Changes in the Progression of Chronic Kidney Disease in Patients Undergoing Fecal Microbiota Transplantation

Abstract

Chronic kidney disease (CKD) is a progressive loss of renal function in which gut dysbiosis is involved. Fecal microbiota transplantation (FMT) may be a promising alternative for restoring gut microbiota and treating CKD. This study evaluated the changes in CKD progression in patients treated with FMT. Patients with diabetes and/or hypertension with CKD clinical stages 2, 3, and 4 in this single-center, double-blind, randomized, placebo-controlled clinical trial (NCT04361097) were randomly assigned to receive either FMT or placebo capsules for 6 months. Laboratory and stool metagenomic analyses were performed. A total of 28 patients were included (15 FMT and 13 placebo). Regardless of CKD stages, patients responded similarly to FMT treatment. More patients (53.8%) from the placebo group progressed to CKD than the FMT group (13.3%). The FMT group maintained stable renal function parameters (serum creatinine and urea nitrogen) compared to the placebo group. Adverse events after FMT treatment were mild or moderate gastrointestinal symptoms. The abundance of Firmicutes and Actinobacteria decreased whereas Bacteroidetes, Proteobacteria and Roseburia spp. increased in the FMT group. CKD patients showed less disease progression after FMT administration. The administration of oral FMT in patients with CKD is a safe strategy, does not represent a risk, and has potential benefits.

Keywords: chronic kidney disease; disease progression; fecal microbiota transplant.

Figure 1

Treatment of patients with chronic kidney disease with fecal microbiota transplantation. Patients (n = 28) with chronic kidney disease (CKD) were treated orally with frozen capsules of fecal microbiota transplantation (FMT) obtained from a healthy donor or with placebo capsules for 6 months. Gut dysbiosis was observed in patients prior to FMT administration, which changed after FMT treatment and healthy microbiota was restored.

Figure 2

Estimates of glomerular filtration rate of patients with chronic kidney disease after fecal microbiota transplantation. The progression of CKD in patients after either fecal microbiota transplantation (FMT) or placebo treatment is shown, expressed as a decrease in the glomerular filtration rate (GFR) > 1 mL/min/1.73 m². In patients with CKD treatment, the estimated GFR loss is 2.3 to 4.5 mL/min/1.73 m² per year. Rapid progression is defined as a sustained decline in GFR > 5 mL/min/1.73 m² per year [4].

Figure 3

Average bacterial composition at the Phylum level. Stool samples from patients (n = 8) subjected to fecal microbiota transplantation (FMT) or placebo (n = 6) treatments were collected before (Day 0) and 30 (Day 30) and 90 (Day 90) days after treatment. After metagenomic analysis, distribution of bacterial composition at the phylum level was assessed and compared in both groups. The distribution of FMT donors was also compared.

Figure 4

Average bacterial composition at the Genera level. Stool samples from patients (n = 8) subjected to fecal microbiota transplantation (FMT) or placebo (n = 6) treatments were collected before (Day 0) and 30 (Day 30) and 90 (Day 90) days after treatment. After metagenomic analysis, distribution of bacterial composition at the Genera level was assessed and compared in both groups. The distribution of FMT donors was also compared.