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Quality of Life in Patients with Chronic Renal Failure

Kamyar Kalantar-Zadeh, MD, MPH
Assistant Professor of Medicine and Pediatrics
David Geffen School of Medicine at UCLA
Harbor-UCLA Medical Center, California, USA

Monitoring a patient’s functional status and the subjective state of well-being, together known as quality of life (QoL) measurements, is of particular importance in patients with end-stage renal disease (ESRD), because the physical debility experienced by patients with uremia can be insidious and have grave consequences 1, 2. QoL measurements are based on a patient’s subjective sense of well-being and are commonly used as an important clinical measure for beneficial extent of medical treatments for patients on MHD 1. In recent years, more attention has been drawn toward reexamining the overall role and potential application of patient self-reported states of well-being and functioning by use of self-administered QoL questionnaires in the dialysis population 2-5.

Patients on maintenance hemodialysis (MHD) or chronic peritoneal dialysis (CPD) experience decreased QoL 6, 7 and significantly greater rates of protein-energy malnutrition and inflammation, together also known as malnutrition-inflammation complex syndrome (MICS) 8, 9. Moreover, dialysis patients have a worse QoL and higher rates of hospitalization and mortality compared with the normal population 10-14 Although the MICS has been correlated with both hospitalization and mortality rates, there are not many studies to examine whether this syndrome is associated with adverse QoL 2, 11, 15. The association between this somewhat subjective outcome, i.e. QoL, and other more objective measures, such as mortality and hospitalization, have been studied only recently in dialysis population.

SF36 QoL Scoring System

The SF36, a short-form QoL scoring system with 36 items, is a self-administered questionnaire that was constructed to fill the gap between much more lengthy surveys and relatively coarse single-item measures of the QoL 2-5. Figure 1 shows the structure of SF36 scoring system. It consists of 36 questions, 35 of which are compressed into eight multi-item scales: (1) physical functioning is a ten-question scale that captures abilities to deal with the physical requirement of life, such as attending to personal needs, walking, and flexibility; (2) role-physical is a four-item scale that evaluates the extent to which physical capabilities limit activity; (3) bodily pain is a two-item scale that evaluates the perceived amount of pain experienced during the previous 4 wk and the extent to which that pain interfered with normal work activities; (4) general health is a five-item scale that evaluates general health in terms of personal perception; (5) vitality is a four-item scale that evaluates feelings of pep, energy, and fatigue; (6) social functioning (SF) is a two-item scale that evaluates the extent and amount of time, if any, that physical health or emotional problems interfered with family, friends, and other social interactions during the previous 4 wk; (7) role-emotional (RE) is a three-item scale that evaluates the extent, if any, to which emotional factors interfere with work or other activities; and (8) mental health is a five-item scale that evaluates feelings principally of anxiety and depression. Hence, in the SF36 scoring system, the scales are assessed quantitatively, each on the basis of answers to two to ten multiple choice questions, and a score between 0 and 100 is then calculated on the basis of well-defined guidelines, with a higher score indicating a better state of health 2. The scales of SF36 are summarized into two dimensions. The first five scales make up the "physical health" dimension, and the last five form the "mental health" dimension. The scales vitality and general health are parts of both dimensions (Figure 1). Hence, each dimension includes three specific and two overlapping scales 2. The SF36 also includes a question about self-evaluation of change in health during the past year (reported health) that does not belong to any score or dimension or the total SF36 score. The scores of the two dimensions and the total SF36 score are based on mathematical averaging of the scale components.

Using Microsoft Excel 97, version 9.0 (Microsoft, Redmond, WA), we have designed a program based on well-defined SF36 guidelines to perform automatic scoring of the scales, dimensions, and the total SF36 results 2. Our reformatted SF36 questionnaire (English version) and the programmed Excel sheet to calculate the results of SF36 analysis along with related instructions as to how perform the questionnaire and its scoring are posted on the internet as an appendix to this article (www.nephrology.rei.edu/qol.htm ).

The SF36 is a well-documented scoring system that has been widely used and validated as a QoL assessment tool for the general population as well as patients on MHD 3-5, 10, 16. It is used both as a stand-alone measure of QoL and as a core component of several major assessment tools, including the Kidney Disease Quality of Life (KDQOL) survey instrument 11, 17-19. The SF36 is one of the most commonly used instruments for QoL evaluation in patients undergoing maintenance dialysis. However, the true utility and applicability of SF36 for patients with ESRD have not been fully elucidated.

Figure 1. The SF36 quality of life (QoL) scoring system and its scales and dimensions. Note that Vitality and General Health scales are overlapping components of both Physical Health and Mental Health dimensions. Question #2, self-evaluation of change in health during the past year (Reported Health), does not belong to any score, dimension or the total SF36 score 2.

