EBM: ROLE OF ACEI/

ARB IN REDUCING
PROTEINURIA/
PROGRESSION OF
DM NEPHROPATHY
 Topic Outline
1. Principle of Evidence Based Medicine (EBM) – revision
2. Diabetic Nephropathy – definition, diagnosis, epidemiology
3. Diabetic Nephropathy – pathophysiology and staging
4. Diabetic Nephropathy – investigation and evaluation based on CPG
5. Diabetic Nephropathy – Management and Treatment based on CPG
6. ACEI/ARB – mechanism of action of ACEI/ARB
Principle of Evidence Based Medicine (EBM)

◦ the conscientious, explicit, judicious and reasonable use of modern, best evidence in making decisions
about the care of individual patients

Component of
EBM
Grading for level of evidence
 Diabetic Nephropathy – definition,
diagnosis, epidemiology
◦ Definition: Glomerular sclerosis & fibrosis caused by the metabolic &
hemodynamic changes of diabetes mellitus
◦ Characterized by :
◦ Persistent albuminuria (>300 mg/d) - confirmed on at least 2 occasions 3-6
months apart
◦ Progressive decline in GFR
◦ Elevated arterial blood pressure
 Epidemiology
◦ DM nephropathy affected one third of people with type 1 or type 2 Diabetes
Mellitus
Pathophysiology
Consequences of glomerulosclerosis and
interstitial fibrosis

Irreversible loss of
nephron

Blood flow shift to a

Decrease in GFR normal functioning
nephron
A
Reduced in
GFR Increase in renin
production

Activation endothelin-1
at efferent arteriole
RAAS activation
Mesangial cell hypertrophy
& proliferate
Increase Na+ and
Efferent arteriole H2O reabsorption
Increase in ECM constriction
production
Increase
systemic BP
Increase in glomerular
permeability Increase
Oedema
albuminuria
REVISION
 Blood flow shift to normal
functioning nephron

Glomerular
Early stage hyperfiltration Late stage

Increase in GFR at Decrease GFR Uremia

normal functioning
nephron
Decrease urine -nausea and vomiting
output
-pruritus
-mental confusion
 Stages of
Diabetic
Nephropathy
Screening and
Investigation
Prognosis of
ckd by gfr and
albuminuria
category
 Management of diabetic nephropathy

a. Good glycaemic control. (Grade A)

-Glycaemic control should be optimised,with FBS <6 mmol/l and or HbA1c<7% FBS= fasting blood
glucose, HbA1c = glycosylated hemoglobin

b. Tight control of blood pressure. (Grade A)

-Target blood pressure in diabetics should be less than 130/80mmHg

c. Reduction of proteinuria with ACEIs or ARBs (Grade A)

-ACEIs in type1 & type 2 diabetics

-ARBs in type 2 diabetics

d. Cessation of smoking. (Grade B)

-Cigarette smoking should be actively discouraged.

e. Lipid control, salt and protein constriction. (Grade B)

Correction of dyslipidemia (diabetic): - if LDL-cholesterol is

>2.6mmol/l therapeutic lifestyle

- if LDL-cholesterol is >3.4mmol/l drug therapy

Diet: i. Moderate protein restriction of

0.6-0.8g/kg/day *may be considered in patients with overt nephropathy and/or renal
impairment

ii. Sodium intake should be restricted to <80mmol/day(or 5g sodium chloride) *in patients with
hypertension and/ or proteinuria
Mechanism of
action of
ACEI/ARB
MOA of ACEi : inhibit
action of ACE - reduce
production of
Angiotensin II
MOA of ARB: block
Angiotensin II receptors
on vascular and adrenal
glomerulosa cells (similar
effects as ACEI).
 Role of ACEi and ARB
● May be considered as first line antihypertensive agents for treatment of hypertension in diabetics (in
the absence of contraindications).
● Shown to reduce microalbuminuria in diabetic patients independent of their effect on blood
pressure.
 What did EBM said about ACEI/ARB in DM
nephropathy?
● Systemic review – Risk of ESRD

○ 40% reduction when using ACEI in type 1 DM compared to placebo

○ 20% reduction when using ARB in type 2 DM compared to placebo

● Both ACEI/ARB reduced rate of microalbuminuria and proteinuria regardless BP

controlled