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PeterGKerrMonashHealth&MonashUniversity

Clayton,Vic,Australia

KDIGO

Disclosure of Interests

•  Amgen Australia – travel support to meetings

•  Quanta Fluid Solutions – advisory board.

KDIGO Controversies Conference on Dialysis Initiation, Modality Choice & Prescription January 25-28, 2018 | Madrid, Spain

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Current status

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All renal replacement therapy:

KDIGO Controversies Conference on Dialysis Initiation, Modality Choice & Prescription January 25-28, 2018 | Madrid, Spain

AJKD Suppl, March 2017

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Dialysis only:

KDIGO Controversies Conference on Dialysis Initiation, Modality Choice & Prescription January 25-28, 2018 | Madrid, Spain

AJKD Suppl, March 2017

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20%

9%

70%

30%

18%

52%

Australia New Zealand

PDHome HDFacility HD

2016 ANZDATA Annual Report, Figure 2.4

Dialysis Modality by Country 2015

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0

20

40

60

80

100P

erc

en

t

QLD NSW/ACT VIC TAS SA NT WA NZ

2016 ANZDATA Annual Report, Figure 2.6

at end of 2015Dialysis Modality by State

PD Home HD Other HD

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0

20

40

60

80

100P

erc

en

t

QLD NSW/ACT VIC TAS SA NT WA NZ

2016 ANZDATA Annual Report, Figure 2.5

at end of 2015RRT Modality by State

APD CAPD Home HDSatellite HD Hospital HD Graft

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0

100

200

300

Freq

uenc

y

0-4 5-14 15-24 25-34 35-44 45-54 55-64 65-74 75-84 85+Age

2016 ANZDATA Annual Report, Figure 6.1

Australia 2015Age distribution of incident home dialysis patients

Home HDPD KDIGO

0

20

40

60

80

0-14

15-24

25-34

35-44

45-54

55-64

65-74 75

+0-1

415

-2425

-3435

-4445

-5455

-6465

-74 75+

PD Home HD

Cum

ulat

ive

inci

denc

e (%

) (95

% C

I)

2016 ANZDATA Annual Report, Figure 6.5

Censored at transplantation; competing risk deathBy age, Australia and New Zealand 2006-2015

Cumulative incidence of home dialysis at 12 months

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ANZDATA 2016 report

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Outcomes

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Technique Survival (HD & PD)

0.00

0.25

0.50

0.75

1.00

0 1 2 3 4 5Years

<40 (n=2035)40-59 (n=4675)60-74 (n=4567)=75 (n=1886)

Age

2016 ANZDATA Annual Report, Figure 6.18

2004-2015Censored for transplant - Australia

Incident home dialysis technique survival

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Technique Survival - Censored

0.00

0.25

0.50

0.75

1.00

0 1 2 3 4 5Years

<40 (n=2035)40-59 (n=4675)60-74 (n=4567)=75 (n=1886)

Age

2016 ANZDATA Annual Report, Figure 6.19

2004-2015Censored for transplant and death - Australia

Incident home dialysis technique survival

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It’s getting better….

0.00

0.25

0.50

0.75

1.00

0 1 2 3 4 5Years

2013-2015 (n=3663)2010-2012 (n=3146)2007-2009 (n=3309)2004-2006 (n=3045)

Cohort

2016 ANZDATA Annual Report, Figure 6.16

2004-2015Censored for transplant and death - Australia

Incident home dialysis technique survival

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Perl J et al, CJASN, 2017, 12:1248.

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Integrated Dialysis

•  Transition from PD to Home HD poor. •  ANZ – 5% only (ANZDATA)

•  Canada – 2 -14% (McCormick BB et al, CJASN)

•  Planned vs emergency KDIGO

Patient Survival

0.00

0.25

0.50

0.75

1.00

0 1 2 3 4 5Years

2013-2015 (n=3663)2010-2012 (n=3146)2007-2009 (n=3309)2004-2006 (n=3045)

Cohort

2016 ANZDATA Annual Report, Figure 6.14

2004-2015Censored for transplant - Australia

Incident home dialysis patient survival

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ANZDATA Analysis

Marshall MR, Kerr PG et al, AJKD, 2016; 67(4):617

•  Dataset •  All adult patients starting renal replacement

therapy in Australia and New Zealand since March 31, 1996, followed up to December 31, 2011

•  n = 38773 (2,054,990 patient-months)

•  Marginal structural model •  Able to adjust for the majority of cases who now

have time-varying medical co-morbidity

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ANZDATA analysis - definitions

•  Separating HD into • Conventional HD: 3 x a week, <=6 hours/session •  “True” Freq / Ext HD: >=5 x a week (no short daily) •  “Quasi” Freq / Ext HD: Anything more than conventional, but less than……..

•  Competing risks regression •  No informative censoring, only censoring for loss to follow up •  Transplantation explicitly modelled as a competing risk using multinomial regression with discretised time (patient moth episodes) in a panel (longitudinal time series) data

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Transplant

PD

All Home HD

All Facility HD

.25 .5 1 1.5

Hazard Ratio

Initial analysis – HR for death

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Transplant

Peritoneal Dialysis

"True" - Freq / Ext Home HD

"Quasi" - Freq / Ext Home HD

Conventional Home HD

"True" - Freq / Ext Facility HD

"Quasi" - Freq / Ext Facility HD

Conventional Facility HD

.25 .5 1 2 4

Hazard Ratio

Detailed analysis – HR for death

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PD v Hospital/Centre HD

Pike E et al, Norwegian Knowledge Center for Health Services, Report No 19-2013.

