RESUMEN
Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.
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Trasplante de Riñón , Humanos , Anciano , Persona de Mediana Edad , Adolescente , Adulto Joven , Adulto , Trasplante de Riñón/efectos adversos , Donadores Vivos , Supervivencia de Injerto , Rechazo de Injerto/etiología , Antígenos HLA , Factores de RiesgoRESUMEN
RATIONALE & OBJECTIVE: Donor acute kidney injury (AKI) activates innate immunity, enhances HLA expression in the kidney allograft, and provokes recipient alloimmune responses. We hypothesized that injury and inflammation that manifested in deceased-donor urine biomarkers would be associated with higher rates of biopsy-proven acute rejection (BPAR) and allograft failure after transplantation. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 862 deceased donors for 1,137 kidney recipients at 13 centers. EXPOSURES: We measured concentrations of interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) in deceased donor urine. We also used the Acute Kidney Injury Network (AKIN) criteria to assess donor clinical AKI. OUTCOMES: The primary outcome was a composite of BPAR and graft failure (not from death). A secondary outcome was the composite of BPAR, graft failure, and/or de novo donor-specific antibody (DSA). Outcomes were ascertained in the first posttransplant year. ANALYTICAL APPROACH: Multivariable Fine-Gray models with death as a competing risk. RESULTS: Mean recipient age was 54 ± 13 (SD) years, and 82% received antithymocyte globulin. We found no significant associations between donor urinary IL-18, KIM-1, and NGAL and the primary outcome (subdistribution hazard ratio [HR] for highest vs lowest tertile of 0.76 [95% CI, 0.45-1.28], 1.20 [95% CI, 0.69-2.07], and 1.14 [95% CI, 0.71-1.84], respectively). In secondary analyses, we detected no significant associations between clinically defined AKI and the primary outcome or between donor biomarkers and the composite outcome of BPAR, graft failure, and/or de novo DSA. LIMITATIONS: BPAR was ascertained through for-cause biopsies, not surveillance biopsies. CONCLUSIONS: In a large cohort of kidney recipients who almost all received induction with thymoglobulin, donor injury biomarkers were associated with neither graft failure and rejection nor a secondary outcome that included de novo DSA. These findings provide some reassurance that centers can successfully manage immunological complications using deceased-donor kidneys with AKI.
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Lesión Renal Aguda , Trasplante de Riñón , Humanos , Adulto , Persona de Mediana Edad , Anciano , Lipocalina 2 , Interleucina-18 , Estudios Prospectivos , Lesión Renal Aguda/patología , Donantes de Tejidos , Biomarcadores , Rechazo de Injerto/epidemiología , Supervivencia de InjertoRESUMEN
BACKGROUND: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association. METHODS: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes. RESULTS: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI. CONCLUSION: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization.
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Lesión Renal Aguda , Trasplante de Riñón , Biomarcadores/orina , Funcionamiento Retardado del Injerto , Femenino , Supervivencia de Injerto , Humanos , Riñón , Trasplante de Riñón/efectos adversos , Masculino , Donantes de TejidosRESUMEN
For most patients with kidney failure, living donor kidney transplant (LDKT) is their best treatment option. Compared with White people, Black people are more likely to have kidney failure but less likely to receive LDKTs. In this study, the investigators will test an educational intervention, Destination Transplant, designed to reduce this disparity, among Black people already listed for kidney transplant. METHODS: The investigators will conduct a parallel group, 2-arm randomized clinical trial among 500 Black kidney transplant candidates. The main objective of this study is to test an educational and behavioral intervention that is designed to increase receipt of LDKT among transplant candidates (persons active on the deceased donor kidney transplant waiting list) who are Black. Candidates on the kidney transplant waiting list will be randomly assigned to 1 of 2 conditions: (1) a control group that will receive Usual Care, or (2) an Intervention group that will receive Destination Transplant, a 9-month intervention that includes an in-person group-based education session, postcards at monthly intervals, and a follow-up phone call from a transplant educator. At baseline and during 18 months of follow-up, demographic and clinical variables will be collected, as well as variables such as transplant derailers (factors that might be sources of delay, difficulty, or challenge to pursuing transplant), transplant knowledge, and health literacy, small steps taken to pursue LDKT, readiness for LDKT, decisional balance and self-efficacy LDKT, decisional conflict, family support, availability of potential living donors, and general health status. CONCLUSIONS: This educational intervention aims to increase both readiness to pursue LDKT and actual receipt of LDKTs among Black and African American patients who are already on the kidney transplant waiting list. The aim of the intervention is to reduce racial disparities in access to LDKT.
