Different outcomes after kidney transplantation between African Americans and Whites: A matter of income? A single-center study.

BACKGROUND: Our center has one of the largest representations of African Americans in listed and transplanted patients. We investigated if and how racial differences affect outcomes in our patient population. METHODS: We performed a retrospective analysis of all kidney transplants in African American and (non-Hispanic) White patients in our center from 1/1/2005 to 12/31/2014. Cox regression was performed to evaluate the adjusted hazard ratios for graft loss. We investigated the influence of socioeconomic status on transplant outcomes. We stratified our patients into three groups based on income: lower (<$50 000 annual household income), medium ($50 000-100 000 annual household income), and higher (>$100 000 annual household income. RESULTS: There were 1333 patients in our study, 696 Whites and 637 African Americans. The 1-, 5-, and 10-year graft survival between the two groups was 96.5% vs 91.1%, 89% vs 80.7%, and 77% vs 66.3%, respectively (P < .001 by Log Rank, Breslow and Taron-Ware). When we compared the two groups separately in each income category, we found no statistical difference between African Americans and Whites in graft survival. In the regression model, income and not race was the significant factor influencing graft survival (P < .001 vs P = .61).

Pre-liver transplant renal dysfunction and association with post-transplant end-stage renal disease: A single-center examination of updated UNOS recommendations.

Simultaneous liver-kidney allocation protocols allocate dual organs based on a sustained eGFR of 30 mL/min or less. A 2017-UNOS update includes CKD3 as dual organ candidates but only when the listing eGFR is <30 mL/min while recommending a "safety net" for prioritized kidney listing post-LT. We retrospectively reviewed adult LTs examine whether the UNOS proposal captured the LT population at highest risk for developing post-LT ESRD. Among 290 LT recipients, 67 had pre-LT CKD3, 141 had AKI, of whom 47 required dialysis (<4 weeks). During follow-up, 25 (8.62%) developed ESRD, while 70 (24.1%) died. In adjusted Cox models, CKD3 had an independent association with post-LT ESRD (adjusted HR 4.8; P = 0.001), independent of AKI. Interestingly, CKD3 with listing GFR >30 mL/min was still significantly associated with post-LT ESRD. AKI was associated with reduced post-LT survival (adjusted HR 1.9; P = 0.02), albeit only in the first-year post-LT. Severe AKI-D was associated with post-LT ESRD and mortality. The safety net would have captured only 60% of all post-LT ESRD cases in our cohort. Pre-LT CKD3 was associated with increased risk of post-LT ESRD above the recommended cutoff for listing GFR. These findings, if generalizable in larger cohorts have important implications for dual organ allocation.

Early conversion to belatacept after renal transplantation.

Belatacept is a non-nephrotoxic immunosuppressive agent, which may make it the ideal agent for patients with delayed or slow graft function on calcineurin inhibitors. There are limited data on conversion of patients to belatacept within 6 months of transplantation. Between January 2012 and December 2015, 16 patients were converted to belatacept for delayed or poor graft function (eGFR<30 mL/min/1.73 m2 , MDRD); three were HIV positive. Conversion protocols were analyzed in patients ≤4 months and 4-6 months post-transplantation. Mean serum creatinine levels after belatacept conversion were compared with preconversion levels. Patient survival was 100%, and graft survival was 88%. The mean creatinine fell from 3.9±1.82 mg/dL prebelatacept conversion to 2.1±1.1 mg/dL at 6 months and 1.9±0.47 mg/dL (median 1.8 mg/dL) at 12 months postconversion. There was no significant increased risk of rejection, infection, or malignancy. HIV parameters remained largely stable. Early conversion to belatacept in patients with DGF or slow graft function is safe and efficacious, in a single-center nonrandomized retrospective analysis.

"Out of Sight, Out of Mind": The Failed Renal Allograft as a Cause of ESA Resistance.

