Editorial

Dialysis Recovery Time: More Than Just Another Serum Albumin

Address correspondence to Rita S. Suri, MD, MSc, Centre deRecherche, Centre Hospitalier de l’Université de Montréal, Uni-versity of Montreal, Montreal, Quebec, Canada. E-mail: rita.suri@lhsc.on.caPublished by Elsevier Inc. on behalf of the National Kidney

Foundation, Inc.0272-6386/$36.00http://dx.doi.org/10.1053/j.ajkd.2014.04.008

Related Article, p. 86

All nephrologists are aware that patients receivingmaintenance hemodialysis have extremely poor

outcomes compared to the general population. Despitesubtle differences between countries1 and slight im-provements over the last decade,2 mortality rates forpatients receiving hemodialysis remain unacceptablyhigh. In the United States, 25% of patients beginninghemodialysis therapy die in the first year, and almost50% die within 3 years.2 Yet, although these overallstatistics are well known, predicting the prognosis foran individual patient remains challenging.During the last 25 years, there have been countless

epidemiologic studies examining associations betweenbaseline risk factors and survival on hemodialysistherapy. Among the earliest and most important ofthese studies identified low serum albumin level as oneof the strongest independent predictors of mortality,especially at levels , 3.5 g/dL.3-6 In a large sample ofUS hemodialysis patients, Owen et al6 found that theodds ratios for death were 1.48 for serum albuminconcentrations of 3.5-3.9 g/dL and 3.13 for concen-trations of 3.0-3.4 g/dL. However, the presence of astrong statistical association does not necessarily indi-cate causality. In the case of serum albumin, this ismostcertainly the case.7 Low serum albumin is a marker ofmalnutrition and inflammation, each of which havebeen shown to be associated with, and may possiblycontribute to, the pathogenesis of atherosclerosis andcardiovascular disease.8,9 It is not surprising then thatno intervention has been shown to increase serum al-bumin level and subsequently improve survival. Inessence, serum albumin level is an excellent prognosticmarker, but not a valid surrogate outcome.In this issue of AJKD, Rayner et al10 report on

the DOPPS (Dialysis Outcomes and Practice PatternsStudy) cohort, a prospective study of more than 6,000randomly selected hemodialysis patients from selectedunits in 12 countries. They asked patients at a singletime point the question, “How long does it take for youto recover from a dialysis session?” Response choiceswere less than 2, 2-6, 7-12, and more than 12 hours.The authors found that longer recovery times wereassociated significantly and independently with shortertime to first hospitalization and higher mortality. Forpatients answering more than 12 hours, for example,the risk of dying was 30%-60% higher than for thoseanswering 2-6 hours, a risk similar in magnitude to thatobserved with having a serum albumin level of 3.5-3.9 g/dL.6 Recovery time was also significantly asso-ciated with quality-of-life measures. They found that

Am J Kidney Dis. 2014;64(1):7-9

long recovery time was associated with long dialysisduration, a perplexing finding given that long dialysisduration correlated with improved survival in a pre-vious DOPPS cohort.11 The authors suggest thatbecause the recovery time question is easy to admin-ister and has high response rates, it can be used toidentify patients with poor quality of life and high riskof dying. It also possibly could be used as an auditmeasure of the quality of dialysis treatment and asurrogate outcome to test dialysis-related interventionsin randomized trials.10

It certainly could be argued that the recovery timequestion adds little to readily available measures suchas serum albumin in predicting poor prognosis. Inaddition, the associations between recovery time andother measures such as low 36-Item Short FormHealth Survey (SF-36) physical and mental compositescores, high kidney disease burden score, being un-employed, and worse insomnia and depression aredifficult to interpret: the cross-sectional nature of thedemonstrated associations precludes inferences aboutcausality. For example, do patients who score poorlyon these other measures do so because their recoverytime is long, or do they score poorly on these mea-sures and have a long recovery time because they areotherwise ill? Finally, to conclude that recovery timeis a valid audit measure or surrogate outcome basedon the association of 1 measurement at a single timepoint with hard outcomes is premature. Ideally, anaudit measure or surrogate outcome requires demon-stration that the measure is responsive to an inter-vention, and that a change in the measure associates(preferably in a dose-dependent manner) with a changein mortality or other hard outcome. Based on thecurrent study, we cannot be certain that recovery timeis amenable to change with treatment any more than isserum albumin level.Although we believe it is inappropriate to view

recovery time as a causal factor or a potential surro-gate outcome, Rayner et al10 should be commendedfor drawing attention to a measure that has inherentvalue as an outcome in its own right due to its po-tential importance to patients. The recent creationof the Patient-Centered Outcomes Research Institute