RESUMEN
BACKGROUND AND OBJECTIVES: BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database. RESULTS: The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95). CONCLUSIONS: In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.
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Lesión Renal Aguda , Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus/etiología , Complicaciones Posoperatorias/etiología , Obtención de Tejidos y Órganos , Infecciones Tumorales por Virus/etiología , Adulto , Anciano , Cadáver , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/epidemiología , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Infecciones Tumorales por Virus/epidemiologíaRESUMEN
BACKGROUND: Post-Transplant erythrocytosis (PTE) has not been studied in large recent cohorts. In this study, we evaluated the incidence, risk factors, and outcome of PTE with current transplant practices using the present World Health Organization criteria to define erythrocytosis. We also tested the hypothesis that the risk of PTE is greater with higher-quality kidneys. METHODS: We utilized the Deceased Donor Study which is an ongoing, multicenter, observational study of deceased donors and their kidney recipients that were transplanted between 2010 and 2013 across 13 centers. Eryrthocytosis is defined by hemoglobin> 16.5 g/dL in men and> 16 g/dL in women. Kidney quality is measured by Kidney Donor Profile Index (KDPI). RESULTS: Of the 1123 recipients qualified to be in this study, PTE was observed at a median of 18 months in 75 (6.6%) recipients. Compared to recipients without PTE, those with PTE were younger [mean 48±11 vs 54±13 years, p < 0.001], more likely to have polycystic kidney disease [17% vs 6%, p < 0.001], have received kidneys from younger donors [36 ±13 vs 41±15 years], and be on RAAS inhibitors [35% vs 22%, p < 0.001]. Recipients with PTE were less likely to have received kidneys from donors with hypertension [16% vs 32%, p = 0.004], diabetes [1% vs 11%, p = 0.008], and cerebrovascular event (24% vs 36%, p = 0.036). Higher KDPI was associated with decreased PTE risk [HR 0.98 (95% CI: 0.97-0.99)]. Over 60 months of follow-up, only 17 (36%) recipients had sustained PTE. There was no association between PTE and graft failure or mortality, CONCLUSIONS: The incidence of PTE was low in our study and PTE resolved in majority of patients. Lower KDPI increases risk of PTE. The underutilization of RAAS inhibitors in PTE patients raises the possibility of under-recognition of this phenomenon and should be explored in future studies.
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Trasplante de Riñón , Policitemia/epidemiología , Complicaciones Posoperatorias/epidemiología , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Donantes de TejidosRESUMEN
Background: De novo post-transplant diabetes mellitus (PTDM) is a common complication after kidney transplant (KT). Most recent studies are single center with various approaches to outcome ascertainment. Methods: In a multicenter longitudinal cohort of 632 nondiabetic adult kidney recipients transplanted in 2010-2013, we ascertained outcomes through detailed chart review at 13 centers. We hypothesized that donor characteristics, such as sex, HCV infection, and kidney donor profile index (KDPI), and recipient characteristics, such as age, race, BMI, and increased HLA mismatches, would affect the development of PTDM among KT recipients. We defined PTDM as hemoglobin A1c ≥6.5%, pharmacological treatment for diabetes, or documentation of diabetes in electronic medical records. We assessed PTDM risk factors and evaluated for an independent time-updated association between PTDM and graft failure using regression. Results: Mean recipient age was 52±14 years, 59% were male, 49% were Black. Cumulative PTDM incidence 5 years post-KT was 29% (186). Independent baseline PTDM risk factors included older recipient age (P<0.001) and higher BMI (P=0.006). PTDM was not associated with all-cause graft failure (adjusted hazard ratio (aHR), 1.10; 95% CI, 0.78 to 1.55), death-censored graft failure (aHR, 0.85; 95% CI, 0.53 to 1.37), or death (aHR, 1.31; 95% CI, 0.84 to 2.05) at median follow-up of 6 (interquartile range, 4.0-6.9) years post-KT. Induction and maintenance immunosuppression were not different between patients who did and did not develop PTDM. Conclusions: PTDM occurred commonly, and higher baseline BMI was associated with PTDM. PTDM was not associated with graft failure or mortality during the 6-year follow-up, perhaps due to the short follow-up time.
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Diabetes Mellitus , Trasplante de Riñón , Adulto , Anciano , Diabetes Mellitus/epidemiología , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Receptores de TrasplantesRESUMEN
BACKGROUND: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown. METHODS: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes. RESULTS: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates. CONCLUSIONS: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers.
