Three year experience of APD in VGHTC

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Three year experience of APD in Taichung Veterans General Hospital 臺中榮民總醫院 腎臟科 陳呈旭 Incident patient counts (USRDS) by first modality Incident ESRD patients; peritoneal dialysis counts include CAPD & CCPD only. USRDS 2008 1

世界各地之 APD 成長概況 North America: increased from 1990 (10%) to 2000 (54%) Australia: increased from 1995 (4%) to 2004 (42%) Global estimated that approximately 1/3 PD in APD Kidney International (2008) 73, 480 488 台灣 APD 病患人數成長圖 1400 1200 1255 1000 854 人數 800 600 400 321 337 382 451 499 547 652 APD 200 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 Year 2

臺灣 CAPD 與 APD 比率 APD 23% CAPD 77% BAXTER 2008 中榮 APD 與 CAPD 的比率 90 80 81 77 CAPD APD 70 63 60 Percent (%) 50 40 37 30 20 19 23 10 0 2006 2007 2008 Year 3

民國人中榮成長快速可能的原因 全民健保 pre-esrd 預防性計畫及病人衛教計畫 Living donation Peritoneal dialysis Initiation can start with APD Hemodialysis Confidence of peritoneal dialysis More solutions were available Extraneal Nutrineal Physioneal 台中榮總年度腎臟移植人數 316 cadaveric + 86 living + 602 off-shore + 20 others = 1024 人數100 90 80 70 60 50 40 30 20 10 0 民國 人數其他醫院海外移植活體移植屍腎移植 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 活體移植人數增多! 4

Historical course of peritoneal dialysis First phase: establishing the therapy Connectology Automation Second phase: Vindication of PD and HD outcomes equivalent Clearance of PD Third phase: Fluid balance Cardiovascular outcome Kidney International, 2002; 62, S17 S22 APD have several advantages over CAPD Lower incidence of peritonitis Better small solute clearances Psychosocial and physical benefits fewer connections free of fluid in abdomen during daytime High transporters rapid solute transfer across peritoneal membrane Not tolerate high intraperitoneal pressure Reduced incidences of hernias Care giver dependent Nephrol Dial Transplant (2007) 22: 2991 2998. 5

Better dialysis acceptability in patients Workers School pupils Elderly or debilitated patients Reduced back pain Body image difficulties Reduced intra-abdominal pressures Alternative to CAPD in all patients is considered suitable Nephrol Dial Transplant (2007) 22: 2991 2998. Peritonitis and infectious complications 6

Infectious complications APD vs. CAPD Peritonitis: most important complications the most frequent cause of technical failure Related complications: Hospitalization Temporary or permanent loss of the catheter Loss of peritoneal membrane function Death: 15.8% Peritonitis incidence: APD < CAPD Kidney International (2008) 73, S76 S80. Complications expressed as episodes per patient-year rate ratio 0.54, 95% CI 0.35 0.83 Peritonitis episodes per patient-year rate ratio 1.00, 95% CI 0.56 1.76 Exit-site infection episodes per patient-year rate ratio 0.60, 95% CI 0.39 0.93 Hospitalization episodes per patient-year Low peritonitis episodes No difference in exit-site infection rates and tunnel Lower hospitalization rates ( 住院次數 ) Rabindranath et al. Nephrol Dial Transplant (2007) 22: 2991 2998. 7

次 /100 人月 Comparison of prevalence of peritonitis in patients on CAPD and APD in VGHTC 1.8 1.6 1.4 1.2 1 0.8 0.6 1.63 1.61 1.29 1.23 1.47 1.34 CAPD APD 0.4 0.2 0 2006 2007 2008 年份 Change of dialysis modality CAPD or APD HD First year (P< 0.0001) Second year (disappear) Transfer to HD was lower in patients on APD than in patients on CAPD overall and in each category of transfer causes (Left) (P<0.0001). This differential was most evident in the first year on PD and tended to disappear during the second year of therapy (Right). Kidney International 2003; 64, (Suppl 88), S3 S12 8

Change of dialysis modality Switching from original PD modality to a different dialysis modality No difference 3 trials, 115 patients, RR 0.50, 95% CI 0.25 1.02 APD not significantly lower risk of switching to HD alone 2 trials, 107 patients, RR 0.45, 95% CI 0.16 1.28 Rabindranath et al. Nephrol Dial Transplant (2007) 22: 2991 2998. Change modality 改變成不同透析方式 改變成 HD 所有原因造成 PD 管拔除 PD 管因腹膜炎拔除 病患住院次數 Rabindranath et al. Nephrol Dial Transplant (2007) 22: 2991 2998. 9

Summary High level of utilization of APD; trends toward: cycler-based therapy reduced peritonitis Reduced rate of hospitalization Quality of life 10

Switch from CAPD to APD Mainly driven by convenience and lifestyle factors For patients and caregivers To a lesser extent for medical reasons Clearance Volume reasons High transporters 2008 年中榮選擇 APD 實際情況 生活 工作型態工作型態 自己要求 :22 位 照顧者需求 :16 位 高通透性腹膜 :8 位 超過濾 / 脫水不佳 :6 位 25 22 低劑量透析者 :4 位 DM:4 位 壓增加引起疝氣者 :1 位 發生腹膜炎者 :1 位 人數 20 15 10 16 8 6 生活需求照顧者高通透性脫水不佳低劑量透析 5 4 4 1 1 DM 疝氣 0 腹膜炎 Reason 11

Quality of life Assessed quality of life ( 單就 APD 及 CAPD 來看 ) Karnofsky score No difference found between patients in either group 1 trial, 24 patients, WMD 6.00, 95% CI 0.00 12.00 Karnofsky scores between the start and end of study ( 自 APD 及 CAPD 起始與結束對生活品質之比較 ) APD: no change (group mean score 86.7) CAPD: small decline (score 82.5 80) Tool Short Form-36 (SF-36) no differences in the scores between either PD-modality APD have significantly more time for work, family and social activities (P<0.0005) Rabindranath et al. Nephrol Dial Transplant (2007) 22: 2991 2998. Health-related quality of life APD at least equal to CAPD APD CAPD APD CAPD APD CAPD CAPD APD CAPD APD Peritoneal Dialysis International 2001; 21:306 312 12

活動能力評估表 (Karnofsky Scale) 完全活動 能維持所有之活動, 不受任何限制 能夠步行及維持自我照顧, 但無法進行辦公或家務 完全無法活動, 不能進行任何自我照顧, 且完全限制在床上或椅子上 Tool Short Form-36 (SF-36) 13

Lifestyle advantages of APD Less procedures daily with APD than CAPD Frees up daytime for other activities Less workload for family members Less workload for staff in nursing homes Lifestyle APD better than CAPD 14

腹內壓增加引起的合併症 導管出口處透析液滲漏 橫隔膜滲漏 : 水胸 生殖器及陰囊水腫 疝氣 Intra-abdominal volume and pressure Sitting Upright IAP: Sitting > upright > supine Supine Tolerance to 3-liter exchanges might be most limited during sleep Kidney International 1983; 23:64-70 15

Intra-abdominal volume, posture and pulmonary function upright sitting supine Volume increasing Abdominal discomfort Inability to take in a full breath Supine can tolerate to 2.5L APD can indicated Kidney International 1983; 23:64-70 生殖器及陰囊積水 < 10% 發生率, 多見於男性病人 長庚醫院 84/5~93/3 腹膜透析的 232 病人中 生殖器及陰囊水腫 :5 人 (2.2%) 導因 : 因腹膜筋膜缺陷使透析液滲漏其中 突發性腹內壓增加 : 搬舉重物 處理方法 : 暫停 PD APD 修補手術 轉 HD 治療 16

