Should we restrict sodium intake in renal patients - a review of the evidence

1. Salt restriction
Jim Ritchie

2. What do we tell patients
?

3. Background
CKD
Impaired sodium
excretion
Increased
BP
Resistance
to RAAS
blockade
Glomerular hyper-
filtration
Increased
proteinuria

4. Current guidelines
Smyth et al. Am J Hyertens 2014 epub ahead of print

5. Current guidelines
• Lower sodium intake to
<90mmol / day (5g salt)
• Advice appropriate to the
stage of CKD (CG182)
• CG127 - Restrict / limit
dietary sodium
• Public health UK:<6g / day
(2015); <3g / day (2025)

6. Blood pressure effect
(CG127)
Unclear if benefits sustained beyond 12 months

7. Cochrane 2014
Relative risk 95% CI
Mortality 1.00 0.86 - 1.15
CV mortality 0.67 0.45 - 1.01
CV events 0.76 0.57 - 1.01
Change in SBP -1.79 -3.23 - -0.26
Change in urinary
Na excretion
-20 -53 - 12

8. Progression of CKD
Smyth et al. Am J Hyertens 2014 epub ahead of print
Author Year Comparison Summary
Cianciaruso 1998
>4.6 (5.3) vs. <2.3 (1.9)
g / day sodium
Mean decline CrCl
0.51±0.09 vs. 0.25±0.07
Amaha 2010
Correlation of intake vs.
eGFR decline
r= -0.29
Vegter 2011
<2.9 / 2.9 - 5.8 / >5.8 g
/day
HR ESRD:
High vs. low 3.3
(1.7 - 6.4)
Medium vs. low 1.4
(0.8 - 2.3)
Lambers 2012
<3.5 / 3.5 - 4.8 / >4.8 g /
day
HR Cr x2
Low vs. high 0.75
(0.53 - 1.05)
Data do not support strict Na restriction

9. Progression of proteinuria
Author Year Comparison Summary
Cianciaruso 1998
>4.6 (5.3) vs. <2.3 (1.9)
g / day sodium
~ 1 g / 24 hour increase
vs. ~1g / 24 hour
decrease.
Amaha 2010
Correlation of intake vs.
proteinuria
r = 0.53
Vegter 2011
<2.9 / 2.9 - 5.8 / >5.8 g
/day
31 / 25 / 20% reduction
in proteinuria
(p for trend = 0.012)
Lambers 2012
<3.5 / 3.5 - 4.8 / >4.8 g /
day
uACR reduction
44 / 16 / 21 mg/g
Smyth et al. Am J Hyertens 2014 epub ahead of print

10. Uncertainties
Assumption of linear effect
between reduction in sodium
intake and improved renal
outcomes.
Will blood pressure reductions
lead to proportionately slower
renal functional loss (BP agent
class effects)
Salt sensitivity / retention / BP
dipping patterns in CKD not
considered

11. Uncertainties
Data linked to CV
outcomes are J-shaped
O’Donnell et al. JAMA 2011(23);306
Retrospective study of
305 PD patients (patient
reported dietary
information); HR death /
1 g/day increase in Na
0.44 (0.2 - 0.9) p=0.04
Dong et al. cJASN 2010(5);240-7
< 3 g/day Na linked with RAAS
activation…
Yoshioka et al. Circ Res 1987(61);531-8

12. Recent data
• JASN 2014 - LowSALT CKD study (n=20)
• BMJ 2011 - HONEST study (n=52)
• KI 2014 - ONTARGET / TRANSCEND (n=29,000)

13. LowSALT
• n=20. 1 week run in.
• Counselled to low sodium diet (60 - 80 mmol/day). Then
crossover period of 120 mmol Na tablet / placebo (2
weeks / 1 week / 2 weeks)
• Age = 69; CKD 3-4 ; proteinuria = 0.5 g/24hours
• Blood pressure 151 / 82 mmHg (3 agents)
• 30% angiotensin blockade; 40% diuretic (4 patients
changed medications during study period)
McMahon et al. JASN 2014. ePub ahead of print

14. Blood pressure effects
Squares - high salt period; triangles low salt period
McMahon et al. JASN 2014. ePub ahead of print

15. Proteinuria
r = -0.1; p = 0.69
McMahon et al. JASN 2014. ePub ahead of print

16. HONEST
• Non-diabetic CKD (n=52)
• Mean age = 52; BMI 28; eGFR ~44 ml/min/1.73m2
• Blood pressure >125 / 75 mmHg in spite of maximal
ACEi (135 / 78 mmHg)
• Residual proteinuria >1 g/24 hours
• Non-study drugs locked in (25% diuretic)
Slagman et al. BMJ 2011; Jul26 p343-344

17. HONEST
Slagman et al. BMJ 2011; Jul26 p343-344
6 WEEK RUN IN PERIOD
40 mg lisonopril
Placebo
A2 blockade
telmisartan 320mg
Low sodium
High sodium
4 x six week periods. No wash out
Low salt = 3g / 24 hours. High salt = 12.6g / 24 hours

18. Proteinuria
1.68 [1.3-2.1]
vs
1.44 [1.1-1.9]
0.86 [0.6-1.1]
vs
0.67 [0.5-0.9]

19. Other results
• Urinary sodium excretion 190 vs. 105 mmol/24
hours
• ~10 mmgHg reduction in systolic blood pressures
• Low salt: reduced odema; albumin 38 -> 40
• 10 umol/L increase in serum creatinine on low salt
diet (reversible)
• 0.1 mmol/L increase in serum potassium

20. ONTARGET /
TRANSCEND
• ONTARGET
• telmisartan / ramipril / combination in patients with
diabetes or vascular disease
• n=25,000
• TRANSCEND
• telmisartan / placebo (ACEi intolerant population)
• n=6000
Smyth et al. KI 2014(86) 1205-12

21. ONTARGET /
TRANSCEND
• Mean age 66; eGFR 68 (30% CKD 3+); angiotensin
blockade >90%
• 15% micro / macroalbuminuria
• Divided by urinary sodium excretion (<2; 2-4; 4-6; 6-
8; >8)
• 56 months follow-up
Smyth et al. KI 2014(86) 1205-12

22. Renal outcomes
Smyth et al. KI 2014(86) 1205-12
Low sodium
3.3g
Moderate
4.7g
High
6.2g
eGFR increase
>30% / RRT
1 0.98 [0.92-1.04] 0.99 [0.89-1.09]
Doubling sCr 1 0.96 [0.84-1.11] 0.94 [0.75-1.19]
Progression of
proteinuria
1 0.96 [0.91-1.02] 0.92 [0.84-1.01]
Hyperkalaemia 1 1.08 [0.98-1.19] 1.09 [0.93-1.28]

23. Renal outcomes
Smyth et al. KI 2014(86) 1205-12
>30% eGFR reduction
Progression between
stages of albuminuria

24. Potassium
Smyth et al. KI 2014(86) 1205-12
>30% eGFR reduction
Progression between
stages of albuminuria

25. Potassium
• Reduces renal vascular resistance and increases renal
blood flow
• Found in “positive’ foods; association with antioxidants
• In rat models, up-regulates kinins which protect from
fibrosis
• Association lost in CKD 3b / 4
• possible confounding (i.e. more advanced CKD may
have had more limited potassium intake)
Smyth et al. KI 2014(86) 1205-12

26. Conclusions
• Sodium restriction likely of benefit but hard to
quantify
• Consideration of patient specific data e.g. nephrosis
• Dietary advice may be dynamic over continuum of
CKD