Approximately 10% of patients treated with erythropoiesis-stimulating agents (ESAs) for the anemia of chronic kidney disease are unresponsive or relatively resistant to therapy. The etiology of this is usually linked to iron deficiency or an independent underlying illness. We describe a hemodialysis patient with a failed renal transplant 1.5 years earlier, who developed progressive erythropoietin resistance and anemia without an apparent cause. He simultaneously developed nonspecific malaise and fatigue. By exclusion, the only possible cause of these signs and symptoms was inflammation from acute and chronic rejection in the retained failed renal allograft. Following pulse steroids and transplant nephrectomy, the patient's symptoms resolved and both his hemoglobin improved and his erythropoietin requirements decreased significantly. The patient never required a blood transfusion and was successfully relisted for a deceased donor renal transplant. Hence, inflammation from a retained transplant allograft may be an under-recognized cause of erythropoietin resistance in dialysis patients. Although transplant nephrectomy remains a controversial practice due to concerns of alloantibody production, it may be considered in patients with failed renal allografts and anemia refractory to treatment with ESAs.

Endovascular Repair of Renal Artery Anastomotic Pseudoaneurysm Following Living Donor Kidney Transplant.

Renal artery anastomotic pseudoaneurysms, an uncommon complication of transplantation, may result in aneurysm rupture and loss of allograft. We report the case of 50-year-old female with back pain 3 weeks post renal transplantation. CT scan revealed transplant renal artery anastomotic pseudoaneurysm arising from anastomosis of two renal arteries joined together to form a single renal artery that was joined to the aorta. Successful endovascular treatment was achieved with covered stents, resulting in preserved renal function. Follow-up ultrasound at one-day post procedure and CT at 2 months revealed satisfactory renal perfusion with no pseudoaneurysm. Endovascular treatment of transplant renal artery pseudoaneurysms with covered stent and ostial flare balloon technology may be preferred in patients with extensive prior pelvic surgery, as illustrated in this case.

Hepatitis C and Human Immunodeficiency Virus Kidney Transplantation: The Mount Sinai Experience.

Mount Sinai Hospital in New York has a long history in the field of organ transplantation. The first kidney transplant at Mount Sinai was performed in 1967 by the late Dr. Lewis Burrows and the first laparoscopic donor nephrectomy in New York was performed at Mount Sinai in 1996. Over 3000 kidney transplantations have been performed at Mount Sinai. In the early 1990s, the first hepatitis C virus (HCV) positive patient at Mount Sinai underwent a kidney transplant and the first kidney transplant in a patient with human immunodeficiency virus (HIV) in New York was performed at Mount Sinai in 2001. In general, these patients have done well after renal transplantation, with outcomes similar to those seen in non-infected patients. This chapter will describe the evolution of immunosuppressive regimens in HCV positive and HIV positive patients, and will describe the outcomes of kidney transplantation in these patients. Given the favorable outcomes, it is reasonable to continue to offer renal transplantation as a treatment for end stage renal disease patients with HCV and/or HIV.

Effect of high-dose intravenous immunoglobulin on anti-HLA antibodies in sensitized kidney transplant candidates.

Limited data exist on the effect of intravenous immunoglobulin (IVIg) on anti-HLA antibodies as determined by solid-phase assays. We reviewed our experience treating sensitized wait-listed kidney transplant recipients with IVIg as a method for desensitization and report our results utilizing Luminex single antigen (LSA) bead assay to quantify antibody reactivity (MFI). Fifteen patients with a cPRA > 40% received 2 g/kg IVIg per month for four months or until transplanted. LSA testing was performed before and after IVIg. Median MFI for anti-class I antibodies fell in 11 (73%) and increased in 4 (27%) patients after IVIg. Similar significant changes in MFI for anti-class II antibodies were observed in 10 patients (66%). Administration of IVIg was associated with a modest decrease in reactivity to both class I and II HLA antigens (median MFI change 493 and 1110, respectively; p < 0.0001) but did not significantly alter mean cPRA (85% before IVIg vs. 80% after IVIg; p = 0.1). Our data suggest a smaller effect of IVIg on HLA antibody reactivity than previously described, leading us to question how best to measure the efficacy of a desensitization protocol in current practice.

Identification of urologic complications after kidney transplant.

