Does calcium channel blockade have a role in prevention of expression of sepsis in renal transplant recipients?

Abstract

Abstract:Many antihypertensive agents have been demonstrated to assist in preservation of kidney function, among them those that modulate calcium channels. Calcium channel blockers may also be of value in protecting hemodialysis patients from complications of sepsis. In diabetic recipients of kidney transplant allografts treated with cyclosporine, calcium channel blockade has been retrospectively linked to improved graft preservation and to fewer episodes of sepsis. This brief review outlines clinical and experimental publications on potential protection from sepsis by addition of calcium channel blockers to standard antibiotic therapy in individuals who may or may not have normal kidney function, or in the presence or absence of immunosuppression. Such mechanisms include blockade of antibiotic cytosolic extrusion in the cases of Pneumococci, Mycobacterium tuberculosis, Plasmodium falciparum malaria, or Schistosoma mansoni; blockade of the calcineurin/calmodulin pathway (in immunosuppressed patients allowing for lower dosage of cyclosporine); stabilization of calcium movement at the level of sarcoplasmic reticulum by which shock (vasopressor instability) is prevented; or of cytosolic calcium influx and cell death (in the case of allograft acute tubular necrosis). Given the high cost of development of new antibiotics, a role for generic calcium channel blockade in sepsis prevention should be pursued by additional studies to investigate potential links between blockade of calcium channels and expression of sepsis in at-risk populations.

Calcium channel blockade and survival in recipients of successful renal transplant: an analysis of the FAVORIT trial results

“…Although there has been considerable interest in blocking of calcium channels for the control of various multidrug resistant infectious diseases including malaria, schistosomiasis, tuberculosis, and inflammatory responses, [5][6][7][8][9][10][11][12][13][14][15][16][17] our retrospective analysis of this large renal transplant trial database does not provide any support for the hypothesis that calcium channel blocking agent use provides protection from infectious, all-cause, or cardiovascular mortality. A recent study also demonstrated that calcium sensitizing agents would not improve organ dysfunction in sepsis.…”

“…In vitro and prior observational studies have suggested that the use of calcium channel blocking agents may decrease the expression of sepsis in resistant infections or enhance antibiotic effectiveness in differing nontransplant populations. [5][6][7][8][9][10][11][12][13][14][15][16][17] Our retrospective study suggested a beneficial impact of calcium channel blocking agents on prevalence of sepsis in immunosuppressed transplant recipients, 1 a population that has not been prospectively studied. We, therefore, performed a post hoc analysis of a large 2 Weinrauch et al prospective trial of renal transplant recipients 18 to determine the difference in prevalence of cardiovascular, noncardiovascular (including infection related), and all-cause deaths between the two groups of patients, ie, those receiving CCB and those not.…”