Can malnutrition in predialysis patients be prevented by dietetic intervention?

RESEARCH BRIEFS

Can Malnutrition in Predialysis Patients Be Prevented by Dietetic Intervention? Marion Cliffe, MSc, SRD,* Lionel L. O. Bloodworth, FRCP,† and Mahdi M. Jibani, MBBS, MRCP‡ Objective: This study aimed to discover if the documented decline in nutritional status in predialysis patients could be prevented by dietetic intervention. Design: Longitudinal prospective interventional study. Setting: General hospital nephrology clinic. Patients: Eleven patients with progressive chronic renal failure not yet requiring dialysis, all with creatinine clearance below 25mL/min were studied. Mean age was 63.9 ⫾ 14.5 years. Intervention: Patients received nutritional counseling from a renal dietitian on at least 3 occasions over a period of 6 months. Following assessment, patients were advised on dietary changes according to individual need, aiming for adequate energy intake to achieve or maintain a body mass index of 20 to 25 and protein intake of 0.8 to 1.0 g/kg/d. Dietary supplements were prescribed when necessary. Outcome measures: Changes in nutritional status were assessed by Subjective Global Assessment, anthropometric measures (weight, triceps skinfold thickness, mid arm muscle circumference, and grip strength), and biochemical markers (serum albumin, serum transferrin, and insulin-like growth factor-1). Results: None of the patients showed decline in Subjective Global Assesment category, and 2 of the patients improved. All anthropometric and biochemical measures of nutritional status were stable or increased over the course of the study, and mid arm muscle circumference increased significantly (P ⬍ .05), contrasting with published data showing a decline in these measures in patients not receiving dietetic intervention. Conclusion: With dietetic intervention, it may be possible to maintain or improve nutritional status in this group. © 2001 by the National Kidney Foundation, Inc.

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T HAS BEEN established that malnutrition in chronic renal failure begins in the predialysis stage.1 Studies show that without intervention, deterioration in renal function is accompanied by deterioration in nutritional status.2-5 Ikizler et al2 showed that in predialysis pa* Renal Dietitian, Northwest Wales National Health Service Trust, Ysbyty Gwynedd, Bangor, UK. † Consultant Physician and Nephrologist, Northwest Wales National Health Service Trust, Ysbyty Gwynedd, Bangor, UK. ‡ Consultant Physician and Nephrologist, Northwest Wales National Health Service Trust, Ysbyty Gwynedd, Bangor, UK. Presented at the 10th International Congress on Nutrition and Metabolism in Renal Disease, Lyon, France, July 6-8, 2000. Address reprint requests to Marion Cliffe, Renal Dietitian, Department of Nutrition and Dietetics, Ysbyty Gwynedd Hospital, Bangor LL57 2PW, UK. © 2001 by the National Kidney Foundation, Inc. 1051-2276/01/1103-0007$35.00/0 doi:10.1053/jren.2001.24363

Journal of Renal Nutrition, Vol 11, No 3 ( July), 2001: pp 161-165

tients not receiving dietetic intervention, spontaneous protein intake decreased significantly as creatinine clearance decreased, and this was accompanied by a worsening in nutritional indices. Baseline cross-sectional data from the modification of diet in renal disease (MDRD) feasibility study, and from the main MDRD study, before any intervention, confirm that dietary intakes, serum, and anthropometrical measures of nutritional status progressively and significantly decline as glomerular filtration rate (GFR) decreases.3-5 Poor nutritional status at initiation of dialysis is associated with poorer outcomes.6 This study aims to discover if dietetic intervention can prevent or treat malnutrition as renal function declines in predialysis patients attending a nephrology clinic. The results are compared with the published data on patients not receiving dietetic intervention. 161

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Table 1. Baseline Patient Characteristics

Sample size Age (y) Gender (% Male/Female) Serum creatinine (umol/L [mg/dL]) Creatinine clearance (mL/min) Serum albumin (g/L [g/dL]) Renal diagnosis: Diabetic nephropathy Glomerulonephritis Hypertension Polycystic kidneys Obstructive uropathy Other

