Proteomics and Kidney Stone Disease

Abstract

Kidney stone disease (nephrolithiasis) is an ancient and common affliction. It has been recognized for a long time with evidence of stone found in approximately 7,000-year-old mummies and remains a common problem worldwide, indicating ineffective prevention in the past. Precise pathogenic and molecular mechanisms of kidney stone formation are still poorly understood and should be further elucidated. Also, identification of novel therapeutic targets for better therapeutic outcome and successful prevention of the occurrence and recurrence of the stone are crucially required. One of the most promising tools for current and future biomedical research is proteomics, which has been extensively and widely applied to the nephrology field during the past 5 years. Its high-throughput capability holds a great promise also to kidney stone research. This chapter provides a brief overview of proteomic methodologies recently used for the investigation of nephrolithiasis and recent proteomic studies of nephrolithiasis are summarized.

Regulation of macromolecular modulators of urinary stone formation by reactive oxygen species: transcriptional study in an animal model of hyperoxaluria

“…All of these processes are modulated by macromolecules produced by the kidneys and/or liver. Numerous studies have been performed to identify crystallization modulators and determine their mode of action (6,43,67,72,83,84). However, regulation of the production of modulating macromolecules during stone formation is poorly understood.…”

Prospects for proteomics in kidney stone disease

“…One of the major obstacles in previous kidney stone research was that almost all of these studies were based entirely on single-angle analysis [3]. These previous studies focused mainly on either (i) identification of proteins entrapped inside stone matrix; or (ii) urinary proteome profiling to identify biomarkers for prognostic/diagnostic purpose [3].…”

“…These previous studies focused mainly on either (i) identification of proteins entrapped inside stone matrix; or (ii) urinary proteome profiling to identify biomarkers for prognostic/diagnostic purpose [3]. In such studies, proteins with changes in abundance or level were frequently the main targets.…”

“…Although identification and characterization of proteins entrapped inside the stone matrix had been widely studied, not every identified protein serves as a modulator or possesses active role(s) in kidney stone disease. They might be simply entrapped inside the stone matrix with no relevant function [3]. Therefore, conclusions should be carefully drawn from those data, which can easily be misinterpreted and misleading.…”

“…Shortly after, when the era of proteomics (defined as the comprehensive characterization of proteins present in a biological sample) began, characterizations of the set of proteins or 'proteome' derived from renal calculi, urine, and renal tubular epithelial cells had been widely done by mass spectrometry (MS)-based proteomic methods [2,3]. It is, however, undeniable that the underlying causes and pathogenic mechanisms of kidney stone disease (or nephrolithiasis) remain unclear.…”