Transcript Dr. Mende - Shasta Regional Medical Center

Hypertension and Kidney
Disease( CKD ) in Diabetes
CHRISTIAN W. MENDE, MD
FACP,FACN,FASN,FASH
Clinical Professor of Medicine,
University of California, San Diego
La Jolla, Calif.
FACULTY DISCLOSURE
Company
 Boehringer
Ingelheim
 Lilly
 Janssen ( J&J )
 Forest
 AstraZenica
Nature of Affiliation
Unlabeled Product
Usage
NONE
Speakers Bureau
Hypertension Incidence ( USA )
33 %
50 %
75 %
90%
US Population
> age 21
> age 60
> age 75
> age 90
70 – 80% Hypertension in Diabetes mellitus
Awareness of Hypertension
On Therapy
CDC ( 2014 )
81 %
75 %
64%*
at Goal !
Go AS. et al 2013 AHA Update ,Circulation 127: 143-52
* Morbidity and Mortality Weekly Report , 2/14/ 2014
DIABETES Incidence 2015 ( USA )
13 % Diabetes
FBS >125 , 2 hr PP > 199
A1C 6.5 % and above
38 % Prediabetes
FBS 100 -125 or 2hr PP 140-199 mg
A1C 5.6 - 6.4%
51 % PREDIABETES and DIABETES
!!
Menke,A. et.al. JAMA 2015;314 (10),1021
CKD Incidence in Diabetes
Stage CKD 3a ( eGFR 45 – 59 ml /min )
> age 21
> age 65
= 22 %
= 43 %
Stage CKD 3b ( eGFR 30 – 44 ml / min )
> age 21
> age 65
= 9%
= 18 %
Bailey RA et.al BMC Research Note ,2014 ;7:421
OBESITY in HYPERTENSION / DIABETES
1)
68 % of US adults are Overweight ( BMI > 25 )
33 %
Obesity ( BMI > 30 )
33 to 38 %
Metabolic Syndrome
2)
~ 75 %
3)
of Obese Patients have Hypertension
70 -80 %
of Type 2 Diabetes are Overweight or Obese
4)
1/3 of US Adults ( 18 and older ) have Hypertension
5)
50% of all Hypertensive have BMI > 30
Linear Relationship between Weight and SBP ( BMI 25- 35 )
1 kg (2.2 lbs ) Weight Gain or Loss = 1 mmHg Systolic BP CHANGE
Definitions
Hypertention ( HTN ) JNC 8 , ASH , ADA , ASN
BP > 140 / 90 mmHg
Chronic Kidney Disease ( KDIGO 2013 )
present ≥ 3 months :
a) eGFR < 60 ml/min / 1.73 m² or
b) Albuminuria ≥ 300 mg
or
c) Abnormal Histology ( Biopsy ) or Transplantation
Definitions
Progression of CKD
a) Loss of ≥ 5 ml eGFR / Year
b) Change of Category ( i.e. CKD 3 to 4 )
c) Loss of ≥ 25 % from Baseline
Resistant Hypertension
Use of 3 antihypertensive Drugs in full Doses
including a Diuretic and BP NOT at Goal.
How to Obtain a Correct Blood Pressure
•
•
•
•
•
•
Sitting with Back Support , both Legs on Floor
Rest for at least 3 min
Ascertain correct Cuff Size
Obtain 3 Readings about 2 min apart
Discard 1st Reading and average 2nd and 3rd
Obtain HOME BP Readings , if possible
JNC 7, JAMA 2003
Office BP Details
How many BP Readings are ideal ?
AHA and JNC 7: Minimum of 2 sitting BP and average out both
NHANES ( 1999 - 2008 )
Using 3 Readings and discarding # 1 and average # 2 and 3
RECLASSIFIES
~ 1/3 ( 35 % ) of Stage I Hypertension as
NORMOTENSIVE
= NO THERAPY Needed
Handler J.et.al
J.Clinical Hypertension , 2012 ;11: 751
HOME BP FACTS
1)
2 : 1 better Correlation of CV events HOME vs. OFFICE BP
2)
Diagnoses MASKED Hypertension
3)
Home BP taken x 2 / week for 48 weeks leads to
4 x More Likely Reaching BP GOAL
( Kim J.et.al. JCH , 2010; 12: 253-260 )
4)
Diagnoses WHITE COAT Hypertension
Hypertension and Dementia
Hypertension is associated with Vascular Dementia
( Micro-Infarcts , CVA and Alzheimer;s Disease )
Systolic BP 110 -139 vs. > 160 mmHg
Odds Ratio = 4.3 for Dementia ( Honolulu Heart )
Antihypertensive Therapy Lowers Risk of Alzheimer’s Disease
Hazard Ratios : HCTZ 0.51 , ACEI 0.5, ARB 0.31
CCB 0.62 , BB 0.58
Gingko Evaluation / Memory study :1900 pat.= 6.1 year F/U
Proteinuria
( > 300 mg/d ) is associated with
Cognitive Decline ( even without CKD )
ADA Blood Pressure Guidelines (2014)
GOAL
< 140 / 90 mmHg
•
Lower target :
•
ACE inhibitor or ARB : including ONE or more BP Drugs at Bedtime
•
Lifestyle :
< 130 / 80 for young Patients ( if no side effects )
DASH style diet
Weight Loss
( if BMI > 25 )
Salt < 6 gm
( 2300 mg Na )
Increase Potassium ( Fruit ,Vegetables )
150 min exercise / week
No Smoking ( Doubles CVD Mortality )
Standards of Medical Care in Diabetes – 2014 Diabetes Care 37,Suppl.1
Bedtime Dosing in Diabetes or CKD
( at least 1 BP drug at HS )
DIABETES
ABPM 48hrs: HTN present, if BP > 135 / 85 or Nocturnal BP > 120 / 70
448 patients on 3 drugs :
using ONE Drug HS
F/U 5.4 years
Each 5 mmHg Nocturnal SBP Decline = 12 % Decline of CV Events
( CVA, MI, CV death )
CKD *
695 patients with eGFR < 60 , 7 years F/U ( ABPM 48hrs as above)
Each 5 mmHg Nocturnal SBP Decline = 14 % Decline of CV Events
Hermida, RC, et.al.
Diabetes Care 2011 ; 134: 1270-1276
*J Am Soc Nephrol. 2011 ; 22: 2313-2321
IDEAL Blood Pressure ?
( > 40,000 Hypertensives )
1)
PROVE – IT- TIMI
4,162 patients
2)
INVEST
6,400 patients with DM + CAD
3)
ON TARGET
15,981 w/o and 9,603 with Diabetes
4)
ACCORD
4,733 with Diabetes
LOWEST EVENT RATE ~ 135 /85 mmHg
Blood Pressure Lowering in Type II
Diabetes
Systematic Review and Meta-analysis
Effect of 10 mmHg Systolic BP Reduction
Macro -vascular Risk Reduction ( ONLY if SBP > 140 at Baseline )
Mortality
CVD , CHD
CVA
Micro -vascular Risk Reduction
Retinopathy
Albuminuria
13 %
12 %
27 %
( Regardless of Baseline SBP )
13 %
17 %
Emden CA et.al. ,JAMA 2015 ;313 (6) :603
SPRINT Trial
9300 hypertensive Patients with CKD or high Risk for CVD divided into
2 Groups :
Systolic BP < 120 vs. < 140 mmHg
( Trial stopped > 2 Years early )
~ 23 % Reduction of Mortality
~ 31 % Reduction of MI , CVA , CHF
( Analysis of Adverse Events and Subgroups to follow )
Exclusions : Diabetes , prior CVA , PCK
( NIH press release 9/11/15 )
Mono /Combo - Therapy
1) Average MONO Therapy ( Placebo corrected )
9.1 / 5.5 mm Hg BP Reduction
( in Stage I Hypertension , Law BMJ , 2003 )
2) NHANES ( 2007- 2010 ) Combination Therapy to Goal
75 % needed 2 drugs
25 % needed 3 drugs
Doubling of Mono – vs. Combo Therapy
Metanalysis of 11,000 patients in 42 Trials
( Wald DS, et.al. Am. J. Med. 2009; 122 :290 )
COMBO - THERAPY = 5 X more likely to
ACHIEVE BP GOAL ( in 6 month )
Combos to AVOID in Hypertension
1)
Beta Blocker
+ Verapamil or Diltiazem
2)
Beta Blocker
+
Centrally acting antihypertensives
( Clonidine)
DUAL RAAS BLOCKADE :
1) ACE Inhibitors + Angiotensin Receptor Blockers
( ONTARGET trial )
2) Aliskiren + ACE inhibotors ( ALTITUDE trial )
3) Aliskiren + ARB
Aldactone and ACE inhibitors or ARB’s are excluded !
