The Malnutrition-Inflammation Score: A Valid Nutritional Tool to Assess Mortality Risk in Kidney Transplant Patients

Abstract

Related Article, p. 101 The malnutrition-inflammation score (MIS) has been used increasingly to evaluate nutritional status in the dialysis setting for research purposes.1Kalantar-Zadeh K. Ikizler T.A. Block G. Avram M.M. Kopple J.D. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences.Am J Kidney Dis. 2003; 42: 864-881Abstract Full Text Full Text PDF PubMed Scopus (737) Google Scholar, 2Kalantar-Zadeh K. Kopple J.D. Block G. Humphreys M.H. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.Am J Kidney Dis. 2001; 38: 1251-1263Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 3Afsar B. Sezer S. Ozdemir F.N. Celik H. Elsurer R. Haberal M. Malnutrition-inflammation score is a useful tool in peritoneal dialysis patients.Perit Dial Int. 2006; 26: 705-711PubMed Google Scholar Results indicate that patients receiving maintenance dialysis with a higher MIS have an increased risk of adverse outcomes.2Kalantar-Zadeh K. Kopple J.D. Block G. Humphreys M.H. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.Am J Kidney Dis. 2001; 38: 1251-1263Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 3Afsar B. Sezer S. Ozdemir F.N. Celik H. Elsurer R. Haberal M. Malnutrition-inflammation score is a useful tool in peritoneal dialysis patients.Perit Dial Int. 2006; 26: 705-711PubMed Google Scholar, 4Ho L.C. Wang H.H. Peng Y.S. et al.Clinical utility of malnutrition-inflammation score in maintenance hemodialysis patients: focus on identifying the best cut-off point.Am J Nephrol. 2008; 28: 840-846Crossref PubMed Scopus (51) Google Scholar In this issue of American Journal of Kidney Diseases, Molnar et al5Molnar M.Z. Czira M.E. Rudas A. et al.Association of the malnutrition-inflammation score with clinical outcomes in kidney transplant recipients.Am J Kidney Dis. 2011; 58: 101-108Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar show evidence that the MIS also has predictive validity to identify kidney transplant recipients with higher risk of adverse outcomes. To assess associations of the MIS with transplant outcomes, they used a prospective cohort study of 993 prevalent kidney transplant recipients 18 years or older followed up at a transplant clinic in Budapest. All patients were white. Exclusion criteria for this study were acute rejection during the previous 4 months, current hospitalization, and transplant performed within the previous 3 months. Using multivariable time-dependent Cox regression analysis, they showed that higher MIS was associated with higher risk of all-cause death, death with a functioning transplant, and death-censored transplant loss (return to maintenance dialysis therapy). Several nutritional measures (eg, serum albumin, serum creatinine, body mass index, and normalized protein catabolic rate) have been used to assess the nutritional status of patients with chronic kidney diseases.6Lowrie E.G. Huang W.H. Lew N.L. Death risk predictors among peritoneal dialysis and hemodialysis patients: a preliminary comparison.Am J Kidney Dis. 1995; 26: 220-228Abstract Full Text PDF PubMed Scopus (162) Google Scholar, 7Combe C. McCullough K.P. Asano Y. Ginsberg N. Maroni B.J. Pifer T.B. Kidney Disease Outcomes Quality Initiative (K/DOQI) and the Dialysis Outcomes and Practice Patterns Study (DOPPS): nutrition guidelines, indicators, and practices.Am J Kidney Dis. 2004; 44: 39-46Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 8Pifer T.B. McCullough K.P. Port F.K. et al.Mortality risk in hemodialysis patients and changes in nutritional indicators: DOPPS.Kidney Int. 2002; 62: 2238-2245Crossref PubMed Scopus (350) Google Scholar, 9Blumenkrantz M.J. Kopple J.D. Gutman R.A. et al.Methods for assessing nutritional status of patients with renal failure.Am J Clin Nutr. 1980; 33: 1567-1585PubMed Google Scholar Although there is no single measure that provides a comprehensive indication of protein-energy nutritional status for these patients,10Kidney Disease Outcome Quality Initiative: clinical practice guidelines for nutrition in chronic renal failure.Am J Kidney Dis. 2000; 35 (No authors listed): S1-S140PubMed Google Scholar the MIS represents an advance over single measures in the assessment of nutritional status. Use of the MIS is consistent with recommendations of the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) to use a panel of measures to assess protein-energy nutritional status.10Kidney Disease Outcome Quality Initiative: clinical practice guidelines for nutrition in chronic renal failure.Am J Kidney Dis. 2000; 35 (No authors listed): S1-S140PubMed Google Scholar The MIS is a more comprehensive scoring system and quantitative assessment tool to assess nutritional status than its predecessors, in other words, Subjective Global Assessment (SGA) and Dialysis Malnutrition Score.2Kalantar-Zadeh K. Kopple J.D. Block G. Humphreys M.H. A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.Am J Kidney Dis. 2001; 38: 1251-1263Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar The MIS is composed of 10 components, each representing different aspects of the malnutrition-inflammation complex. Seven MIS components also are used to determine SGA (weight change, dietary intake, gastrointestinal symptoms, functional capacity, comorbid conditions, fat stores, and muscle wasting). The 3 non-SGA components are body mass index, serum albumin level, and total iron-binding capacity. Each component of the MIS has 4 levels of severity, from 0 (normal) to 3 (severely abnormal). The sum of all 10 MIS components can range from 0 (normal) to 30 (severely malnourished); higher score reflects a more severe degree of malnutrition and inflammation. A large body of evidence has indicated that malnutrition and inflammation are closely linked and frequently present in patients receiving dialysis.1Kalantar-Zadeh K. Ikizler T.A. Block G. Avram M.M. Kopple J.D. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences.Am J Kidney Dis. 2003; 42: 864-881Abstract Full Text Full Text PDF PubMed Scopus (737) Google Scholar, 11Stenvinkel P. Heimburger O. Lindholm B. Kaysen G.A. Bergstrom J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome).Nephrol Dial Transplant. 2000; 15: 953-960Crossref PubMed Scopus (648) Google Scholar The MIS takes into account the link between malnutrition and inflammation in patients with chronic kidney disease. Studies of patients receiving maintenance dialysis have shown that the MIS correlates with several biological markers of inflammation.12Afsar B. Ozdemir N.F. Sezer S. Haberal M. Quality of life is not related with liver disease severity but with anemia, malnutrition, and depression in HCV-infected hemodialysis patients.Hemodial Int. 2009; 13: 62-71Crossref PubMed Scopus (15) Google Scholar, 13Rambod M. Bross R. Zitterkoph J. et al.Association of malnutrition-inflammation score with quality of life and mortality in hemodialysis patients: a 5-year prospective cohort study.Am J Kidney Dis. 2009; 53: 298-309Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar Molnar et al14Molnar MZ, Czira ME, Rudas A, et al. Association between the malnutrition-inflammation score and post-transplant anaemia [published online ahead of print November 29, 2010]. Nephrol Dial Transplant. doi: 10.1093/ndt/gfq690.Google Scholar also have shown data indicating that the MIS reflects both protein-energy wasting and inflammation in kidney transplant recipients. Malnutrition is common in patients receiving maintenance dialysis and has been the subject of a great deal of research.3Afsar B. Sezer S. Ozdemir F.N. Celik H. Elsurer R. Haberal M. Malnutrition-inflammation score is a useful tool in peritoneal dialysis patients.Perit Dial Int. 2006; 26: 705-711PubMed Google Scholar, 4Ho L.C. Wang H.H. Peng Y.S. et al.Clinical utility of malnutrition-inflammation score in maintenance hemodialysis patients: focus on identifying the best cut-off point.Am J Nephrol. 2008; 28: 840-846Crossref PubMed Scopus (51) Google Scholar, 13Rambod M. Bross R. Zitterkoph J. et al.Association of malnutrition-inflammation score with quality of life and mortality in hemodialysis patients: a 5-year prospective cohort study.Am J Kidney Dis. 2009; 53: 298-309Abstract Full Text Full Text PDF PubMed Scopus (251) Google Scholar, 15Bilgic A. Akgul A. Sezer S. Arat Z. Ozdemir F.N. Haberal M. Nutritional status and depression, sleep disorder, and quality of life in hemodialysis patients.J Ren Nutr. 2007; 17: 381-388Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 16Cano N.J. Roth H. Aparicio M. et al.Malnutrition in hemodialysis diabetic patients: evaluation and prognostic influence.Kidney Int. 2002; 62: 593-601Crossref PubMed Scopus (91) Google Scholar, 17Bergstrom J. Anorexia and malnutrition in hemodialysis patients.Blood Purif. 1992; 10: 35-39Crossref PubMed Scopus (11) Google Scholar, 18Lopes A.A. Elder S.J. Ginsberg N. et al.Lack of appetite in haemodialysis patients—associations with patient characteristics, indicators of nutritional status and outcomes in the international DOPPS.Nephrol Dial Transplant. 2007; 22: 3538-3546Crossref PubMed Scopus (79) Google Scholar In kidney transplant recipients, more attention has been placed on excessive weight gain after transplant, although malnutrition has not been studied as well in this population. However, data suggest that 15%-20% of kidney transplant recipients have malnutrition, with comorbid conditions, kidney transplant failure, immunosuppression, inflammation, and oxidative stress some of the potential contributors.19Djukanovic L. Lezaic V. Blagojevic R. et al.Co-morbidity and kidney graft failure-two main causes of malnutrition in kidney transplant patients.Nephrol Dial Transplant. 2003; 18: v68-v70Crossref PubMed Google Scholar, 20de Cal M. Silva S. Cruz D. et al.Oxidative stress and ‘monocyte reprogramming' after kidney transplant: a longitudinal study.Blood Purif. 2008; 26: 105-110Crossref PubMed Scopus (14) Google Scholar, 21Bernardi A. Biasia F. Pati T. et al.Factors affecting nutritional status, response to exercise, and progression of chronic rejection in kidney transplant recipients.J Ren Nutr. 2005; 15: 54-57Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Studies in maintenance hemodialysis populations have shown that approximately half the patients have an MIS greater than 5 points.4Ho L.C. Wang H.H. Peng Y.S. et al.Clinical utility of malnutrition-inflammation score in maintenance hemodialysis patients: focus on identifying the best cut-off point.Am J Nephrol. 2008; 28: 840-846Crossref PubMed Scopus (51) Google Scholar, 22Kalantar-Zadeh K. Kopple J.D. Humphreys MHm Block G. Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients.Nephrol Dial Transplant. 2004; 19: 1507-1519Crossref PubMed Scopus (223) Google Scholar, 23Silva L.F. Matos C.M. Lopes G.B. et al.Handgrip strength as a simple indicator of possible malnutrition and inflammation in men and women on maintenance hemodialysis.J Ren Nutr. 2011; 21: 235-245Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar It has been proposed that an MIS close to the median value (5 points) is the best cutoff to identify maintenance hemodialysis patients who are at higher risk of death.4Ho L.C. Wang H.H. Peng Y.S. et al.Clinical utility of malnutrition-inflammation score in maintenance hemodialysis patients: focus on identifying the best cut-off point.Am J Nephrol. 2008; 28: 840-846Crossref PubMed Scopus (51) Google Scholar Using a multivariable logistic regression model, Ho et al4Ho L.C. Wang H.H. Peng Y.S. et al.Clinical utility of malnutrition-inflammation score in maintenance hemodialysis patients: focus on identifying the best cut-off point.Am J Nephrol. 2008; 28: 840-846Crossref PubMed Scopus (51) Google Scholar estimated that the probabilities of 1-year mortality for long-term dialysis patients with an MIS of 3, 4, and 5 were 10%, 40%, and 80%, respectively. In contrast, in the study by Molnar et al5Molnar M.Z. Czira M.E. Rudas A. et al.Association of the malnutrition-inflammation score with clinical outcomes in kidney transplant recipients.Am J Kidney Dis. 2011; 58: 101-108Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar of kidney transplant recipients, <30% of patients had an MIS greater than 5 points. The median MIS in this study of kidney transplant recipients was 3. Using kidney transplant recipients with MIS <3 as the referent category in a multivariable time-dependent Cox regression analysis, a dose-response association was shown between MIS and hazards of death from any cause, death-censored transplant loss, and death with a functioning transplant. Compared with MIS <6, the hazard of death from any cause was more than 3 times higher for patients with an MIS of 5-7 (adjusted hazard ratio (HR), 3.88; P < 0.001) and almost 7 times higher for those with MIS ≥8 (adjusted HR, 6.82; P < 0.001). The adjusted hazard of death from any cause was only 53% (adjusted HR, 1.53) higher for patients with MIS of 3-4 than for those with MIS <3; this association did not reach statistical significance (P = 0.2). The patterns of associations of the MIS with death-censored transplant loss and death with a functioning transplant were similar to the pattern observed for the association between MIS and all-cause death. These results suggest that, similar to that reported for patients receiving maintenance hemodialysis, a value close to 5 also is an adequate cutoff to identify kidney transplant recipients who are at higher risk of death. However, use of the MIS divided into multiple instead of 2 categories will increase its discriminant power for predicting mortality risk in kidney transplant recipients. The study by Molnar et al5Molnar M.Z. Czira M.E. Rudas A. et al.Association of the malnutrition-inflammation score with clinical outcomes in kidney transplant recipients.Am J Kidney Dis. 2011; 58: 101-108Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar supports the predictive validity of a simple and inexpensive tool, the MIS, for mortality risk in kidney transplant recipients. However, as acknowledged by the investigators, limitations inherent to the observational design should be considered for drawing causal inferences from this study. We also should be cautious to generalize results of this study to a more diverse population of kidney transplant recipients considering that all studied patients were white and from a single center. It is important to observe that the MIS has been associated with both mortality risk and health-related quality of life (HRQoL) in patients receiving maintenance hemodialysis.24Mapes D.L. Lopes A.A. Satayathum S. et al.Health-related quality of life as a predictor of mortality and hospitalization: the Dialysis Outcomes and Practice Patterns Study (DOPPS).Kidney Int. 2003; 64: 339-349Crossref