The Efficacy and Safety of Probiotic Combinations Lobun Forte® Versus Renadyl® in Patients With Chronic Kidney Disease: A Comparative, Phase IV, Randomized, Open-Label, Active-Controlled, Parallel Study

Abstract

Background: Chronic kidney disease (CKD) often leads to gut microbiota imbalance, accelerating disease progression and increasing uremic toxins and inflammation. We conducted a randomized clinical trial comparing outcomes between two multi-strain probiotic supplements Lobun Forte® (Sanzyme P Ltd, Hyderabad, India) containing Streptococcus thermophilus, Lactobacillus acidophilus, Bifidobacterium longum, and Bacillus coagulans and Renadyl^® (Kibow Biotech, LLC., Pennsylvania, United States) containing S. thermophilus, L. acidophilus, and B. longum.

Materials and methods: Sixty patients with stage 3-4 CKD were randomized to receive either Lobun Forte (n=30) or Renadyl (n=30) for six months, with each supplement providing 45 billion CFU/capsule, twice daily. Primary outcomes included quality of life (QoL) (Short-Form 8 (SF-8) score), reductions in uremic toxins (p-cresyl sulfate (PCS), 3-indoxyl sulfate (IS), indole-3-acetic acid (IAA)), blood urea nitrogen (BUN), serum creatinine, and serum uric acid. Secondary outcomes assessed oxidative stress, inflammatory biomarkers, and estimated glomerular filtration rate (eGFR). Results: Both Lobun Forte and Renadyl groups showed significant improvements in QoL, with Lobun Forte achieving a 53.5% improvement (16.43 point increase) and Renadyl a 51.1% improvement (15.27 point increase) in SF-8 scores (p < 0.0001). The levels of IS decreased significantly in both groups (p < 0.0001), with Lobun Forte reducing IS by 29.72% and Renadyl by 24.20%. In terms of other uremic toxins, Lobun Forte showed non-significant (p > 0.05) reductions in mean PCS (7.63%) and IAA (15.57%), whereas Renadyl demonstrated a significant (p = 0.0314) decrease in PCS (20.75%) and a non-significant (p > 0.05) reduction in IAA (12.35%). Both groups showed significant (p < 0.0001) reductions in BUN and serum creatinine levels. Serum uric acid levels showed a significant (p = 0.0448) reduction with Lobun Forte while Renadyl exhibited a non-significant reduction (p = 0.1034). Lobun Forte significantly (p = 0.0359) reduced mean high-sensitivity C-reactive protein (hsCRP) levels, while Renadyl showed a non-significant reduction (p = 0.0876). Both groups had non-significant reductions in interleukin-6 and tumor necrosis factor-alpha levels (p > 0.05). Further, both groups experienced significant (p < 0.0001) increases in mean glutathione levels and nitric oxide levels. Additionally, Renadyl resulted in a significant reduction in mean malondialdehyde, whereas Lobun Forte showed a non-significant reduction. Both probiotics significantly (p < 0.0001) improved eGFR, with Lobun Forte increasing it by 40.4% and Renadyl by 36.9%. Both probiotics were well tolerated, with a favorable safety profile throughout the study. Conclusion: Both Lobun Forte and Renadyl effectively improve the quality of life in patients with stage 3-4 CKD by modulation of uremic toxins, renal parameters, inflammatory biomarkers, oxidative biomarkers, and eGFR. These findings suggest that both probiotics may help delay CKD progression by modulating the gut-kidney axis.

Keywords: chronic kidney disease (ckd); malnutrition; multi-strain probiotic supplement; quality of life (qol); uremic toxins.

Figure 1. Study flow chart and respective evaluations at various study visits

BUN: blood urea nitrogen; eGFR: estimated glomerular filtration rate; GSH: glutathione; hsCRP: high-sensitivity C-reactive protein; IAA: indole-3-acetic acid; IL-6: interleukin-6; IS: 3-indoxyl sulfate; MDA: malondialdehyde; NO: nitric oxide; PCS: p-cresol sulphate; QoL: quality of life; SF-8: short form-8; TNF-α: tumor necrosis factor-alpha. Image Credit: Raja Karthik Kalidindi and Kishan PV

Figure 2. Trajectory of change from baseline to day 180 in various assessments, including renal parameters (A-C), uremic toxins (D-F), and inflammatory biomarkers (G-I)

*A value of p < 0.05 is defined as statistically significant. ^aLobun Forte® group Baseline vs Day 180; ^bRenadyl® group Baseline vs Day 180. (A) Blood urea nitrogen and (B) serum creatinine decreased significantly in both groups (p < 0.0001). (C) Serum uric acid decreased significantly with Lobun Forte® (p < 0.0448). (D) p-cresol sulphate and (E) 3-Indoxyl sulfate reduced significantly with Renadyl® (p < 0.0314 and p < 0.0312, respectively). (F) indole-3-acetic acid showed no significant changes. (G) hsCRP decreased significantly with Lobun Forte® (p < 0.0359). (H) IL-6 and I) TNF-α showed no significant changes in either group. hsCRP: high-sensitivity C-reactive protein; IL-6: interleukin-6; TNF-α: tumor necrosis factor-alpha