SF36 in Patients with Kidney Failure
Because of the increased use of the SF36, it has become possible to compare mean scale scores among groups of patients undergoing dialysis and between different populations of individuals. Several studies have reported that for the physical functioning, SF, and RE scales of the SF36, reliability estimates are the same or even slightly greater in patients undergoing dialysis compared with the nondialytic population 2-5, 12, 20. Diaz-Buxo et al. 7 recently used the SF36 to compare the QoL in patients undergoing maintenance hemodialysis and chronic peritoneal dialysis and found that perception of QoL among these two groups was similar before adjustment but that patients undergoing peritoneal dialysis scored higher for mental processes after adjustments. Laws et al. 21 used the SGA to assess nutritional status in 69 patients on MHD and found that more severe degrees of malnutrition were associated with poorer QoL. Lowrie et al. 10examined the relationship between SF36 and laboratory values and found that the SF36 score was significantly correlated with serum albumin, creatinine, and hemoglobin. We, too, found that hypoalbuminemic MHD patients have lower QoL scores even after adjustment for demographic characteristics 2.

Because the predialysis serum CRP showed a weak correlation with SF36, it is possible that at least part of the correlation between albumin, a visceral protein and an acute phase reactant, and the SF36 may be due to the fact that serum albumin is a marker of malnutrition-inflammation complex syndrome 2, an entity that may be associated with a worse QoL.

SF36 as a Predictor of Mortality and Hospitalization in ESRD Patients
Three recent studies have shown that SF36 is a predictor of clinical outcome in dialysis patients. The first study was conducted by our group 2. In 65 adult outpatients on MHD, the SF36 and its scales and dimensions, scored as a number between 0 and 100, and the nutritional and inflammatory state measured by subjective global assessment, near-infrared (NIR) body fat, body mass index (BMI), and pertinent laboratory values, including hemoglobin, albumin, and C-reactive protein (CRP) were assessed. Twelve-month prospective hospitalization rates and mortality were used as the clinical outcomes. Multivariate (case-mix) adjusted correlation coefficients were statistically significant between SF36 scores and serum albumin and hemoglobin concentrations. There were significant inverse correlations between SF36 scores and the BMI and NIR body fat percentage. Hypoalbuminemic, anemic, and obese patients on MHD had a worse QoL. Prospective hospitalizations correlated significantly with the SF36 total score and its two main dimensions (r between -0.28 and -0.40). The Cox proportional regression relative risk of death for each 10 unit decrease in SF36 was 2.07 (95% CI, 1.08 to 3.98; P = 0.02). Of the eight components and two dimensions of the SF36, the Mental Health dimension and the SF36 total score had the strongest predictive value for mortality. We concluded that in patients on MHD the SF36 appears to have significant associations with measures of nutritional status, anemia, and clinical outcomes, including prospective hospitalization and mortality. Even though obesity, unlike undernutrition, is not generally an indicator of poor outcome in MHD, the SF36 may detect obese patients on MHD at higher risk for morbidity and mortality 2.

The Dialysis Outcomes and Practice Patterns Study (DOPPS) investigators analyzed their data from an international, prospective, observational study of randomly selected MHD patients in the USA (148 facilities), five European countries (101 facilities), and Japan (65 facilities) 11. The total sample size was composed of 17,236 patients. Using the KDQOL, they determined scores for: (1) physical component summary (PCS), (2) mental component summary (MCS), and (3) kidney disease component summary (KDCS). Complete responses on HRQOL measures were obtained from 10,030 patients. Cox models were used to assess associations between HRQOL and the risk of death and hospitalization, adjusted for multiple sociodemographic variables, comorbidities, and laboratory factors. For patients in the lowest quintile of PCS, the adjusted risk (RR) of death was 93% higher (RR = 1.93, P< 0.001) <>and the risk of hospitalization was 56% higher (RR = 1.56, P< 0.001) <>than it was for patients in the highest quintile level. The adjusted relative risk values of mortality per 10-point lower HRQOL score were 1.13 for MCS, 1.25 for PCS, and 1.11 for KDCS. The corresponding adjusted values for RR for first hospitalization were 1.06 for MCS, 1.15 for PCS, and 1.07 for KDCS. Each RR differed significantly from 1 (P< 0.001).<> For 1 g/dL lower serum albumin concentration, the RR of death adjusted for PCS, MCS, and KDCS and the other covariates was 1.17 (P< 0.01).<> They concluded that lower scores for the three major components of QOL were strongly associated with higher risk of death and hospitalization in MHD patients, independent of a series of demographic and comorbid factors. A 10-point lower PCS score was associated with higher elevation in the adjusted mortality risk, as was a 1 g/dL lower serum albumin level. More research is needed to assess whether interventions to improve quality of life lower these risks among hemodialysis patients 11.

