Too much sodium is bad for you. Too much sodium is bad for you 13/09/2014. Salt- intake around the world. Sodium the most famous electrolyte

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Sodium the most famous electrolyte Too much sodium is bad for

Cerebrovascular hemorrhage Gerjan Navis Dept Nephrology, UMCG

nl Gastric cancer Osteoporosis Etc Too much sodium is bad for

Salt- intake around the world The human species has a wide

capacity ensures sodium balance over a wide intake range

Malta Finland UK Holland Denmark Iceland Inuit Yanomami

1 Sodium the most famous electrolyte Too much sodium is bad for you High blood pressure Cardiovascular disease Kidney damage Cerebrovascular hemorrhage Gerjan Navis Dept Nephrology, UMCG Groningen The Netherlands Gastric cancer Osteoporosis Etc Too much sodium is bad for you High blood pressure Cardiovascular disease Kidney damage Cerebrovascular hemorrhage Gastric cancer Osteoporosis Etc Salt- intake around the world The human species has a wide range of nutritional habits across the globe Homeostatic capacity ensures sodium balance over a wide intake range Northern Japan Tibet Southern Japan USA Germany Italy Spain Malta Finland UK Holland Denmark Iceland Inuit Yanomami Recommended grams/day Intersalt study 1

2 Salt- intake around the world Salt- intake around the world Northern Japan Tibet Southern Japan USA Germany Italy Spain Malta Finland UK Holland Denmark Iceland Inuit Yanomami Soy sauce/salted fish Salted yak-butter tea Soy sauce/seasonings Etc Northern Japan Tibet Southern Japan USA Germany Italy Spain Malta Finland UK Holland Denmark Iceland Inuit Yanomami Meditteranean diet Nordic/Western diet Soy sauce/salted fish Salted yak-butter tea Soy sauce/seasonings Etc Recommended grams/day Intersalt study Recommended grams/day Intersalt study quizz QuesMon #1 Gerjan Navis To reduce dietary sodium intake in subjects on a Western diet, avoiding to add salt to food (during cooking and during meals) can reduce overall sodium intake by: A. 1 2% B. 2 4% C. 4 6% D. 6 7% 2

QuesMon #2 Gerjan Navis In the general populamon a high sodium intake is generally associated with: A. high phosphate intake B. low potassium intake C. overweight D.

3 QuesMon #2 Gerjan Navis In the general populamon a high sodium intake is generally associated with: A. high phosphate intake B. low potassium intake C. overweight D. all of these Take home message 1 Sodium epidemiology is NOT sodium physiology InterpretaMon of sodium epidemiology data requires a nutrimonal perspecmve Take home message 1 Sodium epidemiology is NOT sodium physiology Current debate on opmmal sodium intake it is the dose that makes the poison Dosis facit venenum InterpretaMon of sodium epidemiology data requires a nutrimonal perspecmve Epidemiological assessment of dietary sodium intake is usually flawed Dietary recall and spot urines are unreliable, 24h urine often not available Paracelsus

Pathophysiological aspects of sodium intake DISSECT the VARIOUS EFFECTS OF SODIUM ON THE BODY Sodium and cardio- renal damage: old paradigms Excess salt intake ECV expansion

4 Pathophysiological aspects of sodium intake DISSECT the VARIOUS EFFECTS OF SODIUM ON THE BODY Sodium and cardio- renal damage: old paradigms Excess salt intake ECV expansion Hypertension Cardiorenal damage WHICH EFFECT IS HARMFUL, AND TO WHOM? Sodium and cardio- renal damage: old paradigms Excess salt intake ECV expansion Hypertension Cardiorenal damage 4

5 Kg Homeostatic response to a change in salt intake Normal Body weight Rise in sodium intake Kidney adapts UNaV ECV rises (BW) BP stable small rise GFR Part Na+ intake 25 2 Adaptation RAAS-activity & natriuretic peptides mmol/dag 15 1 Na+ excretion Sodium excess in CKD implicamons for prevenmon and treatment Sodium excess Sodium excess in CKD implicamons for prevenmon and treatment Sodium excess Blood pressure Blood pressure 5

6 Sodium excess in CKD implicamons for prevenmon and treatment Sodium excess Sodium excess in CKD implicamons for prevenmon and treatment Sodium excess pharmacotherapy pharmacotherapy Blood pressure Blood pressure Huge impact! Risk- reducmon by RAAS- blockade Residual risk is high, despite evidence- based efficacy RENAAL, NEJM 21 RENAAL, NEJM 21 6

Sodium restricmon and ACEi in essenmal hypertension quizz RAAS- blockade potenmates effect of low Na + diet low Na+ diet potenmates effect of RAAS- blockade RAAS- blockade makes blood pressure sodium

are apparent from reducmon of edema B. are equivalent to the effect of diuremc treatment C. are modified by concomitant RAAS- blockade D.

7 Sodium restricmon and ACEi in essenmal hypertension quizz RAAS- blockade potenmates effect of low Na + diet low Na+ diet potenmates effect of RAAS- blockade RAAS- blockade makes blood pressure sodium sensimve in all paments! Navis, J Cardiovasc Pharm 1987: 9: QuesMon #3 Gerjan Navis QuesMon #4 Gerjan Navis In CKD paments the treatment effects of dietary sodium restricmon: A. are apparent from reducmon of edema B. are equivalent to the effect of diuremc treatment C. are modified by concomitant RAAS- blockade D. can be assessed from its effects on blood pressure In a cohort of diabemc CKD paments (mean creamnine clearance 1 ml/min) under regular nephrology care including RAAS- blockade, habitual salt intake is found to be grams/daily. By dietary intervenmon sodium intake is reduced to 8-1 grams/ day. What do you expect of its clinical effects: A. none or negligible, as the restricted salt intake is smll very high B. reducmon in blood pressure C. reducmon in blood pressure and albuminuria D. reducmon in blood pressure, albuminuria and renal funcmon 7

Salt restricmon and diuremc potenmate ACEi in diabemc nephropathy Salt restricmon and diuremc potenmate ACEi in diabemc nephropathy High salt ~ 22 mmol Na/day Low salt ~ 17 mmol Na/day Kwakernaak et

8 Salt restricmon and diuremc potenmate ACEi in diabemc nephropathy Salt restricmon and diuremc potenmate ACEi in diabemc nephropathy High salt ~ 22 mmol Na/day Low salt ~ 17 mmol Na/day Kwakernaak et al, Lancet Diab End 214 Kwakernaak et al, Lancet Diab End 214 REIN trial by mean salt excremon/2 yrs REIN trial: need for diuremcs Non- diabemc CKD, proteinuria Ramipril vs convenmonal AHT TitraMon of BP towards 14/9 in all MAP, mmhg BP control was independent of sodium intake However, MSD and HSD required more diuretics than LSD Ramipril arm analysed by UNaV TerMles of UNaV LSD: plm 5-7 g/d MSD: plm 1-12 g/d HSD: plm 15 g/d LSD MSD HSD LSD MSD HSD Vegter, JASN 212: 23: Vegter, JASN 212: 23:

Excessive sodium intake is associated with worse renal outcome, DESPITE control of blood-pressure and volume status!!!! Diuretic does not eliminate long term adverse effect of excess salt intake!

9 At inclusion (before ACEi): LSD: 2. g/g MSD: 2.1 g/g (P=.14) HSD: 2.6 g/g (P=.11) (Wilcoxon rank sum test) Results - proteinuria REIN : hard renal end points by sodium intake Low: 5-7 g/d Medium 1-12 g/d High: g/d HS less reducmon in proteinuria, despite similar BP Excessive sodium intake is associated with worse renal outcome, DESPITE control of blood-pressure and volume status!!!! Diuretic does not eliminate long term adverse effect of excess salt intake! 33 Vegter, JASN 212: 23: RENAAL- IDNT: Effect of sodium status on outcome in diabemc nepropathy A: Renal events Proportion with renal events Sodium:creatininetertile: Low Medium High non-raasi based therapy Proportion with renal events Sodium:creatinine tertile: Low Medium High ARB therapy UNaV 152/d 179/d 29/d RENAAL- IDNT: salt excess annihilates renal and CV protecmon by ARB Renal Outcome No. of events / paments Favours Favours Hazard RaMo p for ARB Non- RAASi ARB Non- RAASi (95% CI) trend Na:Cr <121 mmol/g 4/173 75/ ( ) 121<Na:Cr <153 mmol/g 54/175 72/ ( ) <.1 Na:Cr 153 mmol/g 56/151 75/ ( ) Log-rankP= Time (months) Log-rankP= Time (months) Overall 15/ / ( ) B: Cardiovascular events non-raasi based therapy.5 Sodium:creatininetertile:.5 Sodium:creatinine tertile: ARB therapy Cardiovascular Outcome Na:Cr <121 mmol/g 45/173 64/ ( ) Proportion with cardiovascular events Low.4 Medium High Log-rankP= Time (months) Proportion with cardiovascular events Low.4 Medium High Log-rankP= Time (months) 121<Na:Cr <153 mmol/g 62/175 62/ ( ).21 Na:Cr 153 mmol/g 59/151 72/ ( ) Overall 166/ / ( ) Hazard ramo (95% CI) Lambers Heerspink Kidney Int 212: 82:

Resume so far Modest reducmon of dietary salt, towards targets recommended for the general populamon is associated with substanmal renal and CV benefits in non- diabemc and diabemc renal paments!

10 Resume so far Modest reducmon of dietary salt, towards targets recommended for the general populamon is associated with substanmal renal and CV benefits in non- diabemc and diabemc renal paments! The effect is explained by blunmng of the protecmve effect of RAAS- blockade! Modest dietary sodium restricmon provides reno- and cardio- protecmon beyond blood pressure control, and is related to berer proteinuria reducmon. Use of diuremcs does NOT overcome the effect of salt excess on hard renal end points! Long term effect sodium restricmon and diuremc in CKD are not equivalent: sodium volume (?). ImplicaMons: Dietary sodium restricmon is required in CKD even if BP is well- controlled AddiMonal markers for the effects of excess sodium on the body are needed. Possible mechanisms: Non- volume effect of sodium on the body. Adverse effect diuremc? 38 Sodium and cardio- renal damage Part 4 Excess salt intake Blood pressure ECV Non-pressure, non-volume effects Cardiorenal damage Despite interactions, different effects of sodium on the body can act on end organ damage independently. Reliance on BP as the only read-out is a severe limitation in studies on effects of sodium. Multiple read-out assessment of sodium status may allow substantial advances! 1

Managing patients with renal disease

Managing patients with renal disease Hiddo Lambers Heerspink, MD University Medical Centre Groningen, The Netherlands Asian Cardio Diabetes Forum April 23 24, 216 Kuala Lumpur, Malaysia Prevalent cases,