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Background: C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression. Methods: We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome. Results: During a median (interquartile range) follow-up period of 37 (1856) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence. Conclusions: Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.
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Trasplante de Riñón , Recurrencia , Humanos , Trasplante de Riñón/efectos adversos , Biopsia , Masculino , Complemento C3/análisis , Factores de Tiempo , Persona de Mediana Edad , Femenino , Adulto , Glomerulonefritis/patologíaRESUMEN
BACKGROUND AND OBJECTIVES: Kidney transplantation with minimal or no dialysis exposure provides optimal outcomes for children with end-stage kidney disease. We sought to understand disparities in timely access to transplant waitlisting. METHODS: We conducted a retrospective, registry-based cohort study of candidates ages 3 to 17 added to the US kidney transplant waitlist 2015 to 2019. We defined "preemptive waitlisting" as waitlist addition before receiving dialysis and compared demographics of candidates based on preemptive status. We used competing risk regression to determine the association between preemptive waitlisting and transplantation. We then identified waitlist additions age >18 who initiated dialysis as children, thereby missing pediatric allocation prioritization, and evaluated the association between waitlisting with pediatric prioritization and transplantation. RESULTS: Among 4506 pediatric candidates, 48% were waitlisted preemptively. Female sex, Hispanic ethnicity, Black race, and public insurance were associated with lower adjusted relative risk of preemptive waitlisting. Preemptive listing was not associated with time from waitlist activation to transplantation (adjusted hazard ratio 0.94, 95% confidence interval 0.87-1.02). Among transplant recipients waitlisted preemptively, 68% had no pretransplant dialysis, whereas recipients listed nonpreemptively had median 1.6 years of dialysis at transplant. Among 415 candidates initiating dialysis as children but waitlisted as adults, transplant rate was lower versus nonpreemptive pediatric candidates after waitlist activation (adjusted hazard ratio 0.54, 95% confidence interval 0.44-0.66). CONCLUSIONS: Disparities in timely waitlisting are associated with differences in pretransplant dialysis exposure despite no difference in time to transplant after waitlist activation. Young adults who experience delays may miss pediatric prioritization, highlighting an area for policy intervention.
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Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Fallo Renal Crónico , Trasplante de Riñón , Listas de Espera , Humanos , Femenino , Masculino , Adolescente , Niño , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/terapia , Preescolar , Sistema de Registros , Estados Unidos , Estudios de Cohortes , Diálisis Renal , Factores de TiempoRESUMEN
BACKGROUND: Acute kidney injury (AKI) is a common complication of pediatric heart transplant, with a subset of patients developing severe AKI requiring dialysis (AKI-D). We aimed to identify the epidemiology, risk factors, and outcomes of postoperative AKI-D in pediatric heart transplant recipients. METHODS: We retrospectively identified all pediatric first-time, single-organ heart transplants at our institution from 2014 to 2022. Postoperative AKI was defined as AKI within 2 weeks of transplant. Unadjusted and adjusted logistic regression were used to identify characteristics associated with AKI-D, and unadjusted time-to-event analyses were used to determine the association between AKI-D and survival free of kidney failure. RESULTS: Among 177 patients included, 116 (66%) developed postoperative AKI of any stage, including 13 (7%) who developed AKI-D with median time from transplant to dialysis initiation of 6 days (IQR 3-13). In adjusted models, increased cardiopulmonary bypass time (OR 1.19, 95% CI 1.04-1.37, per 15 min increase in bypass time) and higher weight at transplant were associated with higher odds of AKI-D, whereas patient demographics and pretransplant kidney function were not associated with AKI-D. AKI-D was associated with greater mortality during initial hospitalization (46% vs. 1%, p < 0.001) and a lower rate of survival free of kidney failure. CONCLUSIONS: The incidence of AKI-D after pediatric heart transplant was 7%, with extended cardiopulmonary bypass time associated with postoperative AKI-D even in adjusted models. Further research is needed to improve the prediction and management of AKI-D in this population.
