Tomson 24.10 1030-1100 Blood pressure and outcome in PD patientsv2

Blood pressure and outcome in PD patients: lessons fromobservational dataCharlie TomsonBristol, UKMonday 24th October 10.30-11.00Which outcomes?•Surrogate measures of CV damage –LV mass, LV dilatation–Carotid intima-media thickness–Augmentation index, pulse wave velocity •Clinical outcomes–Symptoms, quality of life–TIA, stroke, myocardial infarction, heart failure –Residual renal function, technique survival–DeathWhich factors influence BP in PDpatients?•Intravascular volume•Peripheral vascular resistance •Conduit artery function–Endothelial dysfunction–Structural change, e.g. elastin damage,CaPO4–?Non-osmotic salt storage?•Cardiac output•BP-lowering drugsVolume expansion and LVHCAPD vs HD51 prevalent CAPD pts, 201 HD ptsPD HD pANF (pmol/l)33.8(IQR18.2-63.0)22.7(IQR 14.9-38.7)<0.01LVM (g/m2)157(SD 37)133(SD 39)<0.0001% on anti-hypertensives6538<0.001 Enia G. Nephrol Dial Transplant 2001; 16: 1459-1464Salt restriction/removal normaliseshypertension in PD patients at the expense of loss of residual renal function•47/78 PD patients hypertensive (drug Rx or >140/90)•Antihypertensives discontinued; regularly reinforced advice to restrict NaCl intake (achieved ~ 4 g/d)•37 patients became normotensive with dietary salt restriction alone (20) or with hypertonic UF (17); 7 became ACEI-responsive; 3 “non-compliant”•mean BP fell from 158/96 to 120/78, CTR 48% to 43%, body weight by 2.8kg.•19 patients with residual renal function: mean Kt/Vurea fell from 2.06 to 1.85 due to 28% fall in urine outputGunal AI. Am J Kidney Dis 2001; 37: 588-593Volume control vs preservation ofRRF•The reason that RRF is associated with better survival is because it allows better volume control and higher sodium removal •It is therefore illogical to maintain patients in an overhydrated state simply to avoid loss of RRFvan Biesen W. J Nephrol 2008; 21: 299-304Albumin, total body water, and plasmavolume in PD patients•46 PD patients studied using Deuterium dilution (TBW D ), 125I-albumin dilution (PV), and multifrequency BIA (ECW/TBW BIA )•Plasma albumin < 31.4 g/dL (=median) associated with–Increased ECW/TBW BIA–Increased difference between TBW D and TBW predicted from anthropometry–NO difference in PVJohn B. C J Am Soc Nephrol 2010; 5: 1463-1470Poor relationship between volume status and SBP: EuroBCM studyvan Biesen W et al. Plos One 2011; 6(2): e17148Hypertension in kidney failureover-simplifiedAnephric patientsResults from NECOSAD •Prospective study: 118 incident PD patients:mean follow-up 25 months•Multivariate Cox proportional hazards model for survival:Jager KJ. Kidney International 1999; 55: 1476-1485Salt and water removal rates and survival in incident PD patientsSodium removal (mmmol/24h/1.73m 2:Group 1 <130Group 2 130-181Group 3 181-232Group 4 >232125 Turkish PD patients : 24h clearance measured at 3/12 after start and every 6-12 months thereafterLow sodium removal associated with hypertension and use of antihypertensive drugsRelative risk of death (univariate):Ates K. Kidney International 2001; 60: 767-776•CMS ESRD core indicators project : cohort of 1219 prevalent PD patients (~5% sample) alive on 31/12/96•1-year follow-up, censoring for change in modality (167 HD, 74 Tp) or loss to follow-up (34), leaving 912, with 200 deaths within 12 months •Multivariate logistic regression:Rocco MV. PDI 2002; 22: 371-379Risk factors for early mortality: low DBPPulse pressure and outcome in PD306 pts commencing PD inToronto 1/00-12/05Cox proportional hazardsmodel, adjusting for ageand diabetesFang W. Perit Dial Int 2009; 29: 163-170Pulse pressure and outcome in PDHan SS. Perit Dial Int 2010;30:300-310291 incident patients 1/03-6/08Cardiovascular events153 prevalent PD patients: BP and other predictors recorded at 3/12.30 month follow-upSurvival lower with higher PP (by tertile)Liu JH. Am J Hypertens 2008; 21: 1318-23Relationship between SBP and mortality in PDpatientsUSRDS prospectiveDialysis Morbidityand Mortality Study,wave 2N=1,053Recruitment: 1996-7End of study: Dec1999Mean follow-up 23(SD 14) monthsGoldfarb-Rumyantzev AS. Nephrol Dial Transplant 2005;20: 1693-1701Relationship between BP and mortality in HDpatientsZager PG. Kidney Int 1998; 54: 561-569Port FK. AJKD 1999; 33: 507-517Kalantar-Zadeh K. Hypertension2005; 45: 811-817How the UKRR functions •Quarterly data extraction from IT systems used for clinical care in each renal centre in the UK •Funding by capitation fee; charitable status•Co-morbidity at start of RRT, primary renaldiagnosis, lab variables, modality, some drugtreatment (ESAs, PO4binders, etc)•Data sharing with NHSBT (“UKT”) on all patients listed for transplantation•No consent–opt-out available. Approval to use patient-identifiable data under section 251.•Annual audit report + research publicationsAnsell D, Tomson C. Nephron Clin Pract 2009; 111 Suppl 1: c277-c285BP is <130/<80 in ~28% of PD patients in the UK, with marked centre variationWebb L. Nephron Clinical Practice 2011; 119 Suppl 2: c215-c224UKRR study•All adult incident patients starting RRTbetween 1/1/97 and 31/12/04 and on PDat 180 days after start of RRT in renalunits reporting to UKRR in England andWales•Follow-up until death or 31/12/06•Ethnicity coding updated by linkage to UK Transplant database; by SANGRA; and by imputation based on area of residence Udayaraj U. Am J Kidney Dis 2009; 53:70-78Methods•Mean of the BP recordings in the first twoquarters of each year•Transplant wait listing used as a surrogate for co-morbidity:–Registered within 6/12 of start of RRT (including pre-emptive listing)–Registered beyond 6/12–Not registered at any time•Patients with missing data for BP, primary renal diagnosis, and lab data were excludedUdayaraj U. Am J Kidney Dis 2009; 53:70-78Statistical analysis •Fully adjusted Cox models adjusted for –Age–Gender–Ethnicity–Primary renal disease–Baseline Hb, Ca, PO4–Transplant listing status–Change in modality after 180 days (not censored)•Significant interaction with time on RRT,violating proportionality assumption: time-stratified analyses performedUdayaraj U. Am J Kidney Dis 2009; 53:70-78Study population•2770 included–3086 excluded due to missing data: nodifference in age, gender, %DM, wait-listing,or cumulative survival at 10y–Median age 58y; 58% men; ESRD due to DMin 19.8%.–Patients listed within 6/12 were younger, withlower prevalences of DM and of renalvascular disease–Median duration of follow-up 3.7yUdayaraj U. Am J Kidney Dis 2009; 53:70-78ResultsRelative Hazard per 10 mmHgUdayaraj U. Am J Kidney Dis 2009; 53:70-78Results –days 180-365Relative hazard of death per 10 mmHg BPUdayaraj U. Am J Kidney Dis 2009; 53:70-78Results –year 4-5Relative hazard of death per 10 mmHg BPUdayaraj U. Am J Kidney Dis 2009; 53:70-78Conclusions •Association between BP and survivalvaries over time–Short-term, low BP associated with thepoorest outcome–But, in patients on the transplant waiting list,higher BP associated with higher mortality–Association of low BP with mortality likely tobe due to both being caused by cardiacdiseaseUdayaraj U. Am J Kidney Dis 2009; 53:70-78Where are all the RCTs of BP control in PD patients?BP lowering Rx and outcome indialysis patientsAgarwal R. Hypertension 2009; 53: 860-866BP lowering Rx and outcome indialysis patientsLambers Heerspink H. Lancet 2009; 373; 1009-1015The study by Li et al(n=60, Ramipril vsplacebo in preventingloss of RRF in selectedPD patients) was theonly RCT of BP-lowering drug treatmentin PD patients included(not included: SuzukiAJKD 2004;43;1656-64–Valsartan preserves RRF: n=34)Ramipril preserves residual renalfunction in PD patients Li PK-T. Ann Intern Med 2003; 139: 105-112Open-label single-centre RCTPrevalent PD patientsResidual GFR>= 2 ml/min/1.73m 2BP>=120/70Exclusions: indications for ACEI,recent ACEI/ARB use, recent MIor CVA, malignant hypertension,valvular disease, bilateral renalartery stenosisConclusions•LOW blood pressure is a predictor of short-term mortality in PD patients–This is likely to reflect comorbidity causing both hypotension and increased risk•High BP predicts long-term mortality in PD patients with less comorbidity•High rate of poorly controlled hypertension and target organ damage in PD patients•Salt restriction/aggressive reduction of ECF lowers BP but also reduces residual renal function•Remarkable paucity of trials of BP-lowering drug treatment。