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Background Transplantation of African American (AA) compared to non-AA donor kidneys is generally associated with inferior outcomes. It is unclear whether enhanced genetic risk associated with AA donor kidneys would be counterbalanced by favorable immunologic matching when AA donor kidneys are transplanted into AA recipients. We aimed to compare the outcomes of AA vs non-AA deceased-donor kidneys (DDKs) stratified by kidney donor profile index (KDPI) that were transplanted into AA recipients. Methods Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified AA DDK recipients from 2000 to 2015 who received peri-operative induction followed by calcineurin inhibitor/mycophenolate mofetil maintenance. These patients were divided into 4 KDPI groups (0%-20%, 21%-50%, 51%-85%, and 86%-100%). Adjusted long-term graft and patient outcomes were compared between AA recipients of kidneys from AA vs non-AA donors in each KDPI category using a multivariable Cox model. Results Among a total of 17,516 AA DDK transplant recipients, 3303 were in KDPI 0%-20% (AA donor = 239; non-AA donor = 3064), 5821 in KDPI 21%-50% (AA donor = 1414; non-AA donor = 4407), 6364 in KDPI 51%-85% (AA donor = 1619; non-AA donor = 4745), and 2028 in KDPI 86%-100% (AA donor = 932; non-AA donor = 1096) groups. Adjusted overall graft, death-censored graft, and patient survival were similar between AA recipients of AA vs non-AA donor kidneys across all KDPI groups. Discussion Our study showed similar outcomes for transplanting AA vs non-AA deceased-donor kidneys into AA recipients despite the generally observed inferior outcomes associated with AA donor kidney transplantation.

Objectives Risk of kidney disease is heightened in African American individuals. African American donor ethnicity is one of 10 risk factors in calculating the kidney donor profile index used in assessing organ quality. We aimed to evaluate outcomes of deceased-donor kidney transplants from African American donors stratified by kidney donor profile index. Materials and methods Using the Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified deceased-donor kidney transplant recipients from 2000 to 2015 who received induction and calcineurin inhibitor/mycophenolic acid maintenance. Patients were divided into 4 kidney donor profile index groups (0%-20%, 21%-50%, 51%-85%, and > 85%). Long-term outcomes of each group were compared between African American and non-African American kidney donations using Cox model. Results Among 59 648 patients, 15 250 were in the 0% to 20% group (560 African American donors, 14 690 non-African American donors), 19 355 were in the 21% to 50% group (2807 African American donors, 16 548 non-African American donors), 19 412 were in the 51% to 85% group (2774 African American donors, 16 638 non-African American donors), and 5631 were in the > 85% group (1670 African American donors, 3961 non-African American donors). Adjusted overall and death-censored graft failure risks were higher for recipients of African American donor kidneys in the 51% to 85% (hazard ratio 1.12; 95% confidence interval, 1.01-1.25; P = .009 and hazard ratio 1.12; 95% confidence interval, 1.01-1.25; P = .03) and the > 85% kidney donor profile index (hazard ratio 1.12; 95% confidence interval, 1.04-1.24; P = .025 and hazard ratio 1.33; 95% confidence interval, 1.16-1.51; P Conclusions Inferior graft outcomes in recipients of African American kidneys in our study were limited to those with > 50% kidney donor profile index. Effects of risk factors such as APOL1 risk alleles and sickle cell trait on these observations need further study.

Acute kidney injury is a heterogeneous syndrome defined by rapid (hours to days) decline in the glomerular filtration rate leading to retention of metabolic waste products including creatinine and urea, resulting in declination of the body's ability to manage fluid status and acid-base regulation. Acute kidney injury is seen commonly in acute respiratory distress syndrome and this article will explore the relationship between the 2 entities.

Rationale & Objective The impact of extreme recipient obesity on long-term kidney transplant outcomes has been controversial. This study sought to evaluate the association of various levels of recipient obesity on kidney transplantation outcomes by comparing mate-kidney recipient pairs to address possible confounding effects of donor characteristics on posttransplant outcomes. Study Design Nationwide observational cohort study using mate-kidney models. Setting & Participants In analysis based on the Organ Procurement and Transplant Network/United Network of Organ Sharing database, 44,560 adult recipients of first-time deceased-donor kidney transplants from 2001 through 2016 were paired by donor. Predictors Recipient body mass index (BMI) categorized as 18-25 (n = 12,446), >25-30 (n = 15,477), >30-35 (n = 11,144; obese), and >35 (n = 5,493; extreme obesity) kg/m2. Outcomes Outcomes included patient survival, graft survival, death-censored graft survival, delayed graft function (DGF), and hospital length of stay. Analytical Approach Conditional logistic regression and stratified proportional hazards models were used to compare outcomes as odds ratios and hazard ratios (HRs), adjusted for recipient and transplant factors, using recipients with a BMI >35 kg/m2 as a reference. Results At a median follow-up of 3.9 years, adjusted odds ratios for DGF were 0.42 (95% CI, 0.36-0.48), 0.55 (95% CI, 0.48-0.62), and 0.73 (95% CI, 0.64-0.83) for BMI 18-25, >25-30, and >30-35 kg/m2, respectively (P 25-30 kg/m2 (HRs of 0.66 [95% CI, 0.59-0.74] and 0.79 [95% CI, 0.70-0.88], respectively; P 30-35 kg/m2 (HR, 0.91 [95% CI, 0.81-1.02]; P = 0.09). Length of stay and patient survival did not differ by recipient BMI. Limitations Observational study with limited detail regarding potential confounders. Conclusions Despite an increased risk of DGF likely unrelated to donor organ quality, long-term transplant outcomes among recipients with a BMI >35 kg/m2 are similar to those among recipients with a BMI >30-35 kg/m2, supporting a flexible approach to kidney transplantation candidacy in candidates with extreme obesity.

Vaccine preventable diseases account for a significant proportion of morbidity and mortality in transplant recipients and cause adverse outcomes to the patient and allograft. Patients should be screened for vaccination history at the time of pre-transplant evaluation and vaccinated at least four weeks prior to transplantation. For non-immune patients, dead-vaccines can be administered starting at six months post-transplant. Live attenuated vaccines are contraindicated after transplant due to concern for infectious complications from the vaccine and every effort should be made to vaccinate prior to transplant. Since transplant recipients are on life-long immunosuppression, these patients may have lower rates of serological conversion, lower mean antibody titers and waning of protective immunity over shorter period as compared to general population. Recommendations regarding booster dose in kidney transplant recipients with sub-optimal serological response are lacking. Travel plans should be part of routine post-transplant assessment and pre-travel vaccines and counseling should be provided. More studies are needed on vaccination schedules, serological response, need for booster doses and safety of live attenuated vaccines in this special population.

Kidney transplantation in older recipients: Preemptive high KDPI kidney vs lower KDPI kidney after varying dialysis vintage

BACKGROUND Pediatric en bloc kidneys are considered marginal for transplantation into adults. We aimed to compare the long-term outcomes of pediatric en bloc versus living donor kidney transplantation. METHODS A retrospective review was undertaken on pediatric en bloc and living donor kidney transplants performed at our center between 1990 and 2001. The outcomes compared between the groups included 25 year graft survival and longitudinal glomerular filtration rate. RESULTS There were 72 pediatric en bloc and 75 living donor kidney recipients included in the analysis. Pediatric donors were 16.9 ± 11.2 months old and weighed 10.7 ± 3.8 kg with terminal serum creatinine of 0.50 ± 0.45 mg/dL. Living donors were 40.1 ± 9.4 years old and serum creatinine was 0.90 ± 0.16 mg/dL at the time of donation. En bloc kidney recipients had higher dialysis vintage (23.0 ± 29.2 months vs 14.3 ± 14.7 months; P = 0.03), and longer cold ischemia time (30.5 ± 9.8 hours vs 2.6 ± 0.9 hours, P < 0.001). Kaplan-Meier estimate revealed similar graft survival between the groups up to 27 years of follow up (log rank P = 0.78). Estimated glomerular filtration rate was significantly higher in pediatric en bloc kidney recipients from years 5 through 17 posttransplantation. CONCLUSIONS Pediatric en bloc kidneys conferred long-term graft survival similar to living donor kidneys over a 25-year period after transplantation along with superior graft function. These findings support improved utilization of pediatric kidneys for transplantation into adults which not only helps to alleviate organ shortage but also provide excellent long-term function.

The new kidney allocation system recommends local and regional sharing of deceased donor kidneys (DDK) with 86-100% Kidney Donor Profile Index (KDPI) to minimize discard. Regional sharing can increase cold ischemia time (CIT) which may negatively impact transplant outcomes. Using a same donor mate kidney model, we aimed to define a CIT that should be targeted to optimize outcomes. Using Organ Procurement and Transplant Network/United Network for Organ Sharing database, we identified recipients of DDK from 2000 to 2013 with ≥85% KDPI. From this cohort, three groups of mate kidney recipients were identified based on CIT: group 1 (≥24 vs. ≥12 to

Background: Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a newly described and rare entity that can develop in native and very rarely in transplanted kidneys. We present a patient who developed de novo PGNMID in the kidney allograft along with a review of the literature. Case Presentation: A 38-year old female with type 1 diabetes who underwent successful simultaneous pancreas-kidney (SPK) transplantation 6 years earlier presented with rising serum creatinine, nephrotic range proteinuria and microhematuria. She underwent extensive work up and kidney allograft biopsy revealed mesangial expansion and hypercelluarity on light microscopy, mesangial staining for IgG3, kappa light chains, C1q and C3 on immunofluorescence and abundant mesangial electron dense deposits without substructures on electron microscopy. Serum and urine immunofixation electrophoresis were negative. A diagnosis of de novo PGNMID was made. Patient’s proteinuria improved and serum creatinine stabilized with conservative therapy. Conclusions: PGNMID can rarely develop in kidney allograft as recurrent or de novo disease and may be mislabeled as transplant glomerulopathy if careful immunofluorescence and electron microscopy are not performed on biopsy specimens. Further studies are needed to better understand the pathogenesis of this disease entity and to develop optimal therapeutic approaches.

Background In kidney transplantation, donor recipient human leukocyte antigen (HLA)-DR mismatch signals high immunologic risk and portends inferior outcomes. We compared the impacts of depleting vs non-depleting antibody induction on the outcomes in kidney transplant recipients (KTRs) at different levels of HLA-DR mismatches. Methods Using the Organ Procurement and Transplantation Network/United Network for Organ Sharing database, we identified adult KTRs from 2001 to 2015 who received induction therapy with either depleting (thymoglobulin/alemtuzumab) or non-depleting (basiliximab/daclizumab) antibody and were discharged on calcineurin inhibitor/mycophenolic acid maintenance. Patients were then stratified by the number of donor-recipient HLA-DR mismatches (0, 1, 2) in both living donor (LD) and deceased donor (DD) KTRs. Under each HLA-DR mismatch category, long-term outcomes were compared for depleting vs non-depleting induction using a Cox model. Results A total of 63,821 LD (HLA-DR mismatches: 0, n = 6945 [depleting = 4409, non-depleting = 2536]; 1, n = 19,557 [depleting = 13,558, non-depleting = 6019]; and 2, n = 10,727 [depleting = 7694, non-depleting = 3033]) and 64,922 DD (HLA-DR mismatches: 0, n = 13,915 [depleting = 10,124, non-depleting = 3791]; 1, n = 27,994 [depleting = 20,454, non-depleting = 7540]; and 2, n = 23,013 [depleting = 16,908, non-depleting = 6105]) KTRs were included in the analysis. Adjusted patient death risk was significantly lower in the depleting vs non-depleting antibody induction group among DD kidney recipients (hazard ratio 0.90, 95% CI 0.85–0.96, P = .001) and trended lower among LD kidney recipients (HR 0.88, 95% 0.79–1.01, P = .05) with 2 HLA-DR mismatches. Discussion Our study found a patient survival benefit associated with the use of perioperative induction with depleting when compared to non-depleting antibody in KTRs with 2 HLA-DR mismatches and maintained on a calcineurin inhibitor/mycophenolic acid regimen.

We aimed to evaluate the impact of induction on outcomes in low-immunological risk kidney transplant recipients (KTRs) using a mate-kidney model. Using OPTN/UNOS database, we identified three groups of low-immunological risk KTRs (first transplant, panel reactive antibody

Objectives Immunosuppressive therapy in kidney transplant recipients with hepatitis B virus infection may increase the risk of disease progression. Here, we compared outcomes of depleting (antithymocyte globulin/alemtuzumab) versus nondepleting (basiliximab/daclizumab) antibody induction in kidney transplant recipients at different serologic phases of hepatitis B virus infection. Materials and methods We used the Organ Procurement and Transplantation Network/United Network for Organ Sharing database to identify adult kidney transplant recipients at different serologic phases of hepatitis B virus infection (transplants received from 2001-2011 after patients received perioperative induction with discharge on calcineurin inhibitors/mycophenolate mofetil with/without steroids). We used a Cox model to compare outcomes among patient groups. Results Median follow-up was 50.7 months (range, 28.6 to 82.6 mo). Serologic phase for the 7681 study patients were as follows: 1098 at HBsAg+/anti-HBc- (depleting = 652, nondepleting = 446), 446 at HBsAg+/anti-HBc+ (depleting = 250, nondepleting = 216), and 6117 at HBsAg-/anti-HBc+ (depleting = 3562, nondepleting = 2555) (where anti-HBc denotes hepatitis B core antibody, HBsAg denotes hepatitis B surface antigen, and +/- denote positive/negative). When we compared those with depleting versus nondepleting agents, hazard ratios (95% confidence intervals) for adjusted overall graft, death-censored graft, and patient survival were 0.97 (0.78-1.26; P = .86), 1.20 (0.83-1.60; P = .44), and 0.92 (0.66-1.30; P = .51) in the HBsAg+/anti-HBc-; 0.81 (0.55-1.18; P = .27), 0.59 (0.32-1.12; P = .11), and 0.95 (0.60-1.49; P = .83) in the HBsAg+/anti-HBc+; and 0.96 (0.86-1.05; P = .37), 0.95 (0.60-1.49; P = .97), and 0.92 (0.80-1.05; P = 0.22) in the HBsAg-/anti-HBc+ groups. Conclusions Our study did not show adverse graft and patient outcomes associated with depleting versus nondepleting antibody induction in kidney transplant recipients at different phases of hepatitis B virus infection. This supports the selection and use of induction agents based on immunologic risk in such patients.

AIM To evaluate the outcomes of transplanting marginal kidneys preemptively compared to better-quality kidneys after varying dialysis vintage in older recipients. METHODS Using OPTN/United Network for Organ Sharing database from 2001-2015, we identified deceased donor kidney (DDK) transplant recipients > 60 years of age who either underwent preemptive transplantation of kidneys with kidney donor profile index (KDPI) ≥ 85% (marginal kidneys) or received kidneys with KDPI of 35%-84% (better quality kidneys that older wait-listed patients would likely receive if waited longer) after being on dialysis for either 1-4 or 4-8 years. Using a multivariate Cox model adjusting for donor, recipient and transplant related factors- overall and death-censored graft failure risks along with patient death risk of preemptive transplant recipients were compared to transplant recipients in the 1-4 and 4-8 year dialysis vintage groups. RESUTLS The median follow up for the whole group was 37 mo (interquartile range of 57 mo). A total of 6110 DDK transplant recipients above the age of 60 years identified during the study period were found to be eligible to be included in the analysis. Among these patients 350 received preemptive transplantation of kidneys with KDPI ≥ 85. The remaining patients underwent transplantation of better quality kidneys with KDPI 35-84% after being on maintenance dialysis for either 1-4 years (n = 3300) or 4-8 years (n = 2460). Adjusted overall graft failure risk and death-censored graft failure risk in preemptive high KDPI kidney recipients were similar when compared to group that received lower KDPI kidney after being on maintenance dialysis for either 1-4 years (HR 1.01, 95%CI: 0.90-1.14, P = 0.84 and HR 0.96, 95%CI: 0.79-1.16, P = 0.66 respectively) or 4-8 years (HR 0.82, 95%CI: 0.63-1.07, P = 0.15 and HR 0.81, 95%CI: 0.52-1.25, P = 0.33 respectively). Adjusted patient death risk in preemptive high KDPI kidney recipients were similar when compared to groups that received lower KDPI kidney after being on maintenance dialysis for 1-4 years (HR 0.99, 95%CI: 0.87-1.12, P = 0.89) but lower compared to patients who were on dialysis for 4-8 years (HR 0.74, 95%CI: 0.56-0.98, P = 0.037). CONCLUSION In summary, our study supports accepting a “marginal” quality high KDPI kidney preemptively in older wait-listed patients thus avoiding dialysis exposure.

Adoption of the model for end-stage liver disease score by Organ Procurement and Transplant Network (OPTN) deceased donor liver allocation policy in 2002 has led to an increase in the number of simultaneous liver kidney (SLK) transplantation. Since kidney function recovery following liver transplantation is difficult to predict, allocation of the kidney for SLK transplantation thus far has not been based on much rationale and evidence. Lack of OPTN policy towards SLK organ allocation has resulted in great variations among transplant centers regarding SLK transplantation. Increasing use of kidneys towards SLK transplantation diverts deceased donor kidneys away from candidates awaiting kidney-alone transplantation. Recently OPTN/United Network of Organ Sharing has implemented medical eligibility criteria for adult SLK transplantation which also includes a concept of safety net. Implementation of the new policy is a move in a positive direction, providing consistency in our practice and evidence-based guidelines in selecting candidates for SLK transplantation. This policy needs to be monitored prospectively and modified based on new data that will emerge over time. This review outlines the literature on SLK transplantation and efforts towards developing rational policy on SLK organ allocation.

BACKGROUND Induction immunosuppression decreases the risk for acute rejection and improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the outcomes of induction with Thymoglobulin and alemtuzumab in KTRs through paired-kidney analysis. METHODS Using Organ Procurement and Transplantation Network/United Network for Organ Sharing database from 2003 to 2013, we identified recipients of deceased donor kidneys from the same donor in such a way that 1 patient received Thymoglobulin induction and recipient of the mate kidney underwent alemtuzumab induction. All patients were discharged on maintenance immunosuppression with tacrolimus and mycophenolate mofetil with/without steroids. Outcomes were compared between the groups in an adjusted model. RESULTS Study cohort included 1149 patients each in alemtuzumab and Thymoglobulin groups. Incidence of delayed graft function (25.8% vs 28.6%, P = 0.12), and 1-year rejection (5.7% vs 4.5%, P = 0.97) were similar for alemtuzumab versus Thymoglobulin groups. Adjusted overall graft (hazard ratio, 0.97; 95% confidence interval, 0.82-1.48; P = 0.52) and patient (hazard ratio, 0.86; 95% confidence interval, 0.69-1.05) survivals were also similar for alemtuzumab versus Thymoglobulin groups. Median hospital length of stay was significantly shorter in alemtuzumab group (4 days vs 5 days, P < 0.001). Similar findings were observed in a subgroup of high immune risk patients. There was evidence for clustering of alemtuzumab use within transplant centers which did not impact long-term outcomes. CONCLUSIONS Depleting antibody induction therapy with alemtuzumab and Thymoglobulin appear equally effective in deceased donor KTRs maintained on tacrolimus/mycophenolate mofetil-based regimen along with steroid. Alemtuzumab induction is beneficial in reducing hospital length of stay.

The influence of steroid maintenance on the outcomes of repeat kidney transplant (RKT) recipients with respect to induction type is unclear. Using the Organ Procurement and Transplant Network/United Network of Organ Sharing (OPTN/UNOS) database, we identified patients (≥18 years) who underwent deceased donor RKT from January 2000 to December 2008 after receiving induction with rabbit-antithymocyte globulin (r-ATG), alemtuzumab or an IL-2 receptor blocker (IL-2B) and were discharged on a calcineurin inhibitor/mycophenolate mofetil regimen with or without steroids. Of 5634 patients, 3643 received r-ATG (steroid = 3157, no-steroid = 486), 448 alemtuzumab (steroid = 196, no-steroid = 252) and 1543 an IL-2B (steroid = 1465, no-steroid = 78). Unadjusted graft survivals were similar for the no-steroid versus steroid groups for induction with r-ATG [hazard ratio (HR) 0.85 and 95% confidence interval (95% CI) 0.70-1.03, P = 0.10], alemtuzumab (HR 0.76, 95% CI 0.51-1.14, P = 0.18) and IL-2B (HR 0.77, 95% CI 0.56-1.70, P = 0.23). In the adjusted model, steroid use improved graft survival in alem­tuzumab (HR 0.44, 95% CI 0.25-0.76, P = 0.003) but not in the r-ATG (HR 0.86, 95% CI 0.68-1.09, P = 0.21) or IL-2B (HR 0.98, 95% CI 0.56-1.70, P = 0.94) groups. Steroid use was asso­ciated with inferior patient survival in unadjusted (HR 1.30, 95% CI 1.17-1.44, P

Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV(+) donors to HIV(+) recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV(+) to HIV(+) kidney transplant in the United States and the first HIV(+) to HIV(+) liver transplant in the world were recently performed at the Johns Hopkins University Medical Center.

