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Blood Pressure and Mortality Risk in Patients Treated by

Peritoneal Dialysis

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Related Article, p. 70

t has become increasingly clear that tradi-tional cardiovascular risk factors, including

lood pressure, must be interpreted in the contextf age and comorbid conditions. Therefore, stud-es conducted in the general population may note applicable to specific medical subpopulations.his is especially true for dialysis patients,1 inhom several factors exist that may complicate

he identification of an ideal blood pressure tar-et. These factors include blood pressure variabil-ty due to ultrafiltration and changes in fluidntake, as well as the presence of functioning orailed vascular accesses in the arms, which mayake standardized blood pressure ascertainment

hallenging. Perhaps most importantly, in con-rast to the general population, no adequatelyowered randomized clinical trials examiningard outcomes have been conducted among he-odialysis patients to determine appropriate

lood pressure targets.2,3 Counter to findingsrom general population studies, results fromeveral observational studies conducted usingdministrative data sets from large dialysis orga-izations suggest that mild to moderate hyperten-ion may be well tolerated during the first fewears after initiation of hemodialysis. In contrast,mong kidney transplant recipients, hyperten-ion is an established risk factor for mortality.4,5

Data are particularly scant regarding optimallood pressure targets for peritoneal dialysis pa-ients. The study by Udayaraj and colleagues6 inhis issue of the American Journal of Kidneyiseases presents important new data on the

elationship between blood pressure and mortal-ty among patients treated by peritoneal dialysis.he authors demonstrate that among peritonealialysis patients, higher blood pressures weressociated with decreased mortality in the over-ll cohort. However, this association was notbserved among patients registered on the na-ional transplant waiting list within 6 months ofommencing renal replacement therapy. The re-ults from this study indicate that, with respect tohe relationship between blood pressure and mor-

ality, peritoneal dialysis patients more closely

merican Journal of Kidney Diseases, Vol 53, No 1 (January), 200

esemble hemodialysis patients than they doembers of the general population. Specifically,

he relationship between blood pressure and mor-ality observed by Udayaraj et al in peritonealialysis patients was similar to that observed inemodialysis patients by Stidley et al.7 Duringhe period from day 180 to day 365 after thenitiation of peritoneal dialysis, patients withhat are considered normal blood pressures in

he general population exhibit a higher relativeazard for all-cause mortality. In contrast, amongeritoneal dialysis patients who survive morehan 5 years, high blood pressure was associatedith increased mortality.Udayaraj et al postulate that peritoneal dialy-

is patients who quickly became waitlisted foridney transplantation may be healthier thanhose who took a longer time to become listed.he unexpected finding of higher blood pres-ures being associated with survival may reflectreater underlying comorbid conditions amongatients with lower blood pressures. Accord-ngly, Udayaraj et al use time to listing for kidneyransplantation as a novel surrogate for comorbidonditions. This innovative methodology, whichs a major contribution of this important study,ssumed those patients listed for transplantationithin a short period of time do not have severe

ardiovascular disease and therefore are amonghe healthiest peritoneal dialysis patients. Uda-araj et al were able to link the United Kingdomenal Registry and United Kingdom Transplantata sets using unique patient identifiers, andhen to assess the relationships of blood pressureo mortality among peritoneal dialysis patientsn and off the kidney transplant waiting list.nlike peritoneal dialysis patients who wereever listed for transplantation, and in whomigher blood pressure was associated with betterurvival, peritoneal dialysis patients who wereaitlisted for kidney transplantation within 6

Address correspondence to Philip G. Zager, MD, Dialysislinic, Inc Quality Management, 1500 Indian School RdE, Albuquerque, NM 87102. E-mail: pzag@unm.edu© 2008 by the National Kidney Foundation, Inc.0272-6386/08/5301-0003$36.00/0

doi:10.1053/j.ajkd.2008.10.036

9: pp 9-11 9

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Zager and Rohrscheib10

onths of initiating dialysis exhibited a relation-hip between mortality and blood pressure thatas similar to that of the general population.pecifically, normal blood pressure was not asso-iated with increased mortality from day 180 toay 365 after the initiation of peritoneal dialysismong patients who were quickly listed for trans-lantation. Within this subgroup, patients whoad lower initial blood pressures experiencedower mortality compared to those with hyperten-ion. Although the use of the time to listing as aarker for comorbid conditions may prove to besignificant methodological advance, additionalalidation data that compare time to listing withther, more established measures of comorbidonditions such as the International Classifica-ion of Existing Disease are needed.

