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1.
JAMA Surg ; 156(9): 812-817, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34160572

ABSTRACT

Importance: Policy makers, transplant professionals, and patient organizations agree that there is a need to increase the number of kidney transplants by facilitating living donation. Vouchers for future transplant provide a means of overcoming the chronological incompatibility that occurs when the ideal time for living donation differs from the time at which the intended recipient actually needs a transplant. However, uncertainty remains regarding the actual change in the number of living kidney donors associated with voucher programs and the capability of voucher redemptions to produce timely transplants. Objective: To examine the consequences of voucher-based kidney donation and the capability of voucher redemptions to provide timely kidney allografts. Design, Setting, and Participants: This multicenter cohort study of 79 transplant centers across the US used data from the National Kidney Registry from January 1, 2014, to January 31, 2021, to identify all family vouchers and patterns in downstream kidney-paired donations. The analysis included living kidney donors and recipients participating in the National Kidney Registry family voucher program. Exposures: A voucher was provided to the intended recipient at the time of donation. Vouchers had no cash value and could not be sold, bartered, or transferred to another person. When a voucher was redeemed, a living donation chain was used to return a kidney to the voucher holder. Main Outcomes and Measures: Deidentified demographic and clinical data from each kidney donation were evaluated, including the downstream patterns in kidney-paired donation. Voucher redemptions were separately evaluated and analyzed. Results: Between 2014 and 2021, 250 family voucher-based donations were facilitated. Each donation precipitated a transplant chain with a mean (SD) length of 2.3 (1.6) downstream kidney transplants, facilitating 573 total transplants. Of those, 111 transplants (19.4%) were performed in highly sensitized recipients. Among 250 voucher donors, the median age was 46 years (range, 19-78 years), and 157 donors (62.8%) were female, 241 (96.4%) were White, and 104 (41.6%) had blood type O. Over a 7-year period, the waiting time for those in the National Kidney Registry exchange pool decreased by more than 3 months. Six vouchers were redeemed, and 3 of those redemptions were among individuals with blood type O. The time from voucher redemption to kidney transplant ranged from 36 to 155 days. Conclusions and Relevance: In this study, the family voucher program appeared to mitigate a major disincentive to living kidney donation, namely the reluctance to donate a kidney in the present that could be redeemed in the future if needed. The program facilitated kidney donations that may not otherwise have occurred. All 6 of the redeemed vouchers produced timely kidney transplants, indicating the capability of the voucher program.


Subject(s)
Directed Tissue Donation , Family , Kidney Transplantation , Living Donors , Altruism , Female , Humans , Male , Registries , United States , Waiting Lists
2.
Transplantation ; 104(8): 1591-1603, 2020 08.
Article in English | MEDLINE | ID: mdl-32732836

ABSTRACT

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.


Subject(s)
End Stage Liver Disease/surgery , Graft Rejection/epidemiology , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Organ Preservation/methods , Aged , Allografts/immunology , Allografts/supply & distribution , Cold Ischemia/instrumentation , Cold Ischemia/methods , Cold Ischemia/statistics & numerical data , End Stage Liver Disease/complications , Feasibility Studies , Female , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/immunology , Humans , Kidney/immunology , Kidney Transplantation/ethics , Kidney Transplantation/methods , Kidney Transplantation/statistics & numerical data , Liver Transplantation/ethics , Liver Transplantation/methods , Liver Transplantation/statistics & numerical data , Male , Medical Futility/ethics , Middle Aged , Organ Preservation/instrumentation , Organ Preservation/statistics & numerical data , Perfusion/instrumentation , Perfusion/methods , Perfusion/statistics & numerical data , Renal Insufficiency/etiology , Renal Insufficiency/surgery , Retrospective Studies , Time Factors , Time-to-Treatment/statistics & numerical data , Transplantation, Homologous/adverse effects , Transplantation, Homologous/ethics , Transplantation, Homologous/methods , Treatment Outcome
4.
Anesth Analg ; 127(2): e1-e3, 2018 08.
Article in English | MEDLINE | ID: mdl-29481433

