Publications by authors named "Stanislav V Yuzhakov"

3 Publications

  • Page 1 of 1

Specific populations of urinary extracellular vesicles and proteins differentiate type 1 primary hyperoxaluria patients without and with nephrocalcinosis or kidney stones.

Orphanet J Rare Dis 2020 11 11;15(1):319. Epub 2020 Nov 11.

Division of Nephrology and Hypertension, College of Medicine and Science, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Primary hyperoxaluria type 1 (PH1) is associated with nephrocalcinosis (NC) and calcium oxalate (CaOx) kidney stones (KS). Populations of urinary extracellular vesicles (EVs) can reflect kidney pathology. The aim of this study was to determine whether urinary EVs carrying specific biomarkers and proteins differ among PH1 patients with NC, KS or with neither disease process.

Methods: Mayo Clinic Rare Kidney Stone Consortium bio-banked cell-free urine from male and female PH1 patients without (n = 10) and with NC (n = 6) or KS (n = 9) and an eGFR > 40 mL/min/1.73 m were studied. Urinary EVs were quantified by digital flow cytometer and results expressed as EVs/ mg creatinine. Expressions of urinary proteins were measured by customized antibody array and results expressed as relative intensity. Data were analyzed by ANCOVA adjusting for sex, and biomarkers differences were considered statistically significant among groups at a false discovery rate threshold of Q < 0.20.

Results: Total EVs and EVs from different types of glomerular and renal tubular cells (11/13 markers) were significantly (Q < 0.20) altered among PH1 patients without NC and KS, patients with NC or patients with KS alone. Three cellular adhesion/inflammatory (ICAM-1, MCP-1, and tissue factor) markers carrying EVs were statistically (Q < 0.20) different between PH1 patients groups. Three renal injury (β2-microglobulin, laminin α5, and NGAL) marker-positive urinary EVs out of 5 marker assayed were statistically (Q < 0.20) different among PH1 patients without and with NC or KS. The number of immune/inflammatory cell-derived (8 different cell markers positive) EVs were statistically (Q < 0.20) different between PH1 patients groups. EV generation markers (ANO4 and HIP1) and renal calcium/phosphate regulation or calcifying matrixvesicles markers (klotho, PiT1/2) were also statistically (Q < 0.20) different between PH1 patients groups. Only 13 (CD14, CD40, CFVII, CRP, E-cadherin, EGFR, endoglin, fetuin A, MCP-1, neprilysin, OPN, OPGN, and PDGFRβ) out of 40 proteins were significantly (Q < 0.20) different between PH1 patients without and with NC or KS.

Conclusions: These results imply activation of distinct renal tubular and interstitial cell populations and processes associated with KS and NC, and suggest specific populations of urinary EVs and proteins are potential biomarkers to assess the pathogenic mechanisms between KS versus NC among PH1 patients.
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November 2020

Long-term Recurrence Rates in Uric Acid Stone Formers With or Without Medical Management.

Urology 2019 Sep 31;131:46-52. Epub 2019 May 31.

Department of Urology, University of Florida, Gainesville, FL.

Objective: To determine if medical therapy affects long-term clinical outcomes in uric acid stone formers (UASF).

Methods: We identified 53 UASF who had complete stone clearance following stone procedure by computed tomography (CT) and had ≥1 postoperative 24-hour urine collection and a clinical follow-up ≥6 months with a surveillance CT scan. Patients were divided into "adherent to medical therapy" (compliance with potassium citrate ± allopurinol verified by computerized pharmacy data) or nonadherent groups. Primary outcomes were CT stone recurrence rate and need for surgical stone intervention.

Results: We found 28 of 53 (53%) adherent and 25 of 53 (47%) nonadherent individuals (14 declined medication, 11 intolerant). With median follow-up of 24 months, no significant differences were noted between groups in regards to stone recurrence (32%; P = .99) or in 24-hour urine pH compared to baseline or follow-up (range 5.46-5.62; P = 0.06). Adherent patients, however, had smaller CT stone recurrence sizes (6.3 ± 3.8 vs 11.8 ± 6.2 mm, P = .02), were 28% less likely to require stone surgery compared to those without therapy (P <.01), and trended toward longer time intervals without recurrence (23.1 ± 18.8 vs 10.5 ± 7.5 months, P = .10) compared to nonadherents. Study confounders included a variety of medication dosages and adherences, limited nonadherent follow-up, and small study number.

Conclusion: UASF adherent to medical therapy had smaller recurrence sizes and fewer surgical interventions vs nonadherent, highlighting the protective role of potassium citrate in UA stone disease. The comparable urine pH and stone recurrence rates between groups, however, underscore areas for improvement in future UA stone prevention strategies.
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September 2019