific gene ablation and 2D and advanced 3D imaging of optically cleared kidneys.

Allele-specific RT-PCR for the rapid detection of recurrent SLC12A3 mutations for Gitelman syndrome.

Recurrent mutations in the SLC12A3 gene responsible for autosomal recessive Gitelman syndrome (GS) are frequently reported, but the exact prevalence is unknown. The rapid detection of recurrent SLC12A3 mutations may help in the early diagnosis of GS. This study was aimed to investigate the prevalence of recurrent SLC12A3 mutations in a Taiwan cohort of GS families and develop a simple and rapid method to detect recurrent SLC12A3 mutations.

WNK4 kinase: role of chloride sensing in the distal convoluted tubule.

Purpose Of Review: This review focuses on recent efforts in identifying with-no-lysine kinase 4 (WNK4) as a physiological intracellular chloride sensor and exploring regulators of intracellular chloride concentration ([Cl-]i) in the distal convoluted tubule (DCT).

Recent Findings: The discovery of WNK1's chloride-binding site provides the mechanistic details of the chloride-sensing regulation of WNK kinases. The subsequent in-vitro studies reveal that the chloride sensitivities of WNK kinases were variable.

WNK4 kinase is a physiological intracellular chloride sensor.

With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity.

Generation and analysis of a mouse model of pseudohypoaldosteronism type II caused by KLHL3 mutation in BTB domain.

The Kelch-like 3 ( KLHL3) mutations contributed to the most common causative genes in patients with pseudohypoaldosteronism type II (PHAII); however, the molecular mechanisms of PHAII-causing mutations in BTB domain of KLHL3 in vivo have not been investigated. We generated and analyzed Klhl3 knock-in (KI) mice carrying a missense M131V mutation in the BTB domain (corresponding to human KLHL3 M78V mutation). Klhl3 KI mice exhibited typical PHAII phenotype with an exaggerated diuretic response to hydrochlorothiazide.

Development of Novel Hearing Aids by Using Image Recognition Technology.

Speech is easily affected by different background noise in real environment to reduce the speech intelligibility, in particular, for hearing impaired listeners. In order to improve the above issue, several hearing aids have been developed to enhance the speech signal in noisy environment. Most of current hearing aids were designed to enhance the component of speech and suppress the component of noise.

Functional Analysis of VDR Gene Mutation R343H in A Child with Vitamin D-Resistant Rickets with Alopecia.

The functional study of different mutations on vitamin D receptor (VDR) gene causing hereditary vitamin D-resistant rickets (HVDRR) remains limited. This study was to determine the VDR mutation and the mechanisms of this mutation-causing phenotype in a family with HVDRR and alopecia. Phenotype was analyzed, and in vitro functional studies were performed.

Functional severity of CLCNKB mutations correlates with phenotypes in patients with classic Bartter's syndrome.

Key Points: The highly variable phenotypes observed in patients with classic Bartter's syndrome (BS) remain unsatisfactorily explained. The wide spectrum of functional severity of CLCNKB mutations may contribute to the phenotypic variability, and the genotype-phenotype association has not been established. Low-level expression of the human ClC-Kb channel in mammalian cells impedes the functional study of CLCNKB mutations, and the underlying cause is still unclear.

Identification of the Causes for Chronic Hypokalemia: Importance of Urinary Sodium and Chloride Excretion.

Background: Uncovering the correct diagnosis of chronic hypokalemia with potassium (K) wasting from the kidneys or gut can be fraught with challenges. We identified clinical and laboratory parameters helpful for differentiating the causes of chronic hypokalemia.

Methods: Normotensive patients referred to our tertiary academic medical center for the evaluation of chronic hypokalemia were prospectively enrolled over 5 years.

Novel susceptibility gene for nonfamilial hypokalemic periodic paralysis.

Objective: To identify susceptibility genes to nonfamilial hypokalemic periodic paralysis (hypoKPP) consisting of thyrotoxic periodic paralysis (TPP) and sporadic periodic paralysis (SPP) and explore the potential pathogenic mechanisms.

Methods: We enrolled patients with nonfamilial hypoKPP not carrying mutations in CACNA1S, SCN4A, KCNJ18, or KCNJ2 and conducted genome-wide association analyses comparing 77 patients with TPP and 32 patients with SPP with 1,730 controls in a Han Chinese population in Taiwan. Replication was performed using an independent Han Chinese cohort of 50 patients with TPP, 22 patients with SPP, and 376 controls.

Use of single-negative material as a tunable defect in a dielectric photonic crystal heterostructure.

The defect mode in a photonic crystal heterostructure of (1/2) N (2/1)N tuned by using a single-negative layer as a defect layer; that is, the structure to be considered is (1/2)ND (2/1)N, where 1, 2 are dielectrics, N is the stack number, and D is a defect layer taken to be a single-negative material. The results show that when D is a mu-negative (μ < 0) medium, the defect mode frequency is redshifted as a function of the thickness of D as well as the static permittivity. On the other hand, if D is an epsilon-negative (ε < 0) medium, the defect mode frequency is blueshifted as the defect layer thickness increases, but it is independent of the static permeability.

Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway.

The mechanism by which chronic metabolic acidosis (CMA) regulates sodium (Na(+))-chloride (Cl(-)) cotransporter (NCC) in the renal distal convoluted tubules remains unexplored. We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA. CMA was induced by NH4Cl in wild type mice (WTA mice), SPAK, and WNK4 knockout mice.

Evaluating Hyponatremia in Non-Diabetic Uremic Patients on Peritoneal Dialysis.

Unlabelled: ♦

Background: An approach to hyponatremia in uremic patients on peritoneal dialysis (PD) necessitates the assessment of intracellular fluid volume (ICV) and extracellular volume (ECV). The aim of the study was to evaluate the association of plasma sodium (Na(+)) concentration and body fluid composition and identify the causes of hyponatremia in non-diabetic PD patients. ♦

Methods: Sixty non-diabetic uremic patients on PD were enrolled.

A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter.

Mammalian with-no-lysine [K] (WNK) kinases are a family of four serine-threonine protein kinases, WNK1-4. Mutations of WNK1 and WNK4 in humans cause pseudohypoaldosteronism type II (PHA2), an autosomal-dominant disease characterized by hypertension and hyperkalemia. Increased Na(+) reabsorption through Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule plays an important role in the pathogenesis of hypertension in patients with PHA2.

STE20/SPS1-related proline/alanine-rich kinase (SPAK) is critical for sodium reabsorption in isolated, perfused thick ascending limb.

SPAK [STE20 (sterile 20)/SPS1-related proline/alanine-rich kinase] kinase consists of a full-length (FL-) and an alternatively spliced kidney-specific (KS-) isoform. SPAK regulates the NaCl cotransporter (NCC) in the distal convoluted tubule (DCT). The relative abundance and role of FL- vs.

Etiologic and therapeutic analysis in patients with hypokalemic nonperiodic paralysis.

Background: Hypokalemic nonperiodic paralysis represents a group of heterogeneous disorders with a large potassium (K(+)) deficit. Rapid diagnosis of curable causes with appropriate treatment is challenging to avoid the sequelae of hypokalemia. We prospectively analyzed the etiologies and therapeutic characteristics of hypokalemic nonperiodic paralysis.