Future Perspectives in Peritoneal Dialysis

Transcription

1 Future Perspectives in Peritoneal Dialysis Dialysis Initiatives Nefrologen Meeting September 21, 2017 Joanne M. Bargman MD FRCPC Director, Peritoneal Dialysis Program University Health Network Professor of Medicine, University of Toronto

2 Back in 1995 I was asked to speak about what PD would be like in 2005: home generating and self-regenerating dialysate plug-in dialysate availability in the home (no more bags!) elimination of gram positive peritonitis new catheter biomaterials my predictions were about as accurate as

3 The Jetsons! Life in 2000 as envisioned in 1965

4 Okay, More Modest Predictions PD for heart failure PD for AKI in developing countries The growth of incremental dialysis New osmoles that work better than dextrose Home generation of dialysis fluid

5 What I Am Not Discussing Biocompatible PD solutions Biomarkers

6 Okay, More Modest Predictions PD for heart failure PD for AKI in developing countries The growth of incremental dialysis New osmoles that work better than dextrose Home generation of dialysis fluid

7 James W True Story 71 year old man with type II DM and ischemic cardiomyopathy recurrent episodes of diuretic-resistant CHF necessitating admission to CCU for parenteral diuretics and dobutamine infusion one episode of HD for ultrafiltration 6 hospitalizations in the previous year GFR approximately 20 ml/min

8 James W (2) agreed to a trial of PD to attempt to manage ultrafiltration and avoid hospitalization PD catheter inserted without incident prescribed night cycler 2L exchanges X 3 over 8h, day dry average UF ml

9 James W (3) no episodes of CHF, but rapid decline in RKF to almost anuria over 6 months icodextrin day dwell added, average UF ml years 1,2: NO admissions to hospital for CHF one admission for coag neg staph peritonitis, resolved quickly

10 James W (4) Year 3: worsening of peripheral arterial disease, gangrene of feet arterial stenting unsuccessful patient refused amputation died of sepsis likely from the necrotic feet

11 The Cardiorenal Syndrome (CRS) puts a name to something we see very often acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ (Ronco et al Blood Purif 2009) we will focus on CRS Type 1 (acute heart failure leading to AKI) and CRS Type 2 (chronic heart failure leading to CKD)

12 The Heart-Kidney Connection Decreased cardiac output

13 The Heart-Kidney Connection Decreased cardiac output increased proximal Na+ and H2Oresorption Decreased renal blood flow

14 The Heart-Kidney Connection Decreased cardiac output increased proximal Na+ and H2O resorption increased distal Na+ and H2O resorption Decreased renal blood flow Activation of the renin-angiotensin aldosterone axis

15 The Heart-Kidney Connection Decreased cardiac output Decreased renal blood flow increased proximal Na+ and H2O resorption increased distal Na+ and H2O resorption increas ed H2O resorpt ion ADH Increased sympathetic drive and pre-renal vasocontriction Activation of the renin-angiotensin aldosterone axis

16 The Cardiorenal Syndrome these maladaptive responses lead to salt and water retention edema congestive heart failure diuretic resistance chronic hypoperfusion leads to functional, and then fixed decrease in GFR

17 Hypoperfusion Nephropathy gradual decline in GFR oscillation of serum creatinine episodes of acute on chronic kidney injury gradual shrinkage of kidney mass

18 Three Trials of HD UF Baseline kidney function UNLOAD CARESS-HF RAPID-CHF better worse better Fluid removal UF > diuretics UF = diuretics UF > diuretics Change in creatinine UF vs medical management No difference UF group had increased serum creatinine Adverse events No difference More events in UF group No difference No difference Francois, Ronco and Bargman Blood Purif 2015

19 Rationale for PD continuous therapy, or at least daily therapy better tolerated than HD in the hypotensive patient no extracorporeal circuit to fill up slow, gentle ultrafiltration no myocardial stunning

20 Myocardial Stunning in HD demand-associated transient myocardial ischemia during HD may be asymptomatic repeated episodes are postulated to lead to fixed cardiac structural and functional abnormalities, including systolic dysfunction and heart failure McIntyre. Blood Purif 2010

21 Myocardial Stunning in HD Associated with Reduced Survival patients who experienced regional wall motion abnormalities during HD had greater oneyear mortality No RWMAs RWMAs during HD Burton. Clin J Am Soc Nephrol 2009

22 PD is Not Associated with Myocardial Stunning HD HD HD (ref 1) HD (ref 2) PD 1 0 PD #episodes of regional wall motion abnormalities/pt HD #1 Selby Clin J Am Soc Nephrol 2006 HD #2 Selby Am J Kidney Dis 2006 PD Selby Perit Dial Int 2011

