Sandy Florman

A Phase III Study of Belatacept Versus Cyclosporine in Kidney Transplants from Extended Criteria Donors (BENEFIT‐EXT Study)

Recipients of extended criteria donor (ECD) kidneys are at increased risk for graft dysfunction/loss, and may benefit from immunosuppression that avoids calcineurin inhibitor (CNI) nephrotoxicity. Belatacept, a selective costimulation blocker, may preserve renal function and improve long‐term outcomes versus CNIs. BENEFIT‐EXT (Belatacept Evaluation of Nephroprotection and Efficacy as First‐line Immunosuppression Trial—EXTended criteria donors) is a 3‐year, Phase III study that assessed a more (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adult ECD kidney transplant recipients. The coprimary endpoints at 12 months were composite patient/graft survival and a composite renal impairment endpoint. Patient/graft survival with belatacept was similar to cyclosporine (86% MI, 89% LI, 85% cyclosporine) at 12 months. Fewer belatacept patients reached the composite renal impairment endpoint versus cyclosporine (71% MI, 77% LI, 85% cyclosporine; p = 0.002 MI vs. cyclosporine; p = 0.06 LI vs. cyclosporine). The mean measured glomerular filtration rate was 4–7 mL/min higher on belatacept versus cyclosporine (p = 0.008 MI vs. cyclosporine; p = 0.1039 LI vs. cyclosporine), and the overall cardiovascular/metabolic profile was better on belatacept versus cyclosporine. The incidence of acute rejection was similar across groups (18% MI; 18% LI; 14% cyclosporine). Overall rates of infection and malignancy were similar between groups; however, more cases of posttransplant lymphoproliferative disorder (PTLD) occurred in the CNS on belatacept. ECD kidney transplant recipients treated with belatacept‐based immunosuppression achieved similar patient/graft survival, better renal function, had an increased incidence of PTLD, and exhibited improvement in the cardiovascular/metabolic risk profile versus cyclosporine‐treated patients.

Exploring the Effect of Parathyroidectomy for Tertiary Hyperparathyroidism After Kidney Transplantation

Tertiary hyperparathyroidism (tHPT) usually regresses after renal transplantation. Persistent tHPT after successful renal transplantation may require parathyroidectomy (PTX). PTX has been reported to be associated with deterioration of renal function and graft survival. We retrospectively analyzed 794 kidney transplants performed at our center with at least 3 years of follow-up to examine the effect of PTX on the renal function and graft survival. Forty-nine of the 794 renal transplant recipients were diagnosed with hyperparathyroidism (HPT) before transplant. Nineteen of 49 patients had persistent tHPT and underwent PTX after kidney transplants. Patients with HPT and non-HPT had similar 3-year graft survival (88% versus 84%, P = 0.51). PTX was associated with a decreased glomerular filtration rate at 3 years (44.7 ± 20.0 versus 57.7 ± 23.7 mL/min, P = 0.04); however, there was no statistical difference in the 3-year graft survival (71% versus 88%, P = 0.06). PTX in renal transplant recipients seems to be a safe and effective therapy for persistent tHPT. PTX may be associated with worsening glomerular filtration rate, but it may not be associated with significantly decreased long-term graft survival.

Laparoscopic Procurement of Single Versus Multiple Artery Kidney Allografts: Is Long-Term Graft Survival Affected?

Background. Living donor kidneys with multiple arteries (MA) are increasingly procured laparoscopically for transplant. Methods. We compare long-term graft function and survival of kidneys with single arteries (SA) and MA over a 10-year period. Results. There were a total of 218 grafts with SA and 60 grafts with MA. The MA group had longer operative and ischemic times than SA group. There was a small increase in ureteral complication (8.3% vs. 2.3% P=0.06) and a significantly higher incidence of rejection (23.3% vs. 10.1%, P=0.01) in MA group than in SA group. Graft function was lower in MA group than SA group. The 5-year graft survival by Kaplan Meier analysis was better in SA group than in MA group (P=0.023). The estimated graft survivals at 1, 3, and 5 year were 94.4%, 90.6%, and 86% for SA group and 89.6%, 83.2%, and 71.8% for MA group. There was a higher percentage of graft loss from chronic allograft nephropathy in MA group than in SA group (16.7% vs. 5.5%, P=0.01). The presence of MA (vs. SA) was an independent risk for acute rejection (OR 3.60, 95% CI 1.59–8.14, P=0.002) and for graft loss (HR 2.31, 95% CI 1.05–5.09, P=0.038). Conclusion. Laparoscopic procurement of living donor kidneys with SA may be associated with a lower risk of rejection, better function, and superior long-term survival when compared with kidneys with MA.

Long-Term Outcome of Adults Who Undergo Transplantation with Single Pediatric Kidneys: How Young Is too Young?

BACKGROUND AND OBJECTIVES The optimal donor age for transplanting a single pediatric kidney in an adult recipient remains unknown. En block kidney transplantation is usually performed when the donor age is <5 yr. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We compared the outcomes of adult patients who underwent transplantation with single pediatric kidneys from donors who were younger than 5 yr (group 1, n = 40) and from donors who were aged 5 to 10 yr of age (group 2, n = 39) in our center. RESULTS The donor kidney sizes were significantly smaller in group 1 than in group 2 (P < 0.001), and group 1 required more ureteral stents than group 2 (73 versus 38%). The surgical complications, delayed graft function, and development of proteinuria were similar in both groups. Group 1 had slightly higher rejection episodes than group 2 (25 versus 18%; P = 0.67), and graft function was comparable in both groups. There were no statistical differences between the two groups in patient (P = 0.73) or death-censored graft (P = 0.68) survivals over 5 yr. CONCLUSIONS Single pediatric kidney transplants from donors who are younger than 5 yr can be used with acceptable complications and long-term outcomes as those from older donors.

Utility of CT angiography for evaluation of living kidney donors

We reviewed our initial experience with helical computed tomography (CT) angiography in the evaluation of living kidney donors which, until now, has necessitated arteriography. Nineteen donors (12 women, 7 men) have had their renal anatomy evaluated solely by CT angiography preoperatively.All scans demonstrated normal collecting systems and single ureters. Five donors (26%) had supernumerary renal arteries. Fourteen donors had single, 4 donors had two, and 1 donor had three renal arteries. Helical CT demonstrated small polar vessels in several donors. Two donors (10%) had supernumerary renal veins. Accuracy of vascular anatomy defined on CT was 90% when confirmed at operation. Anatomically all CT findings were consistent with operative findings except in 1 donor who was found to have a 0.8 cm lesion near the renal hilum.At our institution, the total charges for selective renal arteriography are

Management of Metabolic Bone Disease in Kidney Transplant Recipients

3845 and for helical CT with three‐dimensional (3‐D) reconstruction are

The long-term survival of simultaneous pancreas and kidney transplant with basiliximab induction therapy

1546. The amount of contrast dye (approximately 100 mL) is equivalent. Patients uniformly reported that the CT scan was a convenient and painless procedure.The accuracy of helical CT angiography is equivalent to arteriography in assessing renal vascular anatomy (with the additional benefit of imaging venous and parenchymal anatomy). Charges for helical CT are 59% less. There is greater patient acceptance and potentially less morbidity associated with the non‐invasive nature of helical CT. We believe that CT angiography is the radiologic procedure of choice for the assessment of renal anatomy in potential living kidney donors.

A Comparison of Long‐Term Survivals of Simultaneous Pancreas–Kidney Transplant between African American and Caucasian Recipients with Basiliximab Induction Therapy

Bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a different osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Hypovitaminosis D, hyperparathyroidism and hyperaluminemia may resolve after kidney transplant, but many patients have other risk factors of bone loss, such as steroids usage, hypogonadism, persistent hyperparathyroidism, poor allograft function, aging, and chronic diseases. Clinical management requires a comprehensive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D analogues, bisphosphonates and calcitonin. Novel approaches to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fractures in kidney transplant recipients.

Long-term outcome of highly sensitized African American patients transplanted with deceased donor kidneys

Abstract:  Interleukin‐2 receptor (IL2R) antibody has emerged as an attractive induction therapy for organ transplant. However, the long‐term outcome of basiliximab induction in simultaneous pancreas and kidney (SPK) transplant remains speculative. We retrospectively analyzed the long‐term survivals of 91 consecutive SPK recipients with basiliximab as induction, combination of steroid, tacrolimus (TAC) and mycophenolate acid (MFA) – either mycophenolate mofetil (MMF) or sodium mycophenolate (myfortic) as maintenance. At one, three, five, and seven‐yr, the actual patient survival rate were 91.2%, 90.3%, 88.1%, and 88.2%, respectively; kidney graft survivals were 90.1%, 84.7%, 78.6%, and 70.6%, respectively; and pancreas graft survivals were 86.8%, 80.6%, 71.4%, and 58.8% respectively. There was a low incidence of rejection and CMV infection. Basiliximab induction with TAC, MFA, and steroid maintenance therapy can provide excellent long‐term outcome for SPK recipients.

BELATACEPT VS CYCLOSPORINE IN ECD KIDNEY TRANSPLANTS: TWO-YEAR OUTCOMES FROM THE BENEFIT-EXT STUDY: 1394

African Americans (AA) have traditionally been thought to have higher immunologic risk than Caucasians (CA) for rejection and allograft loss. The impact of ethnicity on the outcome of simultaneous pancreas–kidney (SPK) transplant with basiliximab induction has not been reported. In this study, we retrospectively analyze the long‐term results of 36 AA and 55 CA recipients of primary SPK. The actual patient survival rates of AA and CA groups were 91.7% vs. 90.1% at 1 year, 93.3% vs. 88.1% at 3 years, and 94.4% vs. 83.3% at 5 years. The actual kidney survival of AA and CA were 91.7% vs. 89.1% at 1 year, 90% vs. 81% at 3 years, and 83.3% vs. 75% at 5 years. The actual pancreas survival of AA and CA were 88.9% vs. 85.5% at 1 year, 83.3% vs. 78.6% at 3 years and 72.2% vs. 70.8% at 5 years. Death‐censored analyses also found no difference in pancreas and kidney graft survival rates over 5 years. Higher rejection rate, but the same low CMV infection, and comparable quality of graft function were noted in AA group. AA may not have worse long‐term outcomes than CA recipients of SPK with basiliximab induction and tacrolimus (TAC), mycophenolate acid (MFA) and steroid maintenance immunotherapy.