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Lesión Renal Aguda , Trasplante de Corazón , Complicaciones Posoperatorias , Diálisis Renal , Humanos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Niño , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Preescolar , Factores de Riesgo , Adolescente , LactanteRESUMEN
BACKGROUND: We aimed to understand the association between cold ischemia time (CIT) and delayed graft function (DGF) after kidney transplantation and the impact of organ pumping on that association. METHODS: Retrospective cohort study using US registry data. We identified kidney pairs from the same donor where both kidneys were transplanted but had a CIT difference >0 and ≤20 h. We determined the frequency of concordant (both kidneys with/without DGF) or discordant (only 1 kidney DGF) DGF outcomes. Among discordant pairs, we computed unadjusted and adjusted relative risk of DGF associated with longer-CIT status, when then repeated this analysis restricted to pairs where only the longer-CIT kidney was pumped. RESULTS: Among 25 831 kidney pairs included, 71% had concordant DGF outcomes, 16% had only the longer-CIT kidney with DGF, and 13% had only the shorter-CIT kidney with DGF. Among discordant pairs, longer-CIT status was associated with a higher risk of DGF in unadjusted and adjusted models. Among pairs where only the longer-CIT kidney was pumped, longer-CIT kidneys that were pumped had a lower risk of DGF than their contralateral shorter-CIT kidneys that were not pumped regardless of the size of the CIT difference. CONCLUSIONS: Most kidney pairs have concordant DGF outcomes regardless of CIT difference, but even small increases in CIT raise the risk of DGF. Organ pumping may mitigate and even overcome the adverse consequences of prolonged CIT on the risk of DGF, but prospective studies are needed to better understand this relationship.
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Isquemia Fría , Funcionamiento Retardado del Injerto , Trasplante de Riñón , Sistema de Registros , Humanos , Trasplante de Riñón/efectos adversos , Isquemia Fría/efectos adversos , Funcionamiento Retardado del Injerto/etiología , Funcionamiento Retardado del Injerto/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Riñón/fisiopatología , Supervivencia de Injerto , Anciano , Estados Unidos/epidemiología , Donantes de TejidosAsunto(s)
Creatinina , Cistatina C , Tasa de Filtración Glomerular , Trasplante de Corazón , Trasplante de Hígado , Humanos , Cistatina C/sangre , Cistatina C/análisis , Niño , Creatinina/sangre , Masculino , Femenino , Adolescente , Preescolar , Biomarcadores/sangre , Riñón/fisiopatología , Pruebas de Función Renal/métodos , LactanteRESUMEN
Cardiovascular disease, infection, malignancy, and thromboembolism are major causes of morbidity and mortality in kidney transplant recipients (KTR). Prospectively identifying monogenic conditions associated with post-transplant complications may enable personalized management. Therefore, we developed a transplant morbidity panel (355 genes) associated with major post-transplant complications including cardiometabolic disorders, immunodeficiency, malignancy, and thrombophilia. This gene panel was then evaluated using exome sequencing data from 1590 KTR. Additionally, genes associated with monogenic kidney and genitourinary disorders along with American College of Medical Genetics (ACMG) secondary findings v3.2 were annotated. Altogether, diagnostic variants in 37 genes associated with Mendelian kidney and genitourinary disorders were detected in 9.9% (158/1590) of KTR; 25.9% (41/158) had not been clinically diagnosed. Moreover, the transplant morbidity gene panel detected diagnostic variants for 56 monogenic disorders in 9.1% KTRs (144/1590). Cardiovascular disease, malignancy, immunodeficiency, and thrombophilia variants were detected in 5.1% (81), 2.1% (34), 1.8% (29) and 0.2% (3) among 1590 KTRs, respectively. Concordant phenotypes were present in half of these cases. Reviewing implications for transplant care, these genetic findings would have allowed physicians to set specific risk factor targets in 6.3% (9/144), arrange intensive surveillance in 97.2% (140/144), utilize preventive measures in 13.2% (19/144), guide disease-specific therapy in 63.9% (92/144), initiate specialty referral in 90.3% (130/144) and alter immunosuppression in 56.9% (82/144). Thus, beyond diagnostic testing for kidney disorders, sequence annotation identified monogenic disorders associated with common post-transplant complications in 9.1% of KTR, with important clinical implications. Incorporating genetic diagnostics for transplant morbidities would enable personalized management in pre- and post-transplant care.