Resistent and Refractory Hypertension
Definitions :
Resistant
Uncontrolled on 3 or more drugs incl. Diuretic
and BP still > 140 / 90 or
Controlled on 4 or more drugs with BP < 140 / 90
Refractory
Uncontrolled on 5 or more classes of drugs ( Chlorthalidone ,
Aldactone ) and BP still > 140 / 90
Incidence :
Resistant Hypertension 10-15%
Refractory Hypertension
10 %
of all treated Hypertensive Patients
of all Resistent Hypertension
Concern :
High Risk for CV Events ( CVA, CAD, CHF )
Target Organ Damage ( LVH , Albuminuria, CKD )
Framingham CAD Score 2x compared with “ essential Hypertension “
Issues in Resistent Hypertension
1)
1/3 controlled by ABPM and therefore NOT “ Resistent “ (*)
2)
Adherence
German study using urine and blood drug analysis
ONLY 53% Compliance (#)
3)
Low Use
Mineralocorticoid Antagonists ALDACTONE
NHANES
REGARDS
3%
18 %
(#) Jung O et.al. J.Hypertens 2013 ;31: 766-774
REGARDS Study :Calhoun DA. Hypertension 2014; 63 :451
Guidelines to Resistent Hypertension
Exclude White Coat Effect ( 24 hr AMBP , Home BP )
Assure Compliance
( MEMS or Urine screen for drugs )
Use correct 3 Drug Regimen
RAAS blocker , CCB and Diuretic ( Chlorthalidone )
Use Full Dosing of above Listed Drugs
Evaluate for
ALDO excess ( 20% !) Aldo / Renin ratio , CKD , PHEO
OSA ( 96% of Males ! )
Check for
Excessive Salt Intake ( > 6 gm ) = 24 hr Urine
NSAID Use
( may raise BP by 10 / 5 mmHg )
Drug Abuse
( Cocaine, Amphetamine, ETOH excess )
Use Beta Blockers ( Nebivolol / Carvedilol ) for Heart Rate > 80 /min
Add ALDACTONE
12.5 – 25 mg / day !!
CKD
Blood Pressure
( With or Without
Guidelines
DIABETES - KDIGO 2013 )
NO Albuminuria
BP < 140 / 90 mmHg
Albuminuria
> 30 mg / day
BP < 130 / 80 mmHg
Use ACEI or ARB’S if > 30mg /d Albuminuria
Lifestyle :
BMI > 20 – 25 , Salt < 6 gm ( 2400 mg Na )
Exercise 30 min 5 X / week
Cardiovascular Risks in Diabetes and
CKD
1) Cardiovascular Risk in Diabetes ( MI, CVA ,CHF ) greater than CKD
Progression:
70 % CVD Mortality
4 % reach ESRD ( Dialysis , Transplantation )
2) eGFR < 45 ml /min major =
Risk Factor for CVD ( +/- Diabetes )
3) Obesity independent Risk Factor for
=
CVD , CKD , Diabetes
Hypertension
4) Sleep disordered Breathing ( Sleep Apnoe )
Risk Factor for Diabetes, Hypertension , CKD
5) Combination of Diabetes + CKD = 4- fold Risk of CVD and Mortality
BP Level and CVD Risk in T2DM and CKD
Swedish National Diabetes Registry
33,350 patients , aged 75 (+/-9 ) , diabetes duration 10 ( +/- 8 ) years,
follow up 5.3 years
BP 135 –139 / 72-74 mmHg best Outcome for CV Events and Mortality .
