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1.
Am J Transplant ; 22(2): 599-609, 2022 02.
Article in English | MEDLINE | ID: mdl-34613666

ABSTRACT

Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV. To limit bias, matches were within the same center. The primary outcome was BKPyV viremia ≥1000 copies/ml or biopsy-proven BKPyV nephropathy; a secondary outcome was BKPyV viremia ≥10 000 copies/ml or nephropathy. Outcomes were analyzed using weighted and stratified Cox regression. The median days to peak BKPyV viremia level was 119 (IQR 87-182). HCV-viremic KT was not associated with increased risk of the primary BKPyV outcome (HR 1.26, p = .22), but was significantly associated with the secondary outcome of BKPyV ≥10 000 copies/ml (HR 1.69, p = .03). One-year eGFR was similar between the matched groups. Only one HCV-viremic kidney recipient had primary graft loss. In summary, HCV-viremic KT was not significantly associated with the primary outcome of BKPyV viremia, but the data suggested that donor HCV might elevate the risk of more severe BKPyV viremia ≥10 000 copies/ml. Nonetheless, one-year graft function for HCV-viremic recipients was reassuring.


Subject(s)
BK Virus , Kidney Transplantation , Polyomavirus Infections , Tumor Virus Infections , Hepacivirus , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Tumor Virus Infections/etiology , Viremia
2.
Ren Fail ; 44(1): 831-841, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35546431

ABSTRACT

Kidney transplants (KT) from hepatitis C (HCV) viremic donors to HCV negative recipients has shown promising renal outcomes, however, high incidence of cytomegalovirus (CMV) viremia were reported. We performed a prospective cohort study of 52 HCV negative KT recipients from Methodist University Hospital including 41 receiving transplants from HCV aviremic donors and 11 from HCV viremic donors. CMV specific CD4+ and CD8 + T cell immunity was measured by intracellular flow cytometry assay. Primary outcome was the development of positive CMV specific CD4+ and CD8 + T cell immune response in the entire cohort and each subgroup. The association between donor HCV status and CMV specific CD4+ and CD8 + T cell immune response was analyzed by Cox proportional hazard models. Mean recipient age was 48 ± 13 years, with 73% male and 82% African American. Positive CMV specific CD4+ and CD8 + T cell immune response was found in 53% and 47% of the cohort at 1 month, 65% and 70% at 2 months, 80% and 75% at 4 months, 89% and 87% at 6 months, and 94% and 94% at 9 months post-transplant, respectively. There was no significant difference in the incidence of positive CMV specific T cell immune response between recipients of transplants from HCV aviremic donors compared to HCV viremic donors in unadjusted (for CD8+: HR = 1.169, 95%CI: 0.521-2.623; for CD4+: HR = 1.208, 95%CI: 0.543-2.689) and adjusted (for CD8+: HR = 1.072, 95%CI: 0.458-2.507; for CD4+: HR = 1.210, 95%CI: 0.526-2.784) Cox regression analyses. HCV viremia in donors was not associated with impaired development of CMV specific T cell immunity in this cohort.


Subject(s)
Cytomegalovirus Infections , Hepatitis C , Kidney Transplantation , Adult , Antiviral Agents , Cytomegalovirus Infections/epidemiology , Female , Hepacivirus , Humans , Immunity , Kidney Transplantation/adverse effects , Male , Middle Aged , Prospective Studies , T-Lymphocytes , Tissue Donors , Transplant Recipients , Viremia
3.
Am J Kidney Dis ; 77(5): 739-747.e1, 2021 05.
Article in English | MEDLINE | ID: mdl-33333148

ABSTRACT

RATIONALE & OBJECTIVE: Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. EXPOSURE: Predictor(s) of donor infection with HCV. OUTCOMES: Kidney allograft function and allograft biopsy findings during the first year following transplantation. ANALYTICAL APPROACH: We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. RESULTS: The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. LIMITATIONS: Generalizability from a single-center study and small sample size was limited. CONCLUSIONS: Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.


Subject(s)
Delayed Graft Function/epidemiology , Glomerular Filtration Rate , Graft Rejection/epidemiology , Hepatitis C, Chronic/transmission , Kidney Failure, Chronic/surgery , Kidney Transplantation , Adult , Allografts/pathology , Antibodies/immunology , Antiviral Agents/therapeutic use , Cohort Studies , Female , Graft Rejection/prevention & control , Hepatitis C, Chronic/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Linear Models , Male , Middle Aged , RNA, Viral/blood , Retrospective Studies , Tissue Donors
4.
Clin Transplant ; 35(12): e14485, 2021 12.
Article in English | MEDLINE | ID: mdl-34523744

ABSTRACT

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Kidney Transplantation , Antiviral Agents/therapeutic use , Ezetimibe/therapeutic use , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Kidney , Kidney Transplantation/adverse effects , RNA , Retrospective Studies , Tissue Donors , Transplant Recipients
5.
Am J Transplant ; 20(11): 3061-3071, 2020 11.
Article in English | MEDLINE | ID: mdl-32844546

ABSTRACT

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.


Subject(s)
COVID-19/epidemiology , Critical Illness/therapy , Hospitalization/trends , Intensive Care Units/statistics & numerical data , Organ Transplantation , Pandemics , SARS-CoV-2 , Aged , Comorbidity , Critical Illness/epidemiology , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Middle Aged , Risk Factors , Survival Rate/trends , United States/epidemiology
6.
Transpl Int ; 33(12): 1732-1744, 2020 12.
Article in English | MEDLINE | ID: mdl-32935416

ABSTRACT

The kidney donor profile index (KDPI) defines an hepatitis C (HCV) positive donor based on HCV antibody (Ab) and/or nucleic acid amplification test (NAT) positivity, with donors who are not actively infected (Ab+/NAT-) also classified as HCV positive. From Scientific Registry of Transplant Recipients dataset, we identified HCV-negative recipients, who received a kidney transplant from HCV Ab+/NAT- (n = 116) and HCV Ab-/NAT- (n = 25 574) donor kidneys. We then compared recipients' estimated glomerular filtration rate (eGFR) at 6 months in matched cohorts, using combined exact matching (based on KDPI) and propensity score matching. We created two separate matched cohorts: for the first cohort, we used the allocation KDPI, while for the second cohort we used an optimal KDPI, where the HCV component of KDPI was considered negative in Ab+/NAT- patients. The mean ± SD age of the allocation KDPI-matched cohort at baseline was 59 ± 10 years, 69% were male, 61% were white. Recipients' eGFR at 6 months after transplantation was significantly higher in the HCV Ab+/NAT- group compared to the HCV Ab-/NAT- group (61.1 ± 17.9 vs. 55.6 ± 18.8 ml/min/1.73 m2 , P = 0.011) in the allocation KDPI-matched cohort, while it was similar (61.8 ± 19.5 vs. 62.1 ± 20.1 ml/min/1.73 m2 , P = 0.9) in the optimal KDPI-matched cohort. Recipients who received HCV Ab positive, but NAT-negative donor kidneys did not experience worse 6-month eGFR than correctly matched HCV Ab-/NAT- recipients.


Subject(s)
Hepatitis C , Kidney Transplantation , Aged , Cohort Studies , Graft Survival , Humans , Male , Middle Aged , Retrospective Studies , Tissue Donors
7.
Transpl Int ; 33(2): 202-215, 2020 02.
Article in English | MEDLINE | ID: mdl-31647143

