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Endoscopic and histologic findings in a cohort of uric acid and calcium oxalate stone formers.

ABSTRACT: To characterize the endoscopic and histologic renal papillary lesions in a cohort of uric acid (UA) stone formers (SF).Data were prospectively obtained during percutaneous nephrolithotomy between 2009 and 2013. Renal papillae were endoscopically analyzed to quantitate surface area occupied by plaque or plug, and biopsies were obtained. UA SF were compared with non-SF controls and patients with >50% calcium oxalate (CaOx) in the absence of UA.There were 23 UA SF; of which 19 stones (83%) were admixed with CaOx and 4 (17%) were pure. Compared with CaOx SF and controls, UA SF had a higher prevalence of diabetes and obesity, greater serum creatinine and UA levels, lower estimated glomerular filtration rate and urine pH, and elevated UA supersaturation. Characteristics of UA SF were compared with 95 CaOx SF and 19 controls. Overall, 23 (100%) UA SF had endoscopic plaque and 13 (57%) plugs. Endoscopically, UA SF displayed a greater incidence of plugging (57% vs 45% vs 11%; P = .006) relative to CaOx SF and controls. Likewise, UA SF had a greater percentage surface area of plugging (0.1 vs 0.0; P = .002) and plaque (2.0 vs 0.9; P = .006) than controls but similar amounts to CaOx SF. Histologic plugs were similar in UA and CaOx SF, although CaOx SF demonstrated greater interstitial inflammation on endoscopic biopsy.UA and CaOx SF have similar amounts of plaque, whereas UA SF have more endoscopic but not histologic collecting duct plugs. These data suggest an overlap between the pathogenesis of UA and CaOx stones. The anchoring site for UA stones remains uncertain.

SUBMITTER: Viers BR

PROVIDER: S-EPMC4380657 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Endoscopic and histologic findings in a cohort of uric acid and calcium oxalate stone formers.

Viers Boyd R BR Lieske John C JC Vrtiska Terri J TJ Herrera Hernandez Loren P LP Vaughan Lisa E LE Mehta Ramilia A RA Bergstralh Eric J EJ Rule Andrew D AD Holmes David R DR Krambeck Amy E AE

Urology 20150211 4

<h4>Objective</h4>To characterize the endoscopic and histologic renal papillary lesions in a cohort of uric acid (UA) stone formers (SF).<h4>Methods</h4>Data were prospectively obtained during percutaneous nephrolithotomy between 2009 and 2013. Renal papillae were endoscopically analyzed to quantitate surface area occupied by plaque or plug, and biopsies were obtained. UA SF were compared with non-SF controls and patients with >50% calcium oxalate (CaOx) in the absence of UA.<h4>Results</h4>Ther ...[more]

PMID: 25681832

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Project description:BackgroundsPrevious studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs).MethodsBiobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry.ResultsUrine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies.ConclusionsUrinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

Project description:Introduction: About 1 in 11 Americans will experience a kidney stone, but underlying causes remain obscure. The objective of the present study was to separate idiopathic calcium oxalate stone formers by whether or not they showed positive evidence of forming a stone on Randall's plaque (RP). Materials and Methods: In patients undergoing either percutaneous or ureteroscopic procedures for kidney stone removal, all stone material was extracted and analyzed using micro-CT imaging to identify those attached to RP. Twenty-four-hour urine samples were collected weeks after the stone removal procedure and patients were off of medications that would affect urine composition. The endoscopic video was analyzed for papillary pathology (RP, pitting, plugging, dilated ducts, and loss of papillary shape) by an observer blinded to the data on stone type. The percent papillary area occupied by RP and ductal plugging was quantified using image analysis software. Results: Patients having even one stone on RP (N = 36) did not differ from non-RP patients (N = 37) in age, sex, BMI, or other clinical characteristics. Compared with the non-RP group, RP stone formers had more numerous, but smaller, stones, more abundant papillary RP formation, and fewer ductal plugs, both by quantitative measurement of surface area (on average, three times more plaque area, but only 41% as much plug area as in non-RP patients) and by semiquantitative visual grading. Serum and blood values did not differ between RP and non-RP stone formers by any measure. Conclusions: Growth of many small stones on plaque seems the pathogenetic scheme for the RP stone-forming phenotype, whereas the non-RP phenotype stone pathogenesis pathway is less obvious. Higher papillary plugging in non-RP patients suggests that plugs play a role in stone formation and that these patients have a greater degree of papillary damage. Underlying mechanisms that create these distinctive phenotypes are presently unknown.

Dataset Information

Endoscopic and histologic findings in a cohort of uric acid and calcium oxalate stone formers.

Publications

Endoscopic and histologic findings in a cohort of uric acid and calcium oxalate stone formers.

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