Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients

Abstract

Sirolimus, being nonnephrotoxic, is a viable alternative in patients who develop renal insufficiency caused by calcineurin inhibitors (CIs). The aim of this study is to determine whether there is improvement in renal function in liver transplant recipients after switching to sirolimusbased immunosuppression. In this retrospective review, patients who were more than 3 years posttransplantation were selected. Patients who had proteinuria (protein > 300 mg/24 hr), those administered any other nephrotoxic agents, and those with a creatinine clearance (CCr) less than 20 mL/min were excluded. Renal insufficiency was defined as mild (CCr > 70 mL/min), moderate (CCr, 40 to 70 mL/min), or severe (CCr, 20 to 40 mL/min). In the 16 patients studied; there was significant improvement in serum blood urea nitrogen (36 mg/dL; range, 19 to 53 mg/dL; to 25 mg/dL; range, 10 to 37 mg/dL; P ‫؍‬ .002) and serum creatinine levels (median, 1.95 mg/dL; range, 1.3 to 2.8 mg/dL; to 1.5 mg/dL; range, 1.0 to 2.4 mg/dL; P ‫؍‬ .001) 6 months after switching to sirolimus therapy. There also was a trend in improvement in CCr from 43 mL min (range, 24 to 68 mL/min) to 49 mL/min (range, 22 to 152 mL/min). Among 9 patients with moderate renal insufficiency, 2 patients improved to mild renal insufficiency, 4 patients remained unchanged, and 3 patients deteriorated to severe renal insufficiency. Among 7 patients with severe renal insufficiency, 1 patient improved to mild renal insufficiency, 4 patients improved to moderate renal insufficiency, and 2 patients remained unchanged. No patient developed cellular rejection or other graft-related complications. In liver transplant recipients with chronic renal insufficiency, conversion to sirolimus-based immunosuppression allows complete withdrawal of CIs, leading to some improvement in renal function. (Liver Transpl 2003;9:126-129.)

Current Status of Immunosuppression in Liver Transplantation

“…26 Some initial studies showed higher incidence of hepatic artery thrombosis with use of Sirolimus, but it was not subsequently substantiated. 27,28 Conversion of CNI to Sirolimus is also useful for patients with CNI induced nephrotoxicity, [29][30][31] but it causes proteinuria and may worsen renal function in patients with pre-existing renal disease. 32,33 Sirolimus impairs wound healing as it impairs action of TGFb, 34 hence it is usually avoided in the early post operative period.…”

Chronic Kidney Disease after Nonrenal Solid-Organ Transplantation

“…Results have generally been conflicting with both CsA [91][92][93][94] and tacrolimus. 95 Ongoing, prospective clinical trials should establish whether conversion to sirolimus preserves kidney function and whether level of kidney function at the time of conversion determines the utility of this strategy.…”

Sirolimus Conversion Regimen Versus Continued Calcineurin Inhibitors in Liver Allograft Recipients: A Randomized Trial

“…Superior renal function was observed in patients remaining on SRL through 12 to 24 months, particularly those with baseline glomerular filtration rates (GFR) >40 mL/min. For LT recipients, several small studies suggested that introducing SRL with concomitant CNI reduction or elimination in maintenance therapy can improve renal function in patients experiencing renal impairment (7,(9)(10)(11)(12)(13)(14).…”