陰囊積水 陳先生,59 歲, 植管日 : 96/08/20; 開始透析日 :96/08/30; 開始 CAPD 透析劑量 :1.5% Dianeal 2L X 4 次 / 日 96/12/20 陰囊水腫 CAPD 1.5% Dianeal 1.5L X 4 次 / 日, 夜排空 97/09/04 陰囊水腫未改善 轉換為 APD 治療, 總治療量 7500ml 每次 1500ml 5 週期共 10 小時末袋 0, 陰囊水腫改善 日期 D/P 4 hrs D/P0 4 hrs KT/V WCC/L 24 小時總尿量 透析方式 96.09.17 0.65 LA 0.40 LA 2.41 111.37 1405ml CAPD 97.03.28 0.63 LA 0.36 HA 1.87 82.2 1900ml CAPD 97.09.26 0.63 LA 0.39 LA 2.52 83.1 1700ml APD 生殖器及陰囊積水 陰囊積水 : 顯影劑進入 right testis 週圍 腹膜腔內透析液經由睾丸鞘膜 (Tunica vaginalis) 陰囊積水腹膜腔內透析液沿透析管, 穿過筋膜, 到陰部器官造成水腫 17

高通透性腹膜 蕭先生,57 歲, 植管日 :96/04/13 開始透析日 :96/04/24 ; 開始劑量 : CAPD 1.5% 2000ml x 4 包 / 日 症狀 : 下肢水腫 喘 無力 睡眠品質不佳 Lab (96-6-13): Alb: 4.3 2.5 mg/dl BUN/Cr: 77/10.4 75/10.1 K: 4.8 3.6 日期 D/P 4 hrs D/P0 4 hrs KT/V WCC/L 24 小時總尿量透析方式 96. 05.31 0.76 HA 0.29 HA 2.37 92.68 2240ml CAPD 96.11.14 0.64 LA 0.36 HA 2.48 76.35 1550ml APD 高通透性腹膜 96/06/18 透析劑量改為 : 因 Alb 低, 上機前 4 小時 Nutraneal 一包 APD 2500ml 3 次, 白天排空, 症狀改善 97/9/16 Cr 上升為 17.4 更改處方為 2500 x 3 次, 末袋 2500 ml, 白天 1.5% 2000ml x 1 加量 18

Summary APD can improved quality of life Patients and caregivers Reduce intra-abdominal pressure Improve symptoms of high transporters Volume could tolerated to 2.5 L Forced vital capacity reduced above Compliance Inadequate dialysis Morbidity mortality 19

Noncompliance in dialysis In-center hemodialysis therapy missed treatments shortened time on dialysis Peritoneal dialysis dialysis is performed at home 35% noncompliant with prescribed exchanges More technique failure Inadequate dialysis Increase in hospitalized days Am J Kidney Dis 2000; 6 :1104-1110. * University of Pittsburgh Four centers participated in study: 1. University-affiliated inner-city nonprofit dialysis unit 2. University-affiliated inner-city Veterans Administration dialysis unit 3. nonprofit suburban dialysis unit 4. Dialysis unit in a town in a rural area 60 miles from university Follow-up period: April 1995 ~ July 1, 1999 * Charlson comorbidity Index Am J Kidney Dis 2000; 6 :1104-1110. 20

Compliance vs noncompliance Compliant patients: dependent on others to perform their dialysis exchanges (P = 0.05) Logistic regression: Modality to be a significant risk for compliance noncompliance initiating PD with CAPD rather than APD (P <0.03; r=0.71) Comorbidity Index: compliant less just missed significance (P=0.057; r=0.170) Am J Kidney Dis 2000; 6 :1104-1110. Prescribed dialysis doses were not different between the two groups Am J Kidney Dis 2000; 6 :1104-1110. 21

Patient outcomes were significantly worse for patients noncompliant at the first home visit than for compliant patients Compliant patients Less uremic symptoms Less death Less hospitalization Less admission days Am J Kidney Dis 2000; 6 :1104-1110. Summary Compliance: APD > CAPD Detection of APD noncompliance : shorten their treatment times Newer cyclers monitor times of treatments by a computer chip Home visit : improved compliance a simple, direct method to determine compliance with prescribed exchanges Compliance can improve patient morbidity and survival Am J Kidney Dis 2000; 6 :1104-1110. 22

