updated hyperuricemia

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