Finally, Lowrie et al 10 recently examined the data collected from 13,952 prevalent dialysis patients served by Fresenius Medical Care North America. Functioning and well-being were measured via the SF-36 Summary scale scores, PCS, and MCS. Also collected was information about hospitalizations and patient mortality. PCS and MCS were consistent predictors of hospitalizations and mortality rates even after adjustment for clinically relevant factors. They concluded that because PCS and MCS are associated with hospitalization and mortality, administering this self-report measure may serve as a valuable supplement to clinical measures traditionally relied on to predict patient outcomes. Moreover, such information may be unavailable through any other single mechanism 10.

Several recent studies have shown that subjective measure of QoL via self-administered questionnaires is a predictor of hospitalization and mortality in dialysis patients 2, 10, 11. During recent years, more efforts have been dedicated in exploring the potentials of patient self-reported QoL questionnaires in high-risk populations. The task is even more essential when it pertains to patients with ESRD, whose life prolongation via renal replacement therapy has left them with a different and less-well-known life style. Exploring the potentials of self-administered QoL questionnaires in patients with ESRD has been underscored by the contemporary emphasis on dialysis outcome research 2. Patients’ subjectively perceived QoL status may not only be a clinically and psychosocially meaningful outcome per se but a predictor of more objective outcomes such as prospective hospitalization and mortality. If the SF36, which takes a few minutes of patient’s time to complete, is a strong indicator of patient outcome and is indeed a predictor of morbidity and mortality in MHD, serial annual assessments of the QoL that use this simple tool might help to identify high-risk patients who may need intensified attention and risk modification interventions.

It is imperative to examine all aspects of possible associations between such health survey questionnaires as the SF36 and clinically relevant indices such as nutritional state, inflammation and anemia and to explore the potentials of such scoring tools in predicting relevant clinical outcomes. The tool has to be a well-established and adequately validated one, both inclusive and user-friendly, with optimal capability of serving as an interviewer independent, self-administered questionnaire given the increasing time constraint involving health care personnel in charge of patients with ESRD. The SF36 may be a means to that end. Compared with those QoL tools that are tailored for patients undergoing dialysis, the SF36 has the advantage of being nonspecific, hence enabling the investigators to conveniently compare the health state of the patients with ESRD with non-ESRD populations under diverse observational and interventional studies.

Supported by grants from NIDDK, NKF, Amgen, Genzyme, and DaVita.


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    2. Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH: Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis. J Am Soc Nephrol 12:2797-2806, 2001

    3. Maor Y, King M, Olmer L, Mozes B: A comparison of three measures: the time trade-off technique, global health-related quality of life and the SF-36 in dialysis patients. J Clin Epidemiol 54:565-570, 2001

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    6. Chen YC, Hung KY, Kao TW, Tsai TJ, Chen WY: Relationship between dialysis adequacy and quality of life in long-term peritoneal dialysis patients. Perit Dial Int 20:534-540., 2000

    7. Diaz-Buxo JA, Lowrie EG, Lew NL, Zhang H, Lazarus JM: Quality-of-life evaluation using Short Form 36: comparison in hemodialysis and peritoneal dialysis patients. Am J Kidney Dis 35:293-300., 2000

    8. Kalantar-Zadeh K, Ikizler A, Block G, Avram M, Kopple J: Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis, November, 2003 [in press]

    9. Kalantar-Zadeh K, Kopple JD: Relative contributions of nutrition and inflammation to clinical outcome in dialysis patients. Am J Kidney Dis 38:1343-1350, 2001

    10. Lowrie EG, Curtin RB, Lepain N, Schatell D: Medical outcomes study short form-36: A consistent and powerful predictor of morbidity and mortality in dialysis patients. Am J Kidney Dis 41:1286-1292, 2003

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    12. Kalantar-Zadeh K KH, Supasyndh O, Kopple JD: Association between SF36 quality of life and serum albumin, creatinine and total lymphocyte count in hemodialysis patients. 11th International Congress on Nutrition and Metabolism in Renal Diseases, Nagoya, Japan; , March 2002 [abstract]

    13. Kalantar-Zadeh K BG, McAllister CJ, Humphreys MH, Kopple JD: Self-reported subjective appetite correlates with inflammation, nutrition, and anemia and predicts quality of life and mortality in hemodialysis patients. ]. Annual conference of American Society of Nephrology, Am Soc Neph, November 2003 [abstract]

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October 2003