APD and CAPD have similar outcomes even better No difference switch from CAPD to APD for 2 years in VGHTC CAPD APD (N = 13) (N = 13) p-value Total protein (gm/dl) 6.80 ± 0.84 6.62 ± 0.41 0.345 Albumin (gm/dl) 3.68 ± 0.59 3.65 ± 0.34 0.357 Cholesterol (mg/dl) 192.46 ± 32.01 177.00 ± 35.09 0.173 Triglyceride(mg/dl) 131.15 ± 62.82 176.23 ± 107.06 0.075 Glucose[AC] (mg/dl) 101.85 ± 9.98 113.77 ± 40.40 0.530 Creatinine (mg/dl) 10.66 ± 3.30 12.07 ± 3.06 0.087 Na (meq/l) 139.00 ± 3.06 137.85 ± 4.32 0.220 K (meq/l) 4.09 ± 0.76 4.21 ± 1.03 0.752 Cl (meq/l) 98.00 ± 4.30 98.31 ± 6.97 0.726 Ca (mg/dl) 9.60 ± 1.24 9.52 ± 0.67 0.722 P (mg/dl) 5.22 ± 1.24 5.65 ± 1.48 0.421 intact-pth (pg/ml) 262.60 ± 126.29 288.74 ± 429.16 0.686 4 hr Glucose D/D0 0.39 ± 0.14 0.39 ± 0.05 0.893 4 hr Creatinine D/P 0.62 ± 0.17 0.64 ± 0.09 0.893 peritoneal Kt/V 1.46 ± 0.27 1.64 ± 0.44 0.225 Residual renal Kt/V 0.67 ± 0.55 0.34 ± 0.39 0.223 Total Kt/V 2.14 ± 0.40 1.98 ± 0.22 0.500 In the past 2 year, there are 13 patients switched from CAPD to APD. 23

Patients on APD from beginning 1 year follow-up Initial Present (N = 52) (N = 52) p-value Total protein (gm/dl) 6.52 ± 0.59 6.62 ± 0.58 0.231 Albumin (gm/dl) 3.62 ± 0.50 3.64 ± 0.49 0.831 Cholesterol (mg/dl) 192.70 ± 49.57 183.40 ± 45.69 0.196 Triglyceride(mg/dl) 112.68 ± 61.05 133.24 ± 73.64 0.004 Glucose[AC] (mg/dl) 110.52 ± 39.52 104.04 ± 32.68 0.409 Creatinine (mg/dl) 10.01 ± 2.69 11.61 ± 3.08 < 0.001 Na (meq/l) 139.62 ± 3.92 138.38 ± 3.46 0.038 K (meq/l) 4.29 ± 0.66 4.03 ± 0.74 0.036 Cl (meq/l) 99.85 ± 4.77 97.87 ± 4.42 0.008 Ca (mg/dl) 9.13 ± 0.93 9.49 ± 0.80 0.001 P (mg/dl) 5.13 ± 1.45 4.99 ± 1.24 0.669 intact-pth (pg/ml) 314.09 ± 248.98 248.64 ± 264.84 0.331 Patients on APD from beginning 1 year follow-up Initial Present (N = 52) (N = 52) p-value 4 hr Glucose D/D0 0.35 ± 0.09 0.39 ± 0.14 0.533 4 hr Creatinine D/P 0.66 ± 0.12 0.63 ± 0.19 0.575 Peritoneal Kt/V 1.53 ± 0.29 1.75 ± 0.36 0.021 Residual renal Kt/V 0.68 ± 0.50 0.47 ± 0.39 0.026 Total Kt/V 2.21 ± 0.40 2.22 ± 0.35 0.515 Peritoneal creatinine clearance(l/wk) 33.51 ± 12.17 39.00 ± 15.19 0.155 Residual renal clearance(l/wk) 35.57 ± 29.45 24.51 ± 19.90 0.026 Weekly creatinine clearance(l/wk) 69.08 ± 27.63 63.50 ± 13.14 0.722 npna 1.25 ± 0.35 1.21 ± 0.35 0.686 24

The mortality rate during APD treatment was comparable to that during CAPD treatment (ANZDATA) N = 4128 unadjusted hazard ratio = 0.92 95% CI 0.77 1.09 P = 0.336 Kaplan Meier graph showing patient survival: patient survival was comparable during CAPD and APD treatment modalities. Kidney International (2008) 73, 480 488 Survival by patient characteristics Risk factor 1. Age 2. Diabetes 3. Modality APD better than CAPD Kidney International, 2003; 64,S3 S12 25

