1. Optimal Dialysate Sodium
Dr. Prashant G.K.,
MD(Med), DM(Nephro), DNB(Nephro).,
Professor, Nephrology
St. John’s Medical College Hospital
Bangalore

2. Outline Introduction Historical Summary of Dialysate Sodium
Relationship of DNa, IDWG, HTN
High DNa+
Variable Na+ modelling
Individualised Dialysate Na+
New Trials
Conclusions

3. Introduction Dialysate sodium (DNa) prescription is a neglected entity
DNa is usually standard & fixed for a particular centre
depending on popular practice pattern (no evidence
base for default DNa setting)
Completion of dialysis without “intradialytic events” is
primary motive
Often high DNa+ to combat hypotensive episodes,
cramps, to facilitate more ultrafiltration in short HD
time.

4. Source of Sodium Diet
- Dialysate Na+ (Diffuse influx from dialysate to plasma)
- Hypertonic saline infusion in HD

5. Historical Summary of Dialysate Na
Time
Milestones
DNa(mEq/L)
Buffer
Frequency
Kolff, 1940
Scribner 1960
1970
1980
Acute
MHD
Short HD
126.5
~130
~137
Bicarb
Acetate
>24hrs
>76hrs
2.5-3hrs
3-4hrs
On demand
Every 5-7days
3x / week

6. Higher DNa concentration (~140mEq/L) became more
common during transition from acetate to bicarb based
dialysate from 1980 onwards.
The new “standard” dialysate Na 140mEq/L in most centres.
Convective sodium removal become predominant method of
sodium removal.
Concentration shifted from “sodium” to “ultrafiltration”

7. Dialysate Na+ prescription in 1084 thrice weekly HD
Mendoza JM et al. Nephrology Dialysis Treatment 2011:26:

8. DNa – IDWG and Hypertension
High DNa ↓
Na gradient positive
↑ post dialysis Na
↑ thirst
↑salt & water
Volume overload
Hypertension ↓ ↓
High UFR
LVH ↓ ↓
ID Hypo
↑CV mortality

9. Higher DNa+ & even supraphysiological level (Eg mEq/L) are used to combat recurrent hypotension, dialysing older, sick cardiac patients, diabetes with autonomic neuropathy for hemodynamic stability.

10. Barne et al randomized 5 patients to high fixed DNa+ 145, 150 or 155mEq/L in random sequence, 1 month at a time over a 6 month study period.
Noted no “intradialytic symptoms” but progressively greater IDWG with higher DNa (2.2kg, 2.6kgs and 2.9kgs respectively)*
* A randomized double blind trial of dialysate sodiums of 145, 150 and 155mEq/L
ASAIO Trans 34: , 1988

11. 30,000 patients enrolled in DOPPS showed that DNa 142 – highest IDWG
Audit of 7 dialysis centres with DNa ranging from – 140mEq/L by Davenport et al – patients with DNa140 had larger IDWG, higher pre HD, higher post HD BP & needed more antihypertensives*.
* Nephron Clin Pract 104: , 2006

12. Variable DNa Modelling
Tapering DNa concentration beginning high with progressive lowering during dialysis procedure, terminal DNa is similar / lower than patients “serum Na+”.
Benefits of less intradialytic events (cramps / hypo) and greater UF rate, greater net UF volume.

13. Song et al – studied 11 patients on HD with 3 phases (cross over trial)
Phase 1 – DNa138, phase 2 DNa+ modelling 150 to 138 (TAC 140), phase to 133 (TAC 147)
Higher dialysate TAC sodium showed significant ↑ in thirst scores, IDWG and ambulatory BP
Difference between dialysate TAC sodium and patients pre HD serum Na+ had significant correlation with interdialytic ambulatory BP.
* Song et al – AJKD 40: 29 – 301, 2002

14. In Na+ modelling algorithms the patients time average concentration of Na+ is much higher than reflected by terminal DNa+ concentration.
Total exposure to Na+ is important & has impact on patients net Na+ balance.
Increased exposure to higher Na+ may contribute to increased sodium incorporation in chondritin sulphate, hyaluronic acid in tissues, matrix of blood vessels altering blood vessel reactivity to vasoactive substances*.
* Farmer CKT et al. Low sodium hemodialysis without fluid removal improves BP control in HD patients. Nephrology 2000; 5;

15. Na+ modelling in hypotension prone HD patients
Song et al analysed 414 session from 23 patients with varying degrees of hypotension
Randomization to 2 week blocks of fixed DNa 140, linear modelling ( mEq/L) or stepwise (155 x 3hrs, 140x1hr), 4hrs HD, constant UF
Hypotension defined as any SBP <90mmHg, decline of SBP 50mmHg from baseline, any BP drop with symptoms requiring intervention.
Hypotension ↓ significantly in linear & stepped protocol than fixed DNa
Linear & stepped protocol were associated with ↑ IDWG, pre HD SBP & ↑ thirst.