PubMed Scopus (635) Google Scholar, 25Lopes A.A. Bragg-Gresham J.L. Satayathum S. et al.Health-related quality of life and associated outcomes among hemodialysis patients of different ethnicities in the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS).Am J Kidney Dis. 2003; 41: 605-615Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar It seems plausible to expect that, similar to observations in maintenance hemodialysis patients, a higher MIS also is associated with poorer HRQoL in kidney transplant recipients, but this possibility needs to be substantiated by further research. In addition to poor nutritional status, the presence of comorbid conditions, episodes of rejection, side effects of immunosuppressives and other medications, unemployment, and uncertainty about the future are some factors that should be viewed as potential contributors to poor HRQoL in kidney transplant recipients.26Jofre R. Lopez-Gomez J.M. Moreno F. Sanz-Guajardo Dm Valderrabano F. 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Rocha M. et al.Factors associated with health-related quality of life after successful kidney transplantation: a population-based study.Qual Life Res. 2009; 18: 1185-1193Crossref PubMed Scopus (36) Google Scholar A systematic assessment of HRQoL for all kidney transplant recipients, in addition to providing information about individual well-being, likely may help identify patients at higher risk of adverse clinical outcomes. Studies of patients receiving hemodialysis have shown that lower scores in generic and kidney disease–targeted HRQoL components of the Kidney Disease Quality of Life–Short Form (KDQOL-SF) are associated with higher risks of death and hospitalization independent of several risk factors for these outcomes.24Mapes D.L. Lopes A.A. Satayathum S. et al.Health-related quality of life as a predictor of mortality and hospitalization: the Dialysis Outcomes and Practice Patterns Study (DOPPS).Kidney Int. 2003; 64: 339-349Crossref PubMed Scopus (635) Google Scholar, 25Lopes A.A. Bragg-Gresham J.L. Satayathum S. et al.Health-related quality of life and associated outcomes among hemodialysis patients of different ethnicities in the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS).Am J Kidney Dis. 2003; 41: 605-615Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar It is important to note that both the KDQOL-SF and the generic instrument of HRQoL, the Medical Outcomes Study 36-Item Short-Form Health Survey, have been validated for kidney transplant recipients.30Barotfi S. Molnar M.Z. Almasi C. et al.Validation of the Kidney Disease Quality of Life-Short Form questionnaire in kidney transplant patients.J Psychosom Res. 2006; 60: 495-504Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 31Gomez-Besteiro M.I. Santiago-Perez M.I. Alonso-Hernandez A. Valdes-Canedo F. Rebollo-Alvarez P. Validity and reliability of the SF-36 questionnaire in patients on the waiting list for a kidney transplant and transplant patients.Am J Nephrol. 2004; 24: 346-351Crossref PubMed Scopus (39) Google Scholar, 32Butt Z. Yount S.E. Caicedo J.C. Abecassis M.M. Cella D. Quality of life assessment in renal transplant: review and future directions.Clin Transplant. 2008; 22: 292-303Crossref PubMed Scopus (40) Google Scholar Systematic use of an HRQoL instrument in conjunction with the MIS should provide a more comprehensive evaluation of the health status of kidney transplant recipients. In summary, data support the use of the MIS as a proxy for protein-energy wasting and inflammation in kidney transplant recipients. The study by Molnar et al5Molnar M.Z. Czira M.E. Rudas A. et al.Association of the malnutrition-inflammation score with clinical outcomes in kidney transplant recipients.Am J Kidney Dis. 2011; 58: 101-108Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar emphasizes the importance of this simple and inexpensive screening nutritional tool to identify kidney transplant recipients at higher risk of death. In patients receiving maintenance hemodialysis, higher MIS also has been associated with poor HRQoL. The association between MIS and HRQoL remains an interesting question for future research in kidney transplant recipients. Financial Disclosure: The author declares that he has no relevant financial interests. Association of the Malnutrition-Inflammation Score With Clinical Outcomes in Kidney Transplant RecipientsAmerican Journal of Kidney DiseasesVol. 58Issue 1PreviewThe combination of chronic malnutrition and inflammation, often termed malnutrition-inflammation complex syndrome or protein-energy wasting, is common in patients with chronic kidney disease. It is associated with increased mortality in patients on maintenance dialysis therapy. We assessed the association of malnutrition-inflammation score (MIS) with all-cause mortality and death-censored transplant loss or death with a functioning transplant in a sample of kidney transplant recipients. Full-Text PDF