ABSTRACT

Our study of 100 major vascular and renal transplant patients evaluated the 6-minute walk test (6MWT) as an indicator of perioperative myocardial injury, using troponin as a marker. Using logistic regression and the area under the receiving operator characteristic curve, we compared the 6MWT to the Revised Cardiac Risk Index and metabolic equivalents. Only the 6MWT was associated with elevated postoperative troponins (95% CI, 0.98-0.99). However, the 6MWT area under the receiving operator characteristic curve (0.71 [95% CI, 0.57-0.85]) was not different from the Revised Cardiac Risk Index (P = .23) or metabolic equivalents (P = .14). The 6MWT may have a role in cardiac risk stratification in the perioperative setting.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Exercise Test , Kidney Transplantation/adverse effects , Troponin/blood , Adult , Aged , Area Under Curve , Exercise Tolerance , Female , Heart Injuries/blood , Heart Injuries/diagnosis , Humans , Logistic Models , Male , Middle Aged , Myocardium/pathology , Postoperative Complications , Postoperative Period , Prospective Studies , ROC Curve , Regression Analysis , Risk , Walking
5.
Front Med (Lausanne) ; 4: 185, 2017.
Article in English | MEDLINE | ID: mdl-29164120

ABSTRACT

Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR) still occurs in 10-15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all which increase the risk of chronic dysfunction and worsened allograft outcomes. Mitochondria represent intracellular endogenous triggers of inflammation, which can regulate immune cell differentiation, and expansion and cause antigen-independent graft injury, potentially enhancing the development of acute rejection. In the present study, we investigated the role of mitochondrial DNA encoded gene expression in biopsy matched peripheral blood (PB) samples from kidney transplant recipients. Quantitative PCR was performed in 155 PB samples from 115 unique pediatric (<21 years) and adult (>21 years) renal allograft recipients at the point of AR (n = 61) and absence of rejection (n = 94) for the expression of 11 mitochondrial DNA encoded genes. We observed increased expression of all genes in adult recipients compared to pediatric recipients; separate analyses in both cohorts demonstrated increased expression during rejection, which also differentiated borderline rejection and showed an increasing pattern in serially collected samples (0-3 months prior to and post rejection). Our results provide new insights on the role of mitochondria during rejection and potentially indicate mitochondria as targets for novel immunosuppression.

6.
Am J Transplant ; 17(9): 2451-2457, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28489287

ABSTRACT

Concerns regarding the potential for broken chains and "reneges" within kidney paired donation (KPD) and its effect on chain length have been raised previously. Although these concerns have been tested in simulation studies, real-world data have yet to be evaluated. The purpose of this study was to evaluate the actual rate and causes of broken chains within a large KPD program. All patients undergoing renal transplantation through the National Kidney Registry from 2008 through May 2016 were included for analysis. Broken chains and loops were identified. A total of 344 chains and 78 loops were completed during the study period, yielding a total of 1748 transplants. Twenty broken chains and one broken loop were identified. The mean chain length (number of transplants) within broken chains was 4.8 compared with 4.6 of completed chains (p = 0.78). The most common causes of a broken chain were donor medical issues incurred while acting as a bridge donor (n = 8), donors electing not to proceed (n = 6), and kidneys being declined by the recipient surgeon (n = 4). All recipients involved in a broken chain subsequently received a transplant. Based on the results, broken chains are infrequent, are rarely due to lack of donor motivation, and have no significant impact on chain length.


Subject(s)
Donor Selection , Kidney Failure, Chronic/surgery , Kidney Transplantation , Living Donors/supply & distribution , Tissue and Organ Procurement , Humans , Prognosis , Registries , Waiting Lists
7.
Transplantation ; 101(9): 2115-2119, 2017 09.
Article in English | MEDLINE | ID: mdl-28333861

ABSTRACT

BACKGROUND: The waiting list for kidney transplantation is long. The creation of "vouchers" for future kidney transplants enables living donation to occur when optimal for the donor and transplantation to occur later, when and if needed by the recipient. METHODS: The donation of a kidney at a time that is optimal for the donor generates a "voucher" that only a specified recipient may redeem later when needed. The voucher provides the recipient with priority in being matched with a living donor from the end of a future transplantation chain. Besides its use in persons of advancing age with a limited window for donation, vouchers remove a disincentive to kidney donation, namely, a reluctance to donate now lest one's family member should need a transplant in the future. RESULTS: We describe the first three voucher cases, in which advancing age might otherwise have deprived the donors the opportunity to provide a kidney to a family member. These 3 voucher donations functioned in a nondirected fashion and triggered 25 transplants through kidney paired donation across the United States. CONCLUSIONS: The provision of a voucher to potential recipients whose need for a transplant makes them "chronologically incompatible" with their donors may increase the number of living donor transplants.


Subject(s)
Delivery of Health Care, Integrated , Directed Tissue Donation , Donor Selection , Kidney Diseases/surgery , Kidney Transplantation/methods , Living Donors/supply & distribution , Time-to-Treatment , Transplant Recipients , Waiting Lists , Age Factors , Child , Child, Preschool , Delivery of Health Care, Integrated/organization & administration , Disease Progression , Donor Selection/organization & administration , Female , Humans , Kidney Diseases/diagnosis , Male , Middle Aged , Time Factors , Treatment Outcome
8.
Transplantation ; 101(6): 1479-1487, 2017 06.
Article in English | MEDLINE | ID: mdl-27391197

ABSTRACT

BACKGROUND: BK virus infection remains an important cause of loss of allograft function after kidney transplantation. We sought to determine whether polyfunctional T cells secreting multiple cytokines simultaneously, which have been shown to be associated with viral control, could be detected early after start of BK viremia, which would provide insight into the mechanism of successful antiviral control. METHODS: Peripheral blood mononuclear cells collected during episodes of BK viral replication were evaluated by multiparameter flow cytometry after stimulation by overlapping peptide pools of BK virus antigen to determine frequency of CD8+ and CD4+ T cells expressing 1 or more cytokines simultaneously, as well as markers of T-cell activation, exhaustion, and maturation. RESULTS: BK virus controllers, defined as those with episodes of BK viremia of 3 months or less, had an 11-fold increase in frequency of CD8+ polyfunctional T cells expressing multiple cytokines, as compared with patients with prolonged episodes of BK viremia. Patients with only low level BK viremia expressed low frequencies of polyfunctional T cells. Polyfunctional T cells were predominantly of the effector memory maturation subtype and expressed the cytotoxicity marker CD107a. CONCLUSIONS: Noninvasive techniques for immune assessment of peripheral blood can provide insight into the mechanism of control of BK virus replication and may allow for future patient risk stratification and customization of immune suppression at the onset of BK viremia.


Subject(s)
BK Virus/immunology , CD8-Positive T-Lymphocytes/immunology , Kidney Transplantation/adverse effects , Opportunistic Infections/immunology , Polyomavirus Infections/immunology , Tumor Virus Infections/immunology , Adult , Aged , Antiviral Agents/therapeutic use , BK Virus/drug effects , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/virology , Cytokines/immunology , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Opportunistic Infections/diagnosis , Opportunistic Infections/drug therapy , Opportunistic Infections/virology , Phenotype , Polyomavirus Infections/diagnosis , Polyomavirus Infections/drug therapy , Polyomavirus Infections/virology , Predictive Value of Tests , Risk Factors , Time Factors , Treatment Outcome , Tumor Virus Infections/diagnosis , Tumor Virus Infections/drug therapy , Tumor Virus Infections/virology , Viremia/immunology , Viremia/virology
9.
Hum Immunol ; 78(1): 41-48, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27818166

ABSTRACT

UNOS implemented a new Kidney Allocation System (New KAS) on December 4, 2014 with a primary goal of increasing equity to organ transplant for patients that were immunologically or socially disadvantaged by the previous allocation system (Previous KAS) that prioritized long wait times. We examined the effects of the New KAS on patients transplanted from the UCLA deceased donor waitlist during the first year and compared to the last year of the Previous KAS. The total number of deceased donor kidney transplants was increased in the New KAS as compared to the Previous KAS (178 vs 148). Transplant of regraft patients and of highly sensitized patients with cPRA⩾99% was significantly increased in the New KAS (New KAS vs Previous KAS, 29.8% vs 11.5%, p⩽0.0001, and 26.4% vs 2.7%, p⩽0.0001, respectively). In the New KAS, the percentage of patient's receiving allografts imported from outside our local area was also significantly increased (34.8% vs 15.5%, p<0.0001). In the New KAS, 59.7% and 48.3% of imported organs were allocated to very highly sensitized (⩾99% cPRA) or re-graft patients, respectively, as compared to 8.7% and 8.7% during the Previous KAS (p<0.001). Recipients and donors with age differences exceeding 15years were decreased in the New KAS as compared to the Previous KAS (36.5 vs 48.7%, p⩽0.032). There was a 40.1% reduction in transplant to patients in the 65+ age group in the New KAS (p⩽0.025). The percentage of patients transplanted with preformed donor specific antibody (DSA) was similar in the New as compared to the Previous KAS (19.7% vs 15.5%) and, patients were transplanted with a range of 1-3 preformed DSA of weak to moderate strength. Cold ischemic time was significantly increased over all organs, and in patients transplanted with preformed DSA during the New as compared to the Previous KAS (17.5 vs 19.1h and 17.2 vs 22.2, p<0.04 and p<0.03, respectively). Episodes of delayed graft function and the number of biopsies for cause were similar between the New and the Previous KAS. However, there were more events of biopsy proven antibody mediated rejection in patients transplanted since the start of the New KAS. The data show that the New KAS is working at the center level as designed to better age match recipients and donors and to increase transplantation of very highly sensitized patients through broader sharing.


Subject(s)
Government Regulation , Kidney Transplantation , Tissue and Organ Procurement , Transplant Recipients , Academic Medical Centers , Adolescent , Adult , Aged , Aged, 80 and over , Cadaver , Child , Child, Preschool , Clinical Protocols , Female , HLA Antigens/immunology , Histocompatibility Testing , Humans , Isoantibodies/metabolism , Male , Middle Aged , Tissue Donors , United States , Waiting Lists , Young Adult
10.
Pediatr Nephrol ; 31(12): 2345-2352, 2016 12.
Article in English | MEDLINE | ID: mdl-27286686

ABSTRACT

BACKGROUND: Immunosuppression medication nonadherence has been associated with donor-specific antibodies and treatment-refractory rejection. Drug-level monitoring is a practical direct marker for nonadherence, as variations indicate erratic ingestion of medication. We previously reported that high variability in tacrolimus trough levels determined by the percent coefficient of variation (CV %) and standard deviation (SD) were associated with biopsy-proven rejection. We hypothesized that the CV % and SD in patients on a sirolimus/low-dose tacrolimus regimen may associate with self-reported medication nonadherence, rejection and donor-specific antibodies. METHODS: In this pilot feasibility study, we studied 37 biopsies in 23 pediatric renal transplant patients on both sirolimus and tacrolimus immunosuppression; CV %, SD, de novo donor-specific antibodies, rejection, and self-reported adherence were examined. RESULTS: A cut-off sirolimus CV % of 25 maximized the percentage of biopsies correctly classified as rejection (32 of 37, or 86 %, p = 0.001). A cut-off tacrolimus CV % of 31 maximized the percentage of correctly classified biopsies (25 of 37, or 68 %, p = 0.09). Among patients with both high sirolimus and tacrolimus CV %, 67 % developed de novo donor-specific antibodies (p = 0.002) with a DQ predominance and 71 % reported nonadherence (p = 0.05). CONCLUSIONS: In pediatric renal transplantation, sirolimus and tacrolimus CV % is a potential tool for monitoring patients at risk for allograft rejection and donor-specific antibodies secondary to medication nonadherence.


Subject(s)
Antibodies/analysis , Graft Rejection/immunology , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Medication Adherence , Sirolimus/therapeutic use , Tacrolimus/therapeutic use , Tissue Donors , Child , Child, Preschool , Feasibility Studies , Female , Graft Survival , Humans , Infant , Kidney/immunology , Kidney/pathology , Male , Pilot Projects , Retrospective Studies , Treatment Outcome
11.
Haemophilia ; 22(6): 957-965, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27353010

ABSTRACT

INTRODUCTION: Discrepancies have been previously reported for one-stage clotting and chromogenic assays for FVIII activity analysis. Inter-laboratory variations in instruments, method of clot detection, assay set-up, reference standard calibration, reagent source and reagent composition all contribute to assay variability. AIM: To characterise multilaboratory assay variability in measuring ADYNOVATE, OBIZUR and ADVATE FVIII activity in human plasma and survey multinational FVIII activity assay preferences. METHODS: As samples from patients treated with either of the FVIII products are not available in the quantities required for a systematic collaborative study, haemophilia A plasma was spiked in vitro with either ADYNOVATE (PEGylated rFVIII), OBIZUR [Porcine Sequence Antihaemophilic Factor (Recombinant)] or ADVATE at high (0.80 IU or U mL-1 ), medium (0.20 IU or U mL-1 ) and low (0.05 IU or U mL-1 ) FVIII concentrations, based on labelled potencies. Clinical laboratories used their routine FVIII activity assay to determine FVIII activity of each product. Thirty-five data sets using one-stage clotting assay and 11 sets using chromogenic assay were obtained. RESULTS: A vast majority of laboratories (98%) prefer and rely on the one-stage clotting assay. Mean recoveries across all concentrations were 113%, 120% and 127% for ADYNOVATE, OBIZUR and ADVATE respectively. Assay variation was comparable between ADVATE, ADYNOVATE and OBIZUR with inter-laboratory percent coefficients of variation (%CV) ranging from 11 to 22%. Mean chromogenic assay results were 116%, 51% and 113% for ADYNOVATE, OBIZUR and ADVATE respectively. Inter-laboratory CV's were similar for ADYNOVATE, OBIZUR and ADVATE. CONCLUSIONS: One-stage clotting assays can and will be used with sufficient accuracy and precision for the measurement of ADYNOVATE, OBIZUR and ADVATE in plasma samples from subjects with haemophilia A. Chromogenic assay underestimates OBIZUR potency, particularly at lower concentrations.


Subject(s)
Factor VIII/therapeutic use , Hemophilia A/therapy , Hemostasis/immunology , Female , Humans , Male , Surveys and Questionnaires
12.
Clin Imaging ; 40(3): 370-7, 2016.
Article in English | MEDLINE | ID: mdl-27133670

ABSTRACT

PURPOSE: Most living related donor (LRD) kidneys are harvested laparoscopically. Renal vascular anatomy helps determine donor suitability for laparoscopic nephrectomy. Computed tomography angiography (CTA) is the current gold standard for preoperative imaging; magnetic resonance angiography (MRA) offers advantages including lack of ionizing radiation and lower incidence of contrast reactions. We evaluated 3.0T MRA for assessing renal anatomy of LRDs. MATERIALS AND METHODS: Thirty consecutive LRDs underwent CTA followed by 3.0T MRA. Data points included number and branching of vessels, incidental findings, and urothelial opacification. Studies were individually evaluated by three readers blinded to patient data. Studies were reevaluated in consensus with discrepancies revealed, and final consensus results were labeled "truth". RESULTS: Compared with consensus "truth", both computed tomography (CT) and magnetic resonance imaging were highly accurate for assessment of arterial and venous anatomy, although CT was superior for detection of late venous confluence as well as detection of renal stones. Both modalities were comparable in opacification of lower ureters and bladder; MRA underperformed CTA for opacification of upper urinary tracts. CONCLUSIONS: 3.0T MRA enabled excellent detection of comprehensive renal anatomy compared to CTA in LRDs.


Subject(s)
Computed Tomography Angiography , Donor Selection/methods , Kidney Transplantation , Kidney/diagnostic imaging , Living Donors , Magnetic Resonance Angiography/methods , Adult , Female , Humans , Kidney/blood supply , Kidney/surgery , Laparoscopy , Male , Middle Aged , Nephrectomy/methods , Pilot Projects , Prospective Studies , Single-Blind Method
13.
Hamostaseologie ; 32 Suppl 1: S29-38, 2012.
Article in English | MEDLINE | ID: mdl-22961422

ABSTRACT

A longer acting recombinant FVIII is expected to serve patients' demand for a more convenient prophylactic therapy. We have developed BAX 855, a PEGylated form of Baxter's rFVIII product ADVATE™ based on the ADVATE™ manufacturing process. The conjugation process for preparing BAX 855 uses a novel PEG reagent. The production process was adjusted to yield a rFVIII conjugate with a low PEGylation degree of about 2 moles PEG per FVIII molecule. This optimised modification degree resulted in an improved PK profile for rFVIII without compromising its specific activity. PEGylation sites were identified by employing various HPLC- and MS-based methods. These studies not only indicated that about 60% of the PEG chains are localised to the B-domain, which is cleaved off upon physiological activation during the coagulation process, but also demonstrated an excellent lot to lot consistency with regard to PEGylation site distribution. Detailed biochemical characterization further showed that PEGylated FVIII retained all the physiological functions of the FVIII molecule with the exception of binding to the LRP clearance receptor which was reduced for BAX 855 compared to ADVATE™. This might provide an explanation for the prolonged circulation time of BAX 855 as reduced receptor binding might slow-down clearance. Preclinical studies showed improved pharmacokinetic behaviour and clinically relevant prolonged efficacy compared to ADVATE™ without any signs of toxicity or elevated immunogenicity. The comprehensive preclinical data package formed the basis for approval of the phase 1 clinical study by European authorities which started in 2011.


Subject(s)
Drug Design , Factor VIII/administration & dosage , Factor VIII/chemistry , Hemophilia A/drug therapy , Liposomes/chemistry , Polyethylene Glycols/chemistry , Dose-Response Relationship, Drug , Drug Stability , Factor VIII/pharmacokinetics , Half-Life , Hemophilia A/metabolism , Humans , Recombinant Proteins/administration & dosage , Recombinant Proteins/chemistry , Recombinant Proteins/pharmacokinetics
14.
Anal Chem ; 84(18): 7933-7, 2012 Sep 18.
Article in English | MEDLINE | ID: mdl-22881369

ABSTRACT

Kidney transplant recipients who have abnormally high creatinine levels in their blood often have allograft dysfunction secondary to rejection. Creatinine has become the preferred marker for renal dysfunction and is readily available in hospital clinical settings. We developed a rapid and accurate polymer-based electrochemical point-of-care (POC) assay for creatinine detection from whole blood to identify allograft dysfunction. The creatinine concentrations of 19 blood samples from transplant recipients were measured directly from clinical serum samples by the conducting polymer-based electrochemical (EC) sensor arrays. These measurements were compared to the traditional clinical laboratory assay. The time required for detection was <5 min from sample loading. Sensitivity of the detection was found to be 0.46 mg/dL of creatinine with only 40 µL sample in the creatinine concentration range of 0 mg/dL to 11.33 mg/dL. Signal levels that were detected electrochemically correlated closely with the creatinine blood concentration detected by the UCLA Ronald Reagan Medical Center traditional clinical laboratory assay (correlation coefficient = 0.94). This work is encouraging for the development of a rapid and accurate POC device for measuring creatinine levels in whole blood.


Subject(s)
Creatinine/blood , Electrochemical Techniques , Kidney/physiopathology , Polymers/chemistry , Antibodies/immunology , Biosensing Techniques , Humans , Kidney Transplantation , Point-of-Care Systems , Transplantation, Homologous
15.
Am J Transplant ; 12(9): 2429-36, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22812922

ABSTRACT

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.


Subject(s)
Kidney Transplantation , Algorithms , Female , Humans , Male , Treatment Outcome , United States
16.
Transplantation ; 92(4): 388-95, 2011 Aug 27.
Article in English | MEDLINE | ID: mdl-21730889

ABSTRACT

BACKGROUND: Current diagnostic methods of renal allograft rejection are neither sensitive nor specific. Needle biopsies are invasive and associated with patient morbidity. Thus, it is desirable to develop noninvasive tests to predict and diagnose rejection. METHODS: Using a case-control approach, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to identify plasma proteins associated with renal allograft rejection. From each rejection patient (n=16), two plasma samples (one near the biopsy date and the other at a time postbiopsy) were compared. Biopsy-confirmed nonrejection patients (n=48) were further analyzed as controls. Antibody-based quantitative enzyme-linked immunosorbent assay was performed to validate candidate biomarker apolipoprotein A1 (Apo A1) in a subset of the original and a second cohort of biopsy-confirmed rejection (n=40) and nonrejection (n=70) patients. RESULTS: Twenty-two proteins/peptides showed significant differences between rejection and postrejection samples. Peptides 5191 Da and 4467 Da detected rejection with 100% sensitivity and 94% specificity. The 4467 Da peptide was identified as the C-terminal fragment of α-1 antichymotrypsin and a 28 kDa protein was determined as Apo A1. Both protein levels were significantly lower at rejection compared with postrejection. Protein levels of nonrejection patients were similar to the postrejection samples. Apo A1 enzyme-linked immunosorbent assay results showed significantly lower Apo A1 levels (P=0.001 for the original and P=4.14E-11 for the second cohort) at the time of rejection compared with nonrejection which coincides with the SELDI findings. CONCLUSIONS: Together α-1 antichymotrypsin, Apo A1, and the unidentified 5191 Da peptide provide a plasma molecular profile, and this is associated with acute cellular renal allograft rejection.


Subject(s)
Apolipoprotein A-I/blood , Graft Rejection/blood , Kidney Transplantation/adverse effects , alpha 1-Antichymotrypsin/blood , Acute Disease , Adult , Biomarkers/blood , Case-Control Studies , Cohort Studies , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/statistics & numerical data , Female , Graft Rejection/diagnosis , Graft Rejection/etiology , Humans , Male , Middle Aged , Peptide Fragments/blood , Protein Array Analysis , Sensitivity and Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
17.
Curr Opin Organ Transplant ; 16(4): 380-4, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21709555

ABSTRACT

PURPOSE OF REVIEW: Kidney paired donation (KPD) has become a viable option for patients in need of a kidney transplant who have a willing, but incompatible living donor. The purpose of this review is to highlight the recent advances in KPD including shipping live-donor kidneys to their intended recipient, enrolling compatible pairs, and combining KPD with desensitization. RECENT FINDINGS: KPD has been expanded and facilitated by multiple organizations. KPD chains have been extended from single-center two-way 'swaps' to transcontinental KPD chains in which living-donor organs have been shipped without compromising outcomes. Living-donor kidneys have been shipped transcontinentally on commercial airlines with great success. Enrollment of compatible donor--recipient pairs, particularly those with blood group O donors, is one strategy that has been employed to extend KPD to even more patients. It has also become more apparent that KPD can be successfully combined with desensitization in order to transplant our most immunologically challenging patients. SUMMARY: KPD is becoming an established method of transplantation at transplant centers throughout the world. Advancements have been made through shipping living-donor kidneys, combining KPD with desensitization, and enrolling compatible pairs.


Subject(s)
Histocompatibility , Kidney Transplantation/trends , Living Donors/supply & distribution , Tissue and Organ Procurement/trends , Desensitization, Immunologic/trends , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival , Humans , Kidney Transplantation/immunology , Transportation , Treatment Outcome
19.
Biomicrofluidics ; 4(4): 44106, 2010 Nov 10.
Article in English | MEDLINE | ID: mdl-21139700

ABSTRACT

In the quest to create a low-power portable lab-on-a-chip system, we demonstrate the specific binding and concentration of human CD8+ T-lymphocytes on an electrowetting-on-dielectric (EWOD)-based digital microfluidic platform using antibody-conjugated magnetic beads (MB-Abs). By using a small quantity of nonionic surfactant, we enable the human cell-based assays with selective magnetic binding on the EWOD device in an air environment. High binding efficiency (∼92%)of specific cells on MB-Abs is achieved due to the intimate contact between the cells and the magnetic beads (MBs) produced by the circulating flow within the small droplet. MBs have been used and cells manipulated in the droplets actuated by EWOD before; reported here is a cell assay of a clinical protocol on the EWOD device in air environment. The present technique can be further extended to capture other types of cells by suitable surface modification on the MBs.

20.
J Urol ; 183(5): 1941-6, 2010 May.
Article in English | MEDLINE | ID: mdl-20303114

ABSTRACT

PURPOSE: Laparoscopic living donor nephrectomy offers patients the benefits of decreased morbidity and improved cosmesis, while maintaining equivalent graft outcomes and complication rates similar to those of open donor surgery. With expressed concern for donor safety, using a standardized complication scale would allow combining data in a donor registry so potential donors could be adequately followed and counseled. We present the largest series to our knowledge of laparoscopic living donor nephrectomy by a single surgeon. MATERIALS AND METHODS: The institution's initial 750 laparoscopic living donor nephrectomies were included in the study, and a retrospective and prospective chart and database analysis was performed. RESULTS: Mean donor age was 40.5 years and average body mass index was 25.7 kg/m(2). There were 175 patients (23%) with 2 or more renal arteries while 161 (21.5%) had early arterial bifurcations. There were 3 open conversions (0.4%) and the overall complication rate was 5.46%. Median hospital stay was 1 day and the readmission rate was 1.2%. There were 5 reoperations (0.67%), none of which was for the control of bleeding. No patients required a blood transfusion and there were no mortalities. Using a modified Clavien classification of complications for living donor nephrectomy 65.8% were grade 1, 31.7% grade 2 (12.2% grade 2a, 14.6% grade 2b, 4.9% grade 2c) and 2.4% grade 3. There were no grade 4 complications. CONCLUSIONS: With appropriate patient selection and operative experience, laparoscopic living donor nephrectomy is a safe procedure associated with low morbidity. The use of a standardized complication system specific for this procedure is encouraged and could aid in counseling potential donors in the future.


Subject(s)
Kidney Transplantation , Laparoscopy/methods , Living Donors , Nephrectomy/methods , Postoperative Complications/classification , Adolescent , Adult , Aged , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Registries , Reoperation
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