Urologic complications after kidney transplant are important causes of morbidity, hospitalization, and transplant loss. We report 2 cases of clinically unsuspected urine extravasation after kidney transplant that were diagnosed accurately using SPECT/CT (single-photon emission computed tomography/computed tomography) radionuclide renal scan and corrected using surgery. These cases emphasize the value of dynamic radionuclide renal scan using SPECT/CT in the detection of urologic complications.

Antibodies reactive to non-HLA antigens in transplant glomerulopathy.

Although T and B cell alloimmunity contribute to transplant injury, autoimmunity directed at kidney-expressed, non-HLA antigens may also participate. Because the specificity, prevalence, and importance of antibodies to non-HLA antigens in late allograft injury are poorly characterized, we used a protein microarray to compare antibody repertoires in pre- and post-transplant sera from several cohorts of patients with and without transplant glomerulopathy. Transplantation routinely induced changes in antibody repertoires, but we did not identify any de novo non-HLA antibodies common to patients with transplant glomerulopathy. The screening studies identified three reactivities present before transplantation that persisted after transplant and strongly associated with transplant glomerulopathy. ELISA confirmed that reactivity against peroxisomal-trans-2-enoyl-coA-reductase strongly associated with the development of transplant glomerulopathy in independent validation sets. In addition to providing insight into effects of transplantation on non-HLA antibody repertoires, these results suggest that pretransplant serum antibodies to peroxisomal-trans-2-enoyl-coA-reductase may predict prognosis in kidney transplantation.

The first decade of a laparoscopic donor nephrectomy program: effect of surgeon and institution experience with 512 cases from 1996 to 2006.

BACKGROUND: Although the procedure is generally safe, significant morbidity and even mortality have occurred after laparoscopic donor nephrectomy (LDN). The learning curves for both surgeons and institutions with LDN have not been well delineated, and longterm donor data are not well reported. STUDY DESIGN: A retrospective study of the initial 512 patients undergoing LDN performed at Mount Sinai Medical Center between October 1996 and March 2006 was performed. Intraoperative and immediate postoperative surgical outcomes were reviewed. Univariate analysis and multivariate logistic regressions were performed to identify predictors of outcomes, including the experience level of individual surgeons and of the institution. Longitudinal followup data of donor patients between 1 month and 9 years were obtained. RESULTS: Mean donor age was 39.2 years, and 54.6% of patients were women. Left kidneys were procured in 84.0%. Operative time averaged 215.2 minutes, and warm ischemia time, 166.6 seconds. The conversion rate was 1.4%, and hand-assistance was used in 49.9%. The intraoperative complication rate was 5.5%, 30-day complication rate 9.4%, and 1.4% of patients required reoperation. Immediate graft survival was 97.1%, acute tubular necrosis occurred in 8.5%, and delayed graft function in 3.7%. At a mean followup of 37.2 months, delayed donor complications were infrequent, but included chronic pain, hypertension, incisional hernia, and small bowel obstruction. Although individual surgeons and our institution gained experience, operative and warm ischemia times decreased significantly, but complication rates were unchanged. CONCLUSIONS: Although a learning curve was discovered for operative time and warm ischemia time, excellent results can be achieved during the early experience of both surgeons and institutions with LDN, and maintained over time. Younger, female, and nonobese donors were associated with fewer complications. Longterm donor morbidity is uncommon, but mandates better followup.

Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation.

While studies in animal models have linked Toll-like receptor (TLR) 4 signaling to kidney injury induced by ischemia and reperfusion, the relevance of TLR4 activation to allograft injury in human kidney transplants is unknown. Here we show that TLR4 is constitutively expressed within all donor kidneys but is significantly higher in deceased-, compared with living-donor organs. Tubules from deceased- but not living-donor kidneys also stained positively for high-mobility group box-1 (HMGB1), a known endogenous TLR4 ligand. In vitro stimulation of human tubular cells with HMGB1, in a TLR4-dependent system, confirmed that HMGB1 can stimulate proinflammatory responses through TLR4. To assess the functional significance of TLR4 in human kidney transplantation, we determined whether TLR4 mutations that confer diminished affinity for HMGB1 influence intragraft gene-expression profiles and immediate graft function. Compared with kidneys expressing WT alleles, kidneys with a TLR4 loss-of-function allele contained less TNFalpha, MCP-1, and more heme oxygenase 1 (HO-1), and exhibited a higher rate of immediate graft function. These results represent previously undetected evidence that donor TLR4 contributes to graft inflammation and sterile injury following cold preservation and transplantation in humans. Targeting TLR4 signaling may have value in preventing or treating postischemic acute kidney injury after transplantation.

