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Actinomycosis is an invasive infection, which can affect numerous anatomical sites, though rarely the kidney. The rate of nephrectomy is high despite antibiotic therapy. A 51 year old presented with a Proteus mirabilis renal abscess 9 years following a similar renal abscess. The abscess persisted despite appropriate antibiotic treatment and radiological drainage. In addition to P. mirabilis, Actinomyces species was isolated on polymicrobial abscess culture after 6 weeks antibiotic therapy. Despite appropriate antibiotics, nephrectomy was required. Histology confirmed actinomycosis. Actinomycosis should be considered in chronic, destructive infections, especially if failure to respond to appropriate antimicrobials. However, Actinomyces species may be missed by routine culture techniques. Because of the polymicrobial nature of abscesses, good communication with the laboratory is essential to ensure that cultures are prolonged and the isolation of one pathogen does not hinder the isolation of others.

BACKGROUND: Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to be identified. METHODS: Whole-genome sequencing was performed on 320 individuals from 201 families with familial and sporadic NS/FSGS with no pathogenic mutations in any known NS/FSGS genes. RESULTS: Two variants in the gene encoding regulator of calcineurin type 1 (RCAN1) segregate with disease in two families with autosomal dominant FSGS/SRNS. In vitro, loss of RCAN1 reduced human podocyte viability due to increased calcineurin activity. Cells expressing mutant RCAN1 displayed increased calcineurin activity and NFAT activation that resulted in increased susceptibility to apoptosis compared with wild-type RCAN1. Treatment with GSK-3 inhibitors ameliorated this elevated calcineurin activity, suggesting the mutation alters the balance of RCAN1 regulation by GSK-3β, resulting in dysregulated calcineurin activity and apoptosis. CONCLUSIONS: These data suggest mutations in RCAN1 can cause autosomal dominant FSGS. Despite the widespread use of calcineurin inhibitors in the treatment of NS, genetic mutations in a direct regulator of calcineurin have not been implicated in the etiology of NS/FSGS before this report. The findings highlight the therapeutic potential of targeting RCAN1 regulatory molecules, such as GSK-3β, in the treatment of FSGS.