ABSTRACT

There is a dearth of published data regarding the presence of post-transplant donor-specific antibodies (DSA), especially C1q-binding DSA (C1q+DSA), and patient and kidney allograft outcomes in simultaneous liver-kidney transplant (SLKT) recipients. We conducted a retrospective cohort study consisted of 85 consecutive SLKT patients between 2009 and 2018 in our center. Associations between presence of post-transplant DSA, including persistent and/or newly developed DSA and C1q+DSA, and all-cause mortality and the composite outcome of mortality, allograft kidney loss, and antibody-mediated rejection were examined using unadjusted and age and sex-adjusted Cox proportional hazards and time-dependent regression models. The mean age at SLKT was 56 years and 60% of the patients were male. Twelve patients (14%) had post-transplant DSA and seven patients (8%) had C1q+DSA. The presence of post-transplant DSA was significantly associated with increased risk of mortality (unadjusted model: Hazard Ratio (HR) = 2.72, 95% confidence interval (CI): 1.06-6.98 and adjusted model: HR = 3.20, 95% CI: 1.11-9.22) and the composite outcome (unadjusted model: HR = 3.18, 95% CI: 1.31-7.68 and adjusted model: HR = 3.93, 95% CI: 1.39-11.10). There was also higher risk for outcomes in recipients with C1q+DSA compared the ones without C1q+DSA. Post-transplant DSA is significantly associated with worse patient and kidney allograft outcomes in SLKT. Further prospective and large cohort studies are warranted to better assess these associations.


Subject(s)
Isoantibodies/immunology , Kidney Transplantation , Liver Transplantation , Transplant Recipients , Complement C1q/immunology , Female , Graft Rejection , Graft Survival , Humans , Kidney , Liver , Male , Middle Aged , Retrospective Studies , Tissue Donors
8.
Transpl Infect Dis ; 22(5): e13305, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32358827

ABSTRACT

Fever of unknown origin and the clinical picture of thrombotic microangiopathy (TMA) are diagnostic challenges in the early period after kidney transplantation. Here, we report a case of human monocytic ehrlichiosis in a renal allograft recipient who presented with fever and clinical picture of TMA in the first month post-kidney transplant. Despite broad coverage with multiple antimicrobial agents, fever and hematological abnormalities persisted for several days. A history of contact exposure and living in an endemic area raised clinical suspicion for human monocytic ehrlichiosis (HME), and empiric treatment with doxycycline was initiated. Definitive diagnosis of HME was confirmed by polymerase chain reaction (PCR) for Ehrlichia chaffeensis. Human ehrlichiosis should be considered within the differential diagnosis in kidney transplant recipients with the clinical picture of TMA and fever of unknown origin. Furthermore, early treatment with doxycycline enhances rapid resolution of clinical and laboratory recovery.


Subject(s)
Ehrlichia chaffeensis , Ehrlichiosis , Kidney Transplantation , Thrombotic Microangiopathies , Diagnosis, Differential , Doxycycline , Humans , Kidney Transplantation/adverse effects
9.
Ren Fail ; 42(1): 767-775, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32729359

ABSTRACT

BACKGROUND: We aimed to assess the probability and factors associated with the presence of hepatitis C virus (HCV) antibody among HCV seronegative kidney transplant recipients receiving HCV-infected (nucleic acid testing positive) donor kidneys. METHODS: This is a retrospective review examining HCV antibody seroconversion of all kidney transplant recipients receiving an organ from an HCV-infected donor between 1 March 2018 and 2 December 2019 at a high-volume kidney transplant center in the southeast United States. RESULTS: Of 97 patients receiving HCV-infected kidneys, the final cohort consisted of 85 recipients with 5 (5.9%) recipients noted to have HCV antibody seroconversion in the setting of HCV viremia. The HCV RNA level at closest time of antibody measurement was higher in the seroconverted patients versus the ones who never converted [median and (interquartile range): 1,091,500 (345,000-8,360,000) vs 71,500 (73-313,000), p = 0.02]. No other significant differences including type of immunosuppression were noted between the HCV antibody positive group and HCV antibody negative group. Donor donation after cardiac death status [Odds Ratio (OR) and 95% Confidence Interval (CI) was: 8.22 (1.14-59.14)], donor age [OR (95% CI) (+5 years) was: 3.19 (1.39-7.29)] and Kidney Donor Profile Index [OR (95% CI) (+1) was:1.07 (1.01-1.15)] showed a statistically significant association with HCV seroconversion. CONCLUSIONS: HCV antibody should not be considered routine screening for presence of infection in previously HCV naïve kidney transplant recipients receiving kidneys from HCV-infected donors, as only a modest percentage have antibody despite active viremia. The assessment of HCV viral load should be routine in all transplant recipients receiving organs from public health service increased risk donors.


