Home Hemodialysis or Transplantation of the Treatment of Choice for Elderly?

Transcription

1 Home Hemodialysis or Transplantation of the Treatment of Choice for Elderly? Miklos Z Molnar, MD, PhD, FEBTM, FERA, FASN Associate Professor of Medicine Division of Nephrology, Department of Medicine University of Tennessee Health Science Center Memphis, TN, USA

2 Disclosure Merck Co Advisory Board National Institute of Health (NIH) R21AG047306

3 Objectives 1 Select Modality for your Tx Candidate 2 Home/Extended HD versus Conventional HD 3 Home HD versus Kidney Transplantation 4 Results for Comparison of Home HD versus Kidney Transplantation in USA 5 Conclusions

4 Objectives 1 Select Modality for your Tx Candidate 2 Home/Extended HD versus Conventional HD 3 Home HD versus Kidney Transplantation 4 Results for Comparison of Home HD versus Kidney Transplantation in USA 5 Conclusions

5 Your patient 67 years old retired AA policeman with 20 years history of diabetes and diabetic nephropathy with egfr 12 ml/min./1.73m 2 No known CAD, PVD, COPD. 25% stenosis in both carotis arteries and HTN On regular medications (Insulin, ACEI (still), Aspirin, Statin) Unremarkable physical AV access is ready for use, Hgb, PTH, Ca, P are on target Doing daily workout, history of steroid induced psychosis Eligible for kidney transplantation, no living donor Excellent adherence, good diabetes and HTN control Excellent living condition, good candidate for HHD He decided to go with HHD when he is offered a kidney

6 Kidney #1 Living donor kidney from altruistic donor as end of the chain he is the recipient from the list. Donor is 55 years old, White, male. 2 arteries. No DSA. Should he go for it?

7 Kidney #2 SCD donor kidney (KDPI: 35). Donor is 50 years old, White, female, cause of death: accident. No contributory donor information. No DSA. Should he go for it?

8 Kidney #3 ECD donor kidney (KDPI: 80). Donor is 65 years old, African American, male, cause of death: cerebrovascular accident. CIT would be around 23 hours, donor was on vasopressors, donor has history of HTN, IFG. Estimated GFR is around 70 ml/min, good diuresis. One DSA- Class II. Should he go for it?

9 Kidney #4 DCD donor kidney. Donor is 45 years old, African American, female, cause of death: motor vehicle accident. Donor is treated HCV positive, previous drug user Estimated GFR is around 60 ml/min. One DSA- Class I. Should he go for it?

10 Objectives 1 Select Modality for your Tx Candidate 2 Home/Extended HD versus Conventional HD 3 Home HD versus Kidney Transplantation 4 Results for Comparison of Home HD versus Kidney Transplantation in USA 5 Conclusions

11 26,016 patients from Australia and New Zealand Transplant Registry Analysis AJKD, 2011, 58(5): Lack of socioeconomic, medication and laboratory data

12 JASN, 2012, 23: (from 420) propensity score matched HHD patients from France, Canada and US Matched with DOPPS CHD patients

13 JASN, 2012, 23: ,873 propensity score matched HHD patients from US 1:5 matched with 9,365 CHD patients

14 Effect of Extended-Hours Hemodialysis on Survival of Patients with End-Stage Renal Disease in US Analysis Hazard Ratio and 95% CI Including extended-hours HD facility indicator Including extended-hours HD facility indicator & initial vascular access type Restricting to conventional HD patients treated at a facility offering extended-hours HD Model Current dialysis modality, no lag Current dialysis modality, 90-day lag Dialysis modality 30-days prior, no lag Dialysis modality 30-days prior, 90-day lag Dialysis modality 60-days prior, no lag Dialysis modality 60-days prior, 90-day lag Restricting to conventional HD patients treated at a facility offering extended-hours HD or a facility in which extendedhours HD patients were previously treated Favors extendedhours hemodialysis Favors conventional hemodialysis Rivara MB et al., KI, 2016

15 Objectives 1 Select Modality for your Tx Candidate 2 Home/Extended HD versus Conventional HD 3 Home HD versus Kidney Transplantation 4 Results for Comparison of Home HD versus Kidney Transplantation in USA 5 Conclusions

16 Background Kidney transplantation (KTx) is the treatment of choice for patients with end stage renal disease (ESRD). Several studies have compared survival of waitlisted dialysis patients with KTx recipients. One of the largest study of 230,000 dialysis patients showed that mortality was significantly lower among patients who received a KTx compared with transplant wait-listed dialysis patients (3.8 vs. 6.3/100 patient-years). As clinical trial can not be performed to answer this question, welldesigned and conducted observational trials can provide us the best evidence.

17 Canadian HHD from two centers in Toronto US Tx recipients

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19 J Am Soc Nephrol. 2014;25(9): From one center in Toronto, Ontario, Canada Relatively young patients The primary outcome of this study was time-to-treatment failure or death for IHHD patients compared with kidney transplant recipient subtypes 285 events

20 J Am Soc Nephrol. 2014;25(9):

21 J Am Soc Nephrol. 2014;25(9):

22 J Am Soc Nephrol. 2014;25(9):

23 Can we use these results in US? There are several reasons why the comparative effectiveness of the two modalities may differ in the United States; to our knowledge there was no such studies comparing home HD with KTx in the United States. There is a high prevalence of low-flow systems such as NxStage in the United States, which provide lower solute clearances than conventional HD machines used in Canada. In addition, none of the platforms in the United States have been approved for nocturnal HD, and hence most home HD patients undergo short, daily dialysis. Finally, the risk of death in patients undergoing HD or with KTx is in general higher in the United States than in Canada.

24 Objectives 1 Select Modality for your Tx Candidate 2 Home/Extended HD versus Conventional HD 3 Home HD versus Kidney Transplantation 4 Results for Comparison of Home HD versus Kidney Transplantation in USA 5 Conclusions

25 ASN in the Loop News 11/11/2015

26 Flow chart of patients selection Molnar MZ et al., Transplantation, 2016

27 Baseline characteristics of the unmatched cohort Unmatched Home HD KTx (n =2,830) (n = 73,976) Std. Diff. Age (years) 53 ± ± Female (%) Diabetes mellitus (%) Race/Ethnicity (%) Whites African-American Asian Hispanic Other Primary insurance (%) Medicare Medicaid Other Comorbid States (%) Alcohol abuse History of cancer Hypertension Cerebrovascular disease Artherosclerotic Heart Disease Congestive heart failure Other cardiovascular disease Chronic Obstructive Pulmonary Disease Molnar MZ et al., Transplantation, 2016

28 Baseline characteristics of the unmatched cohort Molnar MZ et al., Transplantation, 2016 Access Type at time of Home HD initiation/time of KTx (%) AV Fistula Home HD 57 KTx AV Graft CVC Catheter Other Unknown Cause of ESRD (%) Diabetes Hypertension Glomerulonephritis Cystic kidney disease Other urologic reason Unknown Laboratory Tests at time of Home HD initiation/time of KTx Serum albumin (g/dl) 3.9 ± ± Blood hemoglobin (g/dl) 11.1 ± ± Other Total ESRD time before modality initiation (days) 387 ± ± Body Mass Index (kg/m 2 ) 30 ± 7 28 ±

29 Baseline characteristics of the 1:1 PS matched cohort Molnar MZ et al., Transplantation, 2016 Home HD KTx (n=2,000) (n=2,000) Std. Diff. Age (years) 54 ± ± Female (%) Diabetes mellitus (%) Race/Ethnicity (%) Whites African-American Asian Hispanic Other Primary insurance (%) Medicare Medicaid Other Comorbid States (%) Alcohol abuse History of cancer Hypertension Cerebrovascular disease Artherosclerotic Heart Disease Congestive heart failure Other cardiovascular disease Chronic Obstructive Pulmonary Disease Matched

30 Baseline characteristics of the 1:1 PS matched cohort Home HD KTx (n=2,000) (n=2,000) Std. Diff. Access Type at time of Home HD initiation/time of KTx (%) AV Fistula AV Graft CVC Catheter Other Unknown Cause of ESRD (%) Diabetes Hypertension Glomerulonephritis Cystic kidney disease Other urologic reason Unknown Laboratory Tests at time of Home HD initiation/time of KTx Serum albumin (g/dl) 3.9 ± ± Blood hemoglobin (g/dl) 11.0 ± ± Other Total ESRD time before modality initiation (days) 409 ± ± Body Mass Index (kg/m 2 ) 29 ± 7 29 ± Molnar MZ et al., Transplantation, 2016 Matched

31 Association between renal replacement type (home hemodialysis (Home HD) versus kidney transplantation (Kidney Tx)) and mortality using Kaplan-Meier curves in propensity score matched cohorts Molnar MZ et al., Transplantation, 2016

32 Association between renal replacement type (home hemodialysis (Home HD) versus kidney transplantation (Kidney Tx)) and mortality using Kaplan-Meier curves in propensity score matched cohorts Molnar MZ et al., Transplantation, 2016

33 Association between renal replacement type (home hemodialysis (Home HD) versus kidney transplantation (Kidney Tx)) and mortality using Kaplan-Meier curves in propensity score matched cohorts Molnar MZ et al., Transplantation, 2016

