The Impact of Different Induction Immunosuppressive Therapy on Long-Term Kidney Transplant Function When Measured by Iothalamate Clearance

Abstract

Background: Improvement in short-term outcomes after kidney transplant has been achieved by using different induction and maintenance therapeutic approaches. Long-term outcomes have not matched the expectations of the transplant stakeholders. Our study aimed to address the early impact of induction agents on long-term outcome of kidney transplant when measured by iothalamate clearance.

Methods: All adult kidney transplant recipients between January of 2012 and December of 2016 were reviewed. Six hundred forty-nine patients were divided into three groups based on the induction agent (basiliximab, alemtuzumab, and thymoglobulin). Protocoled 4 months and 48 months kidney allograft function evaluations with iothalamate clearance test were compared among the three groups.

Results: Patients who received basiliximab were significantly older with no difference among African American and Caucasians. The 48 months assessment showed significant decline in median iothalamate clearance in basiliximab group at 49 mL/min vs. alemtuzumab group 64.8 mL/min and thymoglobulin 60 mL/min with P = 0.007. The basiliximab group developed a significant higher proteinuria measured by spot urine to creatinine ratio at 48 months.

Conclusions: The use of basiliximab as an induction agent for kidney transplant is associated with significant decline in kidney function 4 years post transplantation when measured by iothalamate clearance.

Keywords: Allografts; Induction; Iothalamate.

Figure 1

(a) Iothalamate clearance at 48 months. Recipients induced with basiliximab (149 patients) showed significant decline in iothalamate clearance at 49 when compared to alemtuzumab (264 patients) at 64.8 and thymoglobulin (236 patients) at 60 with P = 0.007. (b) Iothalamate clearance at 48 months, after excluding of recipients from donors with KDPI > 85%. Recipients induced with basiliximab (129 patients) showed significant decline in iothalamate clearance at 52 when compared to alemtuzumab (256 patients) at 64 and thymoglobulin (229 patients) at 61 with P = 0.02.

Figure 2

The 48 months protein creatinine ratio measurement showed significantly elevated mean protein/creatinine when measured at 48 months at 0.2 when compared to protein/creatinine of 0.1 with both alemtuzumab and thymoglobulin when used for induction, P < 0.03.

Figure 3

(a) Time to first rejection, based on protocoled or indicated biopsies, showed no significant differences among the three groups (P > 0.05). (b) Tacrolimus level checked within the 24 - 48 h prior to first diagnosed rejection showed acceptable therapeutic levels and no differences among the three groups: 7.7 ± 3.8 ng/mL with thymoglobulin, 6.8 ± 2.5 ng/mL with alemtuzumab and 7.3 ± 3.1 ng/mL with basiliximab group (P > 0.05).

Figure 4

First diagnosed CMV viremia (black), based on screening test and/or symptoms, was reported as percentage of patients who tested positive and showed no difference among the three groups (P = 0.17). Incidence of BK viremia (grey) was higher in patients who received alemtuzumab for induction but not significant (P = 0.18). Incidence of BK viruria (white) was similar in all patients group (P = 0.9). CMV: cytomegalovirus; BK: polyomavirus.