Benefit of B7-1 staining and abatacept for treatment-resistant post-transplant focal segmental glomerulosclerosis in a predominantly pediatric cohort: time for a reappraisal.

BACKGROUND: Primary FSGS manifests with nephrotic syndrome and may recur following KT. Failure to respond to conventional therapy after recurrence results in poor outcomes. Evaluation of podocyte B7-1 expression and treatment with abatacept (a B7-1 antagonist) has shown promise but remains controversial. METHODS: From 2012 to 2020, twelve patients developed post-KT FSGS with nephrotic range proteinuria, failed conventional therapy, and were treated with abatacept. Nine/twelve (< 21 years old) experienced recurrent FSGS; three adults developed de novo FSGS, occurring from immediately, up to 8 years after KT. KT biopsies were stained for B7-1. RESULTS: Nine KTRs (75%) responded to abatacept. Seven of nine KTRs were B7-1 positive and responded with improvement/resolution of proteinuria. Two patients with rFSGS without biopsies resolved proteinuria after abatacept. Pre-treatment UPCR was 27.0 ± 20.4 (median 13, range 8-56); follow-up UPCR was 0.8 ± 1.3 (median 0.2, range 0.07-3.9, p < 0.004). Two patients who were B7-1 negative on multiple KT biopsies did not respond to abatacept and lost graft function. One patient developed proteinuria while receiving belatacept, stained B7-1 positive, but did not respond to abatacept. CONCLUSIONS: Podocyte B7-1 staining in biopsies of KTRs with post-transplant FSGS identifies a subset of patients who may benefit from abatacept. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical outcomes in HIV+/HCV+ coinfected kidney transplant recipients in the pre- and post-direct-acting antiviral therapy eras: 10-Year single center experience.

BACKGROUND: Previous studies have demonstrated inferior patient and graft survival following kidney transplant (KT) in HIV+/HCV+ coinfected patients compared to HIV+/HCV- recipients. However, these studies were conducted prior to the availability of direct-acting antiviral (DAA) agents and data in the modern era are lacking. METHODS: Single center retrospective study of HIV+/HCV+ coinfected KT recipients (2007-2017). Outcomes were assessed for the pre-DAA and post-DAA (ie, after December 2013) eras including 1-year patient survival, death-censored graft survival, and acute rejection; and serious infections (defined as infections requiring admission to the intensive care unit during initial transplant hospitalization or re-admission to the hospital after discharge) within the first 6 months post-transplant. RESULTS: A total of 13 consecutive HIV+/HCV+ recipients were identified. Median time of post-transplant follow-up was 722 days. Seven patients were transplanted in the DAA era; five of them had anti-HCV Ab+ donors, with two donors being HCV NAT positive; all received DAA therapy, six of them post-transplant (median time from KT to DAA: 83 days; IQR, 54-300). All the patients in the pre-DAA era were on a protease inhibitor-containing ART regimen. One-year patient and death-censored graft survivals were 83% and 67%, respectively, for the patients transplanted in the pre-DAA era, and 100% for both outcomes in the subgroup of patients transplanted in the post-DAA era (P > 0.05). Compared to patients in the post-DAA era, those in the pre-DAA era had higher incidence of serious infections (0 vs 67%; P = 0.02). Acute rejection exclusively occurred in the pre-DAA group (n = 1; 17%). CONCLUSIONS: Outcomes of HIV+/HCV+ KT recipients, including HIV-/HCV+ to HIV+/HCV+ transplants, in the DAA era were excellent in this small cohort. Larger studies are needed.

Roux-en-Y gastric bypass is an effective bridge to kidney transplantation: Results from a single center.

Body mass index (BMI) > 35-40 kg/m2 is often a contraindication, while Roux-en-Y gastric bypass (RYGB) is performed to enable kidney transplantation. This single-center retrospective study evaluated pre- and post-transplant outcomes of 31 morbidly obese patients with end-stage renal disease having RYGB before kidney transplantation between July 2009 and June 2014. Fourteen RYGB patients were subsequently transplanted. Nineteen recipients not having GB with a BMI ≥ 36 kg/m2 at transplantation were used as historical controls. Mean BMI (±SE) before RYGB was 43.5 ± 0.7 kg/m2 (range: 35.4-50.5 kg/m2 ); 87.1% (27/31) achieved a BMI < 35 kg/m2 . The percentage having improved diabetes/hypertension control was 29.0% (9/31); 25.8% (8/31) had complications (mostly minor) after RYGB. Among transplanted patients, blacks/Hispanics comprised 78.6% (11/14) and 84.2% (16/19) of RYGB and controls; 57.1% (8/14) and 63.2% (12/19) had a (mostly long-standing) pretransplant history of diabetes. While biopsy-proven acute rejection (BPAR) occurred significantly higher among RYGB vs control patients (6/14 vs 3/19, P = .03), patients developing T-cell BPAR were also significantly more likely to have a tacrolimus (TAC) trough level < 4.0 ng/mL within 3 weeks of T-cell BPAR (P = .0007). In Cox's model, the impact of having a TAC level < 4.0 ng/mg remained significant (P = .007) while the effect of RYGB was no longer significant (P = .13). Infections, graft, and patient survival were not significantly different. Despite obvious effectiveness in achieving weight loss, RYGB will need more careful post-transplant monitoring given the observed higher BPAR rate.

