Optimal nutrition in the dialysis patient is a critical component of nephrology care since malnutrition carries a high risk of mortality, even when all other co-morbitites are adjusted for. Dieticians and nephrologists constantly struggle to improve the overall nourishment of end-stage renal diseases (ESRD) patients because of the perceived conflict between good protein intake and electrolyte abnormalities, such as high phosphorous or potassium. Does providing observed nutritional supplements during dialysis treatment improve albumin? Does it offer a survival benefit? A recent article published in the American Journal of Kidney Diseases discusses this very important topic. Corresponding author and Vice President for Clinical Science, Epidemiology, and Research for Fresenius Medical Care, Dr Eduardo Lacson Jr (EL), and senior author Dr. Raymond Hakim (RH), former Chief Medical Officer for Renal Care Group and for Fresenius Medical Care, spoke with Dr. Kenar Jhaveri (eAJKD), eAJKD Blog Editor. Dr. Frank Maddux (FM), Executive Vice President of Clinical and Scientific Affairs and current Chief Medical Officer for Fresenius Medical Care was also present during the interview.
eAJKD: The study was a retrospective matched cohort analysis of intra-dialytic oral nutritional supplements in patients on dialysis. What led to this study?
RH: I have had a strong interest in the role of nutrition on patient outcomes and we and others had published work on the beneficial impact of oral nutritional supplements on nutrition markers such as albumin. We wanted to evaluate the impact on nutritional parameters, as well as study the hospitalization and mortality effect of our intervention in patients with documented malnutrition (albumin ≤3.5 g/dL).
EL: My interest is in quality initiatives, quality programs, and looking into best practices for ESRD patients. I’ve had this opportunity to work with Dr. Hakim in evaluating the potential for improving nutritional parameters and its impact on outcomes. One key program that was started by Dr. Hakim was the administration of oral nutritional supplements during dialysis treatments for patients with albumin levels at or below 3.5 mg/dL. We were able to compare the mortality of patients given the supplements as compared to patients who were not given the supplements during a 15-month follow-up period.
FM: As we look at the important findings from the oral nutritional supplement (ONS) program, we hope to learn how patients maintain nutritional competence, and the degree to which we can promote resilience in patients’ nutritional status. This becomes most important during times of transitions of care in and out of hospital.
eAJKD: Dual analyses were conducted in your study: intention-to-treat and as-treated. Can you comment on the reason why you did both?
EL: In any trial, your first instinct is to separate groups into those who receive the intervention and those who do not. In doing the comparisons, we identified three groups of patients. There was one group that was eligible and received the supplement, and another that was eligible and did not receive the supplement. During the follow-up period, we identified a third group of patients who were eligible, did not receive supplements during the study inclusion period of 3 months, but subsequently received oral supplements during the follow-up period.
For a pure analysis, we wanted to exclude those patients and look at the outcomes of the treated versus untreated only—this would be the as-treated analysis. However, this might instill a potential bias towards the better outcomes for those who were treated by excluding those patients who were eligible and subsequently received treatment. In order to be able to show a balanced report, we also did the intention-to-treat analysis. In Figure 2, you can see the Kaplan Meier survival curves using both methods. The difference between the groups does diminish in the intention-to-treat analysis, but both the analyses had statistically significant lower mortality for patients receiving the supplements. In the as-treated analysis, which excluded patients who received ONS during the follow-up period, the difference in mortality was 34%.
eAJKD: How did you account for what the patients did in terms of taking supplements at home? In other words, did you find that the patients who were monitored were more likely to take supplements during the non-dialysis days at home?
RH: The whole idea of this study was to compare the outcomes of the patients who qualified (albumin ≤3.5 g/dL) and were taking the supplements while at dialysis. However, we did look into the medical record for nutritional supplement taken outside the oral nutrition supplement program. In Figure 1 of the paper, you will see that we excluded about 2000 patients who may have received nutritional supplement at home, at least on record, that we could find outside of the nutrition program. If it was documented, it is highly specific that they received it; but having no record or documentation does not necessarily mean that they didn’t get any at home.
eAJKD: Is there any physiological reason to offer nutritional support during ESRD treatment?
RH: Yes. There are several studies showing that protein intake is much lower on dialysis days. This might be due to travel time, post-dialysis fatigue, or four hours of treatment time. Also, during the dialysis treatment, patients lose several grams of amino acids, and that translates into muscle protein breakdown.
eAJKD: Did the patients have any preference towards one of the four supplements that you have in Table 1? Do you think the choice of supplement can change the outcomes?
RH: We have not compared the different nutritional supplements. Patients had the option of switching from one to the other to avoid taste fatigue. Some of the supplements had both protein and carbohydrates, and some had only protein. It would be a difficult query because as far as I know, no patient stayed exclusively on only one of the supplements throughout the study period.
eAJKD: The mortality difference was significant. Was there any changes noted in anemia, phosphorous control, or hospitalizations between the two groups?
EL: We did look at hospitalization outcomes, but this was in the as-treated analysis. We presented those results in the ICRNM in June 2012. In the treated group, we found a lower rate of hospitalization. Our original analysis had tracked albumin. Unfortunately, during the follow-up period we had some issues with a calibrator used in the laboratory that resulted in a greater variance in the data, so that the albumin data did not appear reliable. We did not specifically look at hemoglobin and phosphorous, but since these two factors are being actively managed, it would be reasonable to believe that there would be more noise in these two relative to single oral nutritional supplement intake during dialysis treatments.
eAJKD: Do you think the mortality benefit is from improvement in the albumin?
RH: The oral nutritional supplements impact on mortality is possibly due to an improvement in albumin. However, it may be more related to the decline in the catabolic process that occurs during each dialysis. It is an intervention that can have a positive impact early on, even before what other studies have shown to be the time necessary for improvement in albumin. The impact of oral nutritional supplements is not that it’s an improvement in albumin only, but that it reduced or reversed the catabolic process that occurs on every dialysis day because of decreased food intake on dialysis days and increased losses during the dialysis treatment.
eAJKD: How do you get the dieticians involved in such an excellent model?
RH: At the time that we were publishing the data, we had oral nutrient supplements available at all facilities that wanted to participate in this. The other dialysis facilities are getting interested. In all facilities, dieticians have been great champions of the program and have encouraged the patients to maintain compliance with ONS.
FM: A change in mindset has to happen in how we approach nutrition in ESRD patients. Both nephrologists and dieticians need to realize that feeding the patient appropriately is more important than some of the restrictions that traditionally have been applied to the dialysis population. The program has to not only educate the dieticians and physicians into altering their approach, it must identify those patients at the highest risk from a loss of nutritional competence. Our general feeling is that nutrition has been and continues to be a very strong marker of outcomes in this population.