Clearance of Strongyloides stercoralis infection using ivermectin improves kidney function and modulates untargeted urinary metabolomic profile in patients with early-stage chronic kidney disease
Keerapach Tunbenjasiri, Suppakrit Kongsintaweesuk, Kornpatchara Chaiyachate, Aye Myat Mon, Thatsanapong Pongking, Apinya Jusakul, Sirirat Anutrakulchai, Apisit Chaidee, Porntip Pinlaor, Nuttanan Hongsrichan, Ubon Cha’on, David Blair, Somchai PinlaorIntroduction
Strongyloides stercoralis exacerbates the early stages of chronic kidney disease (CKD) through the disruption of metabolic processes. However, the metabolic consequences of infection and of its resolution after treatment remain poorly characterized. This study explores urinary metabolic changes in patients with early-stage CKD following antiparasitic therapy.
Methods
In an exploratory before-and-after longitudinal study design, fifteen patients presenting with concurrent early-stage CKD (stages 1–3) and confirmed strongyloidiasis were monitored at baseline and 17 months following ivermectin anthelmintic treatment. Serum and urine clinical biochemistry assessments were paired with high-resolution untargeted liquid chromatography-quadrupole time-of-flight mass spectrometry (LC/Q-TOF MS) urinary metabolomic profiling executed in both negative and positive ionization modes.
Results
Global multivariate analyses did not demonstrate statistically significant separation between pre- and post-treatment urinary metabolomic profiles. However, univariate analyses identified 91 significantly altered urinary mass features following treatment. Among these, thirteen metabolites (twelve decreased and one increased) were identified as potential markers associated with parasite clearance in patients with CKD. Changes in fasting blood sugar, serum creatinine, and estimated glomerular filtration rate (eGFR) were also observed. Notably, urinary 1-O-galloyl-6-O-cinnamoylglucose was negatively correlated with urine creatinine, while sedoheptulose-7-phosphate levels was negatively correlated with serum creatinine. Additionally, urinary ascorbic acid levels increased following treatment, suggesting their potential relevance to kidney function. Pathway analysis indicated disturbances in amino acid and carbohydrate metabolism, particularly glycine/serine metabolism, tyrosine metabolism, and glycolysis, that partially normalized post-treatment.
Conclusion
These findings suggest that clearance of S. stercoralis infection was associated with changes in urinary metabolomic profiles in patients with CKD. Kidney function and urinary metabolomic profiles were observed in patients with early-stage CKD and S. stercoralis infection. Further investigations of kidney outcomes following S. stercoralis clearance and of the potential value of strongyloidiasis screening in patients with CKD are warranted.