Subject(s)
Hepatitis C Antibodies/blood , Hepatitis C/transmission , Kidney Transplantation/adverse effects , Seroconversion , Tissue Donors/supply & distribution , Viremia/immunology , Adult , Female , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C/virology , Humans , Kidney Failure, Chronic/surgery , Logistic Models , Male , Middle Aged , Postoperative Complications , Retrospective Studies , Risk Factors , Tissue and Organ Procurement/standards , United States , Viral Load , Viremia/pathology , Viremia/virology
10.
Ren Fail ; 42(1): 1083-1092, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33100098

ABSTRACT

BACKGROUND: Deceased-donor kidney transplantation (KT) from hepatitis C (HCV)-infected donors into HCV-uninfected recipients (HCV D+/R-) could become standard care in the near future. However, HCV viral replication by viral transmission might lead to a higher incidence of cytomegalovirus (CMV) infection in these recipients. METHODS: A national-registry-based retrospective cohort study was conducted using the Scientific Registry of Transplant Recipients (SRTR) data set. We assessed the incidence of CMV infection in HCV antibody (Ab) negative recipients receiving kidneys from HCV Ab positive (HCVAb D+/R-) and negative (HCVAb D-/R-) donors. The risk of CMV infection was analyzed by Cox regression analysis in a propensity score (PS) matched-cohort of HCVAb D+/R- (n = 950) versus HCVAb D-/R- (n = 950). Sensitivity analysis was also conducted in the entire cohort (n = 181 082). RESULTS: The mean age at baseline was 54 years, 75% were male, and 55% of the patients were African American in PS-matched cohort. Compared to the HCVAb D-/R - patients, recipients with HCVAb D+/R - showed identical probability for the incidence of CMV infection (Hazard Ratio (HR) = 1.00, 95% Confidence Interval (CI): 0.82-1.22). In the sensitivity analysis, compared to the HCVAb D-/R - patients, the HCVAb D+/R - group had a significantly lower risk of CMV infection in the unadjusted analysis (HR = 0.75, 95%CI: 0.65-0.85), while this risk difference disappeared after the adjusted analysis (HR = 0.99, 95%CI: 0.87-1.14). CONCLUSION: The incidence of CMV infection was similar in recipients who received HCVAb D + and HCVAb D - KT. Further studies are needed to assess this association in KT from HCV nucleic acid positive donors.


Subject(s)
Cytomegalovirus Infections/epidemiology , Hepatitis C , Kidney Transplantation , Postoperative Complications/epidemiology , Adult , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/virology , Female , Humans , Incidence , Kidney/virology , Male , Middle Aged , Postoperative Complications/virology , Proportional Hazards Models , Registries , Retrospective Studies , Tissue Donors , Transplant Recipients , United States/epidemiology
11.
Ren Fail ; 42(1): 40-47, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31875761

