AGGIORNAMENTI
IN NEFROLOGIA CLINICA
XIII Incontro
Teramo, 11-12 ottobre 2013
Il trattamento della ipertensione arteriosa resistente nella IRC:
Le misure igienico-dietetiche e la terapia farmacologica
Alessandro Balducci
Definizione di Ipertensione
Arteriosa Resistente
•
a) PA >140/90(o >130/80 nei diabetici) malgrado l’uso di TRE farmaci, uno dei quali
un diuretico
•
b) PA controllata con QUATTRO o più farmaci
Controllo PA
•
Dati Euroaspire (Kotseva, Lancet, 14/03/2009):
PA elevata nel
•
Survey Italiana(Tocci, J Hypertension, June 2012):
150.000 pz. seguiti nei centri di ipertensione o negli ambulatori di Medicina
Generale dal 2005 al 2011,si otteneva un controllo adeguato nel 37% dei
soggetti.
57%(1995-96)
55%(1999-00)
64%(2006-07)
Frequenza ipertensione resistente
E’ associata ad un maggior rischio di eventi cardiovascolari e renali
• Prevalenza negli ipertesi in generale : 8-10%,negli USA cioè 6 milioni
(Persell,Hypertension,2011), in Italia potrebbe essere di un milione
•
In uno studio brasiliano (Massirier, Arquivos Brasileiros de Cardiologia, July 2012),
la prevalenza è diminuita al 3% una volta escluse le ipertensioni secondarie,la
scarsa compliance e la “white coat”
•
Nei soggetti con CKD la prevalenza sale al 23-25%,dunque almeno TRE volte
superiore rispetto agli ipertesi essenziali (Borrelli,Int J of Hypertension,2013)
Prevalence of Apparent Treatment-Resistant
Hypertension among Individuals with CKD
Results The prevalence of apparent treatment-resistant hypertension was 15.8%, 24.9%, and 33.4% for those
participants with estimated GFR≥60, 45–59, and <45ml/min per 1.73m2, respectively, and 12.1%, 20.8%, 27.7%,
and 48.3% for albumin-to-creatinine ratio <10, 10–29, 30–299, and ≥ 300 mg/g, respectively. The multivariableadjusted prevalence ratios (95% confidence intervals) for apparent treatment-resistant hypertension were 1.25
(1.11 to 1.41) and 1.20 (1.04 to 1.37) for estimated GFR levels of 45–59 and <45 ml/min per 1.73 m2, respectively,
versus ≥ 60 ml/min per 1.73 m2 and 1.54 (1.39 to 1.71), 1.76 (1.57 to 1.97), and 2.44 (2.12 to 2.81) for albumin-tocreatinine ratio levels of 10–29, 30–299, and ≥ 300mg/g, respectively, versus albumin-to-creatinine ratio <10
mg/g.
After multivariable adjustment, men, black race, larger waist circumference, diabetes, history of myocardial
infarction or stroke, statin use, and lower estimated GFR and higher albumin-to-creatinine ratio levels were
associated with apparent treatment-resistant hypertension among individuals with CKD.
Conclusions This study highlights the high prevalence of apparent treatment-resistant hypertension among
individuals with CKD.
Tanner,Clin J Am Soc Nephrol 8: 1583–1590, 2013. doi: 10.2215/CJN.00550113
Table 1: Determinants of resistant hypertension in general population.
Clinical condition
Diabetes mellitus
Older age
Obesity
Drugs
Nonsteroidal anti-inflammatory drugs
Corticosteroids
Oral contraceptive hormones
Erythropoietin
Cyclosporine and tacrolimus
Sympathomimetics (decongestants)
Exogenous substances
Tobacco
Alcohol
Cocaine, amphetamines, and other illicit
drugs
Licorice
Herbal supplements (ginseng,
yohimbine)
Secondary causes
Common
Chronic Kidney disease
Primary aldosteronism (10-20%)
Sleep apnea
(71-85%)
Hyper-hypothyroidism
Renal artery disease
Uncommon
Cushing’s syndrome
Pheochromocytoma
Aortic coarctation
Hyperparathyroidism
Borrelli S,Int J of Hypertension,2013
Agabiti Rosei,Conoscere il Cuore,pag.346, 2013
Borrelli S,Int J of Hypertension,2013
Borrelli S,Int J of Hypertension,2013
Table 1: Determinants of resistant hypertension in general population.