16. Online Plasma Sodium Monitoring
Many factors affect sodium diffusion viz sodium gradient, Gibbs Donnan effect, changing plasma PH, sodium reflection coefficient of dialyser membrane.
Aequilibrium is an automated program of sodium and ultrafiltration profiling that uses online conductivity monitor to estimate plasma sodium during each treatment.
Allows better sodium balance for HD sessions
Studies by Locatelli et al demonstrate some benefit*
* Locatelli et al: Hemodialysis with on line monitoring equipment. Tools or toys?
Nephrol. Dial. Transplant 20: 22-33, 2005

17. Concept of “Set Point” for Sodium
Chronic HD patients have a unique predialysis serum sodium level
This sodium level is relatively constant for an individual for months & is highly conserved by individualised osmolar set point (hypothalamus)
Addition of extra sodium (diet, Dialysis) will induce thirst, increased fluid intake and maintains the sodium & osmolar set points
Sodium set point in dialysis patients is the mean monthly predialysis sodium concentration (preceding 3-4 months).

18. Concept of “Set Point” for Sodium
The average serum sodium among 58 patients was
137.3±2.5mg/dl over 9 to 10 months despite dialysed against
constant dialysate Na+ of 143mEq/L (Keen & Gotch 2007)
The average serum sodium remained constant in 27 patients
at 134±1.4 during the first 3 weeks when dialysed at
138mEq/L and subsequently remained constant at 134±1.5
when dialysed with matched dialysate sodium (individualised
dialysate Na+)*
* De paula FM, Patricio PJ et al – Kidney Int :

19. When dialysing across a physiologic range of dialysate
sodium, the concept of set point remains valid, variation of
predialysis serum sodium is less than 1%.
However when dialysed with higher dialysate sodium (↑to
147 from 140) over 6 months, 11 patients had a small but
statistically significant increased predialysis serum sodium
(138.1 ± 138.6±0.2)*.
* Song et al – AJKD 40:

20. Personalised approach to dialysate sodium reduction
Based on concept of unique sodium set point
Adjustment of dialysate sodium to match the predialysis
plasma sodium level
Isonatremic Dialysis involves Dialysate Sodium = Plasma Na+

21. What happens to interdialytic weight gain, thirst, blood
pressure control when individualized dialysate sodium is
used?
What about intradialytic complications like hypotension,
cramps?

22. 27 non hypotensive prone HD patients, single blind protocol
Subjects underwent 9 consecutive HD sessions (3 weeks)
with dialysate sodium set at 138mEq/L (“standard sodium” HD)
followed by 9 sessions where in dialysate sodium was set to match
the patients average pre HD plasma sodium measured 3 times
during standard sodium HD
Dry weight, dialysis prescription and medications not modified in
the 6 weeks study*
* De paulo FM et al. Clinical consequences of individualised dialysate sodium in HD patients. Kidney Int. 66: 1232 – 38; 2004.

23. Sodium individualisation resulted in lower systolic BP in
uncontrolled hypertension patients (pre HD BP >150/85) but not in
controlled BP group (<150/85)
BP -15.7/-6.5 compared to -6.4 / 4.5mmHg in controlled
hypertension (P0.001)
Decrease thirst score, decreased IDWG, pre HD BP reduction & less
HD related symptoms (in patients with uncontrolled BP).