This study explored the safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants.Using the Organ Procurement and Transplant Network-United Network of Organ Sharing database, we identified patients who underwent expanded criteria deceased-donor kidney transplant between January 2000 and December 2008 after receiving induction with rabbit-antithymocyte globulin (n = 3717), alemtuzumab (n = 763), or interleukin 2 blocking agent (n = 2600) followed by calcineurin inhibitor and mycophenolate mofetil-based maintenance with and without steroid therapy.Adjusted overall graft survival (hazard ratio 1.32; 95% confidence interval, 1.1-1.56; P = .002) and patient survival (hazard ratio 1.46, 95% confidence interval, 1.16-1.83, P = .001) were inferior, whereas death-censored graft survival (hazard ratio 1.13; 95% confidence interval, 0.87-1.47; P = .35) was similar for chronic steroid maintenance versus early steroid withdrawal groups in rabbit-antithymocyte globulin-induced patients. Graft and patient outcomes were similar for chronic steroid maintenance versus early steroid withdrawal groups among alemtuzumab and interleukin 2 blocking agent-induced patients. Among rabbit-antithymocyte globulin-induced patients, adjusted overall graft survival (hazard ratio 1.57; 95% confidence interval, 1.2-2.0; P.001) and patient survival (hazard ratio 1.5; 95% CI, 1.15-2.1; P = .004) were inferior, whereas death-censored graft survival (hazard ratio 1.5; 95% confidence interval, 0.97-2.43; P = .07) trended inferior for chronic steroid maintenance versus early steroid withdrawal groups in recipients60 years old (n = 1729).Our study showed safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants who underwent perioperative induction followed by calcineurin inhibitor and mycophenolate mofetil maintenance. Among rabbit-antithymocyte globulin-induced patients, chronic steroid maintenance was associated with inferior graft and patient outcomes, an effect limited to older recipients.

Antibody-mediated rejection (AMR) following renal transplantation is less responsive to conventional anti-rejection therapies. Plasmapheresis (PP), intravenous immunoglobulin (IVIg), rabbit antithymocyte globulin (rATG) and rituximab deplete immature B-cells but not mature plasma cells. The proteasome inhibitor bortezomib has activity against mature plasma cell, the source of damaging donor-specific antibody (DSA).We present the successful use of bortezomib in 2 patients who developed AMR following kidney transplantation. The first patient was a 54-year-old white female who received living-unrelated kidney transplantation from her husband. She developed severe AMR early after transplantation with rising DSA titers consistent with an anamnestic immune response by memory cells to the donor antigens. Renal function deteriorated despite treatment with pulse methylprednisolone (MP), PP and IVIg. After initiation of therapy with bortezomib, DSA titers became negative and serum creatinine returned to baseline with histological resolution of AMR. The second patient was a 19-year-old white male who received deceased donor kidney transplantation and developed AMR within 2 weeks, refractory to therapy with pulse MP, PP and IVIg with rising DSA. Bortezomib use resulted in disappearance of DSA and renal function improvement. Both patients tolerated the treatment well with stable renal function at last follow-up. The novel mechanisms of action and preliminary results with bortezomib are encouraging, but require larger studies and longer follow-up.

Acute antibody-mediated rejection (AMR) in renal-transplant recipients is generally less responsive to conventional antirejection therapy and has a worse prognosis than acute cellular rejection.This review provides a broad understanding of the pathogenesis of AMR, recent advances in its therapy, and future directions. Conventional therapeutic approaches to AMR have minimal impact on mature plasma cells, the major source of antibody production. Emerging therapies include bortezomib, a proteasome inhibitor, and eculizumab, an anti-C5 antibody. In several reports, bortezomib therapy resulted in prompt reversal of rejection, decreased titers of donor-specific antibodies (DSA), and improved renal allograft function. Eculizumab also reversed AMR and prevented its development in patients with high post-transplantation DSA levels.Despite the small sample size and lack of controls, these studies are encouraging, and although larger studies and long-term follow-up are needed, bortezomib and eculizumab may play a major future role in AMR therapy.

Background: Biofilms are bacterial communities ubiquitous to moist environments. Biofilm formation is a factor in the development and persistence of infectious diseases. In clinical nephrology, biofilms influence the development of kidney stones and affect dialysis systems, including peritoneal and central venous catheters. Biofilms also play critical roles in persistent and resistant renal and urinary tract infections. Objective: To describe the physiology of biofilms and potential effects of biofilms upon infectious diseases, focusing on the role of biofilms in kidney stones, indwelling catheters and dialysis equipment. Methods: A literature search with Medline to identify pertinent English language articles published up to early 2008 using the keywords biofilm, nephrology, renal, calculi and infection. Results/conclusion: Biofilms are ubiquitous in clinical nephrology and play a role in the pathogenesis of resistant infections. Strategies for reducing the effects of biofilms in nephrology are described.

Background: Aliskiren, the first renin inhibitor with sufficient bioavailability for oral use, is now available to clinicians treating hypertension. Objective: The novel mechanism by which aliskiren works was used to provide understanding of its therapeutic and adverse effects. Methods: After reviewing physiology and preclinical studies, human studies of aliskiren in hypertension were reviewed. Effects of aliskiren on serum levels and enzymatic activity of renin were explored. Results/conclusions: Aliskiren has antihypertensive efficacy similar to existing medications such as thiazide diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and can be used in drug combinations. Preclinical studies indicate possible cardioprotective and renoprotective effects, similar to other inhibitors of the renin–angiotensin cascade, but future studies are needed in humans.

Hyponatremia is a common and potentially serious electrolyte disorder, most often caused by excessive arginine vasopressin (AVP) secretion. Conventional management of hyponatremia is based on graded steps starting from water restriction in mild cases to administration of saline in symptomatic cases, which may not be effective. A major new approach in the treatment of hyponatremia is the development of AVP receptor antagonists that directly inhibit the effect of increased AVP which results in the excretion of electrolyte free water. This review summarizes pathophysiology, conventional treatment and future directions in the treatment of hyponatremia.

Antibody-mediated rejection (AMR) accounts for 20 – 30% of all acute rejection episodes following renal transplantation. AMR is generally less responsive to conventional anti-rejection therapy, resulting in poor allograft survival. Introduction of C4d immunostaining of renal allograft biopsies and the demonstration of donor-specific antibodies in the recipients have increased our ability to diagnose AMR. Therapeutic options are evolving and include plasmapheresis, intravenous immunoglobulin, immunoadsorption and rituximab, together with intensification of immunosuppression with a tacrolimus/mycophenolate mofetil combination. Future studies might further define optimal therapeutic approach in renal transplant recipients presenting with AMR.

Background: Microvascular thrombosis is an uncommon pathologic finding in cadaveric kidneys. It is associated with disseminated intravascular coagulation most frequently associated with head injuries and massive blood transfusions. The high rate of non-function published in the literature portends an ominous significance for transplanted organs, which have been discarded by many transplant centers. Methods: In this report, we document the effectiveness of ex vivo thrombolytic therapy with activase®, a plasminogen activator, injected intra-arterially in 12 kidneys with extensive histologic intraglomerular microvascular thrombosis prior to transplantation. All cold stored cadaveric kidneys were flushed for 50 min with 50 mg of activase® diluted in University of Wisconsin solution. Pre-flush and post-flush wedge biopsies were performed on the allografts. Results: All biopsies showed complete resolution of the intraglomerular microthrombi following activase® flush. One kidney clotted in the third week. Three patients developed delayed graft function (25%) of which one experienced allograft thrombosis following one month after transplantation. All remaining grafts are still functioning at a mean follow up of 55.1 months (range: 23–71) with a mean serum creatinine of 1.8 mg/dL (range: 0.8–2.5). Conclusions: Back table flush with activase® rapidly lyses severe intraglomerular microthrombi making them successfully transplantable. Pre-treatment with activase seems to be an effective therapeutic intervention for kidneys with massive intraglomerular thrombosis.

UNLABELLED: Quality of life (QOL) should be an important consideration while choosing therapeutic options for patients with type 1 diabetes mellitus (DM) and end-stage renal disease (ESRD) including dialysis, cadaver (CKT) or living kidney transplant (LKT) or simultaneous pancreas-kidney (SPK) transplant. METHODS: QOL was assessed in four groups of patients with history of type 1 DM and ESRD: recipients of SPK (n = 43), CKT (n = 43), LKT (n = 11) and wait listed (WL) patients (n = 23). Diabetes Quality of Life (DQOL), Short Form-36 (SF-36) and Quality of Well-Being (QWB) questionnaires were utilized. A subset of SPK (n = 19) and CKT (n = 12) recipients underwent longitudinal QOL evaluation. RESULTS: On DQOL questionnaire, SPK group had better satisfaction subscore compared with CKT (1.8 +/- 0.5 vs. 2.2 +/- 0.6, p < 0.01) LKT (1.8 +/- 0.5 vs. 2.4 +/- 0.7, p < 0.05) and WL (1.8 +/- 0.5 vs. 2.6 +/- 0.6, p < 0.001) groups and better impact subscore compared with CKT (1.7 +/- 0.6 vs. 2.1 +/- 0.6, p < 0.05) and WL (1.7 +/- 0.6 vs. 2.3 +/- 0.6, p < 0.01) groups. There were no significant differences on physical/mental composite scores of SF-36. QWB score was better in SPK group vs. WL group (0.62 +/- 0.11 vs. 0.55 +/- 0.04, p < 0.05). Longitudinal decline in satisfaction (2.3 +/- 0.5 vs. 2.6 +/- 0.9, p = 0.058) and impact (2.0 +/- 0.5 vs. 2.2 +/- 0.5, p = 0.019) subscores of DQOL were noted in CKT group. There were no significant changes in the composite scores of SF-36 in both groups. QWB scores declined in the CKT group (0.67 +/- 0.10 vs. 0.61 +/- 0.05, p = 0.01). CONCLUSION: QOL was better in type 1 diabetics with ESRD following transplantation when compared with remaining on WL. SPK transplantation had significant positive effect on diabetes-related QOL which was sustained longitudinally but it was difficult to show an overall improvement in general QOL.

Background The effect of induction agents on kidney transplant outcomes with respect to race is not well studied. We aimed to compare the outcomes of deceased donor kidney (DDK) transplants in African American (AA) and non-African American (non-AA) recipients who underwent induction therapy with rabbit-antithymoglobulin (rATG), alemtuzumab (ALE), or interleukin (IL)-2 receptor blocker (IL-2B) and were maintained on a calcineurin inhibitor, (CNI)/mycophenolate mofetil (MMF)–based regimen with/without steroid. Methods Using OPTN/UNOS database, we identified patients (≥18 years) who underwent DDK transplants from January 2000 to December 2008 and received rATG ( n = 21,506), ALE ( n = 3476), or IL- 2B ( n = 17,869) and were maintained on a CNI/MMF–based regimen with/without steroids. Multivariate analysis was performed adjusting for steroid use and factors known to adversely impact graft outcome. Results The median follow up was 29.6 months (range, 10.7–60.1). ALE induction as compared to rATG had inferior adjusted graft ( P P = .003) survivals in non-AA recipients but similar in AA recipients. In non-AA recipients, IL-2 induction as compared with rATG had similar adjusted graft but inferior patient survival ( P = .04), and in AA recipients had inferior graft ( P = .002) but similar patient survival. Conclusion Our study shows racial differences in renal transplant outcomes with regard to induction modality.

Background. The spectrum of proteinuric renal disease in older adults remains incompletely defined. The purpose of the present study was to determine if differences exist in diagnostic approach, etiology, therapy, and outcome between older (>60 years) and younger (,60 years) patients referred for evaluation of proteinuria. Methods. We conducted a retrospective review of outpatient office charts in a 7-physician, hospital-based nephrology practice. Results. We identified 69 patients with at least 1 subsequent follow-up assessment after reviewing approximately 500 sequential charts. Forty-five were younger (mean 6 SD age, 38 6 2 years), and 24 were older (69 6 1 years). The degree of proteinuria at presentation was similar (4.5 6 0.7 vs 3.9 6 0.6 g/d, older vs younger, p 5 NS), but older patients had higher creatinine levels (1.7 6 0.2 vs 1.2 6 0.07 mg/dl, p , .01), lower creatinine clearances (64 6 7 vs 111 6 7 ml/ min., p , .05), and higher systolic blood pressure (164 6 8/88 6 2 vs 145 6 4/94 6 2 mm Hg, p , .01). Older patients were more likely to decline a renal biopsy (21% vs 7.6%, p , .01). The most common final renal diagnoses were immunoglobulin A nephropathy (31%), focal segmental glomerulosclerosis (24%), hypertension (13%), and membranous nephropathy (11%) in the younger patients, and membranous nephropathy (29%), hypertension (25%), diabetic nephropathy (17%), and minimal change disease (8%) in the older patients. Steroids were given to 17.7% of younger patients and 16.7% of older patients (p 5 NS). The percentage of patients with improvement, defined as a 50% reduction in proteinuria with stable or improved renal function, was similar among older and younger patients (33.3% vs 35.5%). However, older patients were more likely to develop progression of renal disease (33.3% vs 8.8%) and less likely to retain stable renal function (29.2% vs 53.3%). Conclusion. Significant differences exist in proteinuric renal disease between older and younger adults.

To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance (CSM) emerge.Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, we compared the adjusted graft and patient survivals for CSM vs early steroid withdrawal (ESW) among patients who underwent deceased-donor kidney (DDK) transplantation from 2000 to 2008 who were stratified by peak-panel reactive antibody (peak-PRA) titers (0%-30%, 31%-60% and60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF).The study included 42851 patients. In the 0%-30% peak-PRA class, adjusted over-all graft-failure (HR 1.11, 95%CI: 1.03-1.20, P = 0.009) and patient-death (HR 1.29, 95%CI: 1.16-1.43, P0.001) risks were higher and death-censored graft-failure risk (HR 1.06, 95%CI: 0.98-1.14, P = 0.16) similar for CSM (n = 25218) vs ESW (n = 7399). Over-all (HR 1.04, 95%CI: 0.85-1.28, P = 0.70) and death-censored (HR 0.97, 95%CI: 0.78-1.21, P = 0.81) graft-failure risks were similar and patient-death risk (HR 1.39, 95%CI: 1.03-1.87, P = 0.03) higher for CSM (n = 3495) vs ESW (n = 850) groups for 31%-60% peak-PRA class. In the60% peak-PRA class, adjusted overall graft-failure (HR 0.90, 95%CI: 0.76-1.08, P = 0.25) and patient-death (HR 0.92, 95%CI: 0.71-1.17, P = 0.47) risks were similar and death-censored graft-failure risk lower (HR 0.84, 95%CI: 0.71-0.99, P = 0.04) for CSM (n = 4966) vs ESW (n = 923).In DDK transplant recipients who underwent perioperative induction and CNI/MMF maintenance, CSM appears to be associated with increased risk for death with functioning graft in minimally-sensitized patients and improved death-censored graft survival in highly-sensitized patients.

The new kidney allocation scheme (KAS) in effect since December 4(th) 2014 was designed to overcome the shortcomings of previous system. A key feature of the new KAS is preferential allocation of best quality organs to wait-list candidates with the longest predictive survival in a concept called longevity matching. Highly sensitized recipients would get extra points and enjoy widespread sharing of organs in order to increase accessibility to transplant. Wait-list candidates with blood group B will be offered organs from donors with A2 and A2B blood type in order to shorten their wait-list time. Time on the wait list will start from day of listing or date of initiation of dialysis whichever comes first which should benefit candidates with limited resources who might be late to get on the transplant list. Pay back system has been eliminated in the new KAS. These changes in organ allocation policy may lead to increase in median half-life of the allograft and increase the number of transplants; thus resulting in better utilization of a scarce resource. There could be unintended negative consequences which may become evident over time.

It is unclear if simultaneous pancreas-kidney (SPK) transplantation adds to the general quality of life (QOL) achieved with kidney transplantation alone (KTA). This case-controlled study matched 27 successful SPK transplant recipients with 27 successful KTA recipients. Cases were matched for gender, age (+/- 7 years), and year of transplant (+/- 2 years). Both groups had type 1 diabetes and end-stage renal disease. Diabetes-related QOL was assessed using the Diabetes Quality of Life (DQOL) questionnaire. General QOL was assessed using Medical Outcome Health Survey Short Form-36 (SF-36) and Quality of Well Being (QWB) questionnaires. Morbidity data were obtained through chart review. There was a trend for a lower prevalence of coronary artery disease (5 of 27 versus 13 of 27) and peripheral vascular disease (5 of 27 versus 9 of 27) in SPK recipients (P = not significant). Satisfaction with diabetes-related QOL was significantly better in SPK recipients (1.8 +/- 0.5 versus 2.3 +/- 0.5; P < 0.05). SPK and KTA recipients' SF-36 physical (66 +/- 21 and 64 +/- 19) and mental (76 +/- 17 and 71 +/- 22) composite scores were similar. QWB scores also were similar for SPK (0.67 +/- 0.12) and KTA (0.63 +/- 0.10) recipients. In the first 3 months after transplantation, SPK recipients had a significantly higher number of hospital admissions per patient (1.9 +/- 0.9 versus 1.4 +/- 0.6; P < 0.05), more hospital days per patient (25.1 +/- 13.8 days versus 10.1 +/- 4.4 days; P < 0.005), and more intensive care unit days per patient (7.9 +/- 7.1 days versus 0.8 +/- 1.5 days; P < 0.005). Although SPK transplantation enhanced diabetes-related QOL, there was no improvement in overall QOL.

Background Induction therapy improves graft outcomes in kidney transplant recipients (KTRs). We aimed to compare the incidences of antibody-mediated rejection (AMR) and acute cellular rejection (ACR) as well as graft and patient outcomes in KTRs who underwent induction with alemtuzumab versus rabbit-antithymocyte globulin (r-ATG). Methods This was a single-center retrospective study involving patients who underwent kidney transplantation between January 2009 and December 2011 after receiving induction therapy with either alemtuzumab or r-ATG. Maintenance immunosuppression included tacrolimus and mycophenolate mofetil with early steroid withdrawal. Acute rejection was diagnosed using allograft biopsy. Results Among the 108 study patients, 68 received alemtuzumab and 40 got r-ATG. There was a significantly higher incidence of AMR (15% vs 2.5%; P = .008) and similar incidence of ACR (4.4% vs 10%; P = .69) for alemtuzumab versus r-ATG groups. One-year serum creatinine levels (l.68 ± 0.8 mg/dL vs 1.79 ± 1.8 mg/dL; P = .66) as well as graft (91.1 ± 3.5% vs 94.5 ± 3.8%; P = .48) and patient (93.8 ± 3.0% vs 96.4 ± 3.5%; P = .92) survivals were similar for the alemtuzumab versus the r-ATG groups. Conclusion Our study showed a higher incidence of AMR and similar incidence of ACR in KTRs who underwent induction with alemtuzumab compared with those who received r-ATG and were maintained on tacrolimus and MMF. This was despite a lower HLA mismatch in the alemtuzumab group. One-year graft survival, patient survival, and allograft function were similar. Inadequate B-cell suppression by alemtuzumab as well as altered phenotypic and functional properties of repopulating B cells could be contributing to heightened risk of AMR in these patients.

Hyperuricemia may be a risk factor for graft loss in kidney transplant recipients. The purpose of this study was to evaluate the effects of allopurinol in kidney transplant recipients.A single center retrospective case-control study was performed with kidney transplant recipients who were treated with allopurinol (54 patients) and a control group matched for time of transplant (± 3 months) and estimated glomerular filtration rate (54 patients). We evaluated the relation between allopurinol use and estimated glomerular filtration rate, graft survival, blood pressure, and number of anti-hypertensive drugs used.At the start of allopurinol therapy, mean serum uric acid level was greater in the allopurinol (476 ± 119 μmol/L) than control group (404 ± 125 μmol/L; P ≤ .001) and estimated glomerular filtration rate was similar between the 2 groups (allopurinol, 39 ± 16 mL/min; control, 38 ± 16 mL/min; not significant). At 1 year, mean estimated glomerular filtration rate was greater in the allopurinol than control group (allopurinol, 41 ± 15 mL/min; control, 36 ± 13 mL/min; P ≤ .04). At 2 years, mean serum uric acid level was significantly lower in the allopurinol (399 ± 101 μmol/L) than control group (452 ± 95 μmol/L; P ≤ .02). Graft survival, blood pressure, and antihypertensive requirements were similar between the groups.Allopurinol use is associated with preservation of estimated glomerular filtration rate in kidney transplant recipients. There may be potential benefit in treating asymptomatic hyperuricemia in kidney transplant recipients.

Paired-exchange kidney transplantation (PEKT) enables recipients with willing but incompatible donors to find potential matches from a larger pool of donors. It involves transportation of donor kidneys to the intended recipient with a consequent increase in the cold ischemia time (CIT).Our single-center study compared the outcomes of PEKT versus traditional in-center live-donor kidney transplants (ICKT). Retrospective chart review of adult patients who underwent PEKT and ICKT from January 2009 to February 2012 at our institution was performed. Delayed graft function, acute rejection rates, incidence of proteinuria, trends in serum creatinine, and graft and patient survival rates were compared between groups.Baseline demographic data were similar between the PEKT group (n = 15) and the ICKT group (n = 30) except that CIT (13.1 vs 3.8 hours; P .001) and panel reactive antibody titers (12.6% ± 22.9% vs 0.9% ± 4.9%; P = .01) were significantly higher in the PEKT group. No patient developed delayed graft function. At a median follow-up of 12.4 months (range: 2-27.5 months), graft and patient survival rates were 100% in both groups. Serial creatinine levels were similar between the groups. There were no significant differences between groups in acute rejection rates (3 of 15 vs 3 of 30) and development of proteinuria posttransplantation (8 of 15 vs 22 of 30).Our study found similar outcomes between the PEKT and ICKT groups despite longer CIT and higher panel reactive antibody titers in the PEKT group. These findings support the current practice of PEKT with transporting of donor kidneys, with the resultant increase in the chances of living-donor kidney transplantation.

Steroid-free immunosuppression regimens have been enjoying recent success in clinical transplantation. The use of antibodies required for such protocols can be an economic burden. We proposed to study their cost in our center. This retrospective study involved 147 consecutive patients subjected to 4 protocols of immunosuppression. The first received triple therapy. The second group received induction with basiliximab, whereas the third received Basiliximab plus cyclosporine (CSA) plus mycophenolate mofetil (MMF), and the fourth received Thymoglobulin plus CSA plus MMF in conjuction with only 4 days of steroid. Rejection episodes were treated with Solumedrol. Six-month charges were obtained from computerized records of the finance department, the in-house laboratories, and the transplantation service registry. All charges were expressed in 2004 dollars. Statistical analyses were obtained using chi-square, analysis of variance (ANOVA) and Kaplan-Meier tests. The 4 groups were similar with regard to donor and/or recipient gender, race, panel reactive antibodies, cold ischemia, dialysis requirements length of stay and readmission, graft survival, and function. Charges were significantly higher in the last 2 groups as compared with triple therapy.

OBJECTIVES Antibody-mediated rejection after kidney transplant is less responsive to conventional antirejection therapies. The proteasome inhibitor bortezomib has activity against mature plasma cells that produce damaging donor-specific antibodies. We present our experience of using a bortezomib-based regimen in patients with severe antibody-mediated rejection. MATERIALS AND METHODS A retrospective chart review was performed on patients with biopsy-proven antibody-mediated rejection after kidney transplant at our institution over 12 months. Diagnosis of antibody-mediated rejection was made on the basis of positive peritubular capillary C4d staining along with either histologic evidence of acute rejection or positive donor-specific antibody titers. Treatment for antibody-mediated rejection included plasmapheresis, intravenous immunoglobulin, steroids, single-dose rituximab (375 mg/m²) along with bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11. Antibody-mediated rejection was diagnosed in 6 patients. Patients received induction with either alemtuzumab (n=4) or rabbit-antithymocyte globulin (n=2) and were maintained on a tacrolimus/mycophenolate mofetil/early steroid withdrawal protocol. RESULTS Four of 6 patients responded to treatment. Patients had stable kidney function during followup (median 14 months) after bortezomib therapy. CONCLUSIONS In this series, we demonstrated the effectiveness of a bortezomib-based treatment regimen in achieving reduction of donor-specific antibody titers and stable renal function in patients experiencing severe antibody-mediated rejection.

Background Pre-transplant dialysis duration exerts a graded negative influence on outcomes after kidney transplantation. Higher immune reactivity associated with prolonged dialysis with consequent increased acute rejection could be contributory. Methods Using the Organ Procurement and Transplant Network/United Network of Organ Sharing database, we identified patients ≥18 years of age who received deceased-donor kidney (DDK) transplants from 2000 to 2008 after being on maintenance dialysis for ≥4 years. Patients received induction therapy with rabbit antithymocyte globulin (r-ATG), alemtuzumab, or an interleukin-2 receptor blocker (IL-2B) and were discharged on calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF)–based immunosuppression with or without steroid. Unadjusted and adjusted graft/patient survivals were compared in steroid versus no-steroid groups by induction type. Results A total of 14,459 patients were identified, of which 7,684 received r-ATG (steroid, 6,098; no-steroid, 1,586), 1,292 alemtuzumab (steroid, 362; no-steroid, 930), and 5,483 an IL-2B agent (steroid, 5,107; no-steroid, 376). Adjusted graft survivals were similar for steroid versus no-steroid groups in r-ATG (hazard ratio [HR] 1.10, 95% confidence interval (CI) 0.96–1.26, P = .16), alemtuzumab (HR 0.88, 95% CI 0.65–1.19; P = .40), and IL-2B (HR 0.91, 95% CI 0.73–1.13; P = .38) groups. Adjusted patient survival for steroid versus no-steroid groups was inferior in r-ATG (HR 1.41, 95% CI 1.17–1.71; P P = .80) and IL-2B (HR 1.17, 95% CI 0.86–1.58; P = .32) groups. Conclusions Our analysis failed to show a graft survival benefit for the addition of steroid to a CNI/MMF-based immunosuppression after induction with r-ATG, alemtuzumab, or an IL-2B agent in DDK recipients exposed to prolonged pretransplantation dialysis.

Summary Background and objectives Delayed graft function (DGF) is associated with adverse long-term outcomes after deceased-donor kidney (DDK) transplantation. Ischemia-reperfusion injury plays a crucial role in the development of DGF. On the basis of promising animal data, this study evaluated any potential benefits of erythropoietin-alfa (EPO-a)givenintra-arteriallyatthetimeofreperfusionofrenalallograftonthedegreeofallograftfunction,aswellas tubular cell injury measured by urinary biomarkers in the early post-transplant period. Design, setting, participants, & measurements A prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the influence of EPO-a administered intraoperatively on the outcomes of DDK transplantations performed at the study center between March 2007 and July 2009. ResultsSeventy-two patients wererandomlyassigned to EPO-a(n=36)orplacebo(n=36).The incidencesof DGF, slow graft function, and immediate graft function did not significantly differ between the treatment and control groups (41.7% versus 47.2%, 25.0% versus 36.1%, and 33.3% versus 16.7%, respectively; P=0.24). The groups had similar levels of urinary biomarkers, including neutrophil gelatinase-associated lipocalin and IL-18 at multiple times points soon after transplantation; urinary output during the first 3 postoperative days; 1-month renal function; and BP readings, hemoglobin, and adverse effects during the first month. Conclusions This study did not show any clinically demonstrable beneficial effects of high-dose EPO-a given intra-arteriallyduringtheearlyreperfusionphaseinDDKtransplantrecipientsintermsofreducingtheincidence of DGF or improving short-term allograft function. Clin J Am Soc Nephrol 7: 1498–1506, 2012. doi: 10.2215/CJN.01360212

Over the past decades, calcineurin inhibitors (CNIs) have become the cornerstone of transplant immunosuppression. CNIs can exert negative effects on chronic allograft function along with cardiovascular (CV) and metabolic adverse effects. Belatacept , a selective co-stimulation blocker of T cells, is the first US FDA (06/2011) and EMEA (06/2011) approved biologic agent for maintenance immunosuppression in renal transplantation.The authors critically reviewed the literature over the last few years comparing belatacept with current standard of maintenance immunosuppression including CNIs in kidney transplantation.Despite the increased incidence and severity of acute rejection with belatacept in Phase II and III studies, a better preservation of GFR and reduced incidence of chronic allograft nephropathy was observed as compared with CNIs. Patient and graft survivals were similar over 3- and 5-year follow-up post-transplantation. Incidence of adverse events were similar between the groups, but the risk of post-transplant lymphoproliferative disorder, predominantly involving CNS, was higher in Epstein-Barr virus seronegative recipients on belatacept, especially with a more intensive regimen. CV and metabolic end points were more favorable in belatacept versus CNI groups with similar incidences of diabetes after transplantation. Belatacept seems to be a promising drug for the future, but long-term outcomes are awaited.

BACKGROUND Over last several years, alemtuzumab induction has been increasingly used in kidney transplantation especially in patients maintained on steroid-free immunosuppression. It is unclear which induction agent is associated with better graft and patient outcomes in these patients. METHODS Using Organ Procurement and Transplant Network/United Network of Organ Sharing database, graft and patient survivals were compared with multivariate analysis for deceased donor kidney transplant recipients from January 2000 to December 2008 who received induction with rabbit-antithymocyte globulin (r-ATG), alemtuzumab, or an interleukin-2 (IL-2) receptor blocker and were discharged on a calcineurin inhibitor/mycophenolate mofetil/steroid-free immunosuppression. RESULTS When compared with r-ATG (n=5348), adjusted graft survival was inferior with alemtuzumab (n=2428, hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.10-1.43, P=0.001) and IL-2 receptor blocker (n=1396, HR 1.19, 95% CI 1.01-1.39, P=0.04) inductions and patient survival was inferior with alemtuzumab (HR 1.29, 95% CI 1.08-1.55, P=0.006). Alemtuzumab induction was associated with higher adjusted graft failure risks in patients with panel reactive antibody more than 20% (HR 1.30, 95% CI 1.01-1.68, P=0.04), recipients of expanded criteria donor kidneys (HR 1.58, 95% CI 1.23-2.02, P

Collapsing glomerulopathy (CG) is a variant of focal segmental glomerulosclerosis (FSGS) characterized histologically by prominent glomerular capillary tuft collapse with hypertrophy and hyperplasia of podocytes and tubulointerstitial damage. Patients usually present with heavy proteinuria and rapidly progressive renal failure. We report a patient who developed de novo CG with severe clinical manifestations including worsening renal failure and nephrotic syndrome within six months of receiving deceased donor kidney transplant. Secondary work-up was negative, and despite therapy with high-dose steroids and plasmapheresis, allograft function rapidly deteriorated with the need for dialysis. Theories about the pathogenesis of this entity as well as treatment modalities are discussed.

Background Traditionally, kidneys from donors ≥60 years old and pediatric kidneys are considered marginal organs for transplantation. Pediatric donor kidneys are underutilized for transplantation into adult recipients due to concern for poor outcomes. Methods Using data from the Organ Procurement and Transplant Network, we analyzed patterns of pediatric kidney use (single vs en bloc) in the United States from 1987 to 2007. Using the Cox proportional hazards model, graft outcomes of pediatric donor kidneys transplanted as single vs en bloc grafts from different donor weight groups were compared with renal transplantation from donors ≥60 years old in an attempt to define a pediatric donor weight at which kidneys can be justifiably split to expand the donor pool. Results Compared with older donor kidneys, graft failure risk of pediatric single kidneys was consistently lower when the donor weight exceeded 10 kg. On the other hand, graft survival benefit for pediatric en bloc kidneys was evident starting at donor weight ≤10 kg in comparison to older donor kidneys. Pediatric en bloc kidneys performed consistently better than pediatric single kidneys for all donor weight groups. Conclusions Splitting of pediatric donor en bloc kidneys for transplantation into 2 adults when the donor weight exceeds 10 kg was associated with acceptable graft outcomes. This practice, along with increased use of small pediatric donor kidneys, may help to alleviate the waiting list burden in renal transplantation.

Rapid steroid discontinuation immunosuppressive protocols are increasingly used in renal transplant. The optimal immunosuppressive regimen in patients who develop acute rejection while on a rapid steroid discontinuation protocol is less clear. We examined our experience of adding maintenance steroid therapy in renal transplant recipients who developed 1 or more acute rejection episode while on a rapid steroid discontinuation protocol.The outcome of 145 patients who underwent renal transplant from 2002 to 2007 and initiated a rapid steroid discontinuation protocol was analyzed. Patients were divided into the following 5 groups: (i): acute rejection X 1 and no maintenance steroids, (ii): acute rejection X 1 and started on maintenance steroids, (iii): acute rejection X 2 and no maintenance steroids (iv): acute rejection X 2 and started on maintenance steroids, and (v): no acute rejectionCompared with patients with no acute rejection, graft survival was significantly inferior in patients who experienced 2 or more acute rejection episodes-whether they were started on maintenance steroids (P = .003) or not (P = .006) - but was similar in patients who experienced only 1 episode of acute rejection, and were started either on maintenance steroids (P = .87) or were continued on the rapid steroid discontinuation protocol (P = .69). In patients who sustained 2 episodes of acute rejection, addition of maintenance steroids had no impact on graft survival (P = .97).More than 1 episode of acute rejection in renal transplant recipients on rapid steroid discontinuation protocol is associated with poor, long-term, graft survival, which remains unchanged despite starting maintenance steroids. The use of maintenance steroids may not have a positive impact on graft survival after acute rejection.