ABSTRACT

Background: De novo Donor Specific Antibodies (DSA) are considered as a risk factor for the kidney allograft outcomes in recipients after simultaneous liver-kidney transplantation (SLKT). We hypothesized that length of hospital stay (LOS) might be associated with de novo DSA development of due to the increased likelihood of receiving blood transfusions with reduced immunosuppressive regimens.Methods: This study is a single-center, retrospective cohort study consisting of 85 recipients who underwent SLKT from 2009 to 2018 in our hospital. We divided the patients into two groups according to LOS [long hospital stay (L) group (LOS >14 days) and short hospital stay (S) group (LOS ≤14 days)]. Propensity score (PS) has been created using logistic regression to predict LOS greater than median of 14 days. The association between the presence of de novo DSA and LOS was assessed by logistic regression models adjusted for PS.Results: The mean age at transplantation of the entire cohort was 55.5 ± 10.1 years. Sixty percent of the recipients were male and Caucasian. Median LOS in (L) group was three-fold longer than (S) group [L: median 30 days (IQR: 21-52), S: median 8.5 days (IQR: 7-11)]. Eight patients developed de novo DSA after SLKT (9.4%), all of them were in (L) group. Longer LOS was significantly associated with higher risk of development of de novo DSA in unadjusted (OR+ each 5 days: 1.09, 95% CI:1.02-1.16) and PS adjusted (OR+ each 5 days: 1.11, 95% CI:1.02-1.21) analysis.Conclusion: Longer hospitalization is significantly associated with the development of de novo DSA in SLKT.


Subject(s)
Graft Rejection/epidemiology , Isoantibodies/blood , Kidney Transplantation/adverse effects , Length of Stay/statistics & numerical data , Liver Transplantation/adverse effects , Adult , Aged , Allografts/immunology , Blood Transfusion/statistics & numerical data , Female , Graft Rejection/blood , Graft Rejection/immunology , Graft Rejection/prevention & control , Humans , Immunosuppressive Agents/administration & dosage , Incidence , Isoantibodies/immunology , Isoantigens/immunology , Kidney/immunology , Liver/immunology , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors
12.
Am J Transplant ; 19(8): 2294-2305, 2019 08.
Article in English | MEDLINE | ID: mdl-30672107

ABSTRACT

A history of posttraumatic stress disorder (PTSD), if uncontrolled, represents a contraindication for kidney transplantation. However, no previous large study has assessed the association between pretransplant history of PTSD and posttransplantation outcomes. We examined 4479 US veterans who had undergone transplantation. The diagnosis of history of PTSD was based on a validated algorithm. Measured covariates were used to create a matched cohort (n = 560). Associations between pretransplant PTSD and death with functioning graft, all-cause death, and graft loss were examined in survival models. Posttransplant medication nonadherence was assessed using proportion of days covered (PDC). From among 4479 veterans, 282 (6.3%) had a history of PTSD. The mean age ± standard deviation (SD) of the cohort at baseline was 61 ± 11 years, 91% were male, and 66% and 28% of patients were white and African American, respectively. Compared to patients without a history of PTSD, patients with a history of PTSD had a similar risk of death with a functioning graft (subhazard ratio [SHR] 0.97, 95% confidence interval [CI] 0.61-1.54), all-cause death (1.05, 0.69-1.58), and graft loss (1.09, 0.53-2.26). Moreover, there was no difference in immunosuppressive drug PDC in patients with and without a history of PTSD (PDC: 98 ± 4% vs 99 ± 3%, P = .733 for tacrolimus; PDC: 99 ± 4% vs 98 ± 7%, P = .369 for mycophenolic acid). A history of PTSD in US veterans with end-stage renal disease should not on its own preclude a veteran from being considered for transplantation.


Subject(s)
Graft Rejection/mortality , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Medication Adherence/statistics & numerical data , Postoperative Complications/mortality , Stress Disorders, Post-Traumatic/physiopathology , Veterans/psychology , Cause of Death , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Survival , Humans , Kidney Failure, Chronic/psychology , Kidney Failure, Chronic/surgery , Kidney Function Tests , Kidney Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Risk Factors , Stress Disorders, Post-Traumatic/psychology , Survival Rate
13.
Am J Transplant ; 19(11): 3046-3057, 2019 11.
Article in English | MEDLINE | ID: mdl-31306549

ABSTRACT

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.


