Increasing net immunosuppression after BK polyoma virus infection.

BACKGROUND: Reducing immunosuppression can effectively treat BK viremia (BKV) and BK nephropathy, but has been associated with increased risks for acute rejection and development of donor-specific antibodies (DSA). To date there have been no systematic evaluations of re-escalating immunosuppression in transplant patients with resolving BKV. Importantly, the safety of this approach and impact on graft survival is unclear. METHODS: We performed a single-center retrospective review of kidney transplant recipients between July 2011 and June 2013 who had immunosuppression reduction after developing BKV (plasma PCR ≥ 1000 copies/ml). Changes in immunosuppression and patient outcomes were tracked until occurrence of a complication event: biopsy-proven acute rejection (BPAR), detection of de novo DSA, or recurrent BKV. Patients were grouped according to whether or not net immunosuppression was eventually increased. RESULTS: Out of 88 patients with BKV, 44 (50%) had net immunosuppression increased while the other 44 did not. Duration of viremia, peak viremia, induction, and sensitization status were similar between the two groups. In a Kaplan-Meier analysis, increasing immunosuppression was associated with less BPAR (P = .001) and a trend toward less de novo DSA development (P = .06). Death-censored graft survival (P = .27) was not different between the two groups. In the net immunosuppression increase group, recurrent BKV occurred in 22.7% without any BKV-related graft losses. CONCLUSION: These findings support potential benefits of increasing immunosuppression in patients with low-level or resolved BKV, but prospective trials are needed to better understand such an approach.

Safety and efficacy of direct-acting oral anticoagulants versus warfarin in kidney transplant recipients: a retrospective single-center cohort study.

Despite the increased use, comparative safety and efficacy of direct-acting oral anticoagulants (DOACs) against warfarin have not been well studied in kidney transplant recipients. In this single-center retrospective study, we evaluated 197 adult kidney transplant recipients on DOAC or warfarin between January 1, 2011, and June 30, 2018. The primary outcome was incidence of major bleeding defined as a hemoglobin decrease ≥2 g/dl, blood transfusion ≥2 units, or symptomatic bleeding in a critical area or organ. Patients were initiated on anticoagulation therapy at a median of 6.5 years post-transplant and followed for a median of 12.3 months. The rates of major bleeding were 7.2% per year with DOACs vs. 11.4% per year with warfarin (Mantel-Cox P = 0.15). No difference was found in composite bleeding, clinically relevant nonmajor bleeding, or thromboembolic events between the groups. There was a lower incidence of major bleeding with apixaban compared to all other anticoagulants (6.7% vs. 19.0%, P = 0.027). After controlling for potential confounders, DOAC use was not associated with an increased risk of major bleeding (HR 0.73, 95% CI 0.27-1.95). Further research is warranted to definitively determine whether DOACs are effective and safe alternatives to warfarin for anticoagulation in kidney transplant recipients.

The Impact of Obesity on Allograft Failure After Kidney Transplantation: A Competing Risks Analysis.

BACKGROUND: The impact of pretransplant body mass index (BMI) on long-term allograft outcomes after kidney transplantation remains controversial. The conventional approach of using Kaplan-Meier method to calculate the cumulative risk of death-censored allograft failure may overestimate the risk of failure especially when competing failure risks are present. METHOD: A retrospective cohort of adult first-time kidney transplant recipients was drawn from the Organ Procurement and Transplantation Network database (2001 to 2009). Based on World Health Organization obesity classification, BMI was categorized as: less than 18.5, 18.5 to <25, 25 to < 30, 30 to < 35, 35 to <40 and ≥40 kg/m. Both unadjusted and adjusted risk models were used to assess for risk of allograft failure in the presence of death as a competing event. RESULTS: A total of 108 654 recipients were studied. In both unadjusted and adjusted models, increasing BMI level was associated with increased risk of long-term allograft failure. In the adjusted model with BMI 18.5 to less than 25 as the reference, the subhazards ratios (SHRs) for BMI were: less than 18.5: SHR, 0.96; P = 0.41; 25 to less than 30: SHR, 1.05; P = 0.01; 30 to less than 35: SHR, 1.15; P = <0.001; 35 to less than 40: SHR, 1.21; P < 0.001; and greater than 40: SHR, 1.13; P = 0.002. CONCLUSIONS: Handling of death as a competing event demonstrates a graded, detrimental impact of increasing pretransplant BMI on the risk of graft failure after kidney transplantation in both unadjusted and adjusted models. Compared with previous studies, a lower BMI was not associated with an increased risk of graft loss in a competing risk model.

Ureteral complications after hand-assisted laparoscopic living donor nephrectomy.

