Nucleation and Growth of Calcium Oxalate Kidney Stones (Urolithiasis)

This is my 3rd Kidney stone

The aim of this project is to prevent my 4th. In this it has failed miserably so we just changed the goals (prevent the 8th!)

Kidney stones, like other biominerals, are a combination of a mineral phase (in this case calcium oxalate either in the monohydrate or dihydrate form) and an organic matrix phase. The fundamental reasons why stones form and why some people will form multiple stones while others are unaffected by this painful condition are still unknown. In collaboration with Prof George Drach, former head of Urology at University of Arizona Medical School, we used atomic force microscopy (AFM) and low voltage scanning electron microscopy (SEM) to study the microstructure of human calcium oxalate urinary stones. We showed that Calcium Oxalate stones are aggregates of crystallites whose size varies between 50nm and 3000nm.

"Evidence for Aggregation in Oxalate Stone Formation: Atomic Force and Low Voltage Scanning Electron Microscopy", H.H. Dorian, P. Rez and G.W. Drach, J. Urol., 1996, 156, 1833-1837.

Later work definitively identified the facets of the crystallites

“Morphology of crystals in calcium oxalate kidney stones”, S. Sandersius and P. Rez, Urol. Res. 35, (2007),287-293

Presumably organic matrix fills the space between the crystallites. Does it bind the crystallites together? Is it protein? phospholipid?

Many think that Negatively charged amino acids (deprotonated aspartic and glutamatic acid) bind Calcium. Will this work? We did some simple modeling of protein interaction with Calcium Oxalate surfaces using structures form PDB

“Models for protein binding to calcium oxalate surfaces”, A. Gul and P. Rez, Urol. Res. 35, (2007), 63-71.

For the proteins we investigated there were no more than 3 -4 possible contacts irrespective of crystal surface

In collaboration with Prof Pupa Gilbert (U Wisconsin, Madison) we are now using X-ray photoelectron emission microscopy (XPEEM) to map protein and phospholipids between crystalline features

Amorphous Calcium Carbonate

In collaboration with Profs Steve Weiner, Prof Lia Addadi and Yael Politi (Weizmann Institute, Rehovot, Israel) , Prof Pupa Gilbert (University of Wisconsin, Madison)

Calcium Carbonate forms the hard shells of molluscs, brachiopods, and crustaceans. In many cases an amorphous phase is a precursor to the final calcite phase. What is the structure of this amorphous phase? How does it transform to the crystalline phase? What are the thermodynamics?

Synchrotron studies have shown that the Ca L edge changes between calcite and aragonite. ACC is somewhere in between.

We have shown using multiplet codes that a small tetgragonal distortion in the Ca environment is sufficient to explain the changes.

We are using DFT codes (link to that page) to see whether substitution of Ca by Mg or intercalation of water could bring about amorphous disorder

When randomly substituting Mg for Ca the main effect is to change the orientation of the carbonate groups. This is consistent with the observed changes in IR spectra

(with undergraduates Dov Greenberg and Alex Blackwell)