Metrics in Hemodialysis Metrics in Hemodialysis Quality CareQuality Care

Where targets are Where targets are does matter !does matter !

Steve Chen Director of NephrologyTaipei Veterans General Hospital-Hsinchu Branch

Compliance

Dietary complianceDietary compliance

Serum potassium level (SK)Serum phosphate level(SPO4)BUN: dietary protein intakeProtein catabolic rate (PCR): dietary protein

intake

Inter-dialytic weight gain (IDWG): IDWG/DW<5-5.7%: good compliance

ECV excess effectECV excess effectLuik et al, AJKD 30: 466-74, 1997Luik et al, AJKD 30: 466-74, 1997

IDWG ∞ systolic BP ↑∞ LVMI in hypertensives

IDWG ≠ systolic BP↑ in normotensives

IDWG > 6% BW Sympathetic activation Vasoconstrictor neuropeptide Y↑

IDWG and BPIDWG and BPSzczech et al, AJKD 2007(Duke University Medical center)Szczech et al, AJKD 2007(Duke University Medical center)

N= 442: 32295 sessions ↑1% IDWG ( 0.7Kg in a 70-Kg man) ↑1.00 mmHg pre-dialysis SBP p< 0.0001 ↑1.08 mmHg SBP △ p< 0.0001 Relation: modest, conservative, and

modifiable

Rapid ultrafiltration and mortality Rapid ultrafiltration and mortality

No CHF with CHFUFR Adjusted HR p Adjusted HR p

All cause mortality ≤ 10 ml/Hr/Kg 1 110-13 0.8 0.11 1.41 0.008 >13 1.61 0.001 1.59 0.008

CV mortality ≤ 10 ml/Hr/Kg 1 110-13 0.76 0.24 1.41 0.1 >13 1.70 0.02 1.73 0.008

JE Flythe et al: KI 2011: 79, 250-257 (Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA)

Poor dietary compliance: ↑MortalityPoor dietary compliance: ↑Mortality

Serum BUN: > 110 mg/dl or < 60 mg/dl → Mortality ↑

Serum albumin (BCG): < 4.0 mg/dl → Mortality ↑

Serum K: > 6.5 meq/L or < 3.5 meq/L → Mortality ↑

Serum Ca: > 12 mg/dl or < 7 mg/dl →Mortality ↑

Serum P: > 9.0 mg/dl or < 3.0 mg/dl →Mortality ↑

1Dialysis frequency versus dialysis time, that is the question

Raymond M Hakim and Sharmeela Saha

Adjusted associations between prescribed dialysis session length (RxDSL) and mortality on the basis of the Cox regression models

BP targets

How to monitor BPHow to monitor BPHorl et al, AJKD 39: 227-244, 2002Horl et al, AJKD 39: 227-244, 2002

24-H ABP ∞ end-organ damage Home BP (average of 12 pre-dialysis BP within 1 M)

∞ average systolic & diastolic ABP Post-diastolic BP better than pre-diastolic BP ∞

diastolic ABP Pre-systolic BP ∞ systolic ABP ∞ LVMI Casual BP ≠ average systolic &diastolic ABP

Predialysis SBP Predialysis SBP SBP > 160mmHg associated with ↑Late mortality

( 5 years of HD) ≧ Mazzuchi et al, KI 2000

SBP < 110mmHg associated with ↑CV mortality Zager et al, KI 1998

SBP around 150mmHg associated with lowest mortality Amery et al, Lancet 1985

Predialysis SBP : around 150 ～ 160mmHg Low SBP

Heart failure/Autonomic neuropathy(ANS)/Malnutrition

Predialysis DBP Predialysis DBP

DBP < 69mmHg associated with mortality Iseki et al, KI 1997

DBP < 74.5mmHg associated with early mortality(4 ～ 5 years of HD) Mazzuchi et al, KI 2000

DBP 89 vs 81 mmHg associated with ICH

Predialysis DBP: 80 ～ 85mmHg

HTN in dialysis patients HTN in dialysis patients

BP> 150/90mmHg Mittal et al, Clin Nephrol 51: 77-82, 1999

洗腎病患血壓別管太嚴

HTN in the elderly > 80YHTN in the elderly > 80Y

美國老年醫學會期刊 SBP< 140 Hg →Mortality↑

新英格蘭醫學期刊 2008: Multinational study 13 血壓平均 173/91mmHg BP < 150/80 mmHg →CVA ↓30% CV mortality↓ 23% CHF↓ 64%

老年人血壓別管太嚴

Postdialysis SBPPostdialysis SBP

SBP > 180mmHg and <110mmHg associated with mortality (U-shaped) in hemo-dialysis patients Zager et al KI 1988;54: 561-569