Addition of plasmapheresis decreases the incidence of acute antibody-mediated rejection in sensitized patients with strong donor-specific antibodies.

BACKGROUND AND OBJECTIVES: The objective of this study was to investigate the effects of desensitization protocols using intravenous Ig with or without plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention of antibody-mediated rejection and downregulation of donor-specific antibodies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty-five complement-dependent cytotoxicity T cell cross-match-negative but complement-dependent cytotoxicity B cell and/or flow cytometry cross-match-positive kidney transplant recipients were treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment. Donor-specific antibody strength was stratified as strong, medium, or weak by Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor-specific antibodies RESULTS: Whereas no group 1 patients had acute rejection, 66% of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular rejection). The protocol was then changed to the addition of peritransplantation plasmapheresis to patients with strong donor-specific antibodies (group 3). This change resulted in a dramatic decrease in the acute rejection rate to 7%. During a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow-up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%) lost some of donor-specific antibodies and/or decreased the strength of existing donor-specific antibodies. CONCLUSIONS: These results indicated that in patients with strong donor-specific antibodies, the addition of plasmapheresis to high-dosage intravenous Ig decreases the incidence of acute rejection. The majority of the patients, whether they received intravenous Ig alone or with plasmapheresis, lost their donor-specific antibodies during follow-up.

Laparoscopic donor nephrectomy: intraoperative safety, immediate morbidity, and delayed complications with 500 cases.

BACKGROUND: Several large series of laparoscopic donor nephrectomy (LDN) have been published, largely focusing on immediate results and short-term complications. The aim of this study was to examine the results of LDN and collect medium-term and long-term donor followup. METHODS: We examined the results of two surgeons who performed 500 consecutive LDNs from 1996 to 2005. Prospective databases were reviewed for both donors and recipients to record demographics, medical history, intraoperative events, and complications. Patients were followed between 1 month and 9 years after surgery to assess for delayed complications, especially hypertension, renal insufficiency, incisional hernia, bowel obstruction, and chronic pain. RESULTS: Left kidneys were procured in 86.2% of cases. Mean operative time was 3.5 h, and warm ischemia time averaged 3.4 min. Hand-assistance was used in 13.8%, and conversion rate was 1.8%. Intraoperative complication rate was 5.8% and was predominantly bleeding (93.1%). Most (86.2%) of the operative complications occurred during the initial 150 cases of a surgeon, compared with 10.3% in the subsequent 150 cases (p = 0.003). Operative time decreased by 87 min after the initial 150 cases (p < 0.001). Immediate graft survival was 97.5%. Delayed graft function occurred in 3.0% of recipients, and acute tubular necrosis occurred in 7.0%. Thirty-day donor complication rate was 9.8%. Mean donor creatinine was 1.24 on the first postoperative day, 1.27 at 2 weeks, and 1.24 at 1 year. At a mean followup of 32.8 months, long-term donor complications consisted of 11 cases of hypertension, 9 cases of prolonged pain or paresthesia, 2 incisional hernias, 1 small bowel obstruction requiring laparoscopic lysis of adhesions, and 1 hydrocele requiring repair. CONCLUSIONS: LDN can be performed with acceptable immediate morbidity and excellent graft function. Operative time and complications decreased significantly after a surgeon performed 150 cases. Long-term complications were uncommon but included a likely underestimated incidence of hypertension.

CryoPlasty therapy of the superficial femoral and popliteal arteries: a single center experience.