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Why should there be benefits?

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•  Increased hours and frequency – Solute clearances – Fluid management

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9 patients;

90 litres dialysate

Blood flow rate = dialysate flow rate

Same system used for 4,6 or 8 hours

Therefore testing influence of time only with equivalent amount of blood processed.

Eloot S et al, KI, March 2008

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Regimen Urea Creatinine Vancomycin Inulin β2-Microglobulin

Conventional hemodialysis 1 1 1 1 1

Short daily hemodialysis 1.04 1.03 1.06 1.05 1.00

Long 3 times per week 0.96 1.08 1.32 1.54 1.27

Long 5 times per week 1.58 1.80 2.21 2.57 1.73

Long 7 times per week 2.22 2.55 3.12 3.62 2.19

Normalized Equivalent urea clearance (EKR, ml/min) during the different dialysis regimens

Vancomycin – MW 1448; Inulin – MW 5200; B2m – MW 11,800

- Conventional - Short Daily

- Nocturnal regimens

Mathematical modelling – Clark WR et al, JASN, 1999

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Foley RN et al USRDS data to Dec 2010. ASN 2012 FR-P0302

NotseeninAustraliandataexaminingnocturnalHD(3.5+Mmesperweek)

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AssimonMM…FlytheJE,AJKD,2016

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TransientmyocardialischemialeadingtoLVdysfuncMonwhichcanpersistaYerrestoraMonofnormalperfusion

Selbyet al.AJKD2006;47:830

MyocardialStunning

HDistheperfectsetupforSTUNNINGHD [ 6MBF [ RWMA (in absence of coronary disease)

McIntyreet al.CJASN2008;3:19

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Burtonet al.CJASN2009;4:914

WITHHD-inducedRWMA

WITHOUTHD-inducedRWMA

WITHHD-inducedRWMA

WITHOUTHD-inducedRWMA

5.111.626.2

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Jefferies et al. CJASN 2011; 6:1326

CHD SDHD ≥5CHD NHD In-centre Home

Del

ta S

ysto

lic B

P (m

mH

g)

SDHD UF/session 2.12 L UF rate 800 ml/hr

NHD UF/session 1.95 L UF rate 300 ml/hr

CHD SDHD ≥5CHD NHD In-centre Home

Num

ber o

f R

WM

As

CHD SDHD NHD ≥5CHD In-centre Home

UF

Volu

me

(litr

es)

287 mL/hr

141 mL/hr 1100

mL/hr 1200 mL/hr

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Not all sustained – need recurrent reinforcement

ePub 30 Nov, 2017

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Barriers to home dialysis. •  Financial – patient, doctor and institution •  Physical infrastructure – home, hospital training

facilities •  Lack of expertise – nephrologists, nurses •  Lack of industry support – hardware, consumables,

deliveries •  Lack of belief/trust in home dialysis – doctors,

nurses, patients •  Patient – demography, geography, comorbidities

Adapted from Ludlow, Kerr et al, Nephrology, 2011.

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Australian Nephrologists Believe in Home HD

Ludlow MJ … Kerr, PG et al. Nephrology, 2011; 16:446.

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What do the patients want?

AJKD 2015; 65:451

Patients and caregivers perceive that home HD offers the opportunity to thrive; improves freedom, flexibility, and well-being; and

strengthens relationships.

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NZ study of patient preferences

•  Discrete choice study of 143 participants – preferences and trade-offs

•  Preferred home dialysis if unlimited nursing support available

•  Willing to pay US$271/month for that support •  Preferred home Dialysis if out of pocket costs

minimised •  Preferred home Dialysis if nocturnal Dialysis

available •  Willing to pay US$151/month to gain treatment

flexibility Walker RC, Morton RL, ..Tong A et al, CJASN, 2018

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60708090

100

450500550600

8001000120014001600

600700800900

200300400500600

1995

2000

2005

2010

2015

1995

2000

2005

2010

2015

1995

2000

2005

2010

2015

0-24 25-44 45-64

65-74 75+

Freq

uenc

y

Year

2016 ANZDATA Annual Report, Figure 6.12

By ageAustralia 1996-2015

Number of Home Dialysis Patients at End of Year

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Unquestionable Centre Bias

0

20

40

60

80

100

Perc

ent a

t hom

e (9

5% C

I)

0 20 40 60 80Hospital

2016 ANZDATA Annual Report, Figure 6.13

By hospital, Australia 31 Dec 2015Proportion of dialysis patients treated at home

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Need to avoid delays to start

0

20

40

60

0 3 6 9 12 15 18 21 24 0 3 6 9 12 15 18 21 24

PD Home HD

Australia New Zealand

Cum

ulat

ive

inci

denc

e (%

)

Months on dialysis

2016 ANZDATA Annual Report, Figure 6.3

Censored at transplantation; competing risk deathBy country 2006-2015

Time to home dialysis

-  Patients too comfortable in a facility

-  AND -  A long lag will

influence your interpretation of outcomes KDIGO

Economic evaluation, including QoL

Pike E et al, Norwegian Knowledge Center for Health Services, Report No 19-2013.

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Nature Rev Nephrol, 2014; 10:644.

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Home Dialysis: summary

•  Patients prefer it

•  Outcomes are excellent

•  Administrators love it – it‘s cheaper

•  Practicalities will demand it

•  Let‘s do it.

- (but it means you have to support it)

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