Therapeutic Effects of Oral Nutritional Supplements during Haemodialysis : Physician s Experience

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1 30 Journal of the association of physicians of india vol 62 december, 2014 Original Article Therapeutic Effects of Oral Nutritional Supplements during Haemodialysis : Physician s Experience Arun B Shah *, Rupin A Shah **, Anup Chaudhari ***, Neelam Shinde **** Abstract Objectives: To evaluate the effects of predialytic oral nutritional supplementation in chronic kidney disease (CKD) patients on maintenance haemodialysis (MHD) Methods: Nepro HP was provided to 77 CKD patients on maintenance haemodialysis (MHD) over 3 months. Efficacy parameters were improvement in albumin levels, weight and haemoglobin levels; safety parameters were serum potassium and phosphorus values; other parameters were SGA and MIS scores. Results: Mean serum albumin values showed a statistically significant increase. There was a statistically significant improvement in the mean body weight and haemoglobin of the patients in the second and third months of treatment. Serum phosphorus and potassium levels did not change in a statistically significant manner. There was improvement in nourishment status as detected by MIS and SGA scores. Two patients expired during the course of the study. Conclusion: Predialytic oral supplementation with Nepro HP improves nutritional status of CKD patients on MHD. * Consultant Nephrologist, Lilavati Hospital, Bandra, Mumbai; Consultant Nephrologist, Bharatiya Arogya Nidhi Hospital, Juhu, Mumbai; ** Residency in Internal Medicine, St. Lukes Hospital, New York, USA; *** Junior Consultant, Lilavati Hospital, Mumbai; **** Resident Physician, Bharatiya Aroghya Nidhi Hospital, Mumbai Received: ; Revised: ; Accepted: Introduction Poor nutritional status is a well-documented consequence of chronic kidney disease (CKD). It is an important prognostic predictor for patients starting dialysis. 1,2 In fact, the so-called uraemic malnutrition is recognised to be the strongest risk factor for adverse outcomes and death in patients suffering from CKD. 3 Further, protein energy malnutrition (PEM) is also commonly observed in CKD patients undergoing haemodialysis and has been associated with increased morbidity and mortality among these patients. 4 Life-threatening undernutrition was detected in 20-36% of French patients undergoing dialysis in a study reported in The major determinants of nutritional status in this population were reported as protein intake and dialysis efficacy. 5 We report the physician s experience concerning the effects of predialytic oral supplements on nutritional markers and nutritional status in patients receiving maintenance haemodialysis (MHD). Material and Methods Data was collected over a period of 3 months from patients of outpatient haemodialysis unit located in Mumbai, India. All consenting patients with CKD, above 18 years of age, and receiving twice or thrice-weekly maintenance haemodialysis at the outpatient haemodialysis centre were included, and those with intercurrent acute illnesses, body weight less than 40 kg, documented history of dialysis noncompliance, documented malabsorption syndromes, and contraindications to any of the ingredients of the nutritional supplement were excluded.

2 Journal of the association of physicians of india vol 62 december, All the included patients were provided with 89 grams of nutritional supplement in 167 ml of water constituted to form 237 ml of total serving for a total duration of 3 months. The supplement given was Nepro HP (ABBOTT NUTRITION INTERNATIONAL INDIA), which Table 1 : Baseline characteristics of patients enrolled in study Characteristic Value Age (years) >65 Gender Male 39 Female 38 Serum Albumin (g/dl; Mean ± SD) 3.01 ± 0.44 Body Weight (kg; Mean ± SD) ± Serum Hemoglobin (g/dl; Mean ± SD) 9.23 ± 1.88 Serum Potassium (mg/dl; Mean ± SD) 5.22 ± 0.79 Serum Phosphorus (mg/dl; Mean ± SD) 6.65 ± 1.86 Table 2 : Efficacy and safety parameters Parameter Baseline Month 1 Month 2 Month 3 Serum Albumin (g/dl) 3.01 ± ± 0.42 *** 3.58 ± 0.37 *** 3.85 ± 0.32 *** Body Weight (kg) ± ± ± * ± *** Serum Haemoglobin (g/dl) 9.23 ± ± ± 1.64 *** ± 1.82 *** Serum Potassium (mg/dl) 5.22 ± ± ± ± 0.46 Serum Phosphorus (mg/dl) 6.65 ± ± ± ± 1.25 All values are mean ± SD. * p < 0.05; *** p < ; comparisons are versus baseline. Serum Albumin (g/dl) Serum Hb (g/dl) ±0.44 Baseline 9.23 ± *** ± ± *** ± *** ±1.64 *** : P < when compared with baseline Fig. 1 : Serum albumin and haemoglobin values over time provided (per 100 g) 501 kcal of energy, g protein, 25.6 g fat (1.39 g saturated, 2.93 g polyunsaturated, g monounsaturated fatty acids, and no trans fatty acids, 30 mg cholesterol), 43.5 g carbohydrate, 69.1 mg carnitine and 43.1 mg taurine. It contained vitamins A, D2, E, K1, C, B6, B12, beta-carotene, thiamine, riboflavin, niacin, folic acid, biotin, pantothenic acid and choline, and minerals including sodium, potassium, chloride, calcium, phosphorus, magnesium, iron, zinc, copper, manganese, selenium, chromium, molybdenum, and iodine. The change in serum albumin concentration over the study period was the primary efficacy parameter; secondary efficacy parameter was the effect on the body weight and haemoglobin of the patients. The key safety parameters were changes in serum potassium and phosphorus levels. To analyse the effect on nutritional status of patients, subjective global assessment (SGA) scores and malnutrition inflammation scores (MIS) were collected and analysed. 