Study Group

Ikizler et al2

MDRD Feasibility4

11 63.9 ⫾ 14.5 64/36 404.3 ⫾ 75.3 (4.6 ⫾ 0.9) 17.3 ⫾ 6.0 42.5 ⫾ 2.9 (4.25 ⫾ 0.29)

90 53 ⫾ 15 51/49 301 ⫾ 195 (3.4 ⫾ 2.2) 35.1 ⫾ 26.1 38 ⫾ 4.5 (3.8 ⫾ 0.45)

95 48.6 60/40 313.9 (3.5) 28.0 42.7 (4.27)

0 1 3 1 2 4

35 23 8 7 — 17

2 36 9 28 — 20

Note. Mean ⫾ standard deviation.

Methods Patients This was a small, detailed study of 11 patients. Table 1 compares the baseline patient characteristics of this group with the groups studied by Ikizler et al2 and the MDRD feasibility study.4 Patients in the study group were older than in the control groups2,4 and had more advanced renal failure. Therefore, patients in the study group would be expected to be more prone to deterioration in nutritional status than the controls. By chance, the study group did not include any patients with diabetic nephropathy, although they would not have been excluded from the study. Assessment The following assessments were performed at entry to the study, at 3 months, and 6 months. Renal function was assessed by creatinine clearance. Dietary assessments were performed by routine diet histories, and energy and protein intakes were assessed using a 3-day diet diary (estimated record) completed by patients. Nutritional assessment was performed by the same researcher on each occasion. Using Subjective Global Assessment (SGA), patients were allocated an overall ranking of A (well nourished), B (mildly to moderately malnourished), or C (severely malnourished).7 Anthropometric measures recorded were weight, height, triceps skinfold thickness (TST), mid upper arm circumference (MUAC), and grip strength, measured using standard methods. Mid arm muscle circumference (MAMC) was calculated by the equation MAMC (cm) ⫽ MUAC (cm) ⫺ 0.3142 TST (mm).

Biochemical markers assessed were serum albumin measured by the bromocresol green method, serum transferrin measured by the Beckman Transferrin TRF test, and insulin-like growth factor-1 (IGF-1) measured in saved samples by radioimmunoassay.

Dietetic Intervention Patients were offered dietetic interviews with a senior dietitian experienced in renal dietetics at entry to the study, every 3 months at clinic visits, and between each clinic visit by telephone. After nutritional and dietary assessment, patients were advised on changes in type, amount, or frequency of food and drink intake required to move toward achievement of the following aims: adequate energy intake to maintain or achieve body mass index (BMI) 20 to 25, protein intake 0.8 to 1.0 g/kg of ideal body weight (IBW) per day (as recommended by the Renal Association in the United Kingdom),8 serum potassium ⬍ 6 mmol/L, and serum phosphate ⬍ 1.5 mmol/L. Patients who were underweight or were losing excessive weight were advised on changes to increase energy intake, such as the addition of high-calorie snacks between meals. One patient was prescribed 200 mL/d of Fortisip (Nutricia, Trowbridge, England), a nutritionally complete sip feed providing an additional 300 kcal and 10 g protein/d. One was prescribed 240 mL/d of Enlive (Abbott Laboratories, Maidenhead, England), a juice-based sip feed providing 300 kcal and 9.6 g protein/d, and 1 patient was prescribed 100 g/d of Maxijul (SHS International, Liverpool, England), a glucose polymer powder providing an additional 360 kcal/d. Those patients

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PREDIALYSIS PREVENTION OF MALNUTRITION Table 2. Initial and Final Numbers of Patients in Each SGA Category

SGA Category

Initial Number of Patients

Final Number of Patients

A B C

8 3 0

10 1 0

who were overweight (BMI ⬎ 25) or whose protein intake (calculated by dietary analysis) was significantly above the desirable limit of 1 g/kg IBW/d were advised on changes to reduce energy and/or protein intake, respectively. Reasons for any advised changes were explained, and specific food and drink changes were negotiated and agreed on with patients. When necessary, a compromise was reached to ensure quality of life with regard to food intake. Patients were given a personalized written copy of any agreed changes.

