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1.
Indian J Nephrol ; 32(2): 116-126, 2022.
Article in English | MEDLINE | ID: mdl-35603108

ABSTRACT

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.

2.
World J Exp Med ; 11(5): 55-65, 2021 Nov 20.
Article in English | MEDLINE | ID: mdl-34877265

ABSTRACT

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.

3.
Am J Kidney Dis ; 78(4): 501-510.e1, 2021 10.
Article in English | MEDLINE | ID: mdl-33872689

ABSTRACT

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.


Subject(s)
Body Mass Index , Graft Rejection/epidemiology , Graft Survival/physiology , Kidney Transplantation/trends , Obesity/epidemiology , Transplant Recipients , Adult , Aged , Cohort Studies , Female , Graft Rejection/diagnosis , Humans , Male , Middle Aged , Obesity/diagnosis , Obesity/surgery , Retrospective Studies , Treatment Outcome
4.
Transplant Proc ; 53(3): 885-888, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32980134

ABSTRACT

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.


Subject(s)
Black or African American/genetics , Kidney Failure, Chronic/ethnology , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Tissue Donors/statistics & numerical data , Adult , Calcineurin Inhibitors/therapeutic use , Databases, Factual , Female , Graft Survival/genetics , Humans , Kidney , Kidney Failure, Chronic/mortality , Kidney Transplantation/methods , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Proportional Hazards Models , Risk Factors , Tissue and Organ Procurement/statistics & numerical data , Treatment Outcome
7.
Exp Clin Transplant ; 18(2): 144-148, 2020 04.
Article in English | MEDLINE | ID: mdl-31250745

ABSTRACT

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.


Subject(s)
Black or African American , Donor Selection , Kidney Transplantation , Tissue Donors , Databases, Factual , Graft Rejection/ethnology , Graft Rejection/mortality , Graft Survival , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Race Factors , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States/epidemiology
8.
Transplant Proc ; 51(6): 1796-1800, 2019.
Article in English | MEDLINE | ID: mdl-31399165

ABSTRACT

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.


Subject(s)
Blood Group Incompatibility/immunology , Graft Survival/immunology , HLA-DR Antigens/immunology , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Adult , Alemtuzumab/therapeutic use , Antibodies/immunology , Antilymphocyte Serum/immunology , Antilymphocyte Serum/therapeutic use , Basiliximab/immunology , Basiliximab/therapeutic use , Calcineurin Inhibitors/immunology , Calcineurin Inhibitors/therapeutic use , Contraindications, Procedure , Daclizumab/immunology , Daclizumab/therapeutic use , Databases, Factual , Female , Histocompatibility Testing , Humans , Kidney/immunology , Living Donors , Male , Middle Aged , Mycophenolic Acid/immunology , Mycophenolic Acid/therapeutic use , Proportional Hazards Models , Treatment Outcome
9.
Crit Care Nurs Q ; 42(4): 362-370, 2019.
Article in English | MEDLINE | ID: mdl-31449146

ABSTRACT

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.


Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapy , Respiratory Distress Syndrome/complications , Acid-Base Imbalance , Acute Kidney Injury/etiology , Creatinine/urine , Critical Illness/mortality , Critical Illness/therapy , Glomerular Filtration Rate/physiology , Humans , Water-Electrolyte Imbalance
10.
World J Transplant ; 9(1): 1-13, 2019 Jan 16.
Article in English | MEDLINE | ID: mdl-30697516

ABSTRACT

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.

11.
Exp Clin Transplant ; 17(4): 457-460, 2019 08.
Article in English | MEDLINE | ID: mdl-30066624

ABSTRACT

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.


Subject(s)
Alemtuzumab/adverse effects , Antilymphocyte Serum/adverse effects , Basiliximab/adverse effects , Daclizumab/adverse effects , Hepatitis B virus/drug effects , Hepatitis B/virology , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Adult , Alemtuzumab/administration & dosage , Antilymphocyte Serum/administration & dosage , Basiliximab/administration & dosage , Clinical Decision-Making , Daclizumab/administration & dosage , Databases, Factual , Disease Progression , Drug Therapy, Combination , Female , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/drug effects , Hepatitis B/diagnosis , Hepatitis B/immunology , Hepatitis B/mortality , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/blood , Hepatitis B virus/immunology , Humans , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/mortality , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
12.
Clin Transplant ; : e13442, 2018 Nov 08.
Article in English | MEDLINE | ID: mdl-30408257

ABSTRACT

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.

13.
J Clin Transl Hepatol ; 6(3): 289-295, 2018 Sep 28.
Article in English | MEDLINE | ID: mdl-30271741

ABSTRACT

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.

14.
World J Transplant ; 8(4): 102-109, 2018 Aug 09.
Article in English | MEDLINE | ID: mdl-30148076

ABSTRACT

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.

15.
Transplantation ; 102(5): e245-e248, 2018 05.
Article in English | MEDLINE | ID: mdl-29346254

ABSTRACT

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.


Subject(s)
Kidney Transplantation/methods , Living Donors , Adult , Age Factors , Biomarkers/blood , Child, Preschool , Creatinine/blood , Donor Selection , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Infant , Kidney Transplantation/adverse effects , Male , Pennsylvania , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
16.
Transpl Int ; 31(7): 729-738, 2018 07.
Article in English | MEDLINE | ID: mdl-29368361

ABSTRACT

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.


Subject(s)
Cold Ischemia , Graft Survival , Kidney Transplantation/mortality , Delayed Graft Function/epidemiology , Female , Graft Rejection/epidemiology , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Retrospective Studies , United States/epidemiology
17.
J Nephropathol ; 6(3): 220-224, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28975104

ABSTRACT

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.

18.
Transplantation ; 101(10): 2527-2535, 2017 10.
Article in English | MEDLINE | ID: mdl-28475563

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antilymphocyte Serum/therapeutic use , Graft Rejection/immunology , Graft Survival , Immunosuppression Therapy/methods , Kidney Transplantation , Mycophenolic Acid/therapeutic use , Adolescent , Adult , Alemtuzumab , Antineoplastic Agents/therapeutic use , Female , Follow-Up Studies , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Young Adult
19.
World J Nephrol ; 5(4): 300-7, 2016 Jul 06.
Article in English | MEDLINE | ID: mdl-27458559

ABSTRACT

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.

20.
Exp Clin Transplant ; 14(3): 287-93, 2016 06.
Article in English | MEDLINE | ID: mdl-27221720

ABSTRACT

OBJECTIVES: This study explored the safety of early steroid withdrawal in recipients of expanded criteria deceased-donor kidney transplants. MATERIALS AND METHODS: 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. RESULTS: 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 recipients > 60 years old (n = 1729). CONCLUSIONS: 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.


Subject(s)
Donor Selection , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/methods , Steroids/administration & dosage , Tissue Donors/supply & distribution , Age Factors , Aged , Alemtuzumab , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Antilymphocyte Serum/administration & dosage , Basiliximab , Calcineurin Inhibitors/administration & dosage , Daclizumab , Databases, Factual , Drug Administration Schedule , Drug Therapy, Combination , Feasibility Studies , Female , Graft Rejection/immunology , Graft Rejection/mortality , Graft Survival/drug effects , Humans , Immunoglobulin G/administration & dosage , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retrospective Studies , Risk Factors , Steroids/adverse effects , Time Factors , Treatment Outcome , United States
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