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Suri and Gunaratnam

(PCORI) by the US Patient Protection and AffordableCare Act has shifted attention away from researcher-driven questions to those “guided by patients, care-givers, and the broader healthcare community.”12

That quality-of-life measures are associated withmortality and poor outcomes in patients receivinghemodialysis has been known since at least 1991,13

but these correlations are less important than recog-nizing that quality of life itself is a patient-centered,clinically meaningful outcome.14 In a recent webdialogue held by the National Institute of Diabetes,Digestive and Kidney Diseases that compiled res-ponses from more than 1,600 participants, the patient-centered outcomes that were identified included“refinement of the instruments used to measurehealth-related quality of life” and “consideration ofthe broad and vexing set of symptoms within end-stage renal disease.”14 The importance of quality-of-life considerations for patients receiving dialysisshould not be underestimated; in a recent randomizedtrial, almost one-quarter of patients died due to with-drawal from dialysis therapy.15 This high rate isalarming given that these patients were a select groupwho were well enough to meet the inclusion criteriaand participate in a randomized trial. Quality-of-lifeconsiderations likely contribute importantly to a pa-tient’s decision to continue or withdraw from dialysistherapy.16

The recovery time question is appealing for severalreasons. It has high face validity, encompassing theoverall well-being of a patient after a hemodialysistreatment, and is easy for patients to understand.Moreover, unlike the commonly used SF-36 andKidney Disease Quality of Life surveys that containdozens of questions, Rayner et al10 have demonstratedthat the single recovery time question is easy to ad-minister, with higher response rates (97% vs 76%). Itsnovelty and simplicity are reminiscent of the “surprisequestion” in which physicians ask themselves “WouldI be surprised if this patient died in the next year?”17

However, because the recovery time question is askedto patients and allows them to describe somewhatquantitatively how they feel after dialysis, it has thepotential to be affected positively by changes intreatment. In the Frequent Hemodialysis Network(FHN) Daily Trial, increasing in-center dialysis fre-quency from 3 to 6 days per week resulted in clini-cally substantial, statistically significant improvementsin recovery time (FHN Trial Group, personal com-munication, March 2014). Other aspects of the re-covery time questions should be explored further. Forexample, Rayner et al10 gave patients ordinal choices,but the original question and the one used in theFHN trial left the answer open ended.18 Whetherthis discrepancy affects responsiveness of the measureis not clear. Also, there was some between-country

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variation in the study by Rayner et al,10 suggestingthat cultural differences may be important and shouldbe explored as well.A systematic review suggested that nephrology

lags behind all other medical subspecialties in thegeneration of high-quality evidence from randomizedcontrolled trials.19 Although there have been efforts tofill this gap in recent years, conducting large trialswith adequate statistical power to examine mortalityoften has proved difficult, if not impossible, in end-stagerenal disease.20-22 Moreover, mortality repeatedly hasbeen shown to be poorly responsive to interventionsin patients receiving dialysis.23-26 Perhaps becauseend-stage renal disease is a chronic lifelong disease,quality of life and “feeling good” without symptomsmatters equally if not more to patients than mortal-ity.14 For example, erythropoiesis-stimulating agentshave been reimbursed by insurers based on quality-of-life improvements.27 Given these facts, is it time torefocus our attention in hemodialysis from observa-tional studies of prognostic predictors and randomizedtrials evaluating mortality, to less expensive, smaller,and more feasible but equally meaningful trials ofinterventions that have high probability of improvingpatient-centered outcomes, such as recovery time anddialysis-related symptoms? And if such interventionsare shown to be efficacious, will government payorsuphold their commitment to the PCORI initiative bypaying for and promoting them?

Rita S. Suri, MD, MScUniversity of Montreal

Montreal, Canada

Lakshman Gunaratnam, MD, MScWestern University

London, Canada

ACKNOWLEDGEMENTSSupport: None.Financial Disclosure: The authors declare that they have no

relevant financial interests.

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Editorial

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