23 Other Advantages of PD for Cardiorenal Syndromes no need for arteriovenous access high flow fistulas can increase cardiac work and exacerbate heart failure dextrose-based solutions ultrafilter more water than sodium correction of hyponatremia very low risk of bacteremia compared to HD important if there is a pacemaker or LVAD in place (Thomas et al Perit Dial Int 2012)

24 Hemodynamic Consequences of AV Fistulas Rao Semin Dial 2016

25 What Kind of PD Prescription? Lots of RKF Not much RKF (need for solute clearance)

26 What Kind of PD Prescription? Scenario 1: Adequate Solute Clearance by Residual Kidney Function (CAPD) 2.5% 2.5% (dry night) (dry day) icodextrin or 4.25% (APD or NIPD) (dry day) 2.5% 2.5% 2.5%

27 What Kind of PD Prescription? Scenario 2: Need for both solute clearance and fluid removal (CAPD) 2.5% 2.5% (2.5% or icodextrin) (CAPD) (2.5%) (1.5%) (2.5%) icodextrin or 4.25% (APD) (icodextrin or 4.25%) 2.5% 2.5% 2.5%

28 Won t All that Glucose Harm the Peritoneal Membrane? the evidence for the association of glucose exposure and long-term peritoneal membrane dysfunction is theoretical these patients typically don t survive for a long time on dialysis anyway

29 Probably the earliest report: 1923

30 Most of the Studies are from the Peritoneal dialysis before cardiac sugery Ann Thor Surg 1967 Clinical and hemodynamic results of peritoneal dialysis for severe cardiac failure Am Heart J 1968 Removal of refractory oedema fluid by peritoneal dialysis Br J Urol 1968 Peritoneal dialysis for pulmonary edema after acute myocardial infarction Br Med J s

31 PD for CHF: Recent Studies mean daily peritoneal UF 670 +/- 225 ml GFR did not change over the study (mean F/U 15 months) peritonitis very uncommon Sanchez et al Neph Dial Transpl 2010

32 Days in Hospital/Year days before PD on PD Sanchez Neph Dial Transpl 2010

33 Change in Functional Status Before and During PD NYHA Functional Class Before PD During PD 3 patients died of heart failure at 5, 12 and 16 months improved quality of life cost-effective Sanchez Neph Dial Transpl 2010

34 More Recent Studies (continued) 23 patients with chronic cardiorenal syndrome 12 placed on PD, 11 onto HD mean GFR 15 ml/min ischemic/dilated/rheumatic/restrictive cardiomyopathies mean survival about 16 months, no difference PD vs HD improved quality of life

35 The Italian Cohort Study Bertoli et al Perit Dial Int 2014 patients with at least 3 hospital admissions for extracorporeal ultrafiltration in the previous year GFR 20 ml/min 48 patients mean age 74 years mainly ischemic and idiopathic cardiomyopathy

36 The Italian Cohort Study Bertoli et al Perit Dial Int /48 patients used manual exchanges 30/35 used one icodextrin overnight 5/35 used one dextrose and one icodextrin 13/48 patients used NIPD residual renal function stayed stable! 85% survival at one year, 56% at two years

37 French Cohort Study Courivaud et al Perit Dial Int 2014 review of patients started on PD for CHF mean GFR was 33.5 ml/min mainly ischemic, dilated and valvular cardiomyopathies mean age 72 years (30-94 years) mean survival 16 months LVEF improved in those where it was <30% at baseline

38 Survival Comparisons Median survival 16 months Cnossen Neph Dial Transpl 2012 Mean survival 17.3 months Elhalel-Dranitzki Neph Dial Transpl 1998 Mean survival 12.7 months Ryckelynck Adv Perit Dialy 1997

39 PD for Heart Failure may or may not prolong survival reduces days in hospital better for quality of life less expensive than recurrent admissions to the cardiac unit

40 Okay, More Modest Predictions PD for heart failure PD for AKI in developing countries The growth of incremental dialysis New osmoles that work better than dextrose Home generation of dialysis fluid

41 PD for AKI There are an unacceptable number of deaths from AKI in developing countries because of the unavailability of dialysis PD would be more feasible than HD in rural underserviced areas PD has also proven successful in developed countries

42 randomized, controlled trial of PD versus HD for ATN no difference in rate of recovery of kidney function or in mortality rate faster recovery of kidney function in the PD group Kidney Int 2008

43 PD for AKI: Results Improving Over review of the Sao Paulo experience over patients compared to the first 5 years, patients in the second 5 year period had a 13% decreased risk of mortality and a 14% decreased risk of technique failure Time Gabriel PLoS One 2015

44 The 0 by 25 Project of the International Society of Nephrology

45 The 0 by 25 Project

46 An Excellent Guideline

47 Okay, More Modest Predictions PD for heart failure PD for AKI in developing countries The growth of incremental dialysis New osmoles that work better than dextrose Home generation of dialysis fluid

48 What is Incremental PD? Starting with less than the usual PD prescription in patients with residual kidney function (RKF) Increasing the dose of PD over time as the RKF declines

49 Incremental PD A Schema RKF PD RKF PD RKF PD

50 Why Incremental PD? Most PD is an elective start, with significant kidney function (GFR 8 ml/min or more) Small amounts of PD tend to result in symptomatic improvement It doesn t burden the patient with the same prescription that a patient with no kidney function might need It allows time for the patient to become comfortable with the therapy

51 If You Prescribe Incremental PD You must monitor the residual kidney function 24h urine If the patient forgets : if the prescription is the same, and the serum creatinine is the same, the renal function is the same

52 Examples of Incremental PD CAPD 1 icodextrin overnight 1 overnight and 1 (4h) day exchange 2 (6h) day exchanges and dry overnight a day off!

53 Examples of Incremental PD APD 2 or 3 exchanges overnight and dry day (= NIPD) a day off!

54 Example from a Canadian Centre Ankwari Cdn J of Kid Health and Disease 2016

55 So, Any Evidence? That s all very nice, but is there any evidence that incremental PD is safe?

56 incident patients with residual GFR 3-10 ml/min duration of incremental PD (ipd) 17 months ipd: 1-2 exchanges/day

57 Incremental PD - Outcome No difference in peritonitis rates (1/135 pt-months incremental versus 1/52 in standard PD) No difference in survival 8/29 incremental patients were transplanted before ever needing to increase PD dose Sandrini J Nephrol 2016

58 Incremental PD - RKF 7 6 P< RKF start RKF end standard PD Sandrini J Nephrol 2016 incremental PD

59 46 patients receiving 3 or fewer exchanges/day 24 months many were transplanted before moving to standard PD good outcomes Barras Sans Nefrologia 2016

60 Incremental PD Nephroprotective? before PD slope of GFR on incremental -4 slope of GFR Barras Sans Nefrologia 2016

61 Similar to Our Data! P < 0.01 He Perit Dial Int 2016

62 In Other Words PD may be nephroprotective compared to HD or even pre-dialysis incremental PD may be even more nephroprotective than regular PD

63 Okay, More Modest Predictions PD for heart failure PD for AKI in developing countries The growth of incremental dialysis New osmoles that work better than dextrose Home generation of dialysis fluid

64 Hyperbranched Polyglycerol A new compound in investigation for PD fluid Water-soluble polyether polymer Appears to promote better mesothelial cell viability compared to dextrose-based PD solutions Rodent studies only so far Mendelson Perit Dial Int 2013

65 Better Preservation of UF in a Rat Model of Chronic PD Instillation of dextrose-based dialysis fluid (PYS) was compared to instillation of hyperbranched polyglycerol (HPG) for 3 months Less disrupted peritoneal membrane morphology and better membrane function seen with the HPG * Du J Transl Med 2016

66 Okay, More Modest Predictions PD for heart failure PD for AKI in developing countries The growth of incremental dialysis New osmoles that work better than dextrose Home generation of dialysis fluid

67 Home Generation of PD If we can do this for home hemodialysis, why not for home peritoneal dialysis? Solutions Picture courtesy of Dr. I. Teitelbaum

68 Blog: Failed beans

69 And What About the Carbon Footprint of All the Delivery Trucks?

70 Home Generation of PD Not much in the public domain Industry is keeping it quiet for now This would be a great advance for PD Solutions

71 The Two Players in North America (so far) NxStage Medical Details New Features, Hints at Peritoneal Dialysis System Posted in Medical Device Business by mthibault on August 8, 2016 The head of the dialysis company highlights the next-generation features coming soon to its hemodialysis system and explains why NxStage Medical could become a major player in the peritoneal dialysis market.

72 Future Perspectives in PD We will see a growth in the use of PD for diuretic-resistant heart failure Progress in using PD to treat reversible AKI in developing countries More acceptance of the use of incremental dialysis Maybe new osmoles in PD fluid? Maybe in-home generation of PD fluid?