Assessment of Urine Proteomics in Type 1 Primary Hyperoxaluria.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) and idiopathic hypercalciuria (IHC) are stone-forming diseases that may result in the formation of calcium (Ca) oxalate (Ox) stones, nephrocalcinosis, and progressive chronic kidney disease (CKD). Poorer clinical outcome in PH1 is segregated by the highest urine (Ur)-Ox (UrOx), while IHC outcomes are not predictable by UrCa. We hypothesized that differences would be found in selected Ur-protein (PRO) patterns in PH1 and IHC, compared to healthy intra-familial sibling controls (C) of PH1 patients. We also hypothesized that the PRO patterns associated with higher UrOx levels would reflect injury, inflammation, biomineralization, and abnormal tissue repair processes in PH1. METHODS: Twenty four-hour Ur samples were obtained from 3 cohorts: PH1 (n = 47); IHC (n = 35) and C (n = 13) and were analyzed using targeted platform-based multi-analyte profile immunoassays and for UrOx and UrCa by biochemical measurements. RESULTS: Known stone matrix constituents, osteopontin, calbindin, and vitronectin were lowest in PH1 (C > IHC > PH1; p < 0.05). Ur-interleukin-10; chromogranin A; epidermal growth factor (EGF); insulin-like growth factor-1 (IGF-1), and macrophage inflammatory PRO-1α (MIP-1α) were higher in PH1 > C (p = 0.03 to p < 0.05). Fetuin A; IGF-1, MIP-1α, and vascular cell adhesion molecule-1 were highest in PH1 > IHC (p < 0.001 to p = 0.005). CONCLUSION: PH1 Ur-PROs reflected overt inflammation, chemotaxis, oxidative stress, growth factors (including EGF), and pro-angiogenic and calcification regulation/inhibition compared to the C and IHC cohorts. Many of the up- and downregulated PH1-PROs found in this study are also found in CKD, acute kidney injury, stone formers, and/or stone matrices. Further data analyses may provide evidence for PH1 unique PROs or demonstrate a poorer clinical outcome.

Renal Doppler evaluation in the child with hypertension: a reasonable screening discriminator?

BACKGROUND: Hypertension is diagnosed in 1-5% of children, and 5-10% of those hypertensive children have renovascular disease. The gold standard for a diagnosis of renal artery stenosis is arteriography, and Doppler ultrasound (Doppler US) continues to be advocated as a useful screening test. OBJECTIVE: The purpose of this study was to determine the utility of Doppler US in children as a screening tool and to better define clinical features of children in whom arteriography should be performed. MATERIALS AND METHODS: This retrospective study evaluated the imaging and clinical parameters for all children who had a renal US with Doppler followed by a diagnostic arteriogram for the evaluation of hypertension during a 12-year period at a tertiary children's hospital. Sixty-two children were included. We evaluated each child's clinical parameters and placed each child into one of three categories of hypertension: mild, moderate or severe. RESULTS: Eleven of 17 kidneys with proven renal artery stenosis were detected with Doppler US (sensitivity 64%). Six children with renal artery stenosis were missed by Doppler US, four of whom had segmental artery lesions. Of the children with positive renal artery stenosis on arteriography, all but three (79%) were classified as having moderate to severe hypertension. CONCLUSION: Doppler US is a useful screening examination when evaluating children with hypertension, detecting renal artery stenosis in most affected children. The clinical risk classifications are helpful in guiding which children should proceed with arteriography regardless of the Doppler US results.