Data Analysis Mean changes (and the standard error of the mean change) in nutritional intakes and parameters from the beginning to the end of the study were calculated. The significance of these changes was tested using the Wilcoxon signed rank test. Spearman’s rank correlation coefficients and significance (P values) were calculated for correlations between change in creatinine clearance and change in nutritional parameters. These were compared to results from Ikizler et al2 and the MDRD feasibility study.3

Results Mean creatinine clearance decreased by ⫺ 3.5 ⫾ 2.3 mL/min during the course of the

study. Any patients found to have stable or improving renal function on serial measurements of creatinine clearance were excluded from the study so that only those patients with progressive chronic renal failure are described here. Table 2 shows the number of patients in each SGA category at entry to the study and after 6 months of intervention. At entry to the study, 3 patients were classified as SGA category B (mildly to moderately malnourished). By the end of the study, only 1 patient remained SGA category B. Two patients had improved sufficiently to be classified as well nourished by the end of the study. None of the patients became malnourished during the study. Changes in nutritional intakes from the beginning to the end of the study are shown separately in Table 3. None of the changes in energy or protein intake were statistically significant. When analyzed as a whole, the group showed a mean decrease in energy and protein intakes, but when the patients who were advised to maintain or increase intakes are analyzed separately, their intakes increased (although not significantly). Table 4 shows the changes in nutritional parameters from the beginning to the end of the study. All measures of nutritional status were stable or increased over the course of the study. Only the change in MAMC was statistically significant (P ⫽ .04). Correlation coefficients for the relationship between change in creatinine clearance and change in nutritional parameters are shown in Table 5. They are compared with the correlation coefficients found in the studies by Ikizler et al2 and the MDRD feasibility study3 used as controls. As previously discussed, these investigators found

Table 3. Initial and Final Nutritional Intakes Showing the Mean Change Observed During the Course of the Study: Comparison Between Patients Advised to Decrease Intakes and Those Advised to Maintain or Increase Intakes Code A B C

Intake

n

Initial

Final

Change

Standard Error of Mean Change

Energy kcal/kg IBW/d Protein g/kg IBW/d Energy kcal/kg IBW/d Protein g/kg IBW/d Energy kcal/kg IBW/d Protein g/kg IBW/d

11 11 5 7 6 4

34.2 ⫾ 4.7 1.25 ⫾ 0.25 32.7 ⫾ 3.8 1.39 ⫾ 0.18 35.5 ⫾ 5.4 1.00 ⫾ 0.13

32.7 ⫾ 8.8 1.21 ⫾ 0.32 27.3 ⫾ 5.0 1.28 ⫾ 0.32 37.4 ⫾ 8.9 1.08 ⫾ 0.30

⫺1.4 ⫾ 6.6 ⫺0.04 ⫾ 0.25 ⫺5.5 ⫾ 4.3 ⫺0.11 ⫾ 0.27 ⫹1.9 ⫾ 6.5 ⫹0.08 ⫾ 0.20

2.0 0.07 — — — —

NOTE. Values are Mean ⫾ standard deviation. Code A ⫽ all patients. Code B ⫽ patients advised to decrease energy or protein intake, respectively. Code C ⫽ patients advised to increase or maintain energy or protein intake, respectively.