3.85*** ±0.32 Month 1 Month 2 Month *** ±1.82 Baseline Month 1 Month 2 Month 3 Data was collected from the patients before enrolment (baseline). The patients were followed up after 1, 2, and 3 months of study initiation when the same parameters were again recorded. SGA scores and MIS scores were collected with respect to the impact on nutrition were collected from the first follow-up visit onwards. All parametric data were reported as mean ± SD; repeated measures ANOVA with post-hoc Bonferroni s multiple comparison test was used to analyse these data. For the purpose of this study, SGA score interpretation was done as 5 to 14 à severe malnutrition; 15 to 29 à mild malnutrition; and 30 à adequate nutritional status; MIS interpretation was done as 0 to 10 à normal; 11 to 20 à malnourished; 21 to 30 à severely malnourished. SGA and MIS interpretation was depicted as number of patients falling into each category. GraphPad Prism version 5 was used for statistical analysis. Results A total of 77 eligible patients were enrolled for the study. During the three months of the study, two patients expired, both at the time of the second follow-up visit (at month 2). The baseline demographic data is summarised in Table 1. a. Efficacy parameters: Mean serum

3 32 Journal of the association of physicians of india vol 62 december, 2014 Month 1 60 Month 2 Month 3 Month 1 Month 2 Month 3 Fig. 2 : Nourishment status of patients as calculated by SGA and MIS scores albumin values recorded over the period of 3 months showed a statistically significant increase (Table 2, Figure 1). There was a gradual improvement in the mean body weight and haemoglobin of the patients, which was statistically significant in the second and third months (Table 2). b. Safety parameters: There were no statistically significant changes in the serum values of potassium and phosphorus over the duration of the study, as depicted in Table 2. c. Nourishment: As interpreted by the SGA scores, there was a gradual increase in the proportion of well-nourished patients, and a corresponding reduction in the proportion of malnourished patients. None of the patients were severely malnourished; two patients expired during the study period (Figure 2). Similar findings were obtained when nourishment status was calculated using MIS scores. Discussion 56 Patients undergoing dialysis frequently suffer from both malnutrition (characterised by insufficient Number of Patients Well nourished (7 to 16) Malnutrition by SGA score Moderately malnourished (17-28) Malnutrition by MIS score Number of Patients Normal (0 to 10) Malnourished (11 to 20) Expired protein intake) and cachexia (characterised by defective food assimilation or utilisation in the presence of hypercatabolism and systemic inflammation) from the very early stages of the initiation of dialysis. Various factors contribute to the development of these altered nutritional states in dialysis patients: uraemia causing loss of appetite; dialysis treatment leading to loss of amino acids and proteins; premature ageing of dialysis patients; and presence of co-morbid factors that would have led to the causation of CKD. 6 Various other factors also frequently operate together: emotional distress, impaired ability to procure, unpalatable prescribed diets, the catabolic response, loss of blood due to gastrointestinal bleeding, frequent blood sampling, blood sequestered in haemodialyser and tubing, and endocrine disorders of uraemia. 4 Such an altered nutritional status has been shown to increase mortality 9,10 and morbidity 7,8 in these patients. It is therefore imperative that patients on MHD receive adequate nutrition. Studies show that active nutritional support improve outcomes and reduce cost of treatment in severely malnourished patients. 4 Nutritional supplements are often prescribed to dialysis patients in order to maintain or improve the nutritional status. A wide variety of products are currently available with high biological value proteins. 6 The recommended daily energy intake (DEI) for patients undergoing haemodialysis and peritoneal dialysis is kcal / kg per day. The suggested mean dietary protein intake (DPI) is 1.2 g / kg per day in patients on haemodialysis, and 1.3 g / kg per day in patients on peritoneal dialysis. 11,12 Most patients on dialysis, however, have a lower DEI and DPI than the recommended intake. In the present physician s experience, there was a statistically significant increase in serum albumin levels in all the patients over a period of 3 months. This is a significant finding since it is known that serum albumin is a valid and clinically useful measure of protein-energy nutritional status in MHD patients. Further, hypoalbuminaemia is a highly predictive marker of mortality risk. Finally, measurement of serum albumin is inexpensive, easy to perform and widely available. 4 There was also a statistically significant increase in body weight and haemoglobin which further point towards an improvement in the nutritional status of the patients. For evaluating the safety of the nutritional Expired

