Dialysis modality and 2-year outcomes in patients with ischemic cardiomyopathy and end-stage renal disease

Transcription

1 Dialysis modality and 2-year outcomes in patients with ischemic cardiomyopathy and end-stage renal disease Vinay Panday, Zi-Ping Tong, Perryn L. Ng, Evan J. Lee, Titus Lau, Boon-Wee Teo, Horng-Ruey Chua PII: S (14) DOI: doi: /j.ijcard Reference: IJCA To appear in: International Journal of Cardiology Received date: 25 May 2014 Accepted date: 26 July 2014 Please cite this article as: Panday Vinay, Tong Zi-Ping, Ng Perryn L., Lee Evan J., Lau Titus, Teo Boon-Wee, Chua Horng-Ruey, Dialysis modality and 2-year outcomes in patients with ischemic cardiomyopathy and end-stage renal disease, International Journal of Cardiology (2014), doi: /j.ijcard This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 DIALYSIS MODALITY AND 2-YEAR OUTCOMES IN PATIENTS WITH ISCHEMIC CARDIOMYOPATHY AND END-STAGE RENAL DISEASE Research Letter Vinay PANDAY 1, Zi-Ping TONG 2, Perryn L NG (MBBS) 3, Evan J LEE (MMed) 1,3, Titus LAU (MD) 1,3, Boon-Wee TEO (MD) 1,3, Horng-Ruey CHUA (MMed) 1,3 1 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore 2 School of Medicine, Faculty of Health Sciences, University of Queensland, Australia 3 Division of Nephrology, University Medicine Cluster, National University Hospital, Singapore Word Count : 800 words Corresponding author Dr Horng-Ruey CHUA Consultant Nephrologist and Assistant Professor Department of Medicine, National University Health System, Singapore 1E Kent Ridge Road, Level 10 Medicine Office, NUHS Tower Block, S(119228) Republic of Singapore Contact number: / address: horng_ruey_chua@nuhs.edu.sg 1

3 To the Editor: Survival differences with hemodialysis (HD) or peritoneal dialysis (PD) in patients with end-stage renal disease (ESRD), may vary substantially according to demographics or comorbidities 1. In that regard, intra-dialytic hypotension can induce myocardial stunning that contributes to heart failure in HD patients 2, and may be detrimental to ESRD patients with concomitant ischemic cardiomyopathy (ICMP). However, PD obviates the need for a high-flow arteriovenous fistula and allows gradual daily ultrafiltration, both likely favorable for patients with ICMP. Consequentially, PD may be associated with lower risk of congestive heart failure (CHF) compared with HD 3. These theoretical assumptions may influence modality selection in favor of PD, in incident dialysis patients with ESRD and ICMP, and warrant detailed examination. Accordingly, we aim to evaluate 2-year patientcentered outcomes in this cohort with respect to initial dialysis modality. We hypothesize that patients on PD (versus HD) will experience less major adverse cardiac events (MACE), hospitalization days, and mortality over 2 years from dialysis initiation. We conducted a retrospective cohort sub-study, using a single-center, prospectively maintained database of 983 incident dialysis patients with ESRD, from All demographics, comorbidities, and biochemistry were indexed at time of dialysis initiation. Routine 2D-echocardiogram was performed within 1 year of projected dialysis or 3 months of initiation. ICMP was defined as impaired resting left ventricular ejection fraction (LVEF) <45%, with documented coronary artery disease from coronary angiograms, stress tests, or prior acute myocardial infarction (AMI). Using this criterion, we identified 139 patients with ICMP. We examined the 2

4 differences in 2-year mortality, MACE, and hospitalization-days, in ICMP patients established on HD versus PD by 90 days from initiation. MACE includes AMI, coronary revascularization, CHF, and cerebrovascular event. Outcomes were expressed as incidence per 1000-dialysis days, and examined using Poisson regression. Hazard ratio for death was adjusted in the Cox-proportional hazard model, using a composite comorbid UREA5 score that stratifies local first-year mortality risk in ESRD, incorporating baseline mortality predictors including URate, LVEF, Age, Albumin, Alkaline phosphatase, and Arteriopathies (cerebrovascular disease and peripheral vascular disease) 4. The cohort of interest includes 85 HD and 54 PD patients. Their profile and 2-year outcomes are detailed in TABLE 1. 86% had diabetic nephropathy, with median LVEF of 33%. Demographics and UREA5 mortality-risk scores were comparable between HD and PD arms, except for more HD patients initiated on dialysis via temporary vascular access, and subtle differences in serum urate. Cumulative frequency and duration of hospitalization, and incidence of MACE over 2 years, were similar with either modality (TABLE 1). Modality conversions at 1 year were few. More HD patients were admitted for dialysis access malfunction (stenosis, thrombosis, bleeding), while more PD patients were admitted for access-related infection. This difference was not attributed to temporary HD catheter-related infections, which were 0.7 versus 0.4 per 1000-dialysis days in HD and PD groups, respectively (p=0.2). Overall 2-year mortality was near 50%. On multivariate analysis, hazard ratios for 1-year and 2-year mortality for HD versus PD were not statistically significant, before and after adjustment for UREA5 score (TABLE 2). 3

