1. Measurement and preservation of residual renal function (RRF) in haemodialysis patients Elizabeth Lindley and David Keane Leeds Teaching Hospitals NHS Trust

2. What are the benefits of RRF? Better volume control Less restriction on salt and fluid intake Less fluid-related hypertension Lower UF rates - more comfortable sessions Better toxin removal Less dialysis required (2 x week or shorter) Better potassium and phosphate control Less dietary restriction / fewer binders

3. Average UF volume per session Vilar et al, NDT 2009

4. Data from the Convective Transport Study (CONTRAST). Lars Penne et al, CJASN 2011 Phosphate control and use of binders

5. Other benefits..... Better removal of middle molecules like beta-2 microglobulin despite being on twice weekly HD (Lin et al, Nephrology 2008) Better survival despite lower dialysis dose (Vilar et al, NDT 2009) Better quality of life (Shafi et al, AJKD 2010) Lower CRP levels (Shafi et al, AJKD 2010) Lower ESA requirements (Lars Penne et al, CJASN 2011) Reduced left ventricular mass? (Evidence from PD & FHN Trials)

6. Stolic et al, Int Urol Nephrol 2011 ED = Erectile dysfunction

7. Dialysis myths? Peritoneal dialysis preserves residual renal function, in haemodialysis it declines rapidly – Has led to routine monitoring of RRF in PD but not in HD Patients who start dialysis early have better outcomes – Based on ‘conventional wisdoms’ (see Rosansky, CJASN 2011) such as nutrition will improve when dialysis is initiated and that once in CKD stage 5 (eGFR < 15 ml/min/1.73m 2 ), patients will inevitably progress to end stage kidney failure HD patients should have 3 x week dialysis with eKt/V > 1.2

8. Does PD preserve RRF better than HD? McKane et al, KI 2002

9. de Jager et al, NDT 2013 (NECOSAD study) Rate of decline in RRF (from urine collections) before and after starting dialysis

10. Is early start dialysis better? Cooper et al, NEJM 2010 (IDEAL Study) The good effects of the extra clearance of toxins seem to be matched with a bad effect that completely wipes out any benefit of starting dialysis early

11. Should HD patients have 3 x week dialysis with a minimum eKt/V of 1.2? Vilar et al, NDT 2009 ‘Incremental’ HD/HDF: dose increases to maintain target Kt/V including KrU Fernández-Lucas et al, Nephrologia 2012 HD 2 x week until KrU < 2.5 ml/min or symptomatic

12. How do you preserve RRF in HD patients? From Dybtved Kjaergaard et al, NDT 2011 also nephrotoxic drugs like NSAIDs and aminoglycoside antibiotics

13. HD machines will remove fluid whether or not the patient can spare it....

14. Measurement of fluid status with bioimpedance and modelling Resistance 5kHz 1MHz Fluid Model Extracellular water Intracellular water Body Composition Model Lean tissue Adipose tissue Over/under hydration Weight, Height  RR R0R0 Reactance Weight 

15. Introducing the BCM The Fresenius Body Composition Monitor (BCM) uses this modelling to provide an objective measurement of hydration status. After introducing it, we could see why reducing target weight did not always improve blood pressure control.....

16. Some hypertensive patients were already normally hydrated or dehydrated pre-dialysis Dehydrated Normal Overhydrated

17. Hydration status at prescribed target weight for 420 patients on first BCM i.e. with TW established using standard clinical indicators (BP, oedema etc) p<0.001 Normal hydration

18. In patients with RRF, it can lead to increased fluid gains and lower urine output p<0.001 Normal hydration In patients with no RRF, dehydration allows ‘room’ for interdialytic fluid gains

19. Female patients tended to be about 0.5 L more dehydrated than males at their prescribed target weight. This may be why female sex is associated with more rapid decline of RRF (Moist et al, JASN 2000) p=0.002 Normal hydration

21. How do you measure RRF in HD? Inulin and isotopic tracer (e.g. Cr-51 EDTA or Tc-99 DTPA) measurements are accurate but too time-consuming and expensive for routine use. Cystatin C is probably not suitable for measuring low GFRs (Tidman et al, NDT 2007) The most frequently used measure of RRF is the mean of urea and creatinine clearance during a timed urine collection.

23. In CKD and PD – 24 hour timed collections Creatinine in urine24 mmol Urea in urine 400 mmol Estimated volume filtered from urea? 400 mmol  20.0 mmol/L = 20 litres/24 hours Serum creatinine 1.0 mmol/L Serum urea 20.0 mmol/L Estimated volume filtered from creatinine? 24 mmol  1.0 mmol/L = 24 litres/24 hours Take the average, multiply by 1000 to get mLs and divide by 1440 to get mins 22 x 1000  1440 = 15.3 mL/min

24. HD patients are not in steady state Urine output may be affected by post-dialysis dehydration Serum creatinine and urea increase between sessions – (In patients with RRF) It will approach steady state To get a GFR for an HD patient you need a timed urine collection with a time-averaged serum creatinine and urea – 24 hour collections are more difficult to analyse and can give different results depending on the choice of the 24 hour period – Interdialytic collections are more work for the patient but simpler to define (all urine from one session to the next) What do people do? Ask RenalPro....

25. Does your unit carry out urine collections in HD patients with significant residual function? 20 responses from 12 countries

26. How long does your unit ask patients to collect urine for? 19 responses

27. Does your unit use urine collections to adjust fluid allowance or dialysis regime? Fluid allowance Dialysis time and/or frequency 20 responses from 12 countries

28. Suggestion for monitoring RRF 3 x week HD – 48 hour collection for 2 days after monthly bloods – Collect all urine from end of dialysis to start of next session – Use monthly bloods and pre-dialysis sample for next session to estimate the average serum creatinine and urea 2 x week HD – Timed collection for last day of 4 day interval – Collect urine produced from morning before dialysis day (first urine goes in the toilet) until the start of dialysis – Use pre-dialysis sample as average serum creatinine and urea For weekly HD, use eGFR from serum creatinine

29. Preserving RRF Measure it! Avoid post-dialysis dehydration in patients with RRF – Use Body Composition Monitoring if available – If not, make sure that interdialytic fluid gains do not increase when target weight is reduced and watch for patients whose pre-dialysis weight is very consistent Consider 2 x week HD – If clearance is adequate, low fluid gains and good control of potassium and phosphate If GFR reaches ~ 8 ml/min/1.73m2 (depends on individual) try weekly HD to see if the patient can stop dialysis

30. Case study – ‘Nick’ 40 year old Afro-Caribbean male admitted in Nov-11 with severe headache – eGFR of 5 ml/min/1.73m 2, started dialysis the same day – Discharged to out-patient HD 3xweek after two weeks Target weight repeatedly reduced to control high blood pressure. – Interdialytic fluid gains about 3 L – Pre-dialysis creatinine about 700 umol/L BCM measurement in Apr-12 showed severe post dialysis dehydration

31. ‘Nick’ continued Target weight was increased twice based on BCM – Pre-dialysis BP was unchanged – Interdialytic fluid gains dropped to zero – Interdialytic urine collection gave GFR ~ 9 ml/min/1.73m 2 Converted to 2xweek HD in May-12 – GFR increased to ~ 11 ml/min/1.73m 2 – Phosphate well controlled (BP still high) Converted to once weekly dialysis in Jun-12 – eGFR increased to 15 ml/min/1.73m 2 – Moved to low clearance clinic Most recent eGFR was 25 ml/min/1.73m 2

32. Case study – ‘Cathy’ 52 year old Caucasian female with adult polycystic kidney disease, transferred to Low Clearance Clinic in Jan-11 eGFR decreased from 17 to 7 mL/min/1.73m 2 HD started Oct-10 – 3 x week (still unit policy) Transferred to satellite unit Nov-11 – Started ‘shared care’ training with view to home HD – BCM showed no fluid removal required – Interdialytic urine collection showed GFR = 6 mL/min/1.73m 2 – Choose to reduce time but stay on 3 x week

33. HD started eGFR and GFR from urine collections

34. Case study – ‘Cathy’ Completed home HD training in Jul-13 – Home HD patients can choose their regime (up to 6 x week) GFR still ~6 mL/min/1.73m 2 but poor phosphate control Renal function not expected to improve but Cathy is very keen to preserve what function she has - what is the best regime? Based on limited evidence and discussions Cathy chose: – 4 hour sessions 2 x week (or every 3 days) – Review of dietary phosphate, additives from processed meat? – Urine collections every 3 months (or if she feels unwell) – BCM every 3 months (or if her weight starts to increase) – Convert to alternate night nocturnal HD when necessary?

35. The next best thing to functioning kidneys!