Highest Risk for CV Events / Mortality
1) SBP < 120 mmHg = HR 2.3 / 2.4
2) SBP > 160 mmHg = HR 3.0 / 2.0
Afghahi H. et.al. Diabetologia , March 2015 ( online)
OBESITY and Renal Disease
Obesity is an independent Risk Factor for :
CKD
RR 1.83 , ( female > male )
Progression of CKD
ESRD
Renal Calculi
Renal cell carcinoma
Renal Effects of Obesity
1) Hormonal
Activation of RAAS ,SNS, Leptin , ROS
2) Physical
Compression of Renal Parenchyma
3) Structural
Glomerulopathy ( FGS )
Albuminuria
4) Hyperfiltration ( elevated eGFR )
Afferent Vasodilation and efferent Vasoconconstriction
BMI and CKD
Association of Age and BMI on Renal Function and Mortality
3.376,000 US Veterans with a eGFR > 60 ml /min
mean age of 60 and BMI ~ 29 , 7 Year follow up
Results :
1)
8.1 % ( 274.746 ) > age 40 with BMI > 30
Progressive eGFR loss of > 5 ml / year
2) BMI > 25 to < 30 best Clinical Outcome
3) Age 40 and younger had no BMI Risk for eGFR Loss
4) Mortality Risk paralleled eGFR Risk
Lu,JL. et.al Lancet Diabetes Endocrinology, 2015:3 :704-714
Risk Factors for CKD
•
•
•
•
Hypertension ( Uncontrolled )
Age eGFR loss 0.7 – 1.0 ml /year > age 40
Diabetes eGFR loss ~ 2.0 ml /year (good care)
Obesity ( BMI > 30 )
• Albuminuria > 300 mg ( ACR )
• Microalbuminuria < 300 mg No Risk ( per se)
Risk Factors , cont’d
AKI
Recovery from AKI even within 10% of Baseline Value leads
to increased Risk and Progression of CKD
( AKI definition : SCr increase by 0.3mg in 48hrs, or < 0.5ml /kg urine in 6hrs )
Nephrotoxic agents
Dye studies , Antibiotics , NSAID
Smoking
Albuminuria increased , Nephrosclerosis
Diabetes = Doubles Risk of CV Mortality !!
Ethnicity
Afro-Americans ( 3.5x ESRD risk ) and Native Americans ,
Hispanics
Positive Family
History of CKD or ESRD
NSAID use in
Hypertension and CKD

Lower Efficacy of ALL Antihypertensive Drugs ,
incl. Diuretics by 10 -15 % ( except CCB’ s )

Cause Salt Sensitivity ( > 3-4 day use )

In CKD 3 (< 60 ml GFR )
Reduce GFR by 10-15 %
Risk of Hyperkalemia , AKI and CHF
Measures to Slow CKD in Diabetes
Note :
All studies to slow CKD are in Non –Diabetes Subjects
( MDRD , REIN-2 , AASK )
eGFR Loss ( after age 40 )
HYPERTENSION
NO Disease =
Diabetes
=
0.7 – 1.0 ml / year
2.0 ml / year
( most important ! )
BP goal < 140 / 90 mmHg
( may attain < 130 / 80 for Albuminuria and / or Young )
ACE inhibitors or ARB’s slow CKD progression by 20%
ALBUMINURIA
( > 300 mg ACR )
ACE inhibitors or ARB’s lower Albuminuria
30% Reduction of Albumin will decrease ESRD Risk by 24 %
( Lambers-Heerspink ,et.al JASN 2015; 26: 206 )
CKD Slowing Measures ( cont’d )
HYPERGLYCEMIA
Reducing A1C to < 7% will lower Micro – and Macro albuminuria
No data on CKD progression
HYPERLIPIDEMIA
Reducing LDL will lower Cardiovascular Events
No Data on CKD slowing
Other Measures
a)
b)
c)
d)
No smoking
Salt restriction to < 2400 mg Na ( 6 gm Salt )
Weight Loss for BMI > 25
Hyperuricemia > 7.0 mg% consider Allopurinol
( No outcome data )
Salt reduction by 6 gm ( Na 2400 mg ) will reduce Albuminuria by 33%
Specialist Referral for CKD
AKI
CKD 4
Albuminuria
( Acute Kidney Injury )
( eGFR < 30 ml )
> 300mg ACR
CKD Progression
> 5 ml Loss / year or change in Stage
Red cell cast ( Glomerular Disease ) or > 20 RBC w/o cause
CKD and Resistent Hypertension
Not at Goal on 3 Drugs ( CCB, RAAS ,Diuretic)
Recurrent Nephrolithiasis
Hyperkalemia
Hereditary Kidney Disease
( 2 or more episodes )
( persistent )
( i.e. PCK )
ASH Hypertension Guidelines 2013
BP Goals :
Age 80 and older
Age 60 - 79
Age 50 and younger
<
<
<
<
150 / 90
140 / 90
140 / 90
130 / 80
mmHg
mmHg
mmHg
( if tolerated )
CKD or DIABETES:
w /o Proteinuria
with Proteinuria
< 140 / 90 mmHg
< 130 / 80 mmHg ( no consensus )
ASH Guidelines for Hypertension : J.Clinical Hypertension , 2013