5 Our results demonstrate that patients with ESRD and ICMP initiated on PD versus HD did not experience improved 2-year mortality, cardiac and hospitalization outcomes, hence refuting our hypothesis. These findings are consistent with those reported from various registries, involving new ESRD patients with concomitant CHF, which did not report superior outcomes with PD versus HD 5-7. This may be due to several reasons. Peritoneal glucose absorption and loss of protein in the dialysate may predispose patients to an atherogenic serum lipid profile 8. Glucose absorption from the PD solution leads to poorer glycemic control in diabetics. Diabetes and ESRD synergistically increase the risk of cardiovascular events 9. Therefore, theoretical benefits of PD and daily ultrafiltration may not translate to improved clinical outcomes. Nevertheless, HD may not be superior as it predisposes patients to intravascular volume contraction leading to cardiovascular instability, or contributing to earlier loss of residual renal function 10. Our high prevalence of diabetes mellitus may impact negatively on vascular access maturity. Though our study is single-center with small sample size and subjected to selection bias with modality selection, the baseline profile appears well-matched between HD and PD arms in a very specific and unique cohort with advanced comorbidities. Furthermore, we could elaborate upon the disease burden by quantifying the LVEF and degree of vessel involvement on coronary angiography. Additionally, we adjusted the mortality risk with known predictors in our local ESRD cohort 4. In the absence of randomized evidence guiding appropriate modality selection, our findings highlight that extended patient outcomes with PD versus HD in these ESRD 4

6 patients with significant cardiac disease are largely comparable. More attention should perhaps be paid to vascular access suitability for HD, and socio-economic factors affecting access infection risk for PD. These should highly influence clinicians, counselors, and patients in their joint decision for dialysis modality of choice at baseline. Disclosure Statement: The authors declare no conflict of interests. No funding was received for this study and the authors declare no financial competing interests. REFERENCES 1. Vonesh EF, Snyder JJ, Foley RN, Collins AJ. The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis. Kidney Int. 2004;66: Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced cardiac injury: determinants and associated outcomes. Clin J Am Soc Nephrol. 2009;4: Trespalacios FC, Taylor AJ, Agodoa LY, Bakris GL, Abbott KC. Heart failure as a cause for hospitalization in chronic dialysis patients. Am J Kidney Dis. 2003;41: Chua HR, Lau T, Luo N, et al. Predicting First-Year Mortality in Incident Dialysis Patients with End-Stage Renal Disease - The UREA5 Study. Blood Purif. 2014;37:

7 5. Stack AG, Molony DA, Rahman NS, Dosekun A, Murthy B. Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States. Kidney Int. 2003;64: Sens F, Schott-Pethelaz AM, Labeeuw M, Colin C, Villar E, Registry R. Survival advantage of hemodialysis relative to peritoneal dialysis in patients with endstage renal disease and congestive heart failure. Kidney international. 2011;80: Wang IK, Kung PT, Kuo WY, et al. Impact of dialysis modality on the survival of end-stage renal disease patients with or without cardiovascular disease. J Nephrol. 2013;26: Liu J, Rosner MH. Lipid abnormalities associated with end-stage renal disease. Seminars in dialysis. 2006;19: Chang YT, Wu JL, Hsu CC, Wang JD, Sung JM. Diabetes and end-stage renal disease synergistically contribute to increased incidence of cardiovascular events: a nationwide follow-up study during Diabetes Care. 2014;37: Moist LM, Port FK, Orzol SM, et al. Predictors of loss of residual renal function among new dialysis patients. Journal of the American Society of Nephrology : JASN. 2000;11:

8 TABLE 1: Patient profile (HD versus PD as modality by 90 days from dialysis initiation) Variables Entire Cohort HD PD p-value n = 139 n = 85 n = 54 Age, mean (SD), yr 62 (10) 62 (9) 64 (11) 0.3 Male gender, No. (%) 85 (61) 56 (66) 29 (54) 0.2 Cause of ESRD, No. (%) DM nephropathy 119 (86) 72 (85) 47 (87) 0.7 GN (presumed & Bx) 10 (7) 7 (8) 3 (6) 0.7 Hypertension 5 (4) 3 (4) 2 (4) 1.0 Others 5 (4) 3 (4) 2 (4) 1.0 No permanent access at initiation, No. (%) 101 (73) 75 (88) 26 (48) <0.001 CVA, No. (%) 26 (19) 15 (18) 11 (20) 0.7 PVD, No. (%) 30 (22) 20 (24) 10 (19) 0.5 Extent of ischemic heart disease Prior AMI, No. (%) 95 (68) 63 (74) 32 (59) 0.07 LVEF, median (IQR), % 33 (27-38) 35 (28-38) 32 (25-38) 0.4 SVD on COROS, No. (%) 4 (3) 4 (5) 0 (0) 0.2 DVD on COROS, No. (%) 13 (9) 9 (11) 4 (7) 0.8 TVD on COROS, No. (%) 44 (32) 31 (36) 13 (24) 0.1 7