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Secuenciación del Exoma , Pruebas Genéticas , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Pruebas Genéticas/métodos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Complicaciones Posoperatorias/genética , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Receptores de Trasplantes/estadística & datos numéricos , Anciano , Predisposición Genética a la EnfermedadRESUMEN
Although a few registry-based studies have shown associations between receiving kidney allografts from Black donors and shorter allograft survival, detailed, large, single-center studies accounting for common confounding factors are lacking. Furthermore, pathologic alterations underlying this potential disparity have not been systematically studied. We performed a retrospective clinical-pathological study of kidney transplant recipients who received kidney allografts from either Black (n = 407) or White (n = 1,494) donors at Columbia University Irving Medical Center from 2005 to 2018, with median follow-up of 4.5 years post-transplantation. Black donor race was independently associated with allograft failure (adjusted HR = 1.34, p = 0.02) and recipients of kidney allografts from Black donors had a higher incidence of collapsing glomerulopathy [7.4% vs. 1.9%, OR = 4.17, p < 0.001]. When causes of allograft failure were examined, only allograft failure following development of collapsing glomerulopathy was more frequent in recipients of allografts from Black donors [15% vs. 5%, OR = 3.16, p = 0.004]. Notably, when patients who developed collapsing glomerulopathy were excluded from analysis, receiving kidney allografts from Black donors was not independently associated with allograft failure (adjusted HR = 1.24, p = 0.10). These findings revealed that, compared with recipients of kidney allografts from White donors, recipients of kidneys from Black donors have modestly shorter allograft survival and a higher probability of developing collapsing glomerulopathy, which negatively impacts allograft outcome. Identification of collapsing glomerulopathy risk factors may help decrease this complication and improve allograft survival, which optimally may reduce racial disparities post-transplantation.
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Though belatacept is administered with a weight-based dosing schema, there has been higher clearance reported in obese patients. Therefore, we evaluated the association between body mass index (BMI) and transplant outcomes in kidney transplant recipients who were randomized to cyclosporine- or belatacept-based immunosuppression in the BENEFIT and BENEFIT-EXT randomized clinical trials. A total of 666 and 543 patients underwent randomization and transplantation in BENEFIT and BENEFIT-EXT, respectively, of which 1056 had complete data and were included in this analysis. Patients were grouped categorically according to BMI: <25, 25 to <30, and ≥30 kg/m2. BMI did influence both the incidence and severity of acute rejection. Obese patients with BMI >30 kg/m2 in the low intensity belatacept group experienced significantly more rejection at 12 months than did patients with BMI <25 kg/m2 or BMI 25 to <30 kg/m2. In both the moderate intensity belatacept and low intensity belatacept groups, obese patients with BMI >30 kg/m2 experienced significantly more severe acute rejection than did patients with BMI < 25 kg/m2 or BMI 25 to <30 kg/m2. These results suggest that obese kidney transplant recipients are at an increased risk for acute rejection when under belatacept-based immunosuppression when compared to nonobese patients.
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Abatacept , Índice de Masa Corporal , Rechazo de Injerto , Supervivencia de Injerto , Inmunosupresores , Trasplante de Riñón , Obesidad , Humanos , Abatacept/uso terapéutico , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Trasplante de Riñón/efectos adversos , Obesidad/complicaciones , Inmunosupresores/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Incidencia , Supervivencia de Injerto/efectos de los fármacos , Factores de Riesgo , Estudios de Seguimiento , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Tasa de Filtración Glomerular , Pronóstico , Adulto , Pruebas de Función Renal , Complicaciones PosoperatoriasRESUMEN
INTRODUCTION: Anemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management of anemia. PROJECT AIM: The current study aims to describe clinical outcomes associated with packed red blood cell transfusions in the peri-operative management of anemia after transplantation. DESIGN: This was a single-center, retrospective study of adult kidney recipients with anemia at the time of transplantation. 1271 patients were stratified by donor-type due to the potential variability in underlying recipient and transplant characteristics; living donor (n = 698, 62%) or deceased donor (n = 573, 38%). RESULTS: Living donor recipients that received blood during the index hospitalization were more likely to experience rejection within 30 days (18% vs. 10%, p = 0.008) and 1 year of transplant (32% vs. 16%, p = 0.038). In multivariate analysis, receiving both blood and darbepoetin (HR: 1.89 [1.20,3.00], p = 0.006), age at transplant (HR: 0.98 [0.97, 0.99], p = 0.02), number of HLA mismatches (HR: 1.17 [1.05,1.30], p = 0.003), and whether the case was a repeat transplant (HR: 2.77 [1.93,3.97], p < 0.01) were significantly associated with hazard of rejection. For deceased donor recipients, there were no differences in acute rejection, graft failure or mortality at 30 days or 1 year. When analyzing hazard of rejection in a multivariate model, treatment received was not found to be significantly associated with rejection. CONCLUSION: Our findings suggest there may be a role for more aggressive pre-transplant treatment of anemia for those patients undergoing living donor transplants.
