Belatacept conversion in African American kidney transplant recipients with severe renal dysfunction.

OBJECTIVES: Conversion from calcineurin inhibitor-based maintenance immunosuppression to belatacept in kidney transplant recipients has been demonstrated to improve renal function while maintaining efficacy against rejection. However, conversion studies to date have excluded patients with an estimated glomerular filtration rate < 35 mL/min/1.73 m2. METHODS: We describe two patients with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 who underwent conversion from maintenance calcineurin inhibitor to belatacept. RESULTS: Both patients experienced improvement in renal function following conversion. CONCLUSIONS: These results suggest that patients with more severe degrees of allograft impairment may benefit from conversion of maintenance calcineurin inhibitor to belatacept-based immunosuppression. Larger, randomized studies are warranted to evaluate the impact of such an approach.

The benefit of sirolimus maintenance immunosuppression and rabbit antithymocyte globulin induction in liver transplant recipients that develop acute kidney injury in the early postoperative period.

Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%; P < 0.05). The eGFR was significantly (P < 0.05) higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly (P < 0.05) greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period.

Evaluation of antibiotic prescribing patterns in patients receiving sustained low-efficiency dialysis: opportunities for pharmacists.

OBJECTIVES: Sustained low-efficiency dialysis (SLED) is a 'hybrid' form of continuous renal replacement therapy; however, there is very limited information on drug disposition during this procedure. Individuals requiring SLED are often critically ill and require antibiotics. The study aim was to evaluate antibiotic orders for patients requiring SLED compared to literature-based recommendations. We also evaluated whether doses were administered as prescribed and assessed clinical and microbiologic cure. METHODS: A retrospective review was performed over a 2-year period for patients who received concurrent SLED and antibiotic therapy. Demographic data, prescribed antibiotic dosing regimens and doses delivered as prescribed were determined for 10 antibiotics: cefepime (C), daptomycin (Da), doripenem (D), gentamicin (G), imipenem-cilastatin (I), linezolid (L), meropenem (M), piperacillin-tazobactam (P), tobramycin (T) and vancomycin (V). Dosing regimens were compared to recommendations from the literature where available. The incidence of clinical and microbiologic cure was also evaluated. RESULTS: A total of 87 patients met inclusion criteria: mean age 54 ± 14 years, 60% male, 58% white. Prescribed doses were evidence-based for 37% of Da, 97% of L, 15% of M and 7% of V orders. The majority of discrepancies were due to under-dosing. There were 129 (11%) antibiotic doses missed. Of the 13 patients who met criteria for assessment of clinical and microbiologic cure, 10 achieved a microbiologic cure and none reached clinical cure. CONCLUSIONS: Prescribed antibiotic dosing regimens varied substantially and under-dosing was common. There is a need to further define appropriate dosing regimens for antibiotics administered during SLED and determine how pharmacists may help to ensure appropriate therapy.

Performance of methods to assess kidney function in a predominantly overweight sample of patients with liver disease.

The assessment of glomerular filtration rate (GFR) in patients with liver disease is necessary to make decisions about organ allocation. Creatinine is widely used as a marker of GFR; however, it is not reliable in patients with liver disease. The aims of this study were to (1) determine if iodine 125-labeled iothalamate ((125)I-iothalamate) clearance calculated using the plasma decay method is equal to renal clearance of (125)I-iothalamate and (2) estimate kidney function using the creatinine-based Cockcroft-Gault and the Modification of Diet in Renal Disease equations, a cystatin C-based equation, the urine collection method for creatinine clearance, and plasma clearance of vancomycin (V) and compare these estimates to renal clearance of (125)I-iothalamate in adult patients with liver disease. Adults with liver disease received (125)I-iothalamate and V and had a catheter placed for urine collection. Blood and urine samples were collected over 8 h for analysis of (125)I-iothalamate, creatinine, and V to determine kidney function. Estimates were compared to renal (125)I-iothalamate clearance. Eight patients classified as Child-Pugh class B were enrolled: age was 52 ± 6 years; body mass index was 36.5 ± 19 kg/m(2); and Model for End-Stage Liver Disease score was 13 ± 3. Mean estimates of kidney function did not differ significantly from mean renal (125)I-iothalamate clearance (74 ± 38 mL/min/1.73 m(2)). Other methods overestimated kidney function at lower levels of GFR (<60 mL/min/1.73 m(2)) and underestimated kidney function at higher GFR levels. Given the variability in performance of methods to assess kidney function in this population, direct measurement of GFR may be preferable to indirect estimates based on marker compounds such as creatinine and cystatin C until more accurate methods are developed.

Rabbit antithymocyte induction and dosing in deceased donor renal transplant recipients over 60 yr of age.

BACKGROUND: Antithymocyte globulin (rATG) is a commonly used induction agent in renal transplantation; however, data in older kidney recipients are limited. METHODS: We reviewed charts of 301 deceased donor renal transplants who received a protocol consisting of 3-7 doses of rATG and triple maintenance therapy. Outcomes of patients >60 yr of age (n = 45) were compared to those aged 18-59 yr (n = 256). RESULTS: Older recipients had more diabetics, were more likely to receive expanded criteria donor kidneys (p < 0.01), and over 30% were sensitized. Recipients >60 received less cumulative rATG (4.6 vs. 5.1 mg/kg; p < 0.01). Three-yr acute rejection was lower in the >60 group (2% vs. 16%, p < 0.01) although glomerular filtration rates were similar between groups. Actuarial graft survival was similar; however, patient survival in the >60 group at three yr was lower (80% vs. 95%; p = 0.02). Specifically, patients >60 with delayed graft function and rATG cumulative dosing >6 mg/kg had a survival of <50% by two yr. CONCLUSION: Recipients over 60 yr receiving rATG induction have acceptable renal function and a low risk of rejection; however, reduced survival was noted among those receiving >6 mg/kg. These data suggest that when used, lower cumulative dosages of rATG are preferable in the older recipient.

Risk factors and consequences of delayed graft function in deceased donor renal transplant patients receiving antithymocyte globulin induction.

BACKGROUND: Induction rabbit antithymocyte globulin (rATG) is largely used in renal allograft recipients at risk for delayed graft function (DGF) and immunologic rejection. The purpose of our study was to characterize risk factors and outcomes associated with DGF when it occurs in recipients undergoing routine rATG induction. METHODS: We retrospectively reviewed our experience in a predominantly high-risk population receiving modern immunosuppressive regimens. RESULTS: Of 231 deceased-donor transplants, high-risk characteristics included African American race (68%), retransplants (12%), peak panel reactive antibody of atleast 20% (19%), expanded criteria donor kidney (15%), and cold ischemia time exceeding 24 hr (27%). DGF occurred in 29% of patients. rATG was continued to a dose of 7.3 mg/kg in DGF patients and 5 mg/kg in non-DGF patients (P<0.0001). Risk factors for DGF were recipient body mass index greater than 30 kg/m(2) (odds ratio [OR]=1.5, P=0.02), female donor/male recipient pairings (OR=1.5, P=0.033), sirolimus use (OR=1.7, P=0.003), and donor creatinine more than 1.5 mg/dL (OR=1.6, P=0.016). One-year patient survival (99% non-DGF, 91% DGF; P=0.001) and acute rejection incidence through 36 months (11% non-DGF, 22.4% DGF; P=0.025) differed between groups. DGF patients experienced a higher rejection rate during the second and third years posttransplant. Death-censored graft survival was similar throughout 36 months. CONCLUSION: In kidney transplantation with routine rATG induction, DGF was related to size and gender, donor creatinine, and immunosuppressive protocol. Despite low first-year rejection rates, DGF was associated with inferior patient survival. Importantly, patients with DGF continued to be at risk for rejection beyond the first year. Donor and recipient selection impacts short-term outcomes, and induction alone may not confer a long-term advantage without further modification of baseline therapy.