Impact of probiotic supplementation on serum klotho levels and inflammatory status in patients with diabetic kidney disease.

Diabetic kidney disease (DKD) involves complex metabolic and inflammatory pathways, where gut dysbiosis via the gut-kidney axis plays a critical pathophysiological role. Probiotics may resolve renal decline and modulate aging biomarkers, but clinical evidence in DKD remains limited. This study evaluated the effects of Lactobacillus supplementation on serum alpha-Klotho levels, systemic inflammation, and renal biomarkers DKD patients. In an open-label, parallel-group controlled clinical trial, conducted at the Nephrology Department of Eldakhla General Hospital, New Valley Governorate, Egypt on 80 adult DKD patients (stages G1A1 to G4A3) between August 2023 and January 2024 (recruitment: August 2023 - October 2023; intervention & follow-up: October 2023 - January 2024). Participants were assigned to an intervention group (n=40) receiving daily oral enteric-coated capsules containing Lactobacillus acidophilus and L. delbrueckii subsp. Bulgaricus, (5 billion CFU) /day for 12 weeks alongside standard care, a control group (n=40) receiving standard care alone. Primary outcomes were changes in serum alpha-Klotho (ELISA) and high-sensitivity C-reactive protein (hs-CRP). Secondary outcomes included serum creatinine, eGFR (CKD-EPI equation), and urinary albumin-to-creatinine ratio (UACR). Following intervention, serum alpha-Klotho levels significantly increased in the probiotic group compared to controls (adjusted post-treatment median: 114.15 ng/mL vs. 80.0 ng/mL; adjusted between-group p=0.003). Systemic inflammation markedly declined in the probiotic group relative to controls (hs-CRP post-treatment median: 2.1 mg/L vs. 6.9 mg/L; adjusted p = 0.000). Probiotic supplementation yielded significant relative decline in serum creatinine (0.97±0.1 vs.1.08±0.23 mg/dl, p=0.008) and median UACR (24.4 vs. 69.05 mg/g p = 0.000). In addition, probiotic supplementation showed higher post treatment eGFR (81.35±11.98 vs.73.30±18.07 ml/min/1.73 m² p=0.021). Reduction in HDL within-group was observed in both groups with no statistical significance between groups p = 0.419. No serious adverse events occurred. In conclusion, daily Lactobacillus supplementation for 12 weeks upregulates circulating serum alpha-Klotho, attenuates systemic hs-CRP, and improves clinical biomarkers of renal function in patients with diabetic kidney disease.