9 Positive cardiac stress test(s), No. (%) 65 (47) 36 (42) 29 (54) 0.2 RWMA on resting 2DE, No. (%) 112 (81) 70 (82) 42 (78) 0.5 Serum biochemistry at initiation Hb, mean (SD), g/dl 9.4 (1.6) 9.4 (1.6) 9.6 (1.5) 0.5 Albumin, median (IQR), g/l 33 (28-36) 32 (29-36) 34 (28-37) 0.6 egfr, median (IQR), ml/min/1.73m 2 8 (6-10) 7 (6-10) 9 (6-11) 0.2 ipth, median (IQR), pmol/l 22 (14-38) 25 (14-38) 22 (14-38) 0.6 ALP, median (IQR), U/L 87 (72-121) 86 (72-112) 87 (67-130) 0.9 Urate, mean (SD), µmol/l 553 (189) 527 (194) 594 (174) 0.04 Modality switch at 1 yr*, No. (%) 8 (6) 3 (4) 5 (9) 0.3 Hospitalization over 2 years (Poisson)** Total RRT days over 2 years No. of admissions per 1000-days 12 (11-13) 12 (11-13) 13 (12-14) 0.1 Cumulative LOS per 1000-days 102 (99-104) 100 (97-103) 105 ( ) 0.2 MACE, No. per 1000-days 4 (3-4) 3 (3-4) 4 (3-5) 0.4 Pneumonia, No. per 1000-days 1 (0-1) 1 (0-1) 1 (0-1) 0.4 Access infection, No. per 1000-days 1 (1-1) 1 (1-1) 2 (1-2) Access malfunction, No. per 1000-days 2 (1-2) 2 (2-2) 1 (1-1) UREA5 Ψ risk score, median (IQR) 4 (3-5) 4 (3-5) 4 (3-5) 0.1 Mortality at 1 year, No. (%) 51 (37) 29 (34) 22 (41) 0.4 Mortality at 2 years, No. (%) 68 (49) 38 (45) 30 (56) 0.2 8

10 *: Switch of modality from HD to PD and vice versa after 1 year from RRT initiation. **: Hospitalization data presented as incidence per 1000-RRT days over 2 years from RRT initiation (censored for mortality), and significance assessed using Poisson regression. Ψ : UREA5 1st year mortality risk score: calculated from known baseline predictors of early mortality locally, including URate, EF, Age, Albumin, ALP, Arteriopathy (CVA), Arteriopathy (PVD). 2DE: 2D-echocardiogram; ALP: alkaline phosphatase; AMI: acute myocardial infarction; Bx: kidney biopsy; COROS: coronary angiogram; CVA: cerebrovascular accident/disease; d: day; DM: diabetes mellitus; DVD: double vessel disease; EF: ejection fraction (see LVEF); egfr: estimated glomerular filtration rate; ESRD: end-stage renal disease; GN: glomerulonephritis; Hb: hemoglobin; HD: hemodialysis; ipth: intact parathyroid hormone; IQR: interquartile range; LOS: length of stay; LVEF: left ventricular ejection fraction on echocardiography; MACE: major adverse cardiac events; No.: number; PD: peritoneal dialysis; PVD: peripheral vascular disease; RRT: renal replacement therapy; RWMA: regional wall motion abnormalities; SD: standard deviation; SVD: single vessel disease; TVD: triple vessel disease; yr: years. 9

11 TABLE 2: Cox proportional hazard regression for mortality Hazard ratio 95% CI p-value Unadjusted 1st yr mortality HD vs. PD by 90 days from RRT initiation 0.85 ( ) 0.6 UREA5 score (per 1 pt increment from 0 to 5) 1.73 ( ) <0.001 Unadjusted mortality over 2 years from initiation HD vs. PD by 90 days from RRT initiation 0.78 ( ) 0.3 UREA5 score (per 1 pt increment from 0 to 5) 1.65 ( ) <0.001 Mortality prediction adjusted for UREA5 score HD vs. PD on 1st yr mortality 0.96 ( ) 0.9 HD vs. PD on 2 yr mortality 0.90 ( ) 0.7 CI: confidence interval; HD: hemodialysis; PD: peritoneal dialysis; RRT: renal replacement therapy; yr: year. 10