The Efficacy And Safety Of Washed Microbiota Transplantation In Patients With Renal Insufficiency

Background and Aim: Patients with Chronic Kidney Disease(CKD)are often accompanied by change in the gut microbiota composition,and interventions targeting the gut microbiota may be powerful tools to treat CKD.A recent study found that administration of the probiotic Lactobacillus casei Zhang ameliorated gut dysbiosis and slowed disease progression in CKD patients.However,due to the complexity of bacteria–host interactions,this single-species microbiota-targeted intervention was insufficient to halt or reverse the decline in renal function.Fecal microbiota transplantation,as a type of multispecies gut microbiota transplantation,significantly lowered serum creatinine and alleviated kidney pathological injury in CKD mice,indicating that fecal microbiota transplantation(FMT)may reverse the progression of CKD.However,it is unclear whether FMT can prevent or reverse renal function decline in clinical practice.Therefore,this retrospective,real-world study was performed to evaluate the efficacy and safety of washed microbiota transplantation(WMT),a modified FMT,on patients with renal insufficiency.Methods: Consecutive adult inpatients who underwent WMT and had at least one follow-up visit at the First Affiliated Hospital of Guangdong Pharmaceutical University from 1 January 2017 to 30 June 2021 were included in the analysis.We retrospectively collected the following clinical data of patients: demographic information,body mass index(BMI),smoking,alcoholism,history of comorbidities(e.g.,hypertension and type 2 diabetes),RRT,use of medications,indication for WMT(organic or functional disease),route of WMT delivery(lower or upper gastrointestinal tract),AEs of WMT,and laboratory parameters,including serum creatinine(SCr),blood urea nitrogen(BUN),serum uric acid(UA),hemoglobin(Hb),electrolyte and blood lipid.Stool and urine samples of patients before each WMT and stool samples of healthy donors were collected.The following analysis was carried out:(1)The differences of gut microbiota composition between patients with renal insufficiency and healthy donors were analyzed.(2)We analyzed the effects of WMT on renal function indexes and indexes of complications related to CKD.Besides,adverse events related to using WMT and clinical factors which may affect the efficacy of WMT were analyzed.(3)The changes in gut microbiota composition and urine metabolism before and after WMT treatment were analyzed.Results: 253 patients were finally included in this study,including 86 patients with renal insufficiency and 168 patients without renal dysfunction.25 healthy donors passed donor screening.(1)Compared to healthy donors,patients with renal insufficiency showed an obvious decrease in genus-level relative abundances of eubacterium coprostanoligenes group,anaerostipes,monoglobus,and butyricicoccus(all P<0.05).The principal coordinate analysis(PCo A,P=0.010)and nonmetric multidimensional scaling(NMDS,P=0.010)analysis showed a significantly different gut microbiota composition between these two groups.(2)WMT resulted in a significant increase in estimated glomerular filtration rate(e GFR)and decrease in Scr,BUN,and UA in patients with renal insufficiency,but did not markedly influence those in patients without renal insufficiency.(3)Total cholesterol and low-density lipoprotein-cholesterol were significantly reduced in patients with renal insufficiency after WMT treatment.(4)Patients who underwent WMT via the lower gastrointestinal tract rather than the upper gastrointestinal tract seemed to have greater improvement on renal function,including Scr,BUN,UA,and e GFR.(5)The incidence of adverse events related to using WMT to treat renal insufficiency was 2.91%.(6)Additionally,the Shannon index(2.32±0.77 vs.3.09±0.34,P=0.002)of gut microbiota diversity at the genus level in patients with renal dysfunction after WMT treatment were significantly increased,while the Simpson index(0.24±0.22 vs.0.09±0.04,P=0.004)were significantly decreased.PCo A(P=0.001)and NMDS(P=0.001)showed that the profiles of their gut microbiota tended to be closer to those in healthy donors.(7)More importantly,the relative abundances of three toxic metabolites(hippuric acid,cinnamoylglycine,and indole),were higher excreted in the urine of patients with renal insufficiency after WMT(all P<0.05).Conclusions: There were significant differences in gut microbiota composition between patients with renal insufficiency and healthy donors.WMT significantly improved renal function and lipid metabolism abnormalities in patients with renal.Patients who underwent WMT via the lower gastrointestinal tract seemed to have greater improvement.WMT is safe and has a low incidence of adverse events.WMT increased the excretion of toxins in urine significantly and the gut microbiota composition of patients with renal insufficiency tended to be closer to those in healthy donors after WMT.WMT is expected to be a promising treatment for reversing CKD.