Characterization of the Protein Components of Matrix Stones Sheds Light on S100-A8 and S100-A9 Relevance in the Inflammatory Pathogenesis of These Rare Renal Calculi.
OBJECTIVE
Among the different types of kidney stones, matrix stones are uncommon urinary calculi composed of a soft, pliable, amorphous substance with little crystalline content. To gain insight into the pathogenesis we investigated the protein component by analyzing the proteomic profiles of surgically removed matrix stones.


METHODS
A total of 5 stones were harvested from 4 patients who underwent surgery for medical reasons at 3 clinical centers during a 7-year period. Matrix stone proteome characterization was performed by mass spectrometry based techniques using an integrated top-down/bottom-up proteomic platform.


RESULTS
We identified 142 nonredundant proteins and peptides across all samples. Neutrophil defensin 1, and proteins S100-A8 and S100-A9 were the main components of these renal calculi.


CONCLUSIONS
The abundance of identified inflammatory molecules points to an inflammatory process as the event that initializes soft calculi formation rather than as a consequence of such formation. The post-translational oxidative changes in S100-A8 and A9, and the presence of thymosin β-4, granulins and ubiquitin also suggest the intervention of host defenses through a superimposed, vigorous counter inflammatory process. The post-translational changes seen in the proteins and peptides, and the known self-assembling capability of S100-A8 and S100-A9 probably explain the gelatinous consistency of these stones.
Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy.
Claudia
C
Martelli
Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy.
Valeria
V
Marzano
Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy.
Federica
F
Iavarone
Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy.
Liling
L
Huang
Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy.
Federica
F
Vincenzoni
Institute of Chemistry of Molecular Recognition, Italian National Research Council, Rome, Italy.
Claudia
C
Desiderio
Department of Life and Environmental Sciences, Cagliari University, Cagliari, Italy.
Irene
I
Messana
Urology Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
Paolo
P
Beltrami
Urology Clinic, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
Filiberto
F
Zattoni
Nephrology Division, Institute of Internal Medicine, Catholic University, Rome, Italy.
Pietro Manuel
PM
Ferraro
U-merge (Urology in Emerging Countries), London, United Kingdom.
Noor
N
Buchholz
Pathology Division, Department of Surgery, Cagliari University, Cagliari, Italy.
Giorgia
G
Locci
Pathology Division, Department of Surgery, Cagliari University, Cagliari, Italy.
Gavino
G
Faa
Institute of Biochemistry and Clinical Biochemistry, Catholic University, Rome, Italy; Institute of Chemistry of Molecular Recognition, Italian National Research Council, Rome, Italy.
Massimo
M
Castagnola
Nephrology Division, Institute of Internal Medicine, Catholic University, Rome, Italy. Electronic address: giovanni.gambaro@unicatt.it.
Giovanni
G
Gambaro
D040501:Calgranulin A / Q000378:metabolism*; D040502:Calgranulin B / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D012189:Retrospective Studies; D013997:Time Factors; D014545:Urinary Calculi / Q000737:chemistry*
D040501:Calgranulin A; D040502:Calgranulin B
inflammation; kidney calculi; proteomics