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Table 4. Initial and Final Nutritional Parameters Showing the Mean Change Observed During the Course of the Study

Parameter

Initial

Final

Standard Error of Mean Change

Change

Weight (kg) 77.5 ⫾ 19.9 79.4 ⫾ 18.7 ⫹1.9 ⫾ 4.5 BMI(kg/m2) 26.9 ⫾ 5.1 27.5 ⫾ 4.6 ⫹0.6 ⫾ 1.43 TST (mm) 13.5 ⫾ 6.3 14.9 ⫾ 5.5 ⫹1.4 ⫾ 3.0 MAMC (cm) 26.6 ⫾ 3.2 27.2 ⫾ 2.7 ⫹0.6 ⫾ 0.9 Grip strength (kgf) 33.2 ⫾ 10.7 33.4 ⫾ 12.6 ⫹0.2 ⫾ 2.7 Albumin (g/L [g/dL]) 42.4 ⫾ 2.8 [4.24 ⫾ 0.28] 42.0 ⫾ 2.4 [4.20 ⫾ 0.24] ⫺0.4 ⫾ 1.6 [⫺0.04 ⫾ 0.16] Transferrin (g/L [mg/dL]) 2.15 ⫾ 0.31 [215 ⫾ 31] 2.28 ⫾ 0.41 [228 ⫾ 41] ⫹ 0.11 ⫾ 0.32 [11 ⫾ 32] IGF-1 (nmol/L ng/mL) 26.7 ⫾ 14.1 [204 ⫾ 108] 29.0 ⫾ 15.5 [222 ⫾ 118] ⫹ 2.3 ⫾ 5.2 [18 ⫾ 40]

1.3 0.4 0.9 0.3 0.8 0.5 [0.05] 0.09 [9] 1.6 [12]

Note. Values are Mean ⫾ standard deviation.

significant positive correlations between renal function and nutritional parameters in patients who were not offered intervention. In this study, no significant correlations were found between changes in creatinine clearance and changes in any of the parameters measured, ie, with intervention, decline in renal failure did not appear to be accompanied by decline in nutritional status.

Discussion This is a detailed study of a small number of patients over a relatively short period of time and, therefore, does not have sufficient power to provide a definite answer to the question posed; it only suggests whether or not dietetic intervention could be effective and whether or not a larger study may be warranted. Any study attempting to assess the efficacy of nutritional intervention in renal patients is faced with the problem that there is no single absolute marker of nutritional status. Druml9 states that “. . .what is mandatory is the proper observation over time of the patient and

of his physical state and of the evolution of various nutritional indices.” This is what has been attempted here. Using SGA, 3 of 11 patients were categorized as malnourished at entry to the study. This reflects the normal prevalence of malnutrition in the predialysis population in the United Kingdom of 17% (range 2% to 50%), as described in a published survey.10 At the end of the study, only 1 patient remained malnourished, suggesting that dietetic intervention may not only be able to prevent decline in nutritional status in this patient group but also that it may be possible to improve nutritional status and reduce the prevalence of malnutrition. The more sensitive measures of changes in nutritional status seem to support this hypothesis because mean weight, TST, MAMC, grip strength, serum transferrin, and IGF-1 all increased over the course of the study, despite the fact that all of the patients had declining renal function as reflected by decrease in creatinine

Table 5. Correlations Between Change in Creatinine Clearance/GFR and Change in Nutritional Parameters Parameter % IBW TST Arm muscle Grip strength Serum Albumin Serum Transferrin IGF-1 Energy intake Protein intake

Study group ⫺.44 (.06) ⫺.35 (.13) ⫺.09 (.69) ⫺.32 (.16) ⫹.22 (.34) ⫹.04 (.84) ⫹.02 (.91) ⫺.12 (.60) ⫺.06 (.79)

Ikizler et al2 — — — — ⫹.06 (⬎.25) ⫹.42 (⬍.01) ⫹.06 (⬎.25) — ⫹.46 (⬍.0001)

MDRD Feasibility3 ⫹.06 — ⫹.18 — — — — ⫹.18 ⫹.28 (⬍.05)

Note. Spearman’s rank correlation coefficients (and P values) for study group. Pearson’s correlation cooefficients (and P values) from Ikizler et al2 and MDRD feasibility3.