Discordance of influence of HTNDiscordance of influence of HTN

Noriaki et al, AJKD, 2005 Noriaki et al, AJKD, 2005 (Tokyo Medical and Dental University)(Tokyo Medical and Dental University)

N= 164 Population: Age 59; DM 34%Adjustment for age, sex, DM No association between BP and all-cause

mortality Lowest HR for CV events: SBP 140.1 ≦

mmHg

Discordance of influence of HTNDiscordance of influence of HTN

Noriaki et al, AJKD, 2005 Noriaki et al, AJKD, 2005 (Tokyo Medical and Dental University)(Tokyo Medical and Dental University)

0

1

2

3

4

5

6

7

<140.1 140.2-159.6 159.7-172.9 >172.9

AC mortality

CV mortality

CV events

N=113255

H b target

Target H b levels in HDTarget H b levels in HD Symptomatic CAD or cardiac failure higher

group(42%): ↑mortality Besarab et al, NEJM 1998

Asymptomatic c LVH/LVD Target H b: 13.5G/dl Foley et al, KI 2000

Physical performance↑ Target Hb: 14G/dl McMahon et al, NDT 1999

Hct <27%: all-cause mortality↑51%; CV mortality 40% ↑ Ma et al, JASN 1999

→DOQI /K guideline for Hb 33 ～ 36%

Ca/Pi/iPTH/Alk-P targets

Ca/Pi/ i PTH Ca/Pi/ i PTH

Metabolic alkalosis after dialysis session Calcium load peak after dialysis session Ca x Pi > 60mg2/dl2: visceral calcification

Velentzas et al, Int J Artif Organs 2: 6-8, 1979

DOQI/K guideline Ca 8.4 ～ 9.5 Pi 3.5 ～ 5.5 i-PTH 150 ～ 300 Ca x Pi <55 Block et al, AJKD 35: 1226-37, 2000

High Alkaline-P in HDHigh Alkaline-P in HDBlayney et al: KI 2008(Arbor Research Collaborative for Health, Michigan, USA) Blayney et al: KI 2008(Arbor Research Collaborative for Health, Michigan, USA)

Dialysis Outcomes and Practice Patterns Study (DOPPS): prospective observational cohort in 12 contries

Normalized AP by upper limit of laboratory-reported reference range (N=14643, baseline; N=7550, longitudinal)

High normalized AP ↑Morbidity: Fractures, PTX, Hospitalization due to major

adverse cardiac events (MACE), Liver (Viral hepatitis, liver failure, ascites, pancreatitis, or liver biopsy)

↑Mortality; Hospitalization independent of Ca, Pi, and PTH

Alkaline-P in HD: MorbidityAlkaline-P in HD: MorbidityBlayney et al: KI 2008(Arbor Research Collaborative for Health, Michigan, USA) Blayney et al: KI 2008(Arbor Research Collaborative for Health, Michigan, USA)

Hazard ratio

Baseline n AP in HD: mortalityBaseline n AP in HD: mortalityBlayney et al: KI 2008(Arbor Research Collaborative for Health, Michigan, USA) Blayney et al: KI 2008(Arbor Research Collaborative for Health, Michigan, USA)

Hazard ratio

Serum Ca: mortality risk/HRSerum Ca: mortality risk/HRFrancesca Tentori et al: AJKD 2008Francesca Tentori et al: AJKD 2008

Serum Pi: mortality risk/HRSerum Pi: mortality risk/HRFrancesca Tentori et al: AJKD 2008Francesca Tentori et al: AJKD 2008

Serum PTH: mortality risk/HRSerum PTH: mortality risk/HRFrancesca Tentori et al: AJKD 2008Francesca Tentori et al: AJKD 2008

Ca/Pi/PTH in CKD-VCa/Pi/PTH in CKD-VOrganization(Y) Ca Ca (alb) Pi PTH (mg/dl) (mg/dl) (mg/dl) (pg/ml)

ERA-EDTA(2000) 8.8-11 - 2.4-4.6 85-170

UKRA(2002) - 8.8-10.4 <5.6 <4X

NKF(2003) 8.4-9.5 - 3.5-5.5 150-300

CSN(2006) WNL WNL WNL 100-500

ANZSN(2006) - 8.4-9.5 2.5-5.5 1 ～3X

DOPPS 8.6-10.0 7.6-9.5 3.6-5.0 101-600

Lipid targets

Serum lipid and U-shaped survivalSerum lipid and U-shaped survivalKZ et al: JASN 18, 2007(Harbor-UCLA Medical center)KZ et al: JASN 18, 2007(Harbor-UCLA Medical center)

N= 15,859 MHD PTS LDL-C: 70 ～ 100 mg/dl

LDL-C < 70 mg/dl: ↑all-cause mortality , especially among Alb < 3.8 mg/dl and DPI < 1.0G/Kg/D LDL-C > 100 mg/dl in black:↑ CV mortality (p-0.02)

