Can we make haemodialysis better?

1. Can we make haemodialysis better? Elizabeth Lindley Departments of Renal Medicine and Medical PhysicsLeeds Teaching Hospitals NHS Trust, UK

2. What are we trying to avoid? • Symptoms that affect well-being during/after the session • Symptomatic hypotension (dizziness, nausea etc) • Cramps • Headache and visual disturbances • Itching, Restless legs • Post-dialysis fatigue • Longer term harmful effects • Loss of residual function • The ‘Dark side’ of dialysis (transient ischaemia of vascular beds) Some problems may be caused or resolved by medication

3. What can we change? • Assuming that the patient has already optimised their diet and is getting an adequate dialysis dose, with high quality water and a biocompatible blood circuit, in a safe and supportive environment .... • You can easily change: • Target weight • Dialysate composition (some aspects) • Dialysate temperature • You may be able to help with: • Anxiety • Treatment modality • Medications

4. Optimising target weight • Historically we have automatically reduced target weight in hypertensive patients • It was assumed that high blood pressure was mainly the result of fluid overload • So drying the patient out was thought to be an essential element of reducing cardiovascular risk • Some discomfort and fatigue post-dialysiswas considered to be normal • Loss of residual function was not regardedas important in haemodialysis • This approach of ‘probing dry-weight’ leads to a higher rate of intradialytic hypotension (and probably loss of vascular access)

5. 1MHz 5kHz R0 R • Extracellular water • Intracellular water Weight, Height  FluidModel • Lean tissue • Adipose tissue • Over/under hydration Body Composition Model Assessment of hydration with bioimpedanceand modelling Reactance Resistance Weight 

6. Introduction of body composition monitoring • BCM was introduced for our adult HD patients in 2009-10 • After introducing BCM,we could see why reducing target weight did not always improve blood pressure control....

7. Some hypertensive patients were already normally hydrated or dehydrated pre-dialysis DehydratedNormalOverhydrated

8. Introduction of body composition monitoring • BCM was introduced for our adult HD patients in 2009-10 • After introducing BCM,we could see why reducing target weight did not always improve blood pressure control.... • …. and that most of our patients were dehydrated post-dialysis, some to a surprising degree (> 3 L)

9. Individualised target weight The target weight for a haemodialysis patient should, if possible, • enable the patient to remain close to normal hydration(based on BCM measurements) throughout the interdialytic period • with optimal control of blood pressure • without experiencing discomfort and • without compromising residual function

10. Does BCM work in children? • Step one – find some healthy children….

11. Body composition measured using DEXA scan

12. And air displacement plethysmography (Bod-Pod)

13. Body water measured with deuterium dilution Drink 7% D20 in water (1g per kg) 7 ml urine samples collected before deuterium drink and for next 5 nights. NB. Deuterium is not radioactive, it’s a stable, naturally occurring, isotope of hydrogen found at low levels in all water

15. Good agreement between TBW measured with deuterium dilution and BCM

16. And between TBW measured with UKM and BCM

17. Routine BCM measurements started in 2010 BRS 2011

18. Normally hydrated weight determined from BCM

19. Variation in systolic BP with fluid overload

20. BCM measurements? Child’s play!

21. Sodium and thirst in HD patients • ‘Osmometric’ thirst is part of the body’s system for maintaining electrolyte balance • In steady state (salt in = salt out) an anuric HD patient will need to consume about 1 L of water to dilute every 8g salt they eat to maintain a physiologically normal sodium level • The patient will take in fluid with their food, with medications and in beverages for pleasure • If salt consumption gets ahead of fluid intake, osmometric thirst will force the patient to drink • The serum sodium at which thirst is triggeredvaries from person to person and has been called the ‘set-point’ or ‘osmostat’

22. These patients are probably drinking for non-salt related reasons e.g. poor glucose control or social reasons

23. Difference between serum Na and set point Thirst occurs when salt intake gets ahead of water intake More salt than water More water than salt HD HD 08:00 to 12:00

24. What should the dialysate sodium be? • Patients with pre-dialysis serum sodium > dialysate sodium* will lose sodium by diffusion during dialysis and have ‘room’ to gain salt before they feel thirsty • This will mean they gain less fluid between sessions • Lower fluid gains lead to lower ultrafiltration rates which should mean more comfortable dialysis sessions with fewer episodes of intradialytic hypotension provided the lower dialysate sodium does not impair vascular refilling • So when our dialysis prescription was reviewed in 2007, the multidisciplinary team set the standard sodium to 137 mmol/L • There was no obvious increase in IDH with the lower sodium * Serum Na+ ≈ dialysate Na+ at the Gibbs-Donnan equilibrium due to protein dilution

26. Looked at hospitalizations and deaths in 29,593 patients from 12 countries with baseline DNa and SNa as predictors

27. As expected, lower dialysate sodium led to lower interdialytic fluid gains Adjusted for DOPPS phase, country, age, sex, BMI, diabetes, and 13 other comorbid conditions

28. But contrary to expectation, the lower IDFG did not translate to lower mortality Adjusted for DOPPS phase, country, age, sex, BMI, diabetes, 13 other comorbid conditions, RRF, vascular access, serum albumin, haemoglobin, creatinine, ferritin, WBCC and facility clustering

29. Or to lower hospitalisation rates Adjusted for DOPPS phase, country, age, sex, BMI, diabetes, 13 other comorbid conditions, RRF, vascular access, serum albumin, haemoglobin, creatinine, ferritin, WBCC and facility clustering

30. So what should the dialysate Na be? • Although the DOPPS data has been adjusted, the patients who died in the study were likely to be frailer and have lower IDFG • For patients with moderate or low IDFG who experience IDH the DOPPS data provided an argument for using a higher dialysate sodium • This probably helps with vascular refilling • But for patients with high IDFG who do not have IDH there is an argument for using a lower dialysate sodium • High IDFG (despite dietary advice) and IDH is an indication for more frequent dialysis

32. What about potassium? Looked at sudden death (due to cardiac arrhythmia, cardiac arrest, and/or hyperkalemia) in 37,765 patients from 12 countries

34. Individualising potassium • With improved dialysis adequacy, hyperkalaemia is less common and dialysis-induced hypokalaemia is more likely • If pre-dialysis potassium is not elevated, a concentrate giving dialysate potassium level of 3 mmol/L is safe and can be used with any regime • If pre-dialysis potassium is elevated, the dialysate potassium level should depend on the dialysis time e.g. • 3 mmol/L for nocturnal • 2 mmol/L for conventional and short daily (unless K+ very high) • 1 or 1.5 mmol/L for short sessions in patients with high K +

35. Vol 23, 449-51 (2010) Chris McIntyreRecurrent Circulatory Stress: The Dark Side of Dialysis HD is capable of exerting significant recurrent systemic circulatory stress. There is already an appreciation that this may be important in the development of cardiac disease, but it appears that this systemic insult is capable of resulting in perfusion-dependent injury of a wide range of vulnerable vascular beds. McIntyre et al, Kidney Int 2009

36. Chris McIntyre and the Derby team showed that impaired blood flow to the heart during ultrafiltration causes ‘myocardial stunning’ And that the degree of stunning is strongly correlated with survival Assa et alCJASN 2012 We should be concerned about transient ischaemia elsewhere, including the gut (endotoxin leaks), brain (cognitive function), eyes and kidneys

37. Progressive white matter injury • HD patients lose cognitive function, particularly ‘executive function’ • During HD, but also over time • Red areas in scan (diffusion tensor imaging) indicate brain damage over 12 months • Aside: A simple intervention completely prevented this damage….

39. More on dialysate temperature • In response to a reduction in blood volume due to fluid removal, the body can reduce the peripheral circulation • Reduced skin blood flow leads to heat retention and an increased core temperature • If the core temperature gets too high, the peripheral circulation will suddenly open up • This can lead to a rapid drop in blood pressure • If blood volume monitoring is being used, there will be an apparent loss in blood volume due to the Fahraeus effect (the blood going to the peripheral vessels carries proportionally more plasma and less red cells) • The effect is the same as eating on HD…

40. The Fahraeus effect means that blood moving to the gut gives an increase in the haematocrit in the central circulation which looks like a fall in blood volume (and has the same effect on BP etc)

41. If the machine used has the option for thermal control, why not use it? If not, try lowering the dialysate temperature if the patient has IDH(and make sure it is at least 0.5°C below body temperature to protect the brain)

42. Pre-dialysis anxiety • If a patient is very anxious prior to dialysis the adrenaline response will move blood away from the skin • More blood for the heart and muscles • Less blood loss if wounded • And shut down digestive activity • When the needles are in and all is well the body relaxes and the stress hormones return to normal • Blood returns to the skin and gut • This redistribution of blood will look like a rapid decrease in BV • Connecting straight up with the UF off and avoiding food or drink early in dialysis may help maintain blood pressure • It may also help to start with a high dialysate Na

43. What if the patient is still symptomatic? • Can you identify the cause? • Can try isolated UF vs no UF to see if symptoms are fluid related • Low efficiency (low flows) to see if symptoms are linked to solute concentration changes • If new onset, look for changes in consumables or medication • Use trial and error… • Prophylactic mannitol or midodrine if IDH is fluid related* • Exercise if patient has cramps and is not dehydrated (or RLS) • Higher Ca if on low concentration (and if not contraindicated) • Try biofeedback and/or profiling if available on your machines • Some patients respond well to HDF (others feel worse) * See reviews by Dal Hothi et al GOSH

44. Prescribing haemodialysis…. • Optimise target weight to avoid excessive dehydration • Not to normalise blood pressure • Individualise the dialysate sodium and potassium • Where indicated, consider: • Lowering the dialysate temperature or using thermal control • Connecting straight up (if you normally bleed out) • Increasing the dialysate calcium? • Using HDF, profiling or exercise? • Stopping or starting relevant medications? Mannitol? • Checking residual function, can session time be safely reduced? • Switching to short daily HD, nocturnal HD or PD?