BACKGROUND: Urological complications, namely ureteral leak and obstruction, remain a major source of morbidity after renal transplantation. Given that the existing literature on ureteral complications pertains mostly to deceased as opposed to living donors, we aimed to assess the risk factors for ureteral complications solely after living donor nephrectomy. METHODS: We identified 480 consecutive cases of renal transplantation after hand-assisted laparoscopic living donor nephrectomy at our institution from January 2008 to February 2013. We determined the incidence of ureteral complications and assessed the association with a number of perioperative factors, including age, sex, race, and body mass index of both the donor and recipient; arterial and ureteral anatomy; procurement by transplant surgeon versus urologist; history of previous renal transplantations; technique of ureteral anastomosis; use of ureteral stent; total ischemia time; serum creatinine on discharge; and need for temporary posttransplant hemodialysis. RESULTS: Among 480 renal transplantations after living donor nephrectomy, ureteral complications occurred in 18 (3.7%), including ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors were significantly associated with ureteral complications on multivariate analysis: increased donor age and no placement of ureteral stent. CONCLUSIONS: Ureteral complications of renal transplants after living donor nephrectomy are uncommon. The use of a ureteral stent is protective against ureteral complications and increased donor age is associated with an increased incidence of ureteral complications.

Chronic kidney disease stage progression in liver transplant recipients.

BACKGROUND AND OBJECTIVES: There is little information on chronic kidney disease (CKD) stage progression rates and outcomes in liver transplant recipients. Identifying modifiable risk factors may help prevent CKD progression in liver transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective review of 1151 adult, deceased-donor, single-organ primary liver transplants between July 1984 and December 2007 and analyzed kidney outcomes and risk factors for CKD stage progression. Seven hundred twenty-nine patients had an available estimated GFR at 1 year posttransplant to establish a baseline stage. The primary end point was the CKD progression from one stage to a higher stage (lower GFR). RESULTS: Kaplan-Meier estimates of patient survival were 91%, 74%, and 64% at 5, 10, and 15 years, respectively. Estimates of liver allograft survival were 89%, 71%, and 60% at the same time points. At 1 year, 7%, 34%, 56%, 3%, and 1% of patients were in CKD stages 1, 2, 3, 4, and 5. The incidence of stage progression was 28%, 40%, and 53% at 3, 5, and 10 years. The incidence of ESRD was 2.6%, 7.5%, and 18% at 5, 10, and 20 years. Multivariable Cox regression analyses demonstrated that CKD stage at 1 year, pretransplant diabetes and urinary tract infections/hypercholesterolemia in the first year proved to be independent risk factors for stage progression (hazard ratio 1.9, 0.28, 1.39, and 1.46, respectively, P < 0.05). CONCLUSIONS: Future studies will determine whether treatment of risk factors in the first posttransplant year prevent CKD progression in liver transplant recipients.

Alemtuzumab induction and antibody-mediated kidney rejection after simultaneous pancreas-kidney transplantation.

BACKGROUND: The best induction agent for simultaneous pancreas-kidney transplantation (SPKT) remains the subject of debate. Alemtuzumab is effective in preventing acute cellular rejection (ACR) in SPK recipients and has been used to prevent antibody-mediated rejection (AMR) in sensitized kidney transplant candidates. METHODS: A retrospective cohort study was performed including 136 SPK recipients receiving maintenance immunosuppression with tacrolimus, mycophenolic acid prodrugs, and prednisone. Two groups were compared: those who received induction with alemtuzumab (n=97) and those induced with basiliximab (n=39). RESULTS: Kidney ACR was more frequent in SPKT induced with basiliximab (2-year 12.8% vs. 3.1%, P=0.04), but the incidence of AMR was similar (2-year 18% with basiliximab vs. 13.8% with alemtuzumab, P=NS). Kidney rejection was associated with clinical pancreas rejection in 70% of cases, without differences between the groups. Postrejection kidney graft survival was similar in both groups (2-year basiliximab/alemtuzumab 94.7%/91.2%), but death-censored kidney graft survival was lower with alemtuzumab (100%/91.2%, P=0.056). In the basiliximab group, the predominant cause of kidney loss was death-with-function, whereas in the alemtuzumab group AMR accounted for all losses. Pancreas graft survival was similar in both groups, yet more pancreas losses due to acute rejection occurred in alemtuzumab-treated patients (4 vs. 1). CONCLUSIONS: Kidney AMR is more common than ACR in SPKT recipients treated with alemtuzumab, tacrolimus, mycophenolic acid, and steroids. ACR is better prevented by alemtuzumab than basiliximab, but no relevant difference is found in prevention of AMR. Despite the high incidence of AMR, survival rates are excellent in both groups.