Long-term patency remains a significant hurdle in the minimally invasive treatment of arteriosclerosis in the superficial femoral and popliteal arteries. New technologies designed to address the sources of restenosis have recently been introduced. CryoPlasty therapy (Boston Scientific, Natick, Mass) is a new approach designed to significantly reduce injury, elastic recoil, stent implantation, neointimal hyperplasia, and constrictive remodeling. The technique combines the dilatation forces of percutaneous transluminal angioplasty with cold thermal energy applied to the plaque and vessel wall. The cumulative effect of limiting the sources of restenosis with CryoPlasty therapy was shown to demonstrate longer term patency in a prospective, multicenter, Investigational Device Exemption study of the PolarCath Peripheral Dilatation System. The CryoPlasty therapy experience of 1 center is reported, in which 47 lesions in 32 consecutive patients (34 procedures, 33 limbs) were treated. The technical success rate was 96%. There were no type 3 flow-limiting dissections, and only 4 (8.5%) lesions were stented. There were no unanticipated adverse events, specifically no thrombus, acute occlusions, distal embolizations, aneurysms, or groin complications. With an average follow-up of 12 months, only 5 lesions have recurred, 4 requiring re-intervention. The 12-month freedom from restenosis for lesions and limbs treated was 82.2% and 84.4%, respectively. These results are similar to the findings of the Investigational Device Exemption study and are encouraging. CryoPlasty therapy appears to be a viable endovascular therapeutic option to achieve longer term patency without compromising options for future interventions. The lack of early occlusions may be due to a low rate of spiral dissection that may be a particular benefit of this form of angioplasty.

Safety of using hepatitis B virus core antibody or surface antigen-positive donors in kidney or pancreas transplantation.

Hepatitis B virus core antibody (HBcAb) or surface antigen (HBsAg)-positive organ donors have the potential to transmit infection to transplant recipients. We investigated the safety of using HBcAb(+) or HBsAg(+) donors in kidney or pancreas transplant recipients with 1 yr lamivudine prophylaxis. While HBsAb(-) recipients of HBcAb(+) donors received prophylaxis, HBsAb(+) recipients did not. HBsAg(+) organs were only used in patients who were both HBcAb and HBsAb(+). Forty-six patients received HBcAb(+) and four received HBsAg(+) organs (47 kidney, two pancreas, and one kidney/pancreas). All but one recipient were HBsAg(-), 25 were HBsAb(+), and 19 HBcAb(+). During a median 36 months of follow-up (range 6-66 months), with 43 of a total 50 patients having at least 1 yr follow-up and were off lamivudine, and none of the patients developed hepatitis B viremia or seroconversion to HBsAg or HBsAb(+). These results suggest that HBcAb(+) or HBsAg(+) organs can be used safely in selected recipients with lamivudine prophylaxis without requiring hepatitis B immunglobulin.

Pre-donation assessment of kidneys by magnetic resonance angiography and venography: accuracy and impact on outcomes.

Reports on the accuracy of magnetic resonance angiography (MRA) and magnetic resonance venography (MRV) in evaluating living donor renovasculature employ few patients or omit the consequences of inaccurate scans. We retrospectively compared intraoperative findings to MRA/MRV scans in 146 donor-recipient pairs. For detecting accessory arteries and early branching, MRA sensitivity was 57.6%, specificity 96.5%, false positive rate 3.5%, false negative rate 42.4%, positive predictive value 82.6%, negative predictive value 88.6% and overall accuracy 87.7%. By excluding clinically inconsequential accessory arteries, MRA sensitivity rose to 73.1%, specificity to 96.7% and overall accuracy to 92.5%. For MRVs, sensitivity was 56.2%, specificity 99%, false positive rate 1%, false negative rate 43.8%, positive predictive value 90%, negative predictive value 94.8% and accuracy 94.5%. Inaccurate scans were associated with prolonged donor and recipient operations and more frequently reconstructed arteries, but did not affect clinical outcomes. Because most missed accessory arteries are inconsequential, MRA is a useful, less invasive method for defining donor renovascular anatomy.