First year technique survival Risk factor Diabetes poor Age Age > 55 yrs Modality CAPD<APD Kidney International, 2003; 64,S3 S12 Summary APD: use of cycler-based therapy Improving patient outcomes Higher technique success APD patient survival is similar to CAPD 26

Main adverse effect with APD Rapid decline in residual renal function Inadequacy Residual renal function (RRF) Remaining GFR Remaining endocrine functions Erythropoietin production Calcium, phosphorus Vitamin D homeostasis Volume control Removal of middle molecules or low molecular weight proteins J Am Soc Nephrol 2000; 11: 556 564. 27

Residual renal function (RRF) Important in measure of adequacy : Kt/V urea and creatinine clearance (CCr) Associated with mortality (CANUSA study): Every 0.5 ml/min higher GFR was associated with a 9% lower risk of death (relative risk = 0.91) J Am Soc Nephrol 2000; 11: 556 564. Residual renal function (RRF) Clinically important as it contributes to: Adequacy of dialysis Quality of life Mortality J Am Soc Nephrol 2000; 11: 556 564. 28

Factors that protect and preserve RRF Pre-ESRD care: Control BP ACE inhibition Decreasing proteinuria Dietary modification Avoidance of nephrotoxins Glucose control ESRD care: HD vs PD CAPD vs APD HD Biocompatible membranes Cause of ESRD Level of BP Various medications J Am Soc Nephrol 2000; 11: 556 564. Decline of RRF after start of dialysis in HD and PD 觀察 6 個月至 1 年,CAPD 比 HD 殘餘腎功能下降幅度慢! Perit Dial Int 1996; 16: 307 315. 29

Chronological data of mean BP, BW, and Hb concentration in each group over 6 months BP and Hb: no significant differences BW: CCPD > CAPD from initial Perit Dial Int 1996; 16: 307 315. CAPD CAPD CCPD CCPD CAPD CCPD Rapid decline in RRF within 6 months on APD. The mean rate of decline in renal Ccr at 6 months was apparently higher in our APD Perit Dial Int 1996; 16: 307 315. 30

Greater increase in serum betaβ2m with time was observed in APD patients, especially those on CCPD because of the apparent reduction in renal clearance ofβ2m Perit Dial Int 1996; 16: 307 315. Fluid Balance 31

Initial phase: transcapillary ultrafiltration (crystalloid osmotic gradient by Glucose) Initial phase: Starling forces Equilibrium Final phase transcapillary ultrafiltration lymphatic absorption Kidney International, 2002; 62, S17 S22 Proportional distribution of patients in the standard transport categories by PET Kidney International, 2002; 62, S17 S22 32

Ultrafiltration Profiling Kidney International, 2002; 62, S17 S22 Superiority of icodextrin more evident in high and high-average transporters Kidney International, 2002; 62, S17 S22 33

Icodextrin patients experienced statistically significant improvements in net UF J Am Soc Nephrol 16: 546-554, 2005 Icodextrin solution was associated with higher peritoneal clearances of small solute (BUN & Cr) Am J Kidney Dis 2002;39, 862-871 34

Serum Sodium and Sodium Removal The finding of an enhanced dialysate sodium excretion with icodextrin was significant and remained stable throughout the treatment phase. Am J Kidney Dis 2002;39, 862-871 Peritoneal clearance of Cr and BUN Clearance of both small solutes: Control group (4.25% dextrose): unchanged Icodextrin: significantly increased at wk 1 & wk 2 J Am Soc Nephrol 2005; 16: 546-554 35

Summary APD: rapid decline of residual renal function Inadequacy Fluid imbalance Icodextrin: long dwell: significantly positive net UF Increased small solute clearances Not increase of carbohydrate load Conclusions APD is more costly Advantages of APD Less peritonitis Quality of life/lifestyle compliance Potential for enhancing clearance Potential to improve volume status Reduce caregiver burden Better patient survival Main adverse effect of APD: more rapid decline in residual renal function Icodextrin can improve enhanced and sustained ultrafiltration without affecting RRF increases peritoneal clearances some specific metabolic side effects 36

Thanks for your attention! 37