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Individualized treatment strategies for hyperuricemia informed by a semi-mechanistic exposure-response model of uric acid dynamics.
Physiol Rep
March 2018
Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Gaithersburg, MD.
To provide insight into pharmacological treatment of hyperuricemia we developed a semi-mechanistic, dynamical model of uric acid (UA) disposition in human. Our model represents the hyperuricemic state in terms of production of UA (rate, PUA), its renal filtration (glomerular filtration rate, GFR) and proximal tubular reabsorption (fractional excretion coefficient, FE). Model parameters were estimated using data from 9 Phase I studies of xanthine oxidase inhibitors (XOI) allopurinol and febuxostat and a novel uricosuric, the selective UA reabsorption inhibitor lesinurad, approved for use in combination with a XOI.
View Article and Find Full Text PDFPotential Role of Allopurinol in Preventing Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention: A Randomized Placebo-Controlled Trial.
Clin Drug Investig
September 2017
Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
Article Synopsis
- - Contrast-induced nephropathy (CIN) is a common issue during percutaneous coronary intervention (PCI) that may be affected by high uric acid levels and oxidative stress; allopurinol, which inhibits xanthine oxidase, was studied as a potential preventive treatment.
- - In a double-blind, placebo-controlled trial, elective PCI patients were given either allopurinol or placebo before the procedure, and blood tests were conducted to analyze changes in serum creatinine and cystatin-c before and after contrast exposure.
- - The study found no significant difference in CIN rates between the allopurinol and placebo groups, but the allopurinol group did show a statistically lower increase in serum cystatin-c
Changes in Kidney Function and in the Rate of Tubular Dysfunction After Tenofovir Withdrawal or Continuation in HIV-Infected Patients.
J Acquir Immune Defic Syndr
August 2016
Departments of *Infectious Diseases; †Biochemistry; and ‡Nephrology, Ramon y Cajal Hospital, Madrid, Spain.
Introduction: Longitudinal data on the changes in kidney function and tubular abnormalities in case of tenofovir disoproxil fumarate (TDF) withdrawal or continuation are scarce.
Methods: Prospective study of 228 patients receiving TDF, with 3 sequential determinations of serum creatinine, estimated glomerular filtration rate (eGFR), phosphatemia, and different urinary parameters (protein, albumin, phosphaturia, uricosuria, and glycosuria). Changes were analyzed in patients who interrupted TDF as compared to those who continued the same regimen.
Prevalence and significance of proximal renal tubular abnormalities in HIV-infected patients receiving tenofovir.
AIDS
January 2016
aDepartment of Infectious Diseases bDepartment of Biochemistry cDepartment of Nephrology, Ramon y Cajal Hospital, Madrid, Spain.
Objectives: Patients receiving tenofovir, disoproxil, fumarate (TDF) had an increased prevalence of proximal renal tubular dysfunction (PRTD), but contributing factors and its clinical significance remain controversial.
Design And Methods: Cross-sectional evaluation of different urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria) in 200 HIV-infected patients receiving TDF, 26 following TDF discontinuation, and 22 never treated with TDF, included in a prospective cohort study. PRTD was defined as two or more tubular abnormalities.
Objective: The aim of this study was to describe the lithogenic risk profile of pediatric patients with lithiasis.
Methods: We retrospectively analyzed the metabolic studies in 24-hour urine samples in 47 pediatric patients with lithiasis. Biochemical determinations were made in blood and 24-hour urine.
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