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Anemia , Transfusión de Eritrocitos , Rechazo de Injerto , Trasplante de Riñón , Humanos , Anemia/terapia , Masculino , Femenino , Persona de Mediana Edad , Transfusión de Eritrocitos/métodos , Estudios Retrospectivos , AdultoRESUMEN
Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology. Currently, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. In 2022, more than 40,000 patients were added to the kidney wait list and more than 25,000 received a kidney transplant. The Advancing American Kidney Health Initiative, passed in 2019, is aiming to double the number of kidney transplants by 2030 creating a need for additional transplant nephrologists to help care for them. Over the past decade, there has been a decline in the Nephrology-as well Transplant Nephrology-workforce due to a multitude of reasons. The American Society of Transplantation Kidney Pancreas Community of Practice created a workgroup to discuss the Transplant Nephrology workforce shortage. In this article, we discuss the scope of the problem and how the Accreditation Council for Graduate Medical Education recognition of Transplant Nephrology Fellowship could at least partly mitigate the Transplant Nephrology work force crisis.
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Acreditación , Educación de Postgrado en Medicina , Trasplante de Riñón , Nefrología , Humanos , Nefrología/educación , Nefrólogos/educación , Estados Unidos , BecasAsunto(s)
Trasplante de Riñón , Donantes de Tejidos , Obtención de Tejidos y Órganos , Humanos , Trasplante de Riñón/estadística & datos numéricos , Estados Unidos , Obtención de Tejidos y Órganos/estadística & datos numéricos , Obtención de Tejidos y Órganos/métodos , Persona de Mediana Edad , Adulto , Masculino , Femenino , AncianoAsunto(s)
Seguro , Fallo Renal Crónico , Trasplante de Riñón , Anciano , Humanos , Estados Unidos , MedicareRESUMEN
INTRODUCTION: Incidental kidneys cysts are typically considered benign, but the presence of cysts is more frequent in individuals with other early markers of kidney disease. We studied the association of donor kidney cysts with donor and recipient outcomes after living donor kidney transplantation. METHODS: We retrospective identified 860 living donor transplants at our center (1/1/2011-7/31/2022) without missing data. Donor cysts were identified by review of pre-donation CT scan reports. We used linear regression to study the association between donor cysts and 6-month single-kidney estimated glomerular filtration rate (eGFR) increase, and time-to-event analyses to study the association between donor cysts and recipient death-censored graft failure. RESULTS: Among donors, 77% donors had no kidney cysts, 13% had ≥1 cyst on the kidney not donated, and 11% only had cysts on the donated kidney. In adjusted linear regression, cysts on the donated kidney and kidney not donated were not significantly associated with 6-month single-kidney eGFR increase. Among transplants, 17% used a transplanted kidney with a cyst and 6% were from donors with cysts only on the kidney not transplanted. There was no association between donor cyst group and post-transplant death-censored graft survival. Results were similar in sensitivity analyses comparing transplants using kidneys with no cysts versus 1-2 cysts versus ≥3 cysts. CONCLUSIONS: Kidney cysts in living kidney donors were not associated with donor kidney recovery or recipient allograft longevity, suggesting incidental kidney cysts need not be taken into account when determining living donor candidate suitability or the laterality of planned donor nephrectomy.
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Quistes , Trasplante de Riñón , Humanos , Donadores Vivos , Estudios Retrospectivos , Riñón , Tasa de Filtración Glomerular , Supervivencia de InjertoRESUMEN
BACKGROUND: The Organ Procurement Transplant Network (OPTN)/United Network for Organ Sharing (UNOS) registry is an important national registry in the field of solid organ transplantation. Data collected are mission critical, given its role in organ allocation prioritization, program performance monitoring by both the OPTN and the Centers for Medicare & Medicaid Services, and countless observational analyses that helped to move the field forward. Despite the multifaceted importance of the OPTN/UNOS database, there are clear indications that investments in the database to ensure the quality and reliability of the data have been lacking. METHODS: This analysis outlines 2 examples: (1) primary diagnosis for patients who are receiving a second transplant and (2) reporting peripheral vascular disease in kidney transplantation to illustrate the extensive challenges facing the veracity and integrity of the OPTN/UNOS database today. RESULTS: Despite guidance that repeat kidney transplant patients should be coded as "retransplant/graft failure" rather than their native kidney disease, only 59% of new incident patients are coded in this manner. Peripheral vascular disease prevalence more than doubled in a 20-y span when the variable became associated with risk adjustment. CONCLUSIONS: This article summarizes critical gaps in the OPTN/UNOS database, and we bring forward ideas and proposals for consideration as a path toward improvement.