Faculty Bibliography

Hyperoxaluria is a frequent complication of inflammatory bowel diseases, ileal resection and Roux-en-Y gastric bypass and is well-known to cause nephrolithiasis and nephrocalcinosis. The associated prevalence of chronic kidney disease and end-stage kidney disease (ESKD) is less clear but may be more consequential than recognized. In this review, we highlight three cases of ESKD due to enteric hyperoxaluria following small bowel resections. We review current information on the pathophysiology, complications and treatment of this complex disease.

Oxalobacter formigenes, a member of the human colonic microbiota that plays a major role in net colonic oxalate transport and secretion, is protective against formation of calcium oxalate kidney stones. We now describe the prevalence, relative abundance and stability of O. formigenes in healthy young adults in the United States, as revealed by Human Microbiome Project (HMP) data from fecal samples from 242 healthy young adults who had 1-3 study visits. Samples underwent whole-genomic shotgun (WGS) sequencing, and/or 16S rRNA sequencing. Three datasets available from the processed sequence data were studied: WGS metagenomic analysis by alignment to reference genomes (HMSCP) or using MetaPhlAn, or QIIME analysis of the V1-3 or V3-5 16S sequences. O. formigenes was detected in fecal samples using both the WGS and 16S rRNA data. Analysis of the WGS dataset, using HMSCP, showed that 29 (31%) of 94 subjects were O. formigenes-positive while the V1-3 and V3-5 analyses were less sensitive for O. formigenes detection. When present, O. formigenes relative abundance varied over 3 log10, and was normally distributed. For 66 samples studied by all three methods, all assays agreed in 58 (88%). Of 14 subjects who were O. formigenes-positive at baseline, 13 (93%) were positive on follow-up visit, indicating the stability of colonization. O. formigenes appears to be stably present in fewer than half of healthy young USA adults and is most sensitively detected by WGS.

The exposome is the assembly and measure of all the exposures of an individual in a lifetime. An individual's exposures begin before birth and include insults from environmental and occupational sources. The associated field is called exposomics, which relies on the application of internal and external exposure assessment methods. Exposomics has not yet been thoroughly applied to the study of kidney stones although much is known about how diet and fluid intake affect nephrolithiasis. Some other novel exposures that may contribute to kidney stones are discussed including use of antibiotics, urbanization and migration to urban heat islands, and occupation. People whose school and jobs limit their access to fluids and adequate bathroom facilities may have higher prevalence of stones. Examples include athletes, teachers, heathcare workers, and cab drivers. Occupational kidney stones have received scant attention and may represent a neglected, and preventable, type of stone. An exposomic-oriented history would include a careful delineation of occupation and activities.

The prevalence of kidney stones is increasing worldwide. Various etiologies may in part explain this observation including increased prevalence of diabetes, obesity and the metabolic syndrome, increased dietary protein and salt content, and decreased dietary dairy products. We hypothesize an additional and novel potential contributor to increasing kidney stone prevalence: migration to urban settings, or urbanization, and resultant exposure of the population to the higher temperatures of urban heat islands (UHIs). Both urbanization and exposure to UHIs are worldwide, continuous trends. Because the difference in temperature between rural and urban settings is greater than the increase in temperature caused by global warming, the potential effect of urbanization on stone prevalence may be of greater magnitude. However, demonstration of a convincing link between urbanization and kidney stones is confounded by many variables simultaneously affected by migration to cities, such as changes in occupation, income, and diet. No data have yet been published supporting this proposed association. We explore the plausibility and limitations of this possible etiology of increasing kidney stone prevalence.

INTRODUCTION: The gene mutations responsible for cystinuria do not fully explain kidney stone activity, suggesting that specific proteins may serve as promoters of cystine precipitation, aggregation or epithelial adherence. In this study we assessed (1) the differences in the urinary proteins between children with cystinuria and kidney stones (CYS) and healthy controls (HC), with particular attention to the fibrosis-related proteins, and (2) the presence of diagnostic biomarkers for CYS. MATERIAL AND METHODS: We conducted a pilot study comparing individual urinary proteomes of 2 newly diagnosed children with CYS and 2 age- and gender-matched HC, using liquid chromatography-mass spectrometry. Relative protein abundance was estimated using spectral counting. Proteins of interest in both CYS and HC were selected using the following criteria: i) >/=5 spectral counts; ii) >/=2-fold difference in spectral counts; and iii)