Title: Architecture-Guided Fluid Flow Directs Renal Biomineralization

Abstract

Nephrocalcinosis often begins on a calcium phosphate deposit, at the tip of the medullo-papillary complex (MPC) known as Randall’s plaque (RP). Contextualizing proximally observed biominerals within the MPC has led us to postulate a mechanobiological switch that can trigger interstitial biomineralization at the MPC tip, remote from the intratubular biominerals. Micro X-ray computed tomography scans of human MPCs correlated with transmission and scanning electron micrographs, and X-ray energy dispersive spectrometry demonstrated novel findings about anatomically-specific biominerals. An abundance of proximal intratubular biominerals were associated with emergence of distal interstitial RP. The fundamental architecture of the MPC and mineral densities at the proximal and distal locations of the MPC differed markedly. A predominance of plate-like minerals or radially oriented plate-like crystallites within spheroidal minerals in the proximal intratubular locations, and core-shell type crystallites within spheroidal minerals in distal interstitial locations were observed. Based on the MPC anatomic location of structure-specific biominerals, a biological switch within the mineral-free zone occurring between the proximal and distal locations is postulated. The “on” and “off” switch is dependent on changes in the pressure differential resulting from changes in tubule diameters; the “Venturi effect” changes the “circumferential strain” and culminates in interstitial crystal deposits in themore » distal tubule wall in response to proximal tubular obstruction. These distal interstitial mineralizations can emerge into the collecting system of the kidney linking nephrocalcinosis with nephrolithiasis.« less

Authors:

Ho, Sunita P.  ^[1];

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Chen, Ling ^[2]; Allen, Frances I. ^[3]; Hsi, Ryan S. ^[4]; Shimotake, Alex R. ^[2]; Wiener, Scott V. ^[5]; Kang, Misun ^[2]; Minor, Andrew M. ^[3]; Stoller, Marshall L. ^[5]

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+ Show Author Affiliations

1. Univ. of California, San Francisco, CA (United States). Division of Biomaterials and Bioengineering. School of Dentistry. Dept. of Urology. School of Medicine
2. Univ. of California, San Francisco, CA (United States). Division of Biomaterials and Bioengineering. School of Dentistry
3. Univ. of California, Berkeley, CA (United States). Dept. of Materials Science and Engineering; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Center for Electron Microscopy. Molecular Foundry
4. Vanderbilt Univ., Nashville, TN (United States). Dept. of Urologic Surgery. School of Medicine
5. Univ. of California, San Francisco, CA (United States). Dept. of Urology. School of Medicine

Publication Date:

Fri Sep 21 00:00:00 EDT 2018

Research Org.:

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health (NIH) (United States)

OSTI Identifier:

1490705

Grant/Contract Number:  

AC02-05CH11231; R01DE022032; S10RR026645; R21 DK109912; P20DK100863

Resource Type:

Accepted Manuscript

Journal Name:

Scientific Reports

Additional Journal Information:

Journal Volume: 8; Journal ID: ISSN 2045-2322

Publisher:

Nature Publishing Group

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; electron microscopy; kidney