Kidney Week 2025 Annual Meeting-The Far Side of the Nephron: New Insights into Basolateral Transport and Signaling

Video Transcription

Video Summary

This session highlights the “dark side of the moon” in renal physiology: basolateral transport, which receives less attention than apical mechanisms despite major roles in electrolyte, acid–base, and blood pressure regulation. Four speakers focus mainly on distal nephron biology, with one proximal tubule translational talk.<br /><br />Dr. Lisa Sattlin presents evidence that flow-induced potassium secretion (FIKS) in the cortical collecting duct depends on intercalated cells, not just principal cells. Increased tubular flow causes stretch and a biphasic intracellular calcium rise; potassium secretion is mediated by apical BK channels and requires sodium absorption and calcium. High-K diet increases apical BK expression predominantly in intercalated cells. Mechanistically, basolateral Piezo1—upregulated by high K and aldosterone—acts as a mechanosensor of wall tension. Intercalated-cell Piezo1 knockout abolishes flow-induced calcium signaling and eliminates FIKS, implicating Piezo1 upstream of sustained calcium entry (likely via TRPV4). Male knockouts show impaired K handling under load.<br /><br />Dr. Susan Wall reviews pendrin-positive (type B/non-A non-B) intercalated cells in salt balance and hypertension. Pendrin is low on normal salt but upregulated and trafficked apically during salt restriction via RAAS. Pendrin knockout mice exhibit salt wasting, volume contraction, metabolic alkalosis, hypokalemia, and lower blood pressure; overexpression causes salt-sensitive hypertension. Pendrin also secondarily stimulates ENaC, linking chloride/bicarbonate exchange to sodium reabsorption. She further shows mineralocorticoid receptor signaling can regulate pendrin even when aldosterone is low, with corticosterone increasing pendrin abundance partly by increasing pendrin-positive cell number; pendrin is required for corticosterone-induced pressor responses.<br /><br />Dr. Oleg Pochynyuk discusses basolateral CLC-K2/CLC-KB chloride channels. Whole-kidney knockout recapitulates Bartter type 3 (hypotension, low GFR, hypokalemic metabolic alkalosis). Intercalated-cell-specific knockout preserves baseline BP/GFR but still produces hypokalemic alkalosis, downregulates pendrin, and markedly upregulates ENaC activity; it also impairs chloride conservation during chloride restriction and blunts angiotensin II–dependent hypertension, supporting an underappreciated intercalated-cell role in chloride-linked BP control.<br /><br />Finally, pediatric nephrologist Dr. Martine Besso (Groningen) presents clinical data in Fanconi–Bickel syndrome (GLUT2 deficiency) causing glycogen accumulation and severe proximal tubulopathy. Based on reduced glucose influx as therapy, SGLT2 inhibition (dapagliflozin) in 8 patients markedly improved tubular losses—especially in children, allowing discontinuation of supplements, improved bicarbonate/phosphate handling, better growth and rickets, and major cost/quality-of-life benefits—with minimal side effects. Adults improved less, likely due to irreversible chronic tubular damage.

Asset Subtitle

Moderator(s): Mykola Mamenko, Manoocher Soleimani

Presentation(s):

PIEZO1 Channel Is a Critical Determinant of Flow-Induced Potassium Secretion in the Distal Nephron - Lisa Satlin
Pendrin-Positive Intercalated Cells in Renal Salt Handling and BP Control - Susan Wall
Regulation of Ion and Acid-Base Transport in the Distal Nephron by ClC-K2 and Kir4.1/5.1 Channels - Oleh Pochynyuk
SGLT2 Inhibitors Attenuate Renal Proximal Tubulopathy in Fanconi-Bickel Syndrome - Martine Besouw

Meta Tag

Date 11/7/2025

Pathway 1 Kidney Biology and Physiology

Pathway 2 Fluid, Electrolyte, and Acid-Base Disorders

Session ID 505411

Keywords

basolateral transport

distal nephron

cortical collecting duct

flow-induced potassium secretion (FIKS)

intercalated cells

BK channels

Piezo1 mechanosensor

TRPV4 calcium entry

high-potassium diet

pendrin (SLC26A4)

ENaC regulation

RAAS signaling

mineralocorticoid receptor/corticosterone

CLC-K2/CLC-KB chloride channels (Bartter type 3)

Fanconi–Bickel syndrome (GLUT2 deficiency)