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Title: Architecture-Guided Fluid Flow Directs Renal Biomineralization

Journal Article · · Scientific Reports
ORCiD logo [1];  [2];  [3];  [4];  [2];  [5];  [2];  [3];  [5]
  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

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 the 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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1490705
Journal Information:
Scientific Reports, Journal Name: Scientific Reports Vol. 8; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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