25. Intervention time (wk)
Clinical Consequences of dialysate sodium reduction in chronic HD patients
Investigatior
Pt. No.
Intervention time (wk)
Std Na+
Reduced Dialysate Na+
Ref to reduction BP
IWDG
HD sym
Remarks
Lambie 16 NR
136
Upto 6
Random ↓
Worse
Conductivity based
Saya riloglu 18 4
137 or
135
Varied sodium (-2)
Pre HD sodium
IVC
LVD, TR
Thein 52
141
3 ↓ NS
Data base analysis

26. Dialysate sodium, mortality & hospitalization
Study N
Obs. Group
Hospitalization
Mortality
Mc Causland 2012
2272
3x/week HD with varied DNa
Higher DNa associated  mortality with  SNa, not with lower SNa
Hecking 2012
CJASN
29593
DOPPS prospective analysis (12 countries)
High DNa associated with low risk
High DNa not associated with  mortality
Hecking 2012 AJKD
11555
DOPPS
Less risk of mortality in serum sodium <137 with DNa >140

27. Confused?!!
Complex, results are from observational studies and from Database analysis
However “CAUTION” is necessary while manipulating & lowering dialysate sodium
Higher dialysate sodium concentration may be advantageous for some patients with lower plasma sodium levels
?Pre-existing cardiac dysfunction, & hypotensive prone

28. Prospective Study Dialysate Sodium & Cardiovascular outcomes
RESOLVE – Randomized Evaluation of Sodium Dialysate on Vascular Events
Clinical Trials. Gov (U.S. National Institute of Health) NCT
Global study to assess the effect of two default dialysate sodium 140mmol/L & 137mmol/L on major cardiovascular event and death in patients on MHD, open labelled.
Primary outcome – Time to first occurrence of major events (MI, stroke, coronary & cerebral revascularisation) or all cause death
Estimated enrolment
Study start date June 2016
Estimated completion Dec. 2023

29. Basic Science – Clinical Application
Indirect – ion selective electrode method is used to measure plasma sodium. 6% higher than “true sodium” is available for diffusion (93 to 94% of plasma is aqueous).
GibbsDonnon effect: Plasma proteins near dialyser membrane impede diffusion of sodium by ~5%.
1 & 2 nullify each other and hence the same value of laboratory plasma Na+ value can be used to adjust dialysate Na+.

30. Practical Considerations
Tempting to consider individualised approach to dialysate sodium prescription & match predialysis plasma sodium level
Concerns about “prescription errors” in a large Dialysis Unit running HD in 3 or more shifts
Implementation errors by Dialysis staff, lack of knowledge and training
Safety concerns – monitoring for hypotension
Routinely checking the accuracy of HD machine conductivity monitor & recalibrate if required, suggestions – to have spare conductivity monitors, check dialysate sodium periodically.

31. What is “optimal” Dialysate Sodium – Practical Considerations

32. Present evidence base is unclear about optimal dialysate sodium.
Lower dialysate sodium than 140mEq/L may be better.
Facility wide approach – Have a standard low dialysate sodium 135 – 138mEq/L for most patients (Default setting) to begin with to avoid prescription errors / implementation / avoid catastrophy.

33. Personalised Approach – In non hypotension prone patients, patients with difficulty to control hypertension – Dialysate sodium may be matched to patients pre HD sodium. Keep sodium gradient zero.

34. Hypotensive prone patients, Dialysate with higher sodium concentration / sodium modelling may be beneficial.
Progressive slow decrement of DNa in serial dialysis sessions in patients tolerating well should be tried.
Should we probe for lower dialysate sodium below patients plasma sodium??

35. None of these is fixed, patient may have to be moved from one prescription to other depending on clinical profile and need.
Be flexible, but careful / watchful
Always consider comorbidities

36. BASELINE – NEUTRAL sodium balance
- Euvolemia patient
- Optimise BP control,
minimal intradialytic symptoms

37. Conclusions “One size” does not “fit” all
Dialysate sodium prescription has been changed not based on randomized controlled trials but due to evolving practice patterns with primary intention of avoiding intradialytic hypotension / cramps.
Higher dialysate sodium 140 & above and sodium modelling might be beneficial in hypotensive prone patients, patients with cardiac dysfunction.
There is limited evidence for lowering dialysate sodium from uniform 140 to 135 to 138mEq/L

38. Conclusions
“Personalised approach” to match patients pre HD Na+ to dialysate sodium improves IDWG, improves BP control, thirst scores (Isonatremic Dialysis)
Implementing “Personalised Approach” requires greater effort by Nephrologists and also by dialysis team & is labour intensive errors might increase.
Wait for conclusions from Randomized trials for evidence on cardiovascular morbidity & mortality benefits with low dialysate Na+

39. Thank you