Abstract: SA-PO318

Paraquat-Induced CKD in Experimental Animals: Relevance to CKD of Unknown Origin (CKDu)

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Lei, Fan, Baylor College of Medcine, Houston, Texas, United States
  • Li, Qingtian, Baylor College of Medicine, Houston, Texas, United States
  • Tang, Yi, West China Hospital of Sichuan University, Chengdu, Sichuan, China
  • Huang, Luping, Baylor College of Medicine, Houston, Texas, United States
  • Truong, Luan D., The Methodist Hospital, Houston, Texas, United States
  • Sheikh-Hamad, David, Baylor College of Medicine, Houston, Texas, United States
Background

CKDu is typically encountered in farm workers from different regions of the world, and kidney biopsies from representative patients display tubulointerstitial injury and inflammation. Survey of patients with chronic kidney disease of unknown etiology (CKDu) encountered at a safety net hospital in Houston, identified the herbicide Gramoxone (paraquat-based) as a possible etiologic factor for CKDu in migrant workers originally engaged in agricultural/farm work before their immigration to the US. These subjects described repeated and chronic (years) skin exposure to Gramoxone, as protective gear is not ordinarily used during preparation and spray work. We tested the hypothesis that repetitive exposure of mice to paraquat will lead to chronic kidney disease; as such, repetitive exposure to Gramoxone might produce CKD in humans.

Methods

Mice were given 10 i.p. injections of 20 mg/kg paraquat, given weekly, and allowed free access to food and water. This dose was based on titration experiments where a single dose produces no functional or histological changes in the kidney. At the end of week 10, 24h urine was collected and blood samples were obtained for measurement of creatinine clearance. Mice were euthanized and kidneys were subjected to PAS and Trichome stains and immunostain for T cells (CD3) and macrophages (F4/80); parallel examination of lung, liver and spleen was carried out to determine the effects on other organs.

Results

Paraquat-treated mice displayed doubling of serum creatinine, 50% reduction in creatinine clearance, three-fold increase in T-cells and macrophage infiltration, and increased trichrome staining. There were no changes in the morphology or macrophage infiltration in the liver and lung; however, the spleen showed increased macrophage infiltration.

Conclusion


Repetitive exposure of mice to paraquat given i.p. to simulate exposure of farm workers to paraquat (Gramoxone), produced CKD characterized by tubulointerstitial injury and inflammation, reminiscent of the pathological picture observed in patients with CKDu. Our data suggest that chronic exposure to the herbicide Gramoxone by farm workers in different regions of the world should be considered as a possible etiologic factor for CKDu.

Funding

  • Veterans Affairs Support