Nicotinic acetylcholine receptor expression and regulation in the rat kidney after ischemia-reperfusion injury.

The cholinergic anti-inflammatory pathway is a mechanism whereby local inflammation is modulated by the brain via the vagus nerve and nicotinic acetylcholine receptors (nAChRs). The nAChR family are ligand-gated ion channels that consist of many different subtypes formed by the specific assembly of five polypeptide subunits including alpha1-10, beta1-4, gamma, delta, and epsilon. The alpha7 receptor (alpha7nAChR) mediates the anti-inflammatory effects of cholinergic stimulation. We recently demonstrated that cholinergic agonists attenuate renal ischemia-reperfusion (I/R) injury in rats. We also showed that tubular epithelial cells express functional nAChRs in vitro. The current studies report the expression, localization, and regulation of the alpha7nAChR in the rat kidney after I/R injury. We also examined, in this model, potential interactions between cholinergic stimulation and the STAT3 pathway, a key signaling cascade that has been linked to alpha7nAChR activation. RT-PCR and immunohistochemistry showed constitutive expression of many nAChR subunits. Immunohistochemistry localized basal alpha7nAChR expression to the endothelium of cortical peritubular capillaries, and its distribution was upregulated after I/R injury. Western blotting also showed an increase in alpha7nAChR subunit protein after renal I/R injury. Interestingly, pretreatment with nicotine, which improves the outcome after renal I/R injury, reduced the alpha7nAChR protein after I/R injury. Finally, we found that I/R injury stimulated the STAT3 pathway, whereas pretreatment with nicotine downregulated its activation. These results suggest that the alpha7nAChR plays an important role in the pathophysiology of renal I/R injury.

Recurrent membranous nephropathy and leiomyosarcoma in the renal allograft of a lupus patient.

The frequency of membranous lupus nephritis recurrence (World Health Organization (WHO) class V) in the allograft after renal transplantation is unknown, but it appears uncommon (only two reported cases in the literature). Despite the increased incidence of sarcomas in organ transplant recipients (compared to the general population), non-Kaposi's sarcoma is an uncommon malignancy, and primary tumor involvement of a renal allograft is a rare occurrence. Our patient is a 28 year old female with end-stage renal disease (ESRD) secondary to membranous lupus nephritis who received a living related transplant from her mother. At 26 months post-transplant, she presented with proteinuria and a rise in creatinine (Cr). Allograft biopsy was consistent with recurrent membranous nephropathy. Five weeks later, she was found to have a high-grade leiomyosarcoma originating within the allograft. We reviewed the literature on recurrent post-transplant membranous nephropathy and the possible role of the Epstein-Barr virus (EBV) infection in smooth muscle tumors occurring in organ transplant recipients. We also considered the association of membranous nephropathy and malignancy.