RESUMEN
Autosomal dominant polycystic kidney disease (ADPKD), characterized by progressive cyst formation/expansion, results in enlarged kidneys and often end stage kidney disease. ADPKD is genetically heterogeneous; PKD1 and PKD2 are the common loci (â¼78% and â¼15% of families) and GANAB, DNAJB11, and ALG9 are minor genes. PKD is a ciliary-associated disease, a ciliopathy, and many syndromic ciliopathies have a PKD phenotype. In a multi-cohort/-site collaboration, we screened ADPKD-diagnosed families that were naive to genetic testing (n = 834) or for whom no PKD1 and PKD2 pathogenic variants had been identified (n = 381) with a PKD targeted next-generation sequencing panel (tNGS; n = 1,186) or whole-exome sequencing (WES; n = 29). We identified monoallelic IFT140 loss-of-function (LoF) variants in 12 multiplex families and 26 singletons (1.9% of naive families). IFT140 is a core component of the intraflagellar transport-complex A, responsible for retrograde ciliary trafficking and ciliary entry of membrane proteins; bi-allelic IFT140 variants cause the syndromic ciliopathy, short-rib thoracic dysplasia (SRTD9). The distinctive monoallelic phenotype is mild PKD with large cysts, limited kidney insufficiency, and few liver cysts. Analyses of the cystic kidney disease probands of Genomics England 100K showed that 2.1% had IFT140 LoF variants. Analysis of the UK Biobank cystic kidney disease group showed probands with IFT140 LoF variants as the third most common group, after PKD1 and PKD2. The proximity of IFT140 to PKD1 (â¼0.5 Mb) in 16p13.3 can cause diagnostic confusion, and PKD1 variants could modify the IFT140 phenotype. Importantly, our studies link a ciliary structural protein to the ADPKD spectrum.
Asunto(s)
Alelos , Proteínas Portadoras , Predisposición Genética a la Enfermedad , Mutación , Riñón Poliquístico Autosómico Dominante/genética , Adulto , Anciano , Sustitución de Aminoácidos , Bancos de Muestras Biológicas , Cilios/patología , Variaciones en el Número de Copia de ADN , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Riñón Poliquístico Autosómico Dominante/diagnóstico , Análisis de Secuencia de ADN , Reino Unido , Secuenciación del ExomaRESUMEN
Measurement of glomerular filtration rate (GFR) is crucial in assessing kidney function status. Estimating GFR using clearance methodologies is cumbersome, as plasma and urinary concentrations and timed urine collections are required. Recently, a transcutaneous sensor has been developed whereby the rate of renal washout of a fluorescent marker administered intravenously allows calculation of GFR. The challenge is to ensure that the values of GFR obtained using the washout approach are in accord with those obtained conventionally.
Asunto(s)
Tasa de Filtración Glomerular , Humanos , Colorantes Fluorescentes/administración & dosificación , Riñón/fisiopatología , Riñón/fisiología , Pruebas de Función Renal/métodos , Pruebas de Función Renal/normasRESUMEN
Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.
Asunto(s)
Síndrome Hemolítico Urémico Atípico , Microangiopatías Trombóticas , Adulto , Humanos , Riñón/patología , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/terapia , Microangiopatías Trombóticas/patología , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/epidemiología , Proteínas del Sistema Complemento , Pruebas de Función RenalRESUMEN
We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.
Asunto(s)
Isquemia Fría , Funcionamiento Retardado del Injerto , Tasa de Filtración Glomerular , Supervivencia de Injerto , Trasplante de Riñón , Donantes de Tejidos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Donantes de Tejidos/provisión & distribución , Factores de Riesgo , Adulto , Estudios de Seguimiento , Funcionamiento Retardado del Injerto/etiología , Pronóstico , Tasa de Supervivencia , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Rechazo de Injerto/etiología , Pruebas de Función Renal , Obtención de Tejidos y Órganos , Complicaciones PosoperatoriasRESUMEN
African American (AA) kidney recipients have a higher risk of allograft rejection and failure compared to non-AAs, but to what extent these outcomes are due to genetic versus environmental effects is currently unknown. Herein, we tested the effects of recipient self-reported race versus genetic proportion of African ancestry (pAFR), and neighborhood socioeconomic status (SES) on kidney allograft outcomes in multiethnic kidney transplant recipients from Columbia University (N = 1083) and the University of Pennsylvania (N = 738). All participants were genotyped with SNP arrays to estimate genetic admixture proportions. US census tract variables were used to analyze the effect of neighborhood factors. In both cohorts, self-reported recipient AA race and pAFR were individually associated with increased risk of rejection and failure after adjustment for known clinical risk factors and neighborhood SES factors. Joint analysis confirmed that self-reported recipient AA race and pAFR were both associated with a higher risk of allograft rejection (AA: HR 1.61 (1.31-1.96), P = 4.05E-06; pAFR: HR 1.90 (1.46-2.48), P = 2.40E-06) and allograft failure (AA: HR 1.52 (1.18-1.97), P = .001; pAFR: HR 1.70 (1.22-2.35), P = .002). Further research is needed to disentangle the role of genetics versus environmental, social, and structural factors contributing to poor transplantation outcomes in kidney recipients of African ancestry.
Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Riñón , Autoinforme , Humanos , Masculino , Femenino , Persona de Mediana Edad , Rechazo de Injerto/genética , Rechazo de Injerto/etiología , Supervivencia de Injerto/genética , Factores de Riesgo , Adulto , Pronóstico , Estudios de Seguimiento , Población Urbana , Negro o Afroamericano/genética , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/genética , Receptores de Trasplantes , Etnicidad/genética , Características del Vecindario , Tasa de Filtración Glomerular , Pruebas de Función Renal , Estudios de CohortesRESUMEN
The diabetic population is witnessing a rise in obesity rates, creating specific hurdles for individuals seeking pancreas transplantation because they are frequently disqualified due to their elevated body weight. Introducing a robotic-assisted approach to transplantation has been proven to yield improved outcomes, particularly in patients with obesity. A retrospective analysis was conducted between January 2015 and September 2023. The study included a total of 140 patients, with 16 receiving robotic-assisted simultaneous pancreas-kidney transplantation (RSPK) and 124 undergoing open approach simultaneous pancreas-kidney transplantation (OSPK) during the study period. The median age was 45 (36.8-52.7) and 44.5 years (36.8-51.8) (RSPK vs OSPK, P = .487). There were no significant differences in demographics except body mass index (RSPK vs OSPK, 34.9 vs 28.1, P < .001) and a higher percentage of patients with high cardiac risk in the RSPK group. The robotic approach has a lengthier overall operative time and warm ischemia time. Surgical and nonsurgical complications at 30-days and 1-year grafts and patient survival (93.8% vs 96.8%, RSPK vs OSPK, P = .521) were similar. Our findings suggest that employing robotic assistance in simultaneous pancreas-kidney transplantation is safe. Wider adoption and utilization of this technique could potentially improve transplant accessibility for individuals with obesity and diabetes.
Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón , Trasplante de Páncreas , Procedimientos Quirúrgicos Robotizados , Humanos , Trasplante de Riñón/métodos , Estudios Retrospectivos , Trasplante de Páncreas/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Procedimientos Quirúrgicos Robotizados/métodos , Estudios de Seguimiento , Pronóstico , Complicaciones Posoperatorias , Factores de Riesgo , Pruebas de Función Renal , Fallo Renal Crónico/cirugíaRESUMEN
De novo thrombotic microangiopathy (dnTMA), after renal transplantation may significantly alter graft outcomes. However, its pathogenesis and the role of complement alternative pathway dysregulation remain elusive. We studied all consecutive adult patients with a kidney allograft biopsy performed between January 2004 and March 2016 displaying dnTMA. Ninety-two patients were included. The median time of occurrence was 166 (IQR 25-811) days. The majority (82.6 %) had TMA localized only in the graft. Calcineurin inhibitor toxicity and antibody-mediated rejection (ABMR) were the 2 most frequent causes (54.3% and 37.0%, respectively). However, etiological factors were multiple in 37% patients. Interestingly, pathogenic variants in the genes of complement alternative pathway were significantly more frequent in the 42 tested patients than in healthy controls (16.7% vs 3.7% respectively, P < .008). The overall graft survival after biopsy was 66.0% at 5 years and 23.4% at 10 years, significantly worse than a matched cohort without TMA. Moreover, graft survival of patients with TMA and ABMR was worse than a matched cohort with ABMR without TMA. The 2 main prognostic factors were a positive C4d staining and a lower estimated glomerular filtration rate at diagnosis. DnTMA is a severe and multifactorial disease, induced by 1 or several endothelium-insulting conditions, mostly calcineurin inhibitor toxicity and ABMR.
Asunto(s)
Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Riñón , Microangiopatías Trombóticas , Humanos , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/genética , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Pronóstico , Estudios de Seguimiento , Adulto , Factores de Riesgo , Complicaciones Posoperatorias , Pruebas de Función Renal , Fallo Renal Crónico/cirugía , Estudios Retrospectivos , Proteínas del Sistema Complemento/genética , Estudios de Casos y ControlesRESUMEN
Kidney transplant recipients (KTRs) experience more fatigue, anxiety, and depressive symptoms and lower concentration and health-related quality of life (HRQoL) compared with the general population. Anemia is a potential cause that is well-recognized and treated. Iron deficiency, however, is often unrecognized, despite its potential detrimental effects related to and unrelated to anemia. We investigated the interplay of anemia, iron deficiency, and patient-reported outcomes in 814 outpatient KTRs (62% male, age 56 ± 13 years) enrolled in the TransplantLines Biobank and Cohort Study (Groningen, The Netherlands). In total, 28% had iron deficiency (ie, transferrin saturation < 20% and ferritin < 100 µg/L), and 29% had anemia (World Health Organization criteria). In linear regression analyses, iron deficiency, but not anemia, was associated with more fatigue, worse concentration, lower wellbeing, more anxiety, more depressive symptoms, and lower HRQoL, independent of age, sex, estimated glomerular filtration rate, anemia, and other potential confounders. In the fully adjusted logistic regression models, iron deficiency was associated with an estimated 53% higher risk of severe fatigue, a 100% higher risk of major depressive symptoms, and a 51% higher chance of being at risk for sick leave/work disability. Clinical trials are needed to investigate the effect of iron deficiency correction on patient-reported outcomes and HRQoL in KTRs.
Asunto(s)
Trasplante de Riñón , Medición de Resultados Informados por el Paciente , Calidad de Vida , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios de Seguimiento , Pronóstico , Fallo Renal Crónico/cirugía , Tasa de Filtración Glomerular , Receptores de Trasplantes/psicología , Factores de