Cyclophilin a as a Mediator of Tissue Injure and Nephrotoxicity

Cyclophilin A (CypA) belongs to the peptidyl-prolil isomerase (PPlase) family of proteins and it is also known as the cellular receptor for cyclosporine A (CsA). CsA binds to CypA and inhibits the PPIase activity, but the CypA-CsA complex also binds to calcineurin that promotes the expression of genes encoding cytokines and other proteins required for immune response. In addition, the polymorphism variation of CypA promoter seems to have an influence on the expression of CypA in in vitro studies. CypA was also implicated in inflammatory processes (such as, among others, those observed in rheumatoid arthritis, atherosclerotic disease, nephrotoxicity) and it can be secreted by cells in response to inflammatory stimuli. CypA can also have a role in the molecular mechanisms by which CsA induces nephroxicity but these remain poorly understood. Recent studies suggest that CsA inhibition of CypA PPlase activity is a possible mechanism of this drug toxicity. In addition, CypA overexpression could be protective against CsA nephrotoxicity. Finally, the putative common mechanism by which CypA could be involved in CsA nephrotoxicity and tissue injury is related to its proinflammatory effects in cells.

Syphilis and Kidney Disease: A Case Report and Review of Literature

There has been a resurgence in the number of incident cases of syphilis in the United States. Syphilis can affect the kidney and usually causes a glomerular lesion with variable amounts of proteinuria. We present a case of a 24-year old African-American male who presented with both membranous glomerulonephritis and secondary syphilis. His kidney disease resolved after a course of penicillin. Recognizing the association of syphilis and proteinuria is important since antibiotic therapy generally results in complete recovery of the associated nephropathy.

Fibrillary Glomerulonephritis

Fibrillary glomerulonephritis (FGN) is a rare disorder characterized by Congo-red negative fibrillary deposits in the glomeruli. The incidence of FGN in native renal biopsies is only 0.8–1.5%. The pathological hallmark of FGN is fibrillary deposits in the mesangium and glomerular basement membrane. These fibrils are straight, non-branching and randomly oriented. In the majority of patients, FGN presents with nephrotic syndrome. Renal insufficiency is present in two-thirds of patients with a mean serum creatinine of 2.1 mg/dL. Approximately one-half of FGN patients progress to end-stage renal disease (ESRD). Renal biopsy establishes the diagnosis of FGN. Light microscopy findings include amorphous acellular deposits in the glomeruli. In the mesangium these deposits have a smudged texture and form a pseudolinear or confluent granular pattern along the basement membrane. Immunofluorescent studies of the biopsy tissue in FGN show staining for polyclonal Immunoglobulin G (IgG) and complement with a tendency towards higher IgG and C3. Electron microscopy reveals extensive infiltration of the glomerular basement membrane with spike formation. Standard therapeutic treatments for FGN have not been well defined. The clinical outcome of patients with FGN is not encouraging. In a recent study, 44% of patients with FGN progressed to ESRD. The average time to progress to ESRD was 2–4 years. Immuno-suppressant therapies that include corticosteroids, cyclophosphamide and cyclosporine, and most recently rituximab, have not demonstrated uniform clinical success.