TC: 225 ～ 240 mg/dl TG: 200 ～ 249 mg/dl HDL-C: negative

Serum LDL-C and MortalitySerum LDL-C and MortalityKZ et al: JASN 18, 2007(Harbor-UCLA Medical center)KZ et al: JASN 18, 2007(Harbor-UCLA Medical center)

0%

5%

10%

15%

20%

25%

30%

<40 40-70 70-100 100-130 >130

AC mortality

CV mortality

Serum TC and survivalSerum TC and survivalKZ et al: JASN 18, 2007(Harbor-UCLA Medical center)KZ et al: JASN 18, 2007(Harbor-UCLA Medical center)

0%

5%

10%

15%

20%

25%

30%

35%

40%

<95 110-125

150-165

180-195

210-225

240-255

AC mortality

CV mortality

12511095806550

1

Haz

ard

ratio

( 50

mg/

dl e

xces

s in

ser

um T

G

Waist circumference (cm)

Abdominal obesity modify the risk of TG for Abdominal obesity modify the risk of TG for all cause mortality/CV mortalityall cause mortality/CV mortality

Neutral effect

M Postorino et al in CREDIT working group(Italy): KI 79: 765-772, 2011

N=537

UA target

S-UA Quintile on mortality rateS-UA Quintile on mortality rate Hsu et al, NDT 19: 457-462, 2004Hsu et al, NDT 19: 457-462, 2004

00.020.040.060.080.1

0.120.140.160.180.2

<6.5 6.6-7.2 7.3-7.8 7.9-8.9 >9.0

1/100 person-month

Ferritin and TSAT targets

Iron and least AC/CV mortality Iron and least AC/CV mortality Warnock et al: JASN, 2007(Harbor-UCLA Medical center)Warnock et al: JASN, 2007(Harbor-UCLA Medical center)

N=58,058Ferritin 200 ～ 1200 ng/ml Serum iron 60 ～ 120 μg/ml TSAT 30 ～ 50%Survival: IV iron less 400mg/M > No iron

user > IV iron more 400 mg/M Ferritin > 800 ng/ml: ↑mortality MICS

Ferritin and mortalityFerritin and mortalityWarnock et al: JASN, 2007(Harbor-UCLA Medical center)Warnock et al: JASN, 2007(Harbor-UCLA Medical center)

0%5%

10%15%20%25%30%35%40%45%

<50 100-200

300-500

650-800

1000-1200

1500-2000

AC mortality

CV mortality

TSAT and mortalityTSAT and mortalityWarnock et al: JASN, 2007(Harbor-UCLA Medical center)Warnock et al: JASN, 2007(Harbor-UCLA Medical center)

0%

5%

10%

15%

20%

25%

30%

35%

<15 15-20

20-25

25-30

30-35

35-40

40-45

45-50

50-55

55-60

>60

AC mortality

CV mortality

Water purity gradesWater purity grades

Criteria

Microbial contamination

(CFU/mL)

Bacterial endotoxin (IU/mL)

AAMI <200 <2European Phamacopoecia: regular water

<100 <0.25

European Phamacopoecia: ultrapure water

<0.1 <0.03

Sp-Kt/VSp-Kt/VGuidelines

Minimum Suggested

EBPG, 2002 1.4 --

NKF-DOQI, 2001 1.2 1.3

The renal association, 1997

1.2 1.35-1.4

CSN, 1999 1.2 --

Criteria: Protein energy wastingSerum chemistry S-albumin < 3.8 G/dl (BCG) S-pre albumin < 30 mg/dl for maintenance HD patients only Serum cholesterol < 100 mg/dl

Body mass BMI: <23 Unintentional BW loss: 5% at M3; 10% at M6 Total body fat percentage: <10%

Muscle mass Muscle wasting: 5% at M3; 10% at M6 Reduced MACA: >10%

Dietary intake Unintentional low diet protein intake: < 0.8 for at least 2 months for HD < 0.6 for CKD stage 2-5 Unintentional low diet energy intake: < 25 for at least 2 months

Protein energy wasting (PEW) IR, insulin resistance

MIS, malnutrition–inflammation score

PEG, percutaneous endoscopic gastrostomy

SGA, subjective global assessment

Consensus statement the International Society of Renal Nutrition and Metabolism

HBA1c and Hazard ratiosHBA1c and Hazard ratios N=83684

1.14

Hill et al in AJKD 2014

AHR=1.29

HR=1.29 for incident

Serum magnesium is a significant predictor (J shaped) of all-cause mortality in patients undergoing hemodialysis: N=142555 (Yusuke Sakaguchi et al.)

Mg < 2.3 mg/dl Mg > 3.1

mg/dl

< 1.8 >2.8

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