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Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Antígenos HLA/inmunología , Disparidades en Atención de Salud , Histocompatibilidad , Inmunosupresores/uso terapéutico , Isoanticuerpos/sangre , Trasplante de Riñón , Donadores Vivos , Pautas de la Práctica en Medicina , Adulto , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Indicadores de Calidad de la Atención de Salud , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. METHODS: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. RESULTS: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted ß coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. CONCLUSIONS: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.
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Funcionamiento Retardado del Injerto/etiología , Tasa de Filtración Glomerular , Supervivencia de Injerto , Trasplante de Riñón/efectos adversos , Riñón/cirugía , Osteopontina/orina , Donantes de Tejidos , Uromodulina/orina , Adulto , Anciano , Animales , Biomarcadores/orina , Células Cultivadas , Funcionamiento Retardado del Injerto/mortalidad , Funcionamiento Retardado del Injerto/fisiopatología , Femenino , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Riñón/fisiopatología , Trasplante de Riñón/mortalidad , Macrófagos/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados UnidosRESUMEN
Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.
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Trasplante de Riñón , Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes. METHODS: In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m. RESULTS: Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF. CONCLUSIONS: AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.
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Lesión Renal Aguda/diagnóstico , Rechazo de Injerto/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Lesión Renal Aguda/fisiopatología , Lesión Renal Aguda/orina , Adulto , Anciano , Aloinjertos/fisiopatología , Biomarcadores/orina , Creatinina/orina , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Rechazo de Injerto/etiología , Rechazo de Injerto/fisiopatología , Humanos , Riñón/fisiopatología , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Resultado del TratamientoRESUMEN
Deceased-donor acute kidney injury (AKI) is associated with organ discard and delayed graft function, but data on longer-term allograft survival are limited. We performed a multicenter study to determine associations between donor AKI (from none to severe based on AKI Network stages) and all-cause graft failure, adjusting for donor, transplant, and recipient factors. We examined whether any of the following factors modified the relationship between donor AKI and graft survival: kidney donor profile index, cold ischemia time, donation after cardiac death, expanded-criteria donation, kidney machine perfusion, donor-recipient gender combinations, or delayed graft function. We also evaluated the association between donor AKI and a 3-year composite outcome of all-cause graft failure or estimated glomerular filtration rate ≤ 20 mL/min/1.73 m2 in a subcohort of 30% of recipients. Among 2,430 kidneys transplanted from 1,298 deceased donors, 585 (24%) were from donors with AKI. Over a median follow-up of 4.0 years, there were no significant differences in graft survival by donor AKI stage. We found no evidence that pre-specified variables modified the effect of donor AKI on graft survival. In the subcohort, donor AKI was not associated with the 3-year composite outcome. Donor AKI was not associated with graft failure in this well-phenotyped cohort. Given the organ shortage, the transplant community should consider measures to increase utilization of kidneys from deceased donors with AKI.
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Lesión Renal Aguda/fisiopatología , Rechazo de Injerto/epidemiología , Trasplante de Riñón/efectos adversos , Obtención de Tejidos y Órganos/normas , Adulto , Anciano , Aloinjertos/fisiopatología , Aloinjertos/provisión & distribución , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Rechazo de Injerto/fisiopatología , Supervivencia de Injerto , Humanos , Riñón/fisiopatología , Trasplante de Riñón/métodos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Tiempo , Donantes de Tejidos , Obtención de Tejidos y Órganos/métodos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Accumulating evidence implicates the complement cascade as pathogenically contributing to ischemia-reperfusion injury and delayed graft function (DGF) in human kidney transplant recipients. Building on observations that kidney injury can initiate in the donor before nephrectomy, we tested the hypothesis that anaphylatoxins C3a and C5a in donor urine before transplantation associate with risk of posttransplant injury. METHODS: We evaluated the effects of C3a and C5a in donor urine on outcomes of 469 deceased donors and their corresponding 902 kidney recipients in a subset of a prospective cohort study. RESULTS: We found a threefold increase of urinary C5a concentrations in donors with stage 2 and 3 acute kidney injury (AKI) compared donors without AKI (P < 0.001). Donor C5a was higher for the recipients with DGF (defined as dialysis in the first week posttransplant) compared with non-DGF (P = 0.002). In adjusted analyses, C5a remained independently associated with recipient DGF for donors without AKI (relative risk, 1.31; 95% confidence interval, 1.13-1.54). For donors with AKI, however, urinary C5a was not associated with DGF. We observed a trend toward better 12-month allograft function for kidneys from donors with C5a concentrations in the lowest tertile (P = 0.09). Urinary C3a was not associated with donor AKI, recipient DGF, or 12-month allograft function. CONCLUSIONS: Urinary C5a correlates with the degree of donor AKI. In the absence of clinical donor AKI, donor urinary C5a concentrations associate with recipient DGF, providing a foundation for testing interventions aimed at preventing DGF within this high-risk patient subgroup.
