title: Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients.
abstract: Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.
authors.affiliation: Department of Cardiothoracic Surgery, Medical University of Vienna, Währinger Gürtel, 18-20, A-1090 Vienna, Austria.
authors.forename: A Z
authors.initials: AZ
authors.lastname: Aliabadi
authors.forename: E
authors.initials: E
authors.lastname: Pohanka
authors.forename: G
authors.initials: G
authors.lastname: Seebacher
authors.forename: D
authors.initials: D
authors.lastname: Dunkler
authors.forename: D
authors.initials: D
authors.lastname: Kammerstätter
authors.forename: E
authors.initials: E
authors.lastname: Wolner
authors.forename: M
authors.initials: M
authors.lastname: Grimm
authors.forename: A O
authors.initials: AO
authors.lastname: Zuckermann
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D004784:Environmental Monitoring; D005260:Female; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D018579:Patient Selection; D011446:Prospective Studies; D011507:Proteinuria / Q000139:chemically induced*; D020123:Sirolimus / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000305:Adrenal Cortex Hormones; D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus