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

Abstract

John A D’Elia,1–3 Ray E Gleason,3 Anthony P Monaco,2,3 Larry A Weinrauch,1–4 1Kidney and Hypertension Section, Joslin Diabetes Center, Boston, MA, 2Departments of Surgery and Medicine, Beth Israel Deaconess Medical Center, Boston, MA, 3Harvard Medical School, Boston MA, 4Department of Medicine, Mount Auburn Hospital, Cambridge, MA, USA 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. Keywords: renal transplant, transplantation sepsis, calcium channel blockade

Keywords

• Renal transplant Transplantation Sepsis Calcium channel blockade