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Lesión Renal Aguda/orina , Complemento C5a/orina , Funcionamiento Retardado del Injerto/etiología , Selección de Donante , Trasplante de Riñón/efectos adversos , Donantes de Tejidos , Lesión Renal Aguda/diagnóstico , Adulto , Biomarcadores/orina , Complemento C3/orina , Funcionamiento Retardado del Injerto/diagnóstico , Funcionamiento Retardado del Injerto/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Regulación hacia Arriba , UrinálisisRESUMEN
Prior studies demonstrate poor agreement among pathologists' interpretation of kidney biopsy slides. Reliability of representative images of these slides uploaded to the United Network of Organ Sharing (UNOS) web portal for clinician review has not been studied. We hypothesized high agreement among pathologists' image interpretation, since static images eliminate variation induced by viewing different areas of movable slides. To test our hypothesis, we compared the assessments of UNOS-uploaded images recorded in standardized forms by three pathologists. We selected 100 image sets, each having at least two images from kidneys of deceased donors. Weighted Cohen's kappa was used for inter-rater agreement. Mean (SD) donor age was 50 (13). Acute tubular injury had kappas of 0.12, 0.14, and 0.19; arteriolar hyalinosis 0.16, 0.27, and 0.38; interstitial inflammation 0.30, 0.33, and 0.49; interstitial fibrosis 0.28, 0.32, and 0.67; arterial intimal fibrosis 0.34, 0.42, and 0.59; tubular atrophy 0.35, 0.41, and 0.52; glomeruli thrombi 0.32, 0.53, and 0.85; and global glomerulosclerosis 0.68, 0.70, and 0.77. Pathologists' agreement demonstrated kappas of 0.12 to 0.77. The lower values raise concern about the reliability of using images. Although further research is needed to understand how uploaded images are used clinically, the field may consider higher-quality standards for biopsy photomicrographs.
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Bases de Datos Factuales , Procesamiento de Imagen Asistido por Computador/métodos , Riñón/patología , Bancos de Tejidos/organización & administración , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/normas , Biopsia , Femenino , Humanos , Riñón/diagnóstico por imagen , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Efforts to maximize transplantation by matching organ quality to recipient longevity require reliable tools. The US kidney allocation system uses the Kidney Donor Risk Index (KDRI) for this purpose, and many centers additionally rely on donor biopsies. The Leuven score combines donor age with procurement histology (glomerulosclerosis and interstitial fibrosis/tubular atrophy) to predict allograft survival. METHODS: We compared KDRI with Leuven scores for associations with kidney discard, delayed graft function, and allograft function and survival. We used Cox, modified Poisson, and linear regression to calculate risks based on KDRI and (separately) Leuven scores, adjusting for important transplant and recipient variables. RESULTS: From 890 donors, 1729 kidneys were procured and biopsied. Five hundred eighty-five (34%) kidneys were discarded. Median donor age was 53 years (interquartile range [IQR], 44-61 years). Median KDRI and Leuven scores were 1.56 (IQR, 1.28-1.90) and 59 (IQR, 49-69). Relative risk for discard was 1.21 (95% confidence interval [CI], 1.17-1.24) per 0.2-unit increase in KDRI and 1.38 (1.31-1.46) per 10-unit increase in Leuven score. Adjusted relative risks for delayed graft function were 0.98 (95% CI, 0.94-1.02) and 0.94 (95% CI, 0.90-0.99), adjusted hazard ratios for graft failure were 1.10 (95% CI, 1.04-1.16) and 1.11 (95% CI, 1.02-1.21), and adjusted linear regression coefficients for 3-year estimated glomerular filtration rate were -3.88 (-4.63 to -3.13) and -5.18 (-6.19 to -4.18). CONCLUSIONS: In kidneys clinically selected for procurement biopsy, the Leuven score was more strongly associated with discard but performed similarly to KDRI for predicting transplant outcomes, suggesting the need to reevaluate current procurement biopsy practices. Given modest associations for both tools; however, neither KDRI nor the Leuven score should be used in isolation for individual organ acceptance decisions.