Biomarkers in pancreas transplant.

PURPOSE OF REVIEW: The review analyzes the current biomarkers used in monitoring pancreas transplant, from the simple and time-tested, to more sophisticated, including markers of allo- and autoimmunity, that are likely to play a larger role in future studies. RECENT FINDINGS: Evaluation of alloimmunity includes serum levels of donor-specific antibody, and, ultimately, pancreas transplant biopsies with C4d staining. Our center has focused on markers of autoimmunity, including assessment of autoantibodies and autoreactive T cells. We have found that conversion of autoantibodies (including GAD65, IA-2, and ZnT8), or the development of a new positive autoantibody, particularly ZnT8, are associated with type 1 diabetes (T1D) recurrence in the pancreas transplant. Autoreactive T cells have also been identified in the peripheral blood, pancreas transplant and peripancreas transplant-lymph nodes, that have the potential to mediate human ß/islet cell destruction in vivo. SUMMARY: The monitoring of pancreas transplant biomarkers, particularly those associated with autoimmunity, has led to new insights into the pathogenesis of T1D. Progress in the elucidation of mechanisms of autoimmunity may lead to novel therapeutic approaches to both T1D recurrence of the pancreas transplant and perhaps also new onset T1D.

How to Deal With Kidney Retransplantation-Second, Third, Fourth, and Beyond.

Kidney transplantation is the best health option for patients with end-stage kidney disease. Ideally, a kidney transplant would last for the lifetime of each recipient. However, depending on the age of the recipient and details of the kidney transplant, there may be a need for a second, third, fourth, or even more kidney transplants. In this overview, the outcome of multiple kidney transplants for an individual is presented. Key issues include surgical approach and immunologic concerns. Included in the surgical approach is an analysis of transplant nephrectomy, with indications, timing, and immunologic impact. Allograft thrombosis, whether related to donor or recipient factors merits investigation to prevent it from happening again. Other posttransplant events such as rejection, viral illness (polyomavirus hominis type I), recurrent disease (focal segmental glomerulosclerosis), and posttransplant lymphoproliferative disease may lead to the need for retransplantation. The pediatric recipient is especially likely to need a subsequent kidney transplant. Finally, noncompliance/nonadherence can affect both adults and children. Innovative approaches may reduce the need for retransplantation in the future.

No Benefit of Prophylactic Surgical Drainage in Combined Liver and Kidney Transplantation: Our Experience and Review of the Literature.

Background: Contrasting results have emerged from limited studies investigating the role of prophylactic surgical drainage in preventing wound morbidity after liver and kidney transplantation. This retrospective study analyzes the use of surgical drain and the incidence of wound complications in combined liver and kidney transplantation (CLKTx). Methods: A total of 55 patients aged ≥18 years were divided into two groups: the drain group (D) (n = 35) and the drain-free group (DF) (n = 20). Discretion to place a drain was based exclusively on surgeon preference. All deceased donor kidneys were connected to the LifePort Renal Preservation Machine® prior to transplantation, in both simultaneous and delayed technique of implantation of the renal allograft. The primary outcome was the development of superficial/deep wound complications during the study follow-up. Secondary outcomes included the development of delayed graft function (DGF) of the transplanted kidney, primary non-function (PNF) and early allograft dysfunction (EAD) of the transplanted liver, graft failure, graft and patient survival, overall post-operative morbidity rate and length of hospital stay. Results: With a median follow-up of 14.4 months after transplant, no difference in the incidence of superficial/deep wound complications, except for hematomas, in collections size, intervention rate, PNF, EAD, graft failure and patient survival, was observed between the 2 groups. Significantly lower level of platelets, higher INR values, DGF, morbidity rates and length of hospital stay were reported post-operatively in the D group. Pre-operative hypoalbuminemia and longer CIT were included in the propensity score for receiving a drain and were associated with a significantly higher rate of developing a hematoma post-transplant. Conclusions: Absence of the surgical drain did not appear to adversely affect wound morbidity compared to the prophylactic use of drains in renal transplant patients during CLKTx.

Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation: A retrospective, single center study.

BACKGROUND: There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount. AIM: To identify risk factors associated with delayed graft function (DGF). METHODS: Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF. RESULTS: The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min. CONCLUSION: We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.

Never events and hospital-acquired conditions after kidney transplant.

INTRODUCTION: Never events (NE) and hospital-acquired conditions (HAC) after surgery have been designated as quality metrics in health-care by the Centres for Medicare and Medicaid Services (CMS). METHODS: The Nationwide Inpatient Sample (NIS) database 2002-2012 was used to identify patientswho underwent kidney transplant. Multivariate analysis using logistic regression was used to identify outcomes and risk factors of HAC and NE after transplantation; however, we were limited by using a retrospective database missing some important variables specified for the kidney transplant, such as some operative factors, donor factors, and cold and warm ischemia times. RESULTS: Among 35 058 patients who underwent kidney transplant, there were 11 NEs, all of which were due to retained foreign bodies. Among HAC after surgery, falling was the most common (44.9%), followed by poor glycemic control (21.7%), vascular catheter-associated infection (21%), and catheter-associated urinary tract infection (8%). HAC and NE after surgery lead to a significant increase in mortality (adjusted odds ratio [AOR] 2.49; p=0.04), hospitalization length (13 vs. 7 days; p<0.01), and total hospital charges ($231 801 vs. $146 717; p<0.01). A significantly higher risk of HAC or NE was seen for patients who had more loss of function before surgey (AOR 3.25; p<0.01) and patients expected to have higher postoperative mortality before operation (AOR 1.62; p=0.03). CONCLUSIONS: Despite the limitations of the study, we found HAC and NE significantly increase mortality, hospitalization length, and total hospital charges of kidney transplant patients. Quality improvement initiatives should target HAC and NE in order to successfully reduce or prevent these events.

A nationwide analysis of re-operation after kidney transplant.

INTRODUCTION: We aimed to report the rate and short-term outcomes of patients undergoing re-operation following kidney transplant in the U.S. METHODS: The Nationwide Inpatient Sample (NIS) database was used to examine the clinical data of patients undergoing kidney transplant and re-operation during same the hospitalization from 2002-2012. Multivariate regression analysis was performed to compare outcomes of patients with and without re-operation. RESULTS: We sampled a total of 35 058 patients who underwent kidney transplant. Of these, 770 (2.2%) had re-operation during the same hospitalization. Re-operation was associated with a significant increase in mortality (30.4% vs. 3%; adjusted odds ratio [AOR] 4.62; p<0.01), mean total hospital charges ($249 425 vs. $145 403; p<0.01), and mean hospitalization length of patients (18 vs. 7 days; p<0.01). The most common day of re-operation was postoperative Day 1. Hemorrhagic complication (64.2%) was the most common reason for re-operation, followed by urinary tract complications (9.9%) and vascular complications (3.6%). Preoperative coagulopathy (AOR 3.35; p<0.01) was the strongest predictor of need for re-operation, hemorrhagic complications (AOR 3.08; p<0.01), and vascular complications (AOR 2.50; p<0.01). Also, hypertension (AOR 1.26; p<0.01) and peripheral vascular disorders (AOR 1.25; p=0.03) had associations with hemorrhagic complications. CONCLUSIONS: Re-operation after kidney transplant most commonly occurs on postoperative Day 1 and occurs in 2.2% of cases. It is associated with significantly increased mortality, hospitalization length, and total hospital charges. Hemorrhage is the most common complication. Preoperative coagulopathy is the strongest factor predicting the need for re-operation, vascular complications, and hemorrhagic complications.

Renal Transplantation in a Patient With Unsuspected Inferior Vena Cava Obliteration.

Vena cava thrombosis can represent a surgical challenge in the context of kidney transplantation. Selection of venous drainage in this setting should provide adequate venous outflow and minimize the risk of thrombosis and subsequent graft failure. We report the case of an adult female patient who presented for a deceased donor kidney transplant with incidental finding of complete inferior vena cava (IVC) and obliteration. After exploration of the retroperitoneal space up to the level of the obliterated IVC, a collateral venous branch was identified at the confluence of the right and left iliac veins. This was utilized as the site of the renal vein venous anastomosis. The patient recovered with immediate graft function. Follow-up ultrasound demonstrated patent vasculature without evidence of thrombosis or outflow obstruction. This report offers a surgical alternative to proceed in the case of an adult with unsuspected caval system obliteration.

Impact of antiretroviral therapy on clinical outcomes in HIV + kidney transplant recipients: Review of 58 cases.

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients.  Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant.  Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01).  Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.