PREDIALYSIS PREVENTION OF MALNUTRITION

clearance. The increase in MAMC reached statistical significance. Because it was expected that these parameters would decline without intervention, the fact that an actual increase was observed with intervention is noteworthy. However, mean serum albumin decreased slightly, although not significantly over the course of the study. Unfortunately, C relative protein levels were not measured at the time of the study and so the role of inflammation is unknown. Although no significant correlations were found between decline in renal function and decline in nutritional parameters in this study, caution must be exercised in comparison with the published controls because of the differences in sample size. Longitudinal results from the feasibility phase of the MDRD study and the main MDRD study support the hypothesis that dietary intervention may be able to prevent malnutrition in this group. Patients included in the study received dietetic assessment and counseling at monthly meetings with a dietitian, including advice on protein intake according to the treatment group. Malnourished patients were excluded from the study, but mean weight, body fat, arm muscle area, and serum transferrin remained unchanged in patients whose initial GFR was ⬎ 25 mL/min, suggesting that patients with less advanced renal failure could avoid decline in nutritional status with dietetic advice even when protein intake is restricted.3,11 This study suggests that dietetic intervention may prevent decline in nutritional status in predialysis patients. A larger, longer-term, randomized, and controlled study would be required to confirm this and discover if this has an effect on quality of life, life expectancy, and cost of patients on dialysis. However, as stated in a recent review article, this would be a costly undertaking and difficult to justify to patients.12 In the meantime, because an improvement in nutritional parameters was achieved in those identified as malnourished on initial screening, it would seem wise to ensure that all predialysis patients are screened and

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intervention is offered where appropriate. This recommendation has been supported by the recently published National Kidney Foundation DOQI guidelines on nutrition in chronic renal failure.1

Acknowledgment The authors thank the Wales Office of Research and Development for Health and Social Care, and Gwynedd Hospitals National Health Service Trust for grants to fund this research. The authors also thank John Harty, Donald Frazer, Avril Owen, Liz James, and Linda Griffiths for their help.

References 1. National Kidney Foundation: NKF-DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure. Am J Kidney Dis 35:S17-S104, 2000 (suppl 2) 2. Ikizler TA, Greene JH, Wingard RL, et al: Spontaneous dietary protein intake during progression of chronic renal failure. J Am Soc Nephrol 6:1386-1391, 1995 3. MDRD Study Group: Kopple JD, Berg R, Houser H, et al: Nutritional status of patients with different levels of chronic renal insufficiency. Kidney Int 36:184-194, 1989 (suppl 27) 4. MDRD Study Group: The modification of diet in renal disease study: Design, methods, and results from the feasibility study. Am J Kidney Dis 20:18-33, 1992 5. MDRD Study Group: Kopple JD, Greene T, Chumlea WC, et al: Relationship between nutritional status and the glomerular filtration rate: Results from the MDRD study. Kidney Int 57:1688-1703, 2000 6. Barrett BJ, Parfrey PS, Morgan J, et al: Prediction of early death in end-stage renal disease patients starting dialysis. Am J Kidney Dis 29:214-222, 1997 7. Detsky AS, McLaughlin JR, Baker JP, et al: What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr 11:8-13, 1987 8. The Renal Association: Treatment of Adult Patients with Renal Failure (ed 2). Royal College of Physicians, London. 1997 9. Druml W: Malnutrition is bad, but how can one detect malnutrition? Nephrol Dial Transplant 12:2225-2227, 1997 10. Gilmour E, Hartley G: Managing malnutrition. Br J Ren Med Autumn 2:22-24, 1997 11. MDRD Study Group: Kopple JD, Chumlea WC, Gassman JJ, et al: Nutritional response to diet prescription in the MDRD study. J Am Soc Nephrol. 5:335, 1994 (abstr) 12. Wolfson M: Effectiveness of nutrition interventions in the management of malnourished patients treated with maintenance dialysis. J Ren Nutr 9:126-128, 1999