1. Hypertension In Chronic Kidney Disease

2. Introduction loss of nephrons Renal disease Systemic hypertension
Proteinuria
Progressive
decline
in GFR

3. CKD: Common pathway in disease progression
RENAL INJURY
Nephron mass
Glomerular capillary hypertension
Glomerular permeability to macromolecules
Filtration of plasma proteins  Proteinuria
Excessive tubular protein reabsorbtion
Tubulo-interstitial inflammation
SYSTEMIC
HYPERTENSION
RENAL SCARRING

4. CKD: Common pathway in disease progression
Therapeutic intervention inhibiting this common pathway may succeed in slowing the rate of progression of CRF irrespective of the initiating cause

5. How important is systemic blood pressure control?
Relative risk of ESRD according to quintile BP
MRFIT study
N= 332,544 men

6. What should be the treatment goal?
Treatment goal for hypertension in the general population has remained relatively the same for the last decade.
Guidelines
BP target
British Hypertension Society (2004)
< 140/85
Malaysian Hypertension Society
<140/90
JNC VII (2003)

7. What should be the treatment goal
for renal disease?
Should be lower than the general population
Should be tailored according to :
the severity of renal failure
the severity of the proteinuria

8. Proteinuria and target BP control
Aggressive BP control to 125/75 mmHg showed better preservation of GFR for those with proteinuria >3g/day.
No additional benefit if proteinuria is < 1g/day
Klahr S, Levey AS: NEJM 1994; 330:877

9. What should be the treatment goal
for renal disease?
Guidelines
Target BP
British Hypertension Society (2004)
<130/80
Malaysian Hypertension Society
JNC VII (2003)

10. What should be the treatment goal for non diabetic renal disease?
Treatment goal should depend on the severity of proteinuria
Proteinuria (g/d)
BP target (mm Hg)
>1
125/75
<1
130/80

11. Proteinuria
There is indisputable evidence from animal, laboratory and clinical studies that proteinuria per se contributes to progressive renal injury

12. Proteinuria and renal disease progression
Klahr S, Levey AS: NEJM 1994; 330:877

13. Proteinuria and renal disease progression
REIN SUBSTUDY : Progression of renal disease
according to severity of proteinuria

14. Proteinuria and renal disease progression
It is now clear that different classes of antihypertensive agents have different antiproteinuric capacity
ACEI and ARB have been showed to exhibit the highest capacity to diminish protein excretion in urine

15. ACE Inhibitors In Nephropathy
REIN Study : KIDNEY SURVIVAL

16. ACE Inhibitors In Nephropathy
REIN Study

17. ACEI, ARB and combination treatment in Nephropathy
COOPERATE STUDY: Median urinary protein excretion

18. ACEI, ARB and combination treatment in Nephropathy
COOPERATE STUDY: proportion reaching endpoints

19. Choice of antihypertensive agent for non diabetic renal disease
ACEI or ARB should be the first choice antihypertensive agent in patient with significant proteinuria.

20. Choice of antihypertensive agent for non diabetic renal disease
Dose of ACEI or ARB should be titrated to achieve both target BP and the disappearance of proteinuria

21. Choice of antihypertensive agent for non diabetic renal disease
If target blood pressure is not achieved and especially in the presence of persistent proteinuria, an ARB should be added.

22. Precautions when starting ACEI or ARB
Check Cr and K+ within 7-14 days after starting treatment especially in the presence of renal impairment
An acute rise in Cr of 30% should be tolerated if BP is adequately reduced (<140/90), hyperkalaemia is absent and the patient is euvolaemic
If Cr continues to rise, or hyperkalaemia persist, stop drugs; assess for bilateral RAS

23. Choice of antihypertensive agent for non diabetic renal disease
Choice of combination antihypertensive agents depend on the existing comorbidity

24. Drug(s) for the compelling indication
Diuretic
B-blocker
ACE I
ARB
CCB
Aldosterone antagonist
Heart failure 
Post-myocardial infarction
High coronary risk
Diabetes
Chronic Kidney Disease
Recurrent stroke prevention

25. Choice of Anti-Hypertensive drugs in patient with concomitant disease
Diuretics
B-blockers
ACEI
Ca channel blocker
Alpha- blocker
ARB
Diabetes
Careful
careful
yes
Gout No
Yes
Yes/no
Hyperlipidaemia
IHD
Heart Failure
Asthma
PVD
Renal Impairment
Renal A Stenosis
Elderly with no co morbid cond.

26. Choice of antihypertensive agent for non diabetic renal disease
Since studies have demonstrated that most hypertensive patients will require multiple drugs to achieve target BP, the argument about which one is superior has become almost irrelevant
We must provide all of the drugs needed to achieve maximal protection with the fewest adverse effects

27. Summary Control Blood Pressure Proteinuria (g/d) BP target (mm Hg)
>1
125/75
<1
130/80

28. Summary Choice of antihypertensives Kidney Disease Agents BP target
Diabetic Kidney Disease
ACE inhibitors
or ARB
<130/80
Non diabetic kidney disease
Urine PCR
>200 mg/g
Or ARB
<125/75
<200 mg/g
None preferred
130/80