Blood pressure and mortality risk in peritoneal dialysis patients in England and

Wales

Udaya P.Udayaraj , R.Steenkamp, F.Caskey,

D.Ansell, C.Tomson

UK Renal Registry, Bristol, UKwww.renalreg.org

Introduction

• General population – linear or ‘J’ shaped association of BP with mortality

Lewington et al. Lancet, 2002; 360:1903-13

Introduction

• ‘Reverse J’ or ‘U’ association well described in hemodialysis (HD) patients

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Kalantar-Zadeh. Hypertension, 2005;45:811-17Zager et al. KI,1998;54:561-69

Introduction

• Is this ‘reverse’ association related to HD procedure?– Creation of AV fistula can predispose to myocardial

ischemia ‡

– Hypotension during HD can precipitate myocardial ischemia * and is associated with increased mortality †

‡ Savage et al. AJKD 2002; 40: 753-59* Selby et al. Semin Dial 2007; 20:220-28 † Shoji et al. KI 2004; 66:1212-20

Introduction

• Previous studies in peritoneal dialysis (PD) patients – inconsistent results due to small sample size † or short follow up ‡

• Low BP associated with lower mortality in kidney transplant recipients

• Association of BP and survival amongst dialysis patients awaiting transplantation is not known

‡ Rumyantazev et al. NDT 2005;20:1693-1701 Rocco et al. Perit Dial Int 22: 371-379, 2002

† Lynn et al. KI 2002;62:2281-2287 Ates et al. Kidney Int 60: 767-776, 2001 Jager et al. Kidney Int 55: 1476-1485, 1999

Aim

To study the association of BP and mortality in

• a larger cohort of peritoneal dialysis patients

• a subgroup of patients who are registered on the kidney transplant waiting list

Methods (Databases)

• UK Renal Registry (UKRR)– Established in 1997– 100 % coverage of England and Wales expected by 2007– Fully electronic data extraction from clinical information system – Quarterly biochemical and clinical data on all patients on renal

replacement therapy (RRT)

• UK Transplant (UKT)– Maintains national organ donor register– Holds data on kidney transplant waiting list

Study population

Incident RRT patients 1997-2004 in England and Wales– Inclusion criteria

• From centres with >85% ethnicity data completeness †

• Age >18 years• On Peritoneal dialysis at day 90

– Exclusion criteria• Missing data on age/gender/ cause of renal failure/ethnicity• Transplant prior to day 90• Missing BP data in 1st or 2nd quarter

† No difference in survival or baseline characteristics of patients in centres with > 85 % and < 85% data

Statistical analysis

• BP measurements– Mean BP value in the 1st/2nd quarter of RRT– Systolic, Diastolic, Mean arterial and pulse pressure studied

• Cox regression model• BP as a continuous variable ( linear and non linear terms)• Factors adjusted in multivariate model

– Age, gender, ethnicity, cause of renal failure, haemoglobin, corrected calcium, phosphate, serum albumin

– Change of RRT modality as time dependent variable ( i.e. patients not censored at modality change)

– Time to inclusion on Transplant waiting list as surrogate for co-morbidity

• Outcome– All cause mortality after day 90– All patients followed until 31.12.05 or death

• Subgroup analyses– Diabetics and non diabetics– Transplant waiting list registration status in 1st year of

RRT ( all cause mortality from 1 year after start of RRT)

• Waitlisted within 1st year from start of RRT• Not waitlisted within the 1st year from start of RRT

Results (Study cohort)

Cohort selection no. of patientsincluded

PD at day 90 ( centres >85 % ethnicity data) 3,991With data on ethnicity, cause of renal failure, 3,822 previous transplant With SBP/DBP data* 2,061With data on lab parameters and date of 2,035Transplant waitlisting

* No difference in baseline characteristics and survival between those included and excluded except % males was more in excluded cohort (62.8% vs 58.2%)

Baseline Characteristics

Number of patients 2035median age years (range) 59 (18 -90)Males % 58Cause of renal failure %Diabetes 20.2Glomerulonephritis 13.4Hypertension 6.4Others 12.2Polycystic kidney disease 8.7Pyelonephritis 8.8Renovascular disease 6.2Uncertain etiology 24.0

Ethnicity %Asian 6.6Black 2.6Other 1.1White 89.7Median duration of followup years (range) 2.98 (0.27 -9.0)

P< 0.0002

P= 0.01

†Adjusted for age, gender, cause of renal failure, ethnicity, lab parameters, treatment modality, time to transplant waiting list

Cox regression models

†

†Adjusted for age, gender, cause of renal failure, ethnicity, lab parameters, treatment modality, time to transplant waiting list

†

Cox Regression models

P= 0.0007P=0.05

Subgroup analyses – Time to transplant waiting list (WL)

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Mean arterial pressure mmHg

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† Survival after 1 year, Adjusted for age, gender, cause of renal failure, ethnicity, lab parameters, treatment modality

P =0.07

P= ns

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Diastolic Blood pressure mmHg

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P = ns

p =0.01

P = ns

WL < 1 year (n=675) HR per 10 mmHg 1.14, 95 % CI 0.99-1.31HR per 10 mmHg 1.29, 95 % CI 1.05-1.59

HR per 10 mmHg 1.33, 95 % CI 1.07-1.67

Subgroup analyses - Diabetes

• Diabetic – no association of any BP component with mortality

• Non diabetic – U shaped for SBP and reverse J for MAP (as for entire study cohort)

† Adjusted for age, gender, ethnicity, lab parameters,treatment modality, time to transplant waiting list

Summary

Pattern of association of BP and mortality was– For the entire study population

• U shaped for SBP• Reverse J for MAP • No association for DBP and PP

– For those registered on the transplant waiting list within first year• Linear for SBP, DBP, MAP• No association for PP

– For patients with diabetes • No association with any BP components

• Strengths– Largest study to date on PD patients– First to describe the association of BP and survival in

patients on the transplant waiting list– Novel analytic strategy of adjusting for modality change

allowed extended follow up of patients without censoring• Limitations

– BP measurement not standardised– Lack of data on co-morbidity, residual renal function

dialysis dose– No data on cardiac function or anti HT medications

Conclusions

• High and low SBP are risk factors for increased mortality in incident PD patients

• Low SBP was not associated with increased mortality in a subgroup of patients activated early on the transplant waiting list

• Association of low SBP and mortality seen in entire study cohort could reflect poor cardiac function/ health status

• The BP associated with best survival may vary for different patient subgroups

Baseline Characteristics

SBP mean + SD mmHg 143 + 22DBP mean + SD mmHg 81 + 12MAP mean + SD mmHg 102 + 14PP mean + SD mmHg 62 + 17

Haemoglobin mean + SD g/dl 11.2 + 1.5Corr. Calcium mean + SD mmol/L 2.4 + 0.2Serum phosphate mean + SD mmol/L 1.6 + 0.4

< 6months 22.2 > 6 months 25 not waitlisted 52.8

Time to Transplant waitling list from start of RRT %