updated hyperuricemia
TRANSCRIPT
الرحيم الرحمن الله بسم
علما) ( زدنى رب وقل
العظيم الله صدق
Asymptomatic hyperuricemia;
Friend or foe ?Dr. Abdallah El-Sayed AllamMSc of Physical Medicine, Rheumatology and Rehabilitation. Faculty of Medicine. Tanta University. EgyptMSK US fellowship. National Taiwan University. Taiwan
Treat or not to treat
Foe
Friend
Review
Hyperuricemia, usually defined as PUA >7 mg/dL
Hershfield MS et al 2010
Alexander So and Bernard Thorens (2010): Uric acid transport and disease, JCI. 120(6):1791–1799.
Reno-vascular or Parenchymal disease
Friend
UA accounts for approximately half of the
antioxidant properties of human plasma
Masseoud D, Rott K, Liu-Bryan R, Agudelo C. Overview of hyperuricaemia and gout. Curr Pharm Des 2005;11:4117-24.
PUA protects humans from cancer and other life-
shortening disorders.
low PUA is a cause of neurodegenerative diseases
and that raising PUA may be an effective therapy for
these disorders
Hershfield MS et al 2010
Uric acid protects cultured rat hippocampal
neuronal cells from oxidative stress, and
administration of uric acid 24 hours prior to
middle artery occlusion also attenuated brain
injury induced by acute ischemia in rats
Yu ZF et al(1998): Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo. JNR. 53:613–625
How does uric acid perform its beneficial function?
Alexander So and Bernard Thorens (2010): Uric acid transport and disease, JCI. 120(6):1791–1799.
Alexander So and Bernard Thorens (2010): Uric acid transport and disease, JCI. 120(6):1791–1799.
365Peri- and postmenopausal
Women (60.5ys)
Baseline BMD + BMIDEXA
At least 1 repeat measure on average 9.7 ys later
Annual rate of change in BMD was calculated
UA was measured at each visit
Calciotropic hormones and bone turnover markers were measured at final visit only
↑SERUM URIC ACIDANTI OXIDANT
OXIDATIVE STRESS ↓ BMD
URIC ACID ↓ OXIDATIVE STRESS ↑ BMD (NOT
FOR HIP MAY BE MECHANICAL)
↑BMI ↑ BMD
BMI IS DIRECTLY CORRELATED WITH SERUM URIC
ACID MAY BE AN EXPLANATION FOR INCREASE
SERUM URIC ACID↑ BMD
THE HIGHER THE SERUM URIC ACID THE
HIGHER CHOLESTEROLE & TRIGLYCERIDES
AND THE LOWER LDL ATHEROGENIC LIPID
PROFILE LOW BMD
Joanna Makovey et al concluded Higher serum UA
levels appear to be protective for bone loss in peri-
and postmenopausal women and this relationship is
not affected by changes in body composition
measures
Foe
Ito S et al 2012
Meek I L et al 2014
Brian F. Mandell CLEVELAND CLINIC VIRTUAL GRAND ROUNDS 2013
What is the mechanism?
Alexander So and Bernard Thorens (2010): Uric acid transport and disease, JCI. 120(6):1791–1799.
Sautin Y Y and Johnson R J (2008): URIC ACID: THE OXIDANT–ANTIOXIDANT PARADOX, Nucleosides Nucleotides Nucleic Acids; 27(6): 608–619.
Hyperuricemia
Cell
Purine
Uric Acid
SMC Proliferation
Vasoconstriction
Inflammation
Kidney
RAS
COX-2HypertensionInflammation
Renal disease progressionEndothelial dysfunction and
CVD
Tissue hypoxia
Cell deathInsulin resistance
Friend or Foe?
URIC ACID :THE OXIDANT–ANTIOXIDANT
PARADOX
OXIDANT ANTIOXIDANT
Intra cellular Plasma
Hydrophobic Hydrophilic
Adipose tissue
And LDL
Ascorbic acid
And methionine
Treat or not to treat?
Carnovale C et al 2014