Oral protein-based supplements versus placebo or no treatment for people with chronic kidney disease requiring dialysis

Jia Yee Mah, Suet Wan Choy, Matthew A Roberts, Anne Marie Desai, Melissa Corken, Stella M Gwini, Lawrence P McMahon, Jia Yee Mah, Suet Wan Choy, Matthew A Roberts, Anne Marie Desai, Melissa Corken, Stella M Gwini, Lawrence P McMahon

Abstract

Background: Malnutrition is common in patients with chronic kidney disease (CKD) on dialysis. Oral protein-based nutritional supplements are often provided to patients whose oral intake is otherwise insufficient to meet their energy and protein needs. Evidence for the effectiveness of oral protein-based nutritional supplements in this population is limited.

Objectives: The aims of this review were to determine the benefits and harms of using oral protein-based nutritional supplements to improve the nutritional state of patients with CKD requiring dialysis.

Search methods: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 December 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: Randomised controlled trials (RCTs) of patients with CKD requiring dialysis that compared oral protein-based nutritional supplements to no oral protein-based nutritional supplements or placebo.

Data collection and analysis: Two authors independently assessed studies for eligibility, risk of bias, and extracted data from individual studies. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference and 95% CI for continuous outcomes.

Main results: Twenty-two studies (1278 participants) were included in this review. All participants were adults on maintenance dialysis of whom 79% were on haemodialysis (HD) and 21% peritoneal dialysis. The follow-up period ranged from one to 12 months. The majority of studies were at unclear risk of selection, performance, and reporting bias. The detection bias was high for self-reported outcomes. Oral protein-based nutritional supplements probably lead to a higher mean change in serum albumin compared to the control group (16 studies, 790 participants: MD 0.19 g/dL, 95% CI 0.05 to 0.33; moderate certainty evidence), although there was considerable heterogeneity in the combined analysis (I2 = 84%). The increase was more evident in HD participants (10 studies, 526 participants: MD 0.28 g/dL, 95% CI 0.11 to 0.46; P = 0.001 for overall effect) and malnourished participants (8 studies, 405 participants: MD 0.31 g/dL, 95% CI 0.10 to 0.52, P = 0.003 for overall effect). Oral protein-based nutritional supplements also probably leads to a higher mean serum albumin at the end of the intervention (14 studies, 715 participants: MD 0.14 g/dL, 95% CI 0 to 0.27; moderate certainty evidence), however heterogeneity was again high (I2 = 80%). Again the increase was more evident in HD participants (9 studies, 498 participants: MD 0.21 g/dL, 95% CI 0.03 to 0.38; P = 0.02 for overall effect) and malnourished participants (7 studies, 377 participants: MD 0.25 g/dL, 95% CI 0.02 to 0.47; P = 0.03 for overall effect). Compared to placebo or no supplement, low certainty evidence showed oral protein-based nutritional supplements may result in a higher serum prealbumin (4 studies, 225 participants: MD 2.81 mg/dL, 95% CI 2.19 to 3.43), and mid-arm muscle circumference (4 studies, 216 participants: MD 1.33 cm, 95% CI 0.24 to 2.43) at the end of the intervention. Compared to placebo or no supplement, oral protein-based nutritional supplements may make little or no difference to weight (8 studies, 365 participants: MD 2.83 kg, 95% CI -0.43 to 6.09; low certainty evidence), body mass index (9 studies, 368 participants: MD -0.04 kg/m2, 95% CI -0.74 to 0.66; moderate certainty evidence) and lean mass (5 studies, 189 participants: MD 1.27 kg, 95% CI -1.61 to 4.51; low certainty evidence). Due to very low quality of evidence, it is uncertain whether oral protein-based nutritional supplements affect triceps skinfold thickness, mid-arm circumference, C-reactive protein, Interleukin 6, serum potassium, or serum phosphate. There may be little or no difference in the risk of developing gastrointestinal intolerance between participants who received oral protein-based nutritional supplements compared with placebo or no supplement (6 studies, 426 participants: RR 2.81, 95% CI 0.58 to 13.65, low certainty evidence). It was not possible to draw conclusions about cost or quality of life, and deaths were not reported as a study outcome in any of the included studies.

Authors' conclusions: Overall, it is likely that oral protein-based nutritional supplements increase both mean change in serum albumin and serum albumin at end of intervention and may improve serum prealbumin and mid-arm muscle circumference. The improvement in serum albumin was more evident in haemodialysis and malnourished participants. However, it remains uncertain whether these results translate to improvement in nutritional status and clinically relevant outcomes such as death. Large well-designed RCTs in this population are required.

Trial registration: ClinicalTrials.gov NCT00561093 NCT00895401 NCT01234441 NCT03367000 NCT02163070 NCT01813851 NCT00179140 NCT02933151 NCT00179205 NCT00244075 NCT00367198 NCT02418065 NCT02989688 NCT02371018.

Conflict of interest statement

Jia Yee Mah: none known
Suet Wan Choy: none known
Matthew A Roberts: none known
Anne Marie Desai: none known
Melissa Corken: none known
Stella M Gwini: none known
Lawrence McMahon has received funding from Fresenius for research unrelated to this review.