4 Journal of the association of physicians of india vol 62 december, supplement, we analysed the serum levels of phosphorus and potassium in the patients over the treatment duration. There were no significant changes in these values, suggesting that the nutritional supplement is not associated with any biochemical abnormality. Also, there was no history suggestive of any adverse reaction associated with the nutritional supplement. Two of the 77 patients expired during the study period, however, this death was not associated with intake of the nutritional supplement. Thus, we can conclude that the nutritional supplement is safe. The SGA is a well-validated tool for screening for malnutrition. SGA is the only screening tool recommended by the american society for parenteral and enteral nutrition (ASPEN). The modified subjective global assessment score, which is a fully quantitative scoring system consisting of 7 components with total score ranging between 7 (normal) and 35 (severely malnourished) has been developed using components of conventional SGA. This modified SGA has other advantages as well: it can be performed in few minutes, is free of cost, and determines definitely the nutritional status of haemodialysis patients. 4 The MIS is a quantitative assessment tool based on SGA and predicts mortality and morbidity in MHD patients. It was created using the seven components of the conventional SGA and combining them with three new elements: body mass index (BMI), serum albumin, and total iron-binding capacity (TIBC) to represent serum transferrin. 13 The MIS consists of four sections: nutritional history, physical examination, BMI, and laboratory values. Each of the 10 components is to be scored from 0 (normal) to 3 (severely malnourished). As a result, the sum of the components varies between 0 and 30; higher the score, more severe is the degree of malnutrition and inflammation. 14 In our experience, we categorised the SGA scores and MIS for a better clarity in the interpretation of the results. There was a gradual improvement in the nutritional status of the patients with only 2/75 (2.67%) patients remaining malnourished at the end of 3 months. The findings of our study are similar to those reported in a recent review by Kalantar-Zadeh et al, where the authors examined the effects of enteral nutritional interventions examined in clinical trials involving malnourished patients on dialysis. They concluded that in most of the studies, enteral nutritional supplementation was associated with improved nutritional status or other clinical outcomes. Also, it is interesting to note that eight out of nine randomised trials considered in this review had used serum albumin concentration as a surrogate outcome measure, and had reported statistically significant improvements in serum albumin levels after the nutritional support, very similar to our study. 2 Another study in India reported similar findings: 15 subjects who were on MHD received a multi-nutrient formulation for a period of 3 months. There were statistically significant increments in anthropometric measurements, biochemical parameters including albumin levels, and decrease in MIS at the end of the study (all p 0.01). 15 The major limitation of the present study is that it is not a controlled clinical trial but a documentation of physician s experience. Also, we had not included the presence of other comorbid conditions and concomitant medications in our study. Based on the results of this study, well-designed clinical trials involving patients not only on MHD but also on peritoneal dialysis are warranted and are expected to throw light on the benefits of oral nutritional supplementation in Indian patients undergoing haemodialysis. To conclude, we found that predialytic oral supplementation of CKD patients on MHD with Nepro HP for a duration of 3 months resulted in statistically significant improvements in serum albumin, body weight, haemoglobin, and nourishment status as depicted by SGA and MIS scoring systems, and was not associated with any significant adverse events or biochemical derangements in phosphorus and potassium levels. Controlled clinical trials are warranted to validate the present findings. Conflicts of interest None declared Source of Funding Self-funded Acknowledgements To the staff and technicians of Dialysis Unit at Bharatiya Arogyanidhi Hospital, Juhu, Mumbai. References 1. 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5 34 Journal of the association of physicians of india vol 62 december, 2014 national cooperative study. French Study Group for Nutrition in Dialysis. Nephrol Dial Transplant 1999;14: Locatelli F, Fouque D, Heimburger O, Drüeke TB, Cannata-Andía JB, Hörl WH, Ritz E. Nutritional status in dialysis patients: a European consensus. Nephrol Dial Transplant 2002;17: Ikizler TA, Wingard RL, Harvell J, Shyr Y, Hakim RM. Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: a prospective study. Kidney Int 1999;55: Herselman M, Moosa MR, Kotze TJ, Kritzinger M, Wuister S, Mostert D. Protein-energy malnutrition as a risk factor for increased morbidity in long-term hemodialysis patients. J RenNutr 2000;10: Owen WF Jr, Lew NL, Liu Y, Lowrie EG, Lazarus JM. The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med 1993;329: Pifer TB, McCullough KP, Port FK, Goodkin DA, Maroni BJ, Held PJ, Young EW. Mortality risk in hemodialysis patients and changes in nutritional indicators: DOPPS. Kidney Int 2002;62: National Kidney Foundation. Clinical practice guidelines for nutrition in chronic renal failure. [Last Accessed 2013 Dec 01]. Available from URL: updates/doqi_nut.html 12. Beto JA, Bansal VK.Medical nutrition therapy in chronic kidney failure: integrating clinical practice guidelines. J Am Diet Assoc 2004;104: Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH. A malnutritioninflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients. Am J Kidney Dis 2001;38: Afşar B, Sezer S, Ozdemir FN, Celik H, Elsurer R, Haberal M.Malnutritioninflammation score is a useful tool in peritoneal dialysis patients. Perit Dial Int 2006;26: Roy LG, Shetty MS, Urooj A. Effect of nutritional intervention on malnutrition indicators in patients on haemodialysis. J Ren Care 2013;39:39-46.