Subject(s)
Graft Survival , Hepatitis C/transmission , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Tissue Donors/supply & distribution , Transplant Recipients/statistics & numerical data , Adult , Antiviral Agents/therapeutic use , Female , Follow-Up Studies , Glomerular Filtration Rate , Hepacivirus/isolation & purification , Hepatitis C/drug therapy , Hepatitis C/virology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Tissue and Organ Procurement/methods
14.
J Ren Nutr ; 29(3): 188-195, 2019 05.
Article in English | MEDLINE | ID: mdl-30819599

ABSTRACT

OBJECTIVE(S): Prealbumin, a transport protein mostly synthesized in the liver, is a marker of nutrition. Although decreased prealbumin levels are associated with increased mortality in end-stage kidney disease patients, its association with mortality in kidney transplant recipients remains unknown. We evaluated the association between prealbumin levels and outcomes in kidney transplant recipients. DESIGN: This was a prospective prevalent cohort study. This study included 991 kidney transplant recipients enrolled from December 31, 2006, to December 31, 2007, and followed over a 6-year period. Sociodemographic, past medical history, clinical, and laboratory data were collected at the study entry. Associations between prealbumin levels and death with functioning graft, all-cause mortality, and graft loss were examined using survival models. RESULTS: Serum prealbumin levels showed significant negative correlation with estimated glomerular filtration rate (R = -0.28; P < .001) and high-sensitive C-reactive protein (R = -0.24; P < .001). Each 5 mg/dL lower serum prealbumin level was associated with 20% higher risk of death with functioning graft (subdistribution hazard ratio [95% confidence interval]: 1.20 [1.08-1.35]; P = .001), which persisted after multivariable adjustments (subdistribution hazard ratio [95% confidence interval]: 1.13 [1.00-1.28]; P = .039). Qualitatively similar trend was observed in all-cause mortality; however, there was no association between prealbumin levels and graft loss. CONCLUSION(S): Lower serum prealbumin level is associated with increased risk of death with functioning graft in prevalent kidney transplant recipients.


Subject(s)
Graft Survival/physiology , Kidney Transplantation , Prealbumin/analysis , Adult , Aged , C-Reactive Protein/analysis , Cohort Studies , Female , Glomerular Filtration Rate , Graft Rejection/epidemiology , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Prospective Studies , Treatment Outcome
16.
Clin J Am Soc Nephrol ; 18(11): 1466-1475, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37574663

ABSTRACT

BACKGROUND: Acceptable post-transplant outcomes were reported in kidney transplant recipients from donors with coronavirus disease 2019 (COVID-19); however, there are no comparative studies with well-matched controls. METHODS: This multicenter, prospective observational study, which included three transplant centers in the United States, enrolled 61 kidney recipients from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected deceased donors. Using optimal matching methods, we matched every recipient to three comparators receiving kidneys from SARS-CoV-2-negative deceased donors with otherwise highly similar characteristics in the same transplant centers to compare 6-month eGFR. RESULTS: Among recipients of SARS-CoV-2-infected donor kidneys, one recipient died with a functional graft within 6 months. Mean 6-month eGFR was not significantly different between SARS-CoV-2-infected and noninfected donor groups (55±21 and 57±25 ml/min per 1.73 m 2 , respectively; P = 0.61). Six-month eGFR in recipients from SARS-CoV-2-infected donors who died of reasons other than COVID-19 was not significantly different from those from SARS-CoV-2-negative donors (58±22 and 56±25 ml/min per 1.73 m 2 , respectively; P = 0.51). However, recipients from donors who died of COVID-19 had significantly lower 6-month eGFR than those from SARS-CoV-2-negative donors (46±17 and 58±27 ml/min per 1.73 m 2 , respectively; P = 0.03). No donor-to-recipient SARS-CoV-2 transmission was observed. CONCLUSIONS: Six-month eGFR was not significantly different between recipients of kidneys from SARS-CoV-2-infected and noninfected donors. However, those receiving kidneys from donors who died of COVID-19 had significantly lower 6-month eGFR. Donor-to-recipient SARS-CoV-2 transmission was not observed.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Death , Graft Survival , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , SARS-CoV-2 , Tissue Donors , Transplant Recipients , United States/epidemiology , Prospective Studies
17.
Transplant Direct ; 8(6): e1342, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35651584

ABSTRACT

Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts. Methods: Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29). Results: Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55-85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26-30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3-F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk (P = 0.55). Conclusions: Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology.