34 Molnar MZ et al., Transplantation, 2016 Association between renal replacement type (home hemodialysis (Home HD) versus kidney transplantation (Kidney Tx)) and mortality using Kaplan-Meier curves using alternative censoring in propensity score matched cohorts in All patients (Panel A), African Americans (Panel B) and Whites (Panel C)

35 Mortality risk of home hemodialysis patients compared to kidney transplant recipients using propensity score matched cohorts in the first year and thereafter Molnar MZ et al., Transplantation, 2016

36 Mortality risk of home hemodialysis patients compared to kidney transplant recipients in group of patients with different donor characteristics using propensity score matched cohorts Molnar MZ et al., Transplantation, 2016

37 Flow chart of patients selection Molnar MZ et al., JAGS, 2016

38 Association between renal replacement type (home hemodialysis (Home HD) versus kidney transplantation (Kidney Tx)) and mortality using Kaplan-Meiers curves in elderly patients Molnar MZ et al., JAGS, 2016

39 Association between renal replacement type (home hemodialysis (Home HD) versus kidney transplantation (Kidney Tx)) and mortality using Kaplan-Meiers curves in elderly patients Molnar MZ et al., JAGS, 2016

40 Mortality risk of home hemodialysis elderly patients compared to elderly kidney transplant recipients in groups of patients with different recipient and donor characteristics using the propensity score matched cohort Molnar MZ et al., JAGS, 2016

41 Strengths It is the first comparison of mortality for home HD patients and KTx recipients from the United States. This is the first study using a PS matched approach to balance measured confounders. Moreover, we were able to compare the mortality risk of home HD with KTx from different types of kidney donors. In addition, we performed sensitivity analyses with an alternate censoring method by continuing to follow patients after home HD therapy ended, which confirmed our results. Furthermore, we also performed sensitivity analyses using competing risk regression analyses to take into account informative censoring due to the selective removal of a healthier group of transplant eligible home HD patients. The results of these analyses were qualitatively similar to our main results. Finally, we assessed the effect modification of race in the association of modality type with the mortality outcome.

42 Limitations First, home HD data were derived from facilities operated by a single dialysis provider. However, this constitutes almost one-third of all patients undergoing maintenance dialysis in the US. Second, we acknowledge that our sample size and event numbers in home HD patients are small. The relatively small sample size may have a bearing on the proportion of African American patients (n=728) given small number of events (n=55), where the effect size exhibited large variability, i.e., as low as 16% but as high as 367% for higher mortality risk. Hence, our result should be qualified in this context and need to be confirmed in larger studies involving more African American patients and more events. In addition, our result may not be applicable to populations outside the US, as the nocturnal home hemodialysis practice is significantly different in Canada or Europe.

43 Limitations Furthermore, median follow-up time in home HD patients was relatively short. The main reason for this was that our home HD patients were transferred to other dialysis modalities after a relatively short period of time. Further studies are needed to identify the cause of this phenomenon. We did not have data regarding the home HD patients waitlist status, consequently we were not able to perform subgroup analysis in this subcohort. Lastly, despite the fact that we were able to PS-match our cohorts for many confounding factors, there are likely remaining unmeasured or unknown confounders that could have affected the results of this study.

44 Objectives 1 Select Modality for your Tx Candidate 2 Home/Extended HD versus Conventional HD 3 Home HD versus Kidney Transplantation 4 Results for Comparison of Home HD versus Kidney Transplantation in USA 5 Conclusions

45 Conclusions Previous studies showed that home/extended hemodialysis provides better survival than in-center HD. Canadian patients who received KTx had significantly better survival regardless of kidney donor type compared to home HD patients. Canadian patients receiving KTx reported higher hospitalization rate and duration compared to patients on intensive home hemodialysis in the first year. This disappears after the first year. US patients who received KTx had significantly better survival regardless of kidney donor type compared to home HD patients. African American home HD patients had similar first year survival to African American KTx patients without a living donor in US.

46 My very biased personal recommendation to our patient is: Kidney #1 /altruistic living, 2 arteries, no DSA/: go for it Kidney #2 /SCD, 50y, White, female, no DSA/: go for it Kidney #3 /ECD, 65y AA, Hx-HTN, egfr:70, DSA-class II/: would wait on HHD for a better offer Kidney #4 /DCD, 45y AA, HCV+, drug addict, egfr:60, DSA-class I/: wait on HHD for a better offer

47 Collaborators University of Tennessee Health Science Center, Memphis: Csaba P. Kovesdy, MD University of Washington, Seattle: Rajnish Mehrotra, MD Matthew B. Rivara, MD University of California, Irvine: Kamyar Kalantar-Zadeh, MD, MPH, PhD Elani Streja, MPH, PhD Vanessa Ravel, MPH

48 Thank you for your attention!

49 Questions?