An Unusual Case of Anti-Glomerular Basement Membrane Disease and Phospholipase A2 Receptor-Associated Membranous Nephropathy After Exposure to Hydrocarbons.

We present a rare case of a patient with toluene exposure manifesting as anti-glomerular basement membrane (GBM) disease on a background of phospholipase A2 receptor (PLA2R)-associated membranous nephropathy. A 23-year-old man presented to the emergency department with hypertension, headache, hemoptysis, anemia, acute kidney injury, glomerular hematuria, and proteinuria. He endorsed repeated exposure to toluene-containing products while repairing dirt bikes. Serologies were positive for anti-GBM antibodies. Kidney biopsy showed crescentic glomerulonephritis with linear immunoglobulin G and granular PLA2R staining by immunofluorescence. He was initially treated with high-dose steroids, plasmapheresis, and hemodialysis for pulmonary-renal syndrome followed by oral cyclophosphamide and prednisone, which were discontinued after 3 months when follow-up biopsies confirmed little chance for renal recovery. He remained on dialysis 1 year later. This case exhibits a unique presentation of anti-GBM syndrome and underlying membranous nephropathy following repeated hydrocarbon exposure. Inhaled toxins promote recurrent localized inflammation, unmasking previously hidden epitopes. Early diagnosis and appropriate use of immunosuppressive and extracorporeal therapies are necessary to prevent morbidity and to improve survival in this rare condition.

Induction Therapy and Outcomes following Kidney Transplantation in Recipients of Previous Heart or Liver Transplants.

Introduction: Optimal induction for kidney transplantation in patients with previous nonrenal organ transplantation is unclear. We aimed to evaluate the impact of induction therapy on the outcomes following kidney transplantation in patients who underwent prior heart or liver transplantation. Methods: Using the UNOS database, patients who underwent isolated heart or liver transplant from 2000 to 2016 followed by subsequent kidney transplant and maintained on calcineurin inhibitor (CNI)/mycophenolic acid (MPA) regimen were identified and stratified into three groups according to the induction used for kidney transplant: No induction, induction with interleukin-2 receptor antibody (IL-2RA), or T-cell depleting induction with Thymoglobulin. The outcomes were compared between no induction vs. IL-2RA and T-cell depleting induction, and IL-2RA vs. T-cell depleting induction. Results: Adjusted risk for delayed graft function was significantly higher for T-cell depleting vs. no induction (OR 4.56, 95% CI 1.14-18.3, P = 0.03) and trended higher for IL-2RA vs. no induction (OR 2.96, 95% CI 0.84-10.33, P = 0.08) among kidney after heart group and significantly higher for T-cell depleting vs. no induction (OR 2.88, 95% CI 1.40-5.95, P = 0.004) and IL-2RA induction (OR 1.88, 95% CI 1.12-3.17, P = 0.02) among kidney after liver patients. Adjusted graft failure and patient death risks were similar in patients who got IL-2RA or depleting inductions vs. no induction and IL-2RA vs. depleting induction groups in kidney after heart and kidney after liver groups. Conclusions: The use of induction was not associated with graft or patient survival benefits for kidney transplantation in patients who had prior heart or liver transplants and maintained on CNI and MPA regimen.

Emerging role of cell-free DNA in kidney transplantation.

Monitoring kidney transplants for rejection conventionally includes serum creatinine, immunosuppressive drug levels, proteinuria, and donor-specific antibody (DSA). Serum creatinine is a late marker of allograft injury, and the predictive ability of DSA regarding risk of rejection is variable. Histological analysis of an allograft biopsy is the standard method for diagnosing rejection but is invasive, inconvenient, and carries risk of complications. There has been a long quest to find a perfect biomarker that noninvasively predicts tissue injury caused by rejection at an early stage, so that diagnosis and treatment could be pursued without delay in order to minimize irreversible damage to the allograft. In this review, we discuss relatively novel research on identifying biomarkers of tissue injury, specifically elaborating on donor-derived cell-free DNA, and its clinical utility.

Recipient Obesity and Kidney Transplant Outcomes: A Mate-Kidney Analysis.

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 < 0.001 for all). Death-censored graft failure was less frequent for BMI ≤25 and >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 < 0.001 for both), but not for BMI >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.

Donor Ethnicity and Kidney Transplant Outcomes in African Americans.

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.

Impact of Donor Ethnicity on Long-Term Kidney Transplant Outcomes: Analysis by Kidney Donor Profile Index Categories.

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 < .001) groups. 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.

Induction Type and Outcomes in HLA-DR Mismatch Kidney Transplantation.

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.

Does Induction Type Influence Outcomes in Kidney Transplant Recipients at Different Phases of Hepatitis B Infection?

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.

Cognitive and Behavioral Profile of Treatment-Naïve Children Aged 6-14 Years with Neurocysticercosis from North India.

BACKGROUND: Neurocysticercosis (NCC) produces a progressive organic brain damage by altering brain function with alterations in memory, difficulties in learning, and behavioral changes. The present study was designed to compare the cognitive and behavioral profile of school-going children aged 6-14 years with newly diagnosed NCC with their age-matched controls. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted among children aged 6-14 years with newly (<7 days) diagnosed NCC. Age- and gender-matched typically developing children with minor illness attending outpatient facility served as control. Intelligence and behavioral assessment were performed using Malin's Intelligence Scale for Indian Children and Childhood Behavior Checklist (CBCL) (school age version CBCL/6-18). CBCL T-scores were computed and scores < 60 were considered as normal, 60-63 as borderline, and > 63 as clinical range. RESULTS: A total of 35 cases and 35 controls were enrolled. Baseline demographic characteristics were comparable between the two groups. Verbal intelligence quotient (IQ) scores were comparable between the cases (96.14 [10.23]) and controls (100.17 [10.89]) (P = 0.11). The behavioral assessment revealed normal T-scores (<60) in both the groups. CONCLUSIONS: The study revealed comparable IQ and normal behavioral profile of treatment-naïve children with recently diagnosed NCC to their age-matched peers. Further studies with larger sample size and longitudinal study design are required to evaluate the role of NCC on cognition and behavior in Indian children.

Role of induction therapy in low immunological risk-kidney transplant recipients: A mate-kidney analysis.

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 <20%, human leukocyte antigen mismatches ≤3) with each group containing recipients of mate-kidneys from same donor and differed by induction received: group 1: no induction vs interleukin-2 receptor antibody (IL2RA) induction; group 2: no induction vs depleting antibody induction; group 3: IL2RA vs depleting antibody induction. Outcomes were compared between mate-kidney recipients in each group in an adjusted model. Total of 1034 mate-kidney recipients were identified: group 1, n = 192; group 2, n = 362 and group 3, n = 480. Adjusted risk for DGF was higher (OR 1.89, 95% CI 1.09-3.25,.P = 0.02) and one-year acute rejection trended lower (OR 0.53, 95% CI 0.25-1.11, P = 0.09) among depleting antibody induced patients in group 2. Adjusted five-year graft survivals were similar between mate-kidney recipients in all three groups. Adjusted patient death risk was significantly lower in depleting antibody induced patients in group 2 (HR 0.48, 95% CI 0.26-0.88, P = 0.02) and trended lower in IL2RA induced patient in group 1 (HR 0.32, 95% CI 0.10-1.01, P = 0.05). Perioperative antibody induction was associated with lower patient death risk in low-immunologic risk KTRs.

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

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.RESUTLSThe 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.

Impact of cold ischemia time on the outcomes of kidneys with Kidney Donor Profile Index ≥85%: mate kidney analysis - a retrospective study.

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 <24 h), group 2 (≥24 vs. <12 h), and group 3 (≥12 to <24 vs. <12 h). Adjusted delayed graft function (DGF), and graft and patient survivals were compared for mate kidneys. DGF risk was significantly lower for patients with CIT <12 vs. ≥24 h in group 2 (adjusted OR: 0.25, 95% CI: 0.12-0.57, P < 0.001) while trending lower for CIT ≥12 to <24 vs. ≥24 h in group 1 (adjusted OR: 0.78, 95% CI: 0.59-1.03, P = 0.08) and CIT <12 vs. ≥12 to <24 h in group 3 (adjusted OR: 0.74, 95% CI: 0.55-1.0, P = 0.05). Adjusted graft and patient survivals were similar between mate kidneys in all groups. Minimizing CIT improves outcomes with regional sharing of marginal kidneys.

Long-term Outcomes of Pediatric En Bloc Compared to Living Donor Kidney Transplantation: A Single-Center Experience With 25 Years Follow-Up.

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.

Depleting Antibody Induction and Kidney Transplant Outcomes: A Paired Kidney Analysis.

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.

Role of steroid maintenance in sensitized kidney transplant recipients.

AIM: To evaluate whether there is a threshold sensitization level beyond which benefits of chronic steroid maintenance (CSM) emerge. METHODS: 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% and > 60%). All patients received perioperative induction therapy and maintenance immunosuppression based on calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF). RESULTS: 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, P < 0.001) 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 the > 60% 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). CONCLUSION: 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.

Changing organ allocation policy for kidney transplantation in the United States.

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.