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Cell Rep. 2018 Dec 4;25(10):2668-2675.e3. doi: 10.1016/j.celrep.2018.11.021.

Optical Clearing in the Kidney Reveals Potassium-Mediated Tubule Remodeling.

Author information

1
Division of Nephrology and Hypertension, Oregon Health & Science University, Portland, OR 97239, USA; Division of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Aachen 52074, Germany. Electronic address: tsaritas@ukaachen.de.
2
Division of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Aachen 52074, Germany; III. Department of Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg 20246, Germany; Department of Nephrology, Monash Health, Melbourne, VIC 3168, Australia.
3
Division of Nephrology and Hypertension, Oregon Health & Science University, Portland, OR 97239, USA.
4
Department of Physiology, University of Maryland, Baltimore, MD 21201, USA; Fondation LeDucq Transatlantic Networks of Excellence, Paris 75116, France.
5
Division of Nephrology and Hypertension, Oregon Health & Science University, Portland, OR 97239, USA; Fondation LeDucq Transatlantic Networks of Excellence, Paris 75116, France; Renal Section, Veterans Affairs Portland Health Care System, Portland, OR 97239, USA.

Abstract

Distal nephron remodeling contributes to the pathophysiology of many clinically relevant scenarios, including diuretic resistance and certain Mendelian disorders of blood pressure. However, constitutive genetic disruptions are likely to have substantial developmental effects in this segment, and whether tubule remodeling upon physiological stimuli is a normal homeostatic mechanism is not known. Since the distal nephron acts as a potassium sensor, we assessed proliferation and tubule length in three dimensions upon dietary or inducible genetic manipulation by using optical clearing of adult mouse kidneys, whole-mount immunolabeling, and advanced light microscopy. We show that dietary potassium restriction leads promptly to proliferation of various nephron segments, including the distal convoluted tubule, whereas disruption of the potassium sensor Kir4.1 causes atrophy, despite ambient hypokalemia. These results provide proof that kidney tubules adapt rapidly to diet and indicate the power of clearing approaches to assess cell number and tubule length in healthy and diseased kidney.

KEYWORDS:

AQP2; CLARITY; DCT; Kir4.1; NCC; ethyl cinnamate; hypokalemia; low-potassium diet; optical kidney clearing; tubule remodeling

PMID:
30517856
DOI:
10.1016/j.celrep.2018.11.021
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