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BACKGROUND: Kidney transplant (KT) recipients experience high rates of early (≤30 days) hospital readmission (EHR) after KT, and existing studies provide limited data on modifiable discharge factors that may mitigate EHR risk. METHODS: We performed a retrospective cohort study of 468 adult deceased donor KT recipients transplanted between 4/2010 and 11/2013 at 5 United States transplant centers. We fit multivariable mixed effects models to assess the association of two potentially modifiable discharge factors with the probability of EHR after KT: (i) weekend discharge and (ii) days to first scheduled follow-up. RESULTS: Among 468 KT recipients, 38% (n = 178) experienced EHR after KT. In fully adjusted analyses, compared to weekday discharges, KT recipients discharged on the weekend had a 29% lower risk of EHR (adjusted odds ratio [aOR] 0.71, 95% confidence interval [CI] 0.41-0.94). Compared to follow-up within 2 days of discharge, KT recipients with follow-up within 3 to 6 days had a 28% higher probability of EHR (aOR 1.28, 95% CI 1.13-1.45). CONCLUSIONS: These findings suggest that clinical decisions related to the timing of discharge and follow-up modify EHR risk after KT, independent of traditional risk factors.
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Rechazo de Injerto/prevención & control , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Alta del Paciente/estadística & datos numéricos , Readmisión del Paciente/estadística & datos numéricos , Donantes de Tejidos/estadística & datos numéricos , Adulto , Cadáver , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Pruebas de Función Renal , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de RiesgoRESUMEN
INTRODUCTION: Maximizing education about living donor kidney transplant (LDKT) during the in-person evaluation at the transplant center may increase the numbers of kidney patients pursuing LDKT. Research Questions and Design: To test the effectiveness of a 1-time LDKT educational intervention, we performed a cluster-randomized trial among 499 patients who presented for evaluation of kidney transplant. We compared usual care education (n = 250) versus intensive LDKT education (n = 249), which was implemented only on the evaluation day and consisted of viewing a 25-minute video of information and stories about LDKT and discussion of LDKT possibilities with an educator. Our primary outcome was knowledge of LDKT, 1 week after the transplant evaluation. RESULTS: One week after evaluation, patients who received intensive education had higher knowledge than patients who received usual care (12.7 vs. 11.7; P = .0008), but there were no differences in postevaluation readiness for LDKT. Among patients who had not previously identified a potential living donor, receiving intensive education was associated with increased willingness to take steps toward LDKT. DISCUSSION: In conclusion, expansion of LDKT education within the evaluation day may be helpful, but interventions that are implemented at multiple times and for greater duration may be necessary to ensure larger and long-term behavioral changes in pursuit of LDKT.
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Educación en Salud/organización & administración , Conocimientos, Actitudes y Práctica en Salud , Trasplante de Riñón/educación , Donadores Vivos , Receptores de Trasplantes/educación , Toma de Decisiones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown. STUDY DESIGN: Cross-sectional analysis from multicenter prospective cohort. SETTINGS & PARTICIPANTS: Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation. PREDICTORS: (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement. OUTCOME: Histologic acute tubular injury. RESULTS: Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1. LIMITATIONS: The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population. CONCLUSIONS: Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.
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Lesión Renal Aguda/metabolismo , Creatinina/sangre , Proteínas de Unión a Ácidos Grasos/orina , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Interleucina-18/orina , Lipocalina 2/orina , Donantes de Tejidos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/patología , Adulto , Área Bajo la Curva , Biomarcadores/metabolismo , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Trasplante de Riñón , Túbulos Renales/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
We report the utility of surface-enhanced Raman scattering (SERS) analysis of urine from deceased donors for prognosis of kidney transplant outcomes. Iodide-modified silver nanoparticles were used as the enabler for sensitive measurements of urine proteins. Principal component analysis (PCA) and linear discriminant analysis (LDA) were employed for the statistical analysis of the SERS data. Thirty urine samples in three classes were analysed. The ATN class consists of donors whose kidneys had acute tubular necrosis (ATN), the most common type of acute kidney injury (AKI) with high risk of poor graft performance in recipients, yet yielded acceptable transplant outcome. The DGF class is comprised of donors whose kidney had delayed graft function (DGF) in recipients. The control class includes donors whose kidneys did not have donor ATN or recipient DGF. We show a sensitivity of more than 90â % in differentiating the ATN class from the DGF and control classes. Our methodology can thus help clinicians choose kidneys in the high-risk ATN category for transplant which would otherwise be discarded. Our research is impactful in that it could serve as a valuable guidance to expand the deceased donor pool to include those perceived as high-risk AKI type based on common urinary biomarkers. Picutre: Scheme of SERS analysis of urine samples from deceased donors for kidney transplant outcome indication.