18.
Nephron ; 144(3): 126-137, 2020.
Article in English | MEDLINE | ID: mdl-32007998

ABSTRACT

INTRODUCTION AND OBJECTIVE: The impact of pretransplant donor-specific antibodies (DSAs), especially class II DSAs, on kidney allograft outcomes remains unclear in simultaneous liver-kidney transplantation (SLKT) recipients. METHODS: We examined 85 recipients who consecutively underwent SLKT between 2009 and 2018 in our center. Associations between pretransplant DSA and worsening kidney function (WKF), kidney allograft loss, composite kidney outcome (WKF and/or antibody-mediated rejection and/or death-censored kidney allograft loss), death with functioning graft, and overall mortality were examined in survival analysis. WKF was defined as an eGFR decrease of 30% or greater from baseline, or 2 or more episodes of proteinuria, at least 90 days apart from each other. RESULTS: The mean age at SLKT was 56 ± 10 years, and 62% of the recipients were male. More than one quarter (26%) of our recipients were African American. The 2 major causes of end-stage liver disease were hepatitis C (28%) and alcoholic hepatitis (26%). Nineteen recipients (22%) had pretransplant DSAs at the time of SLKT. The DSA(+) group and DSA(-) group had similar risk of WKF (unadjusted model: hazard ratio [HR] = 0.77, 95% confidence interval [CI]: 0.29-2.05 and adjusted model: HR = 0.36, 95% CI: 0.12-1.08); similar risk of composite kidney outcome (unadjusted model: HR = 1.04, 95% CI: 0.45-2.43 and adjusted model: HR = 0.53, 95% CI: 0.20-1.39); and similar risk of overall death (unadjusted model: HR = 1.23, 95% CI: 0.45-3.36 and adjusted model: HR = 1.28, 95% CI: 0.42-3.87). We found similar results when comparing different DSA subclasses (class I and II DSAs) with recipients without DSAs. CONCLUSIONS: The presence of pretransplant DSAs was not associated with worse kidney allograft outcomes from our single-center experience. Further prospective larger studies are strongly warranted.


Subject(s)
Antilymphocyte Serum/pharmacology , Histocompatibility Antigens Class II/immunology , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Liver Transplantation , Adult , Aged , Allografts , Female , Graft Rejection/etiology , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Tissue Donors
20.
BMJ Case Rep ; 20132013 Dec 05.
Article in English | MEDLINE | ID: mdl-24311415

ABSTRACT

Tacrolimus is an immunosuppressant frequently used following solid organ transplantation, including renal transplantation. Peripheral neuropathy is an uncommon neurological side effect of tacrolimus and has rarely been reported in renal transplantation. We report a patient who received a living-related donor kidney transplant and presented with altered mental status and new-onset bilateral foot drop. Laboratory tests including cerebrospinal fluid tests excluded infection, and MRI of the brain showed chronic microvascular ischaemic changes. Electromyography and nerve conduction study confirmed bilateral common peroneal nerve demyelination. He was also found to have inadvertently overdosed on tacrolimus at home. After switching from tacrolimus to cyclosporine, the patient's symptoms improved within 5 months. His renal function was maintained with an immunosuppressant regimen of cyclosporine, prednisone and mycophenolic acid. The prompt recognition of tacrolimus as a potential neurotoxic drug in a patient with renal transplant and substituting tacrolimus with a different immunosuppressant may prevent permanent neurological damage.


Subject(s)
Brain Diseases/chemically induced , Immunosuppressive Agents/adverse effects , Kidney Transplantation , Polyneuropathies/chemically induced , Tacrolimus/adverse effects , Aged , Brain Diseases/diagnosis , Diagnosis, Differential , Electromyography , Humans , Male , Neural Conduction , Polyneuropathies/diagnosis , Risk Factors
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