Clinical condition
Diabetes mellitus
Older age
Obesity
Drugs
Nonsteroidal anti-inflammatory drugs
Corticosteroids
Oral contraceptive hormones
Erythropoietin
Cyclosporine and tacrolimus
Sympathomimetics (decongestants)
Exogenous substances
Tobacco
Alcohol
Cocaine, amphetamines, and other illicit
drugs
Licorice
Herbal supplements (ginseng,
yohimbine)
Secondary causes
Common
Chronic Kidney disease
Primary aldosteronism (10-20%)
Sleep apnea
(71-85%)
Hyper-hypothyroidism
Renal artery disease
Uncommon
Cushing’s syndrome
Pheochromocytoma
Aortic coarctation
Hyperparathyroidism
Borrelli S,Int J of Hypertension,2013
(26%GFR<60ml/min)
(Pedrosa,Hypertension,2011,58,811-17)
(Pedrosa,Hypertension,2011,58,811-17)
Misure Igienico-Dietetiche
•
Calo ponderale
•
Riduzione introito di alcool
•
Esercizio fisico (Dimeo, Hypertension 2012):
50 soggetti con RI, treadmill per 8-12 settimane: si aveva un calo della PA,
non dati per CKD
•
Dieta iposodica:
la diminuzione dello introito sodico potenzia gli effetti antiipertensivi e anti
proteinurici degli ACEI,con un probabile effetto antinfiammatorio che riflette
la diminuzione del volume extracellulare
Tanner,Clin J Am Soc Nephrol 8: 1583–1590, 2013. doi: 10.2215/CJN.00550113
Misure Igienico-Dietetiche
•
Calo ponderale
•
Riduzione introito di alcool
•
Esercizio fisico (Dimeo, Hypertension 2012):
50 soggetti con RI, treadmill per 8-12 settimane: si aveva un calo della PA,
non dati per CKD
•
Dieta iposodica:
la diminuzione dello introito sodico potenzia gli effetti antiipertensivi e anti
proteinurici degli ACEI,con un probabile effetto antinfiammatorio che riflette
la diminuzione del volume extracellulare
Ten recommendations to restrict sodium in your diet
Borrelli S,Int J of Hypertension,2013
Projected Effect of Dietary Salt Reductions
on Future Cardiovascular Disease
Results
Reducing dietary salt by 3 g per day is projected to reduce the annual number of
new cases of CHD by 60,000 to 120,000, stroke by 32,000 to 66,000, and myocardial
infarction by 54,000 to 99,000 and to reduce the annual number of deaths from
any cause by 44,000 to 92,000.
Such an intervention would be cost-saving even if only a modest reduction of 1 g per
day were achieved gradually between 2010 and 2019 and would be more cost-effective
than using medications to lower blood pressure in all persons with hypertension.
Conclusions
Modest reductions in dietary salt could substantially reduce cardiovascular events
and medical costs and should be a public health target.
(Bibbins-Domingo,NEJM,18 february 2010,pag.590)
(Bibbins-Domingo,NEJM,18 february 2010,pag.590)
(De Nicola,Kidney and BP Research,2011,34,58-67)
(De Nicola,Kidney and BP Research,2011,34,58-67)
I Farmaci
•
Farmaci long-acting per consentire la monosomministrazione
•
Una dose serale ? (non-dipper)
•
Diuretici ( ↑ ANP e BNP in CKD)
clortalidone (azione più potente e maggiore emivita)
diuretici dell’ansa(se GFR< 30 ml/min)
spironolattone( i livelli di aldosterone sono spesso elevati
in CKD: relativo iperaldosteronismo col fenomeno dello
dello escape)
(Bomback,NCP Nephrology,2007,3,9,pag.486)
Fig. 2. A graphical representation of relative hyperaldosteronism
in various disease and experimental states.
(Bomback,Blood Purification,2012,33,119-24)
Spironolattone
32 pz. stadio 3 trattati per un anno con spironolattone (Pisoni, J Hum Hypert, August
2012) :
•
Potassio
4→4,4
p<0.0001
•
Creatinina
1,5 → 1,8
p<0.0004
•
GFR
48,6 → 41,2
p<0.0002