Roundup intoxication and a rationale for treatment.

A 51-year-old man with no history ofrenal disease was admitted to our hospital after an intentional ingestion of Roundup, a glyphosate-based herbicide. His course was significant for the development of acute renal failure with oliguria and severe hypoxia. Although efficacy data are sparse and controversial, we proceeded with hemodialysis in an effort to correct his worsening volume status and to potentially clear toxins that are normally excreted by the kidney. His condition improved immediately and his renal function returned to normal over the course of several weeks. We argue that hemodialysis in the setting of such herbicide ingestions may facilitate significant intoxicant clearance, especially in the setting of impaired glomerular filtration. We also make recommendations regarding possible toxin-related sequelae that may warrant initiation of hemodialysis therapy.

WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease.

Peroxisome proliferator-activated receptor alpha (PPARalpha) ligands are medications used to treat hyperlipidaemia and atherosclerosis. Increasing evidence suggests that these agents are immunosuppressive. In the following studies we demonstrate that WY14,643, a PPARalpha ligand, attenuates expression of anti-glomerular basement membrane disease (AGBMD). C57BL/6 mice were fed 0.05% WY14,643 or control food and immunized with the non-collagenous domain of the alpha3 chain of Type IV collagen [alpha3(IV) NC1] in complete Freund's adjuvant (CFA). WY14,643 reduced proteinuria and greatly improved glomerular and tubulo-interstitial lesions. However, the PPARalpha ligand did not alter the extent of IgG-binding to the GBM. Immunohistochemical studies revealed that the prominent tubulo-interstitial infiltrates in the control-fed mice consisted predominately of F4/80(+) macrophages and WY14,643-feeding decreased significantly the number of renal macrophages. The synthetic PPARalpha ligand also reduced significantly expression of the chemokine, monocyte chemoattractant protein (MCP)-1/CCL2. Sera from mice immunized with AGBMD were also evaluated for antigen-specific IgGs. There was a significant increase in the IgG1 : IgG2c ratio and a decline in the intrarenal and splenocyte interferon (IFN)-gamma mRNA expression in the WY14,643-fed mice, suggesting that the PPARalpha ligand could skew the immune response to a less inflammatory T helper 2-type of response. These studies suggest that PPARalpha ligands may be a novel treatment for inflammatory renal disease.