Sodium elimination and dialysate sodium. How much? Does it matter?

Transcription

1 Sodium elimination and dialysate sodium How much? Does it matter? A. Bock Nephrologie

2 Dialysis visit Aarau kg dialysis patient: 5 kg over dry weight Recent dyspnea. Minimal leg edema RBV in recent dialyses hardly falls < 90% even when removing > 3 kg His serum Na+ is 134 Standard dialysate Na+ is 140 Should we lower dialysate Na+? To avoid positive Na+ balance? To decrease his thirst?

3 Na+ balance in this patient with dialysate Na+ 140 Predialysis: 95 kg 19.0 L ECV 19.0 * 134 = 2546 mmol Na+ Postdialysis: 90 kg 18.0 L ECV 18.0 * 140 = 2520 mmol Na+ Na+ balance - 26 mmol (negative) Na balance with 134 serum Na+, 140 dialysate Na+ and various weights Dry weight (kg) Excess weight (kg) Note: Hyponatremia due to drinking implies weight gain! (e.g. for 134 Na: 90 dry weight > L // 70 dry weight > L etc.) No need to decrease dialysate Na+ if hyponatremia due to drinking!

4 Predialysis Na+ is determined by the relation of Na + and H 2 O intake H 2 O intake ~ IDWG Kimura & Gotch, Int J Artif Org 1984

5 2 concepts.. "Na + setpoint" Thirst threshold Thirst Thirst Na P osmo

6 Osmotic thirst threshold in CRF is normal! 1. Osmotic thirst threshold in normals and ESRF 2. Urea infusion does not cause thirst Normal ESRF Argent, Kidney Int 1991 Zerbe, Am J Physiol 1983

7 Why do dialysis patients drink? One reason: Xerostomia 1/3 of dialysis patients have hyposalivation Thirst Bots, Kidney Int 1994

8 Thirst in dialysis patients Osmo-thirst curve not different from non-dialysis! No evidence for "sodium setpoint" You can not suppress thirst by lowering dialysate Na below "normal" But lowering serum Na below normal "puts you further away" from the thirst threshhold

9 Other effects of lowering dialysate Na+ Negative sodium balance Hemodynamically instability Cramps Less/no thirst? -> less drinking

10 Effect of increasing dialysate sodium Hemodynamic stability Counteracts the urea effect (intravascular volume depletion) Combats post-dialysis dysequilibrium syndromes Believed to be 2nd to brain edema In theory: increases thirst Consecutively: increases interdialytic weight gain Potentially positive salt balance

11 Effect of various manoeuvers to minimize intradialytic hypotension Seq UF -> HD Na Dialysate 144 Na modelling Crossover, 10 HD patients Dheehan & Henrich, KI 2001

12 Na profile: not helpful 9 HD patients, all with UF profile; randomized trial of Na profile Iselin, Tsinalis, Brunner: Swiss Medical Wkly 2001

13 The apparent problem(s): low serum Na

14 The apparent problem(s) "Lower predialysis Na + is associated with an increased risk of death" 2011 "The lower mortality observed in patients with Na + <137 dialysed against dialysate Na + > 140 is intriguing " "In the absence of randomized prospective studies, the benefit of reducing IDWG by decreasing dialysate Na+ should be weighed against an increased risk "

15 1. Low predialysis Na + is associated with mortality: HEMO ex-post-analysis All-cause mortality versus quartiles of serum Na + Hazard ratio increase per 4 mmol/l serum Na + increase Na 136 Na>141 Predictors of predialysis Na + : with p 0.001: Diabetes, glucose, UF volume Serum albumin, Creatinine N=1546 Covariate adjustment : - Cardiovascular mortality n.s. - Overall mortality sig. Waikar, Am J Med 2011

16 2: DOPPS I/III patients w/ Na + data Mortality highest with lowest predialysis Na + N=11555 Hecking, AJKD 2012

17 Why is low predialysis Na + associated with mortality???? Predialysis Na correlates negatively with - Interdialytic weight gain - Diabetes - Glucose - Neuropsych disorder Predialysis Na correlated positively with - Age - Male gender - Dialysis vintage - BMI - Albumin - Creatinine Hecking, Am J Kid Dis 2012

18 Interdialytic weight gain associates with mortality DaVita HD patients 1.25 ( ) Kalantar-Zadeh, Circulation 2009

19 What is the problem? Interdialytic weight gain

20 Does decreasing dialysate-na + lower IDWG? Yes: a little bit In center nocturnal HD 3x8h/week 15 patients Blood flows 300 ml/min Dialysate Na 140 -> 136 > 140 Mean pre-dialysis Na + : 136 Post-dialysis Na + : = Na Dialysate Mean interdialytic weight gain 4.2 -> 3.6 -> 4.1 kg (p~0.02) No difference in symptoms Na D Mendoza, AJKD 2011

21 Does increasing Na dialysate increase IDWG? Yes: but not by much ~ 0.8 kg ~ 0.6 kg (3rd dialysis) p< 0.05 vs Na>140 Pan Thames Renal Audit, Int J Artif Organs 2008; 31:

22 Question Does lowering IDWG by lowering dialysate Na+ improve mortality?

23 2: DOPPS I/III patients w/ Na + data Dialysate Na + made a difference within Serum Na + tertiles. Mortality Higher dialysate Na improved mortality! N=11555 Hecking, AJKD 2012

24 3. DOPPS I-IV patients Mortality: decreases with rising serum-na + but there is no correlation with (high) dialysate Na + (if anything it's less) N=29594 Hecking, CJASN 2012

25 3. DOPPS I-IV patients Interdialytic weight gain (IDWG) decreases with rising serum-na + but increases with rising dialysate Na + N=29594 Hecking, CJASN 2012

26 Taken together Low predialysis Na+ is associated with higher mortality Low predialysis Na+ is associated with high IDWG Low dialysate Na+ slightly decreases IDWG But high dialysate Na is associated with improved survival despite more IDWG!

27 Garden of associations Other? Mortality Low Predialysis Na + IDWG Dialysate Na +

28 What have we learned? Benefits of high dialysate Na+ are Better hemodynamic stability Potentially better survival Benefits of low dialysate Na+ are Less IDWG Negative Na+ balance Low predialysis Na + is associated with mortality This association is only partly explained by interdialytic weight gain Low predialysis Na + is associated with other risk factors (e.g. diabetes, nutrition) Interventions to decrease interdialytic weight gain which may include low NaCl diet, drinking restriction low dialysate Na+ a) are effective in reducing IDWG b) may make life easier (mainly of the nephrologist) c) but are NOT shown to be safe with respect to mortality! low NaCl diet -> poor nutrition? low dialysate Na+ -> hemodynamic instability

29 Thank you!

30 Now what is the message???? AND: Patients treated with higher dialysate Na + (>142) had less hospitalisations

31 What Na + are we talking about? Pre-dialysis Na + Post-dialysis Na + ~ Dialysate Na + Mortality Symptoms Cramps BP drops ID weight gain Na Na +

32 Pre- and postdialysis Na + Pre-dialysis Na + Determined by patient factors NaCl intake H 2 O intake Thirst Statistically depends on Interdialytic weight increase ( ) Diabetes, Glucose ( ) Albumin, creatinine ( ) Post-dialysis Na + Determined by doctor ± = Dialysate Na + Depends on (nothing?)? Some doctor factors such as? predialysis Na? hemodynamic stability

33 Now what is the message????

34 Does decreasing IDWG by lowering Na Dialysate decrease mortality?probably not!

35 The questions: 1. Why is low predialysis Na inversely associated with interdialytic weight gain? 2. Why is low predialysis Na associated with mortality? is ist IDWG? 3. What is the effect of dialysate sodium on mortality?

36 Predialysis Na+ and mortality Is it interdialytic weight gain? IDWG covaries with Na, but corr of mortality with (low) Na is stronger Angiotensin II as dipsogenic hormone? Toxic effect of osmolarity cycling? Some uremic toxin which causes thirst? Uncompensated effect of diabetes?

37 The problem How to eliminate salt and water during dialysis without causing Cramps blood pressure drops collapse While avoiding Thirst Weight gain Volume expansion hypertension

38 Evolution of dialysate sodiums 1960s: No ultrafiltration Dialysis times 6 12 h Na s: Ultrafiltration, still 4-5 hours Na s: Rapid dialysis, 3-3 ½ hours Na > :?? 138

39 Sodium "equilibrium" along the dialysis membrane "Outside": e.g. 140 mmol/l "Inside" (Blood): Ionometric Na 140 Plasma water Na 147 Active Na (Gibbs-Donnan) 139 Effective at equilibrium: dialysate 2 mmol/l lower than (ionometric) blood

40 Consequences of positive salt balance E.g. dialysate 144 / plasma 138 No net change of total body water, just increase in sodium concentration Thirst? Third space sodium?

41 "Sodium setpoint"? Bases on the observation that Between-patients variation of predialysis Na+ is much bigger than Within-patient variation Predialysis Na+ is taken as "setpoint" Pre-dialysis sodium: mean 138 mmol/l 132 dialysis patients (Vienna) Hecking, Am J Nephrol 2011

42 Evidence for "Na + setpoint" (the fact that most patients have a tendency to reach similar predialysis sodium values).. which could also be explained by Normal thirst threshold plus Modifying factors Dry mucosae High glucose (diabetes) Psychology

43 Not sodium but thirst drives interdialytic weight gain Thirst Bots, Kidney Int 1994

44 Third space sodium Based on Observations in healthy humans with excessive amounts of salt intake (> 300 mmol/d) Na Balance discrepancies Animal experiments Role in dialysis patients simply unknown

45 Strategies to alter dialysate sodium "Ramping" protocols Beware of elevated mean sodium

46 Altering dialysate sodium: Epidemiological evidence

47 Interaction of dialysate natrium with pre-hd serum natrium Hecking, Am J Kid Dis 2012

48 Flash summary It is unclear whether positive sodium balance has negative effects beyond the potential increase in thirst Patients with low predialysis sodium drink for other reasons than sodium No good evidence for a sodium setpoint Increased dialysate sodium may be helpful for dialysis associated symptoms As long as there is no increase in interdialytic weight As long as blood pressure (measurement) is not altered