Kidney Week 2025 Annual Meeting-Fluids and Electrolytes: Bench and Bedside

Video Transcription

Video Summary

The session covered new research on renal electrolyte handling, urine concentration, and related clinical trials. Jane Warsaw presented a new genetic tool (Prox1-CreERT2) to target the ascending thin limb (ATL) of the loop of Henle, revealing striking interdigitating “finger-like” ATL cell protrusions. Single-nucleus RNA-seq identified claudin-10B as highly enriched in ATL, localized to protrusion interfaces, and potentially mediating paracellular sodium transport. ATL-specific claudin-10 deletion disrupted protrusions and caused a urinary concentrating defect, providing direct in vivo evidence that the ATL is required for maximal urine concentration.<br /><br />A second talk revisited thiazide-induced hypocalciuria using DCT/CNT-enriched single-nucleus transcriptomics, tubular length measurements, lithium clearance to estimate distal calcium delivery, and acute gentamicin inhibition of TRPV5. Results supported a dual mechanism: thiazides increase proximal calcium reabsorption and also enhance distal calcium reabsorption in a TRPV5-dependent manner, with segment remodeling (DCT1 loss, CNT hypertrophy).<br /><br />Maria Castaneda Bueno described WNK kinase biomolecular condensates. Optogenetically induced WNK condensation increased WNK activity beyond simple concentration effects and may involve altered chloride microenvironments. In a familial hyperkalemic hypertension model, persistent “WNK bodies” correlated with failure to suppress NCC phosphorylation; hypotonic dissolution reduced NCC/SPAK phosphorylation.<br /><br />Joshua Curry reported thick ascending limb–specific Kir4.1 knockout mice showing metabolic alkalosis, polyuria, reduced NKCC2 abundance/function (blunted furosemide response), distal transporter compensation, and unexpected hypermagnesemia.<br /><br />Viola D’Ambrosio summarized “cosmic kidney disease,” integrating multi-species spaceflight and radiation datasets showing kidney remodeling, injury pathways, and nephrolithiasis signals.<br /><br />Clinically, the SALSA2 RCT found rapid intermittent D5W bolus correction for severe hypernatremia (≥155) was as safe/effective as slow infusion, with faster early correction and less total fluid. PRONATRIUS retrospective data in profound hyponatremia (≤105) linked faster correction to higher ODS risk and supported strict correction limits and DDAVP clamp use. Additional talks reviewed inpatient SGLT2 inhibitors as adjunct diuresis in acute heart failure and a human study suggesting urinary oxalate rises are associated with increased urinary citrate, potentially via transporter linkage.

Asset Subtitle

Moderator(s): Christine Klemens, Niralee Patel

Presentation(s):

Dual Regulation of Ascending Thin Limb Structure and Function - Jane Warshaw
TRPV5-Driven Distal Reabsorption Contributes to Hypocalciuria in Sodium-Chloride Cotransporter Blockade - Jessica Bahena-López
WNK Condensate Formation Drives Kinase Activation and Regulates Electrolyte Homeostasis - Maria Castañeda-Bueno
Thick Ascending Limb-Specific Kir4.1 Deletion in Mice Increases Urine Output and Induces Metabolic Alkalosis Independent of Sodium-Chloride Cotransporter (NCC) - Joshua Curry
Pathway Analysis of Cosmic Kidney Disease: Just How Bad Does Spaceflight Get? - Viola D'Ambrosio
Efficacy and Safety of Rapid Intermittent Bolus Compared with Slow Continuous Correction in Patients with Severe Hypernatremia (SALSA II Trial) - Sejoong Kim
Treatment (Rx) and Outcomes of Profound Hyponatremia - Richard Sterns
Add-On SGLT2 Inhibitors: New Era of Diuresis in Acute Heart Failure - Amer Belal
The Citrate and Oxalate Association - Megan Prochaska

Note: Continuing education credits are not being offered for this session.

Meta Tag

Date 11/6/2025

Session ID 519852

Keywords

renal electrolyte handling

urine concentrating mechanism

ascending thin limb (ATL)

Prox1-CreERT2

claudin-10B

paracellular sodium transport

thiazide-induced hypocalciuria

TRPV5

distal convoluted tubule remodeling

WNK kinase condensates

NCC/SPAK phosphorylation

Kir4.1 thick ascending limb knockout

SALSA2 hypernatremia trial