HYPERTENSION IN CKD

DR PRATIK TRIPATHI
D.M ( Nephrology)
Fortis Escorts Hospital
Jaipur
 Definition of CKD
Structural or functional abnormalities of
the kidneys for >3 months, as manifested
by either:
1. Kidney damage, with or without decreased
GFR, as defined by
○ pathologic abnormalities
○ markers of kidney damage, including abnormalities
in the composition of the blood or urine or
abnormalities in imaging tests
2. GFR <60 ml/min/1.73 m2, with or without
kidney damage
Epidemiology And Staging of CKD

Stage 5: GFR <15 (0.2% of US population)

Stage 4: GFR 15-29 (0.2% of US population )

Stage 3: GFR 30-59 (4.3% of US population )

Stage 2: GFR 60-89 (3.0% of US population )

Stage 1: GFR ≥90 (3.3% of US population )

* Data from NHANES III
Incidence and Prevalence of End-
Stage
Renal Disease in the US
Risk factors associated CVD RISK
with CKD FACTORS
TRADITIONAL NONTRADITIONAL
● Older age > ● Albuminuria
55yrs for men ● Homocysteine
& 65yrs for ● LP(a) and apo (a)
women isoforms
● Male sex ● Lp remnants
● HTN ● Anemia
● Higher LDL ● Abnormal Ca/PO4
cholesterol metabolism
● Lower HDL ● ECF overload
cholesterol ● Oxidative stress
● DM ● Inflammation (CRP)
● Smoking ● Malnutrition
● Physical ● Thrombogenic
inactivity factors
● Menopause ● Endothelial
● F History of dysfunction
CVD
● LVH
 Cardiovascular Disease in CKD
●CKD patients are at very high risk for CVD

●CKD patients have higher risk of dying from

CVD than end stage renal disease

●CKD is a risk factor equal to diabetes mellitus

 Approximate Prevalence % of
CVD
POPULATION CAD LVH CHF

General 5-12 20 5

CRF NA 25-50 NA

HD 42 75 40

PD 40 75 40

Tx recipient 15 50 NA
 Hypertension and Kidney

●Hypertension is an important cause of

ESRD
●Hypertension is common in patients with
CKD and accelerates progression of
renal failure
●SBP>160 torr &/or DBP>100 torr
associated with X 10 risk of developing
CKD than normotensive counter-parts.
Prevalence of Abnormalities at each level of
GFR

*>140/90 or antihypertensive p-trend < 0.001 for each

 Pathophysiology of Hypertension in
CKD
● Some patients have HTN that leads to CKD
○ Hypertensive nephrosclerosis
● More patients have HTN because of CKD
○ Sodium + fluid retention
○ Increased activity of RAS (due to regional ischemia
induced by scarring) despite normovolemia
○ Enhanced activity of sympathetic nervous system
○ Secondary hyperparathyroidism raises intracellular calcium
concentration →vasoconstriction →hypertension
○ Treatment with erythropoietin
○ Impaired nitric oxide synthesis and endothelium-mediated
vasodilatation
Hypertensive Nephrosclerosis
CKD: Common pathway in disease
progression
RENAL INJURY

Nephron mass
Glomerular capillary hypertension
SYSTEMIC Glomerular permeability to macromolecules
HYPERTENSION Filtration of plasma proteins Proteinuria
Excessive tubular protein reabsorbtion
Tubulo-interstitial inflammation

RENAL SCARRING
Importance of Proteinuria in CKD
REASONS WHY ALBUMINURIA IS
RISK FACTOR FOR CVD
●Is assoc with high prevalence of traditional
risk factors
●May reflect generalised endothelial
dysfunction, increased vascular permeability
and abnormality of coagulation system
●May be assoc with markers of inflammation
●May indicate the severity of end organ
damage
SURVIVAL RATE IN ESRD AND
GENERAL POPULATION
Age-Standardized Rates of Death from Any Cause
(Panel A) and Cardiovascular Events (Panel B),
According to the Estimated GFR among 1,120,295
Ambulatory Adults

Go, A, et al. NEJM 351:

Goals of Treatment of HTN in CKD

●To preserve renal function:

maintain GFR and reduce
proteinuria

●To reduce CV morbidity and

mortality
:most clinical trials in past have
 Treatment of Hypertension

●CKD patients with spot urine

Albumin/Creat ratio of > 300mg/g should
be treated with ACEI or ARB, regardless
of BP
●All CKD patients with HTN should be
treated with an ACE-I or ARB especially if
proteinuric
Reno protective Action of ACE
Inhibitors
●Captopril in Type 1 diabetics reduced
the combined endpoints of death, dialysis,
and transplantation by 50%
●UKPDS , ABCD & HOPE trials revealed
superior control of microalbuminuria in
Type 2 Diabetes Mellitus by ACEI
●REIN & AASK studies in patients with
nondiabetic revealed superiority of ACEI
Reno protective Effects of AT1
Receptor Blockers
●IRBESARTAN MICROALBUMINURIA
STUDY proved that ARBs reduce
microalbuminuria in patients with Type 2
Diabetes, independent of BP control

●Excellent renoprotection shown in Type 2

Diabetes in IRBESARTAN DIABETIC
Advantages of ACE-I and ARBs
●Blockage of RAS has anti-proteinuria and
anti-hypertensive effects

●RAS blockade slows progression of

proteinuric nephropathies
 Combination Therapy
●COOPERATE Study in nondiabetic renal
disease revealed trandolapril + losartan
reduced progression of renal disease more
effectively than monotherapy

●CALM study revealed similar results in

Type 2 Diabetes Mellitus
 Progression to ESRD Occurs
Despite RAS Blockade
● Patients with BP control on RAS blockade continue to
lose renal function.WHY?
● ‘Aldosterone escape’ – due to high K+ & AT2 R effect
● Increased activation of intrarenal RAS
● Non-ACE pathways- ACEI ineffective
● High PRA due to ACEI/ARB overcomes drug blockade---
ACE escape
● Direct pro-fibrotic role of renin , independent of its Ang-
generating effect.
● AT2 receptors induced activation of NF-B in mesangial
and endothelial cells
 Risks of Combination Therapy
●Worsening of anemia in CKD
●Hyperkalemia
Circumstances in which ACE Inhibitors /ARBs
Should Not Be Used
Pregnancy ,History of angioedema ,Cough due to
ACEI ,Allergy to ACEI/ ARB ,Bilateral renal artery
stenosis or renal artery stenosis in renal graft or a
solitary kidney ,Drugs causing hyperkalemia ( use
with caution)
 Pathologic Effects of Aldosterone

●Expands extracellular volume resulting in

hypertension

●Controls sodium reabsorption in distal nephron

●Acts with angiotensin II to increase PAI-1 to

contribute to nephrosclerosis
 Benefits of Aldosterone
Antagonists in CKD
●Becker et al found 54% decrease in proteinuria
from baseline by adding spironolactone (25mg/d)
●ACE inhibitor + spironolactone decreased
proteinuria by 41% compared with ACE inhibitor
alone
●Adding spironolactone to an ARB decreased
proteinuria (13%) in patients with chronic GN as
compared to the ARB alone in patients with
eGFR > 30ml/min.

STOP IF
 Eplerenone in CKD
●In a study with Type 2 diabetes+ HTN+
microalbuminuria, patients received either
Eplerenone, Enalapril, or combination
●After 24 weeks, the Eplerenone group had
a greater reduction in proteinuria (62% vs.
45%) and a 74% reduction in the
combination group but a higher incidence
of hyperkalemia
STOP IF
New Modalities for Hypertension
Therapy
●ACE-I-NEP inhibitors (vasopeptidase
inhibitors e.g Omapatrilat )
●Endothelin inhibitors (Darusentan)
●Direct renin Inhibitors (Aliskerin)
●Implantable carotid sinus nerve stimulators
Blood Pressure Is Poorly
Controlled In CKD

Coresh. Arch Intern Med. 2001;161:1207.

 Clinical Practice Guidelines for
Management of Hypertension in CKD
Type of Kidney Disease Blood Pressure Preferred Agents Other Agents
Target for CKD, with or to Reduce CVD Risk
(mm Hg) without and Reach Blood
Hypertension Pressure Target
Diabetic Kidney Disease Proteinuria<1g/24hr
s:BP<130/80
Proteinuria>1g/24hr
s:BP<120/75 ACE inhibitor Diuretic preferred,
or ARB then BB or CCB
Non diabetic Kidney
Disease with Urine Total
Protein-to-Creatinine
Ratio 200 mg/g <130/80
Non diabetic Kidney Diuretic, ACE
Disease with Spot Urine inhibitor/ARB, BB or
Total Protein-to- CCB,AB
None preferred
Creatinine ratio <200 mg/g
Kidney Disease in Kidney CCB, diuretic, BB,
Transplant Recipient ACE inhibitor,