Udayaraj et al also explored the potentialmpact of diabetes mellitus on the relationshipetween blood pressure and mortality. The Ameri-an Diabetes Association (ADA), American Heartssociation (AHA), and National Kidney Foun-ation (NKF) in the United States, and the Na-ional Institute for Health and Clinical Excel-ence (NICE) in the United Kingdom have calledor lower blood pressure targets among patientsith diabetes mellitus.8-11 These recommenda-

ions appear to be applicable to peritoneal dialy-is patients since Udayaraj et al demonstratedhat an increase in systolic blood pressure wasssociated with increased mortality among dia-etic patients after 3 years of peritoneal dialysis.It may not be surprising that peritoneal dialy-

is patients share epidemiologic patterns withemodialysis patients given the common fea-ures of chronic hypervolemia and inflammation.owever, the question of whether the modalityf dialysis affects the relationship of blood pres-ure and mortality remains unanswered. It is nowell recognized that the abrupt and dramatic

hanges in blood volume associated with ultrafil-ration during hemodialysis result in reducedyocardial blood flow and transient regionalall motion abnormalities. Nephrologists are well

ware of the need to minimize antihypertensiveherapy immediately prior to hemodialysis inrder to reduce the risk of symptomatic hypoten-ion during the procedure. Although peritonealialysis does not share the same deterrence tontihypertensive therapy given its continuous

ature and much lower rates of ultrafiltration, u

ata from Udayaraj et al suggest that the relation-hip of mortality and blood pressure is similarmong hemodialysis and the majority of perito-eal dialysis patients.That normal or target blood pressure can be a

redictor of better or worse clinical outcomesepending on the population studied underscoreshe complex nature of assessing risk and select-ng therapy in dialysis patients. Blood pressure isetermined by the extracellular volume and thetate and function of the heart and blood vessels.eritoneal and hemodialysis patients share theigh burdens of cardiovascular disease, height-ned sympathetic nervous system tone, hypervole-ia and sodium retention, and chronic inflamma-

ion. With respect to blood pressure levels, youngdults with kidney failure treated by dialysisesemble elderly patients in the general popula-ion, and the prevalence of both systolic andiastolic dysfunction is very high among dialysisatients. Thus, it is not surprising that dialysisatients resemble the elderly and patients withongestive heart failure in that those with low orormal blood pressure values experience in-reased mortality.

The results of the study by Udayaraj et al mayot be applicable to patients in the United States.ince the incidence and prevalence of treatedidney failure is much lower in the United King-om than in the United States,12 there are signifi-ant differences in age and comorbid conditionsf dialysis patients in the 2 countries. In thenited States, the median age of incident dialysisatients is 65 years, which is considerably olderhan that in the study by Udayaraj et al. Theercentage of treated patients with diabetes mel-itus is lower in the United Kingdom than in thenited States.12 Kidney transplantation rates in

he United Kingdom are significantly lower thanhose in the United States, France, and Spain.12

We commend the authors not only for provid-ng a thoughtful epidemiologic analysis, but alsoor coordinating the informatics systems en-bling them to study a large cohort of patients.hile epidemiologic studies are hypothesis gen-

rating, they leave us short of understandingause and effect relationships. By identifyingnformative subgroups of patients, it is possibleo effectively power prospective studies in uniqueut relatively small populations such as those

ndergoing peritoneal dialysis.

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Editorial 11

The study by Udayaraj et al also has signifi-ant limitations including the lack of standardiza-ion of blood pressure measurements across dialy-is facilities and the fact that only the mean of 2lood pressure values, 1 from each of the first 2uarters of peritoneal dialysis, were used to con-uct the analyses. It is likely that estimated dryeight was not yet established in many patients.herefore, blood pressure may have declinedubsequent to this period. Moreover, the availabil-ty of only a small number of blood pressureeasurements may not accurately reflect the true

verage blood pressure since blood pressure mayary greatly within end-stage renal disease pa-ients.13

Until the results of prospective randomizedontrolled trials become available, newer statisti-al techniques are necessary to analyze observa-ional data. The use of baseline variables in theresent study does not fully account for theynamic nature of disease progression and disal-ows real-time evaluation of survival probability.ewer dynamic techniques such as accelerated

ailure time models can be helpful.The limitations inherent in observational stud-

es, no matter how carefully conducted, precludedentification of the optimal blood targets andherapy in dialysis patients. Randomized trialsere necessary to demonstrate that patients with

ystolic heart failure, another medical subpopula-ion that exhibits higher mortality in associationith low blood pressure, benefit from the use offixed dose combination of isosorbide dinitrate

nd hydralazine whatever their starting bloodressure.14 It remains uncertain if treatment ofnormotensive” peritoneal or hemodialysis pa-ients will confer a similar benefit. Therefore,andomized controlled trials, powered for hardutcomes, are necessary to determine the impactf antihypertensive therapy on survival amongemodialysis and peritoneal dialysis patients asell as the appropriate targets for these patients

tratified by race, sex, age and comorbid condi-ions.

Philip G. Zager, MD1,2

Mark R. Rohrscheib, MD1,2

1University of New Mexico Health SciencesCenter

2Dialysis Clinic, Inc

Albuquerque, New Mexico 2

ACKNOWLEDGEMENTS

Financial Disclosure: Drs Zager and Rohrscheib receivealary support from Dialysis Clinic, Inc.

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argets in clinical practice guidelines are associated withmproved survival in a large dialysis organization? J Am Socephrol 18:2377-2384, 20072. Burt VL, Whelton P, Roccella EJ, et al: Prevalence of

ypertension in the US adult population. Results from thehird National Health and Nutrition Examination Survey,988-1991. Hypertension 25:305-313, 19953. Klassen PS, Lowrie EG, Reddan DN, et al: Association

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lood pressure on the effectiveness of a fixed-dose combina-ion of isosorbide dinitrate and hydralazine in the African-merican Heart Failure Trial. J Am Coll Cardiol 49:32-39,

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