QUẢN LÝ ĐỒNG THỜI TĂNG HUYẾT ÁP TĂNG URIC ACID MÁU trong ĐÁI THÁO ĐƯỜNG

QUẢN LÝ ĐỒNG THỜI
TĂNG HUYẾT ÁP
&
TĂNG URIC ACID MÁU
trong
ĐÁI THÁO ĐƯỜNG
•
• Prof Phạm Văn Bùi
• BV Nguyễn Tri Phương
• ĐH YK Phạm Ngọc Thạch
• GS Thỉnh giảng ĐH Liège , Belgium
• Chủ tịch Hội Thận-Lọc Máu, Tp HCM


ACID URIC LÀ YẾU TỐ NGUY CƠ TIM
MẠCH & THẬN ĐƯỢC GHI NHẬN ĐẦU
TIÊN TRONG LỊCH SỬ


Does gouty nephropathy exist, & it is
more important than we think?,





25% gout subjects → kidney failure,
50% →↓kidney function, and
# all had kidney disease at autopsy.
Hyperuricemia → cause & accelerate CKD via hemodynamic & cellular
effects of soluble uric acid on the glomeruli, vasculature, & tubules.

 Urate crystal deposition in the kidney could also be contributing to kidney
injury
 DECT scanning: urate deposits can occur in extra-articular tissues of
subjects with gout, including the aorta and coronary arteries.

Federica Piani & Richard J. Johnson. Kidney International(2021) 99, 31-33
Bardin T. Kidney International(2021) 99: 218-220



URIC ACID & T2DM
Phân tích gộp 11N/C:
[Uric Acid] ↑1mg/dL→ ↑ 17% nguy cơ
T2DM

Kodama S et al(2019). Diabetic Care

5


URIC ACID & CVD




UA: yếu tố nguy cơ độc lập cho các biến cố tim mạch:
bệnh mạch vành, mạch máu não, suy tim sung huyết
↑[UA] 1mg/dL→
 † tim mạch: 20%
 † toàn thể: 9%

Gaubert m et al(2018): Purinergic Signals
Zuo T et al(2016). BMC Cardiovasc Disord
6


CVD More Common in Patients With
Hyperuricemia, Gout
Study (Renal Associates, LLC in Columbus, Georgia) 513 pts with
hyperuricemia (257 pts) or gout (256 pts) and 613 practice pts:
 Prevalence of CVD events was 32.3% / hyperuricemia + gout
pts (study group) compared with 17.6% among practice pts
 Among patients with CKD stage 3, the prevalence of CVD
events was about 32% in the study group compared with 13%
of practice patients.

Alappan UD, Alappan R. Symptomatic hyperuricemia (gout) patients have higher
occurrence of cardiovascular and coronary artery disease.Data presented at the live
virtual 2020 National Kidney Foundation Spring Clinical Meetings held March 257
28. ePoster 197


Relationship between uric acid and blood
pressure (Lee et al. Clinical Hypertension (2015) 21:14. DOI 10.1186/s40885-015-0022-9)


High prevalence and low awareness of
hyperuricemia in hypertensive patients

Yang Zhang ET AL(2022). BMC Cardiovascular Disorders 22(1) DOI:10.1186/s12872-02102427-2

BP, Uric Acid Linked in Adolescents
• National Health and Nutrition Examination
Survey: 6,036 individuals aged 12-17 years
• Each 0.1 mg/dL increment in uric acid is
associated with a 38% increased odds of
having elevated BP
• The association between uric acid and BP
persisted after adjusting for body mass index.
• It remains unclear if uric acid is merely a
marker or is involved in the causal pathway
leading to HTN
Lauren F. L et al . Hypertension (2017)


11


Uric acid and Hypertension

Lanaspa, M.A., Andres-Hernando, A. & Kuwabara, M. Uric acid and hypertension. Hypertens Res 43, 832–
834 (2020). />

Hyperuricemia May Be a Risk Factor for
Stroke Mediated by Severe Hypertension
REGARDS (Reasons for Geographic and Racial Differences in
Stroke) study:
• 30,239 community-dwelling individuals ≥45 years were
recruited between 2003 and 2007
• Hyperuricemia was found to be associated with ischemic

stroke (hazard ratio [HR], 1.40; 95% CI, 1.10-1.78).
• Treatment-resistant hypertension was found to mediate
45% of the association between hyperuricemia and
stroke,
Chaudhary NS, Bridges SL Jr, Saag KG, et al(2020). Severity of hypertension
mediates the association of hyperuricemia with stroke in the REGARDS case
cohort study Hypertension. 2020;75(1):246-256.




Does gouty nephropathy exist, & it is
more important than we think?,
 Microcrystalline deposits in kidney → local
tubulointerstitial disease (→ proinflammatory responses
involving activation of inflammation & caspase cascade.
 Local inflammation in kidney →:
 Renal dysfunction,
 Hypertension ( by blocking natriuresis)
 Trigger systemic inflammation & possible
atherosclerotic processes.
Uric acid is a true mediator of CKD.
Federica Piani & Richard J. Johnson., Kidney International(2021) 99, 31-33
F. Martinon, et al. Nature, 440 (2006), pp. 237-241
Krishnan. PLoS One, 7 (2012), Article e50046


Does gouty nephropathy exist, & it is
more important than we think?,
 “Asymptomatic hyperuricemia,”: very common in CKD and

is present ≥ 1/3 subjects with CKD( stage ≥ 3)
 Patients w gout history are most at risk for renal crystalline
deposits.
 Intracellular UA may be more important than sUA in
causing CKD (more likely to occur if intracellular
production from high xanthine oxidase is high),

Federica Piani & Richard J. Johnson., Kidney International(2021) 99, 31-33
F. Martinon, et al. Nature, 440 (2006), pp. 237-241
Krishnan. PLoS One, 7 (2012), Article e50046


Hyperuricemia and progression of
CKD: to treat or not to treat?
 Patients with asymptomatic hyperuricemia or gout can
develop urate crystals in sites other than the joints and
skin, including the vasculature and kidneys.
 Soluble UA may cause kidney disease by inducing
metabolic effects within the cell (inducing mitochondrial
& intracellular oxidative stress, ↓ endothelial NO
bioavailability, & stimulating the intracellular RAS →
intracellular rather than sUA level critical in driving
disease.
Jürgen Floege, Kidney Int(2021) 99: 14-16
Bardin T et al. Kidney Int. (2021); 99: 218-226
Johnson R.J. et al.Nephrol Dial Transplant. 2013; 28: 2221-2228


Does gouty nephropathy exist, & it is
more important than we think?,

There has always been a strong
relationship between gout, as well
as hyperuricemia, and kidney and
cardiovascular disease,

Federica Piani & Richard J. Johnson. Does gouty nephropathy exist, and it is more
important than we think?, Kidney International(2021) 99, 31-33
F.


HYPERTENSION
+
HYPERURICEMIA


Related
diseases
Clinical
events

Blood Pressure
Target organ
damage
Treatment


Factors contributing to develop or
progress to more serious DKD
• ↑ [albuminuria] in microalbuminuria range,

• Macroalbuminuria,
• ↓GFR
• ↑ BP
• Presence of retinopathy,
• ↑Lipids and/or Uric acid concentrations
• Family history: hypertension, macrovascular disease,
or DKD.
Kidney International Supplements (2013) 3, 1


Treatment of asymptomatic hyperuricemia in CKD

Maria Erika G et al. Journal of Advanced Research. Volume 8, Issue 5, September 2017, 551‐554


Thời điểm can thiệp phù hợp?
Schematic presentation of the decline in GFR over years in a patient
with albuminuria and in a patient with normal urinary albumin excretion.
Indicated is the (proven) change in slope when intervention to lower
albuminuria is started in a late phase and the (expected) change in slope
in case intervention is started early.

Age- and gender-adjusted risk to develop a cardiovascular event (defined as a fatal or
nonfatal myocardial infarction or cerebrovascular accident) and to develop a renal event
(defined as an eGFR slope of more than three times the mean of the normal genderstratified population) in the PREVEND cohort that had at least three eGFR
measurements available during 7 yr of follow-up

Can thiệp sớm là chìa khóa để cải thiện kết cục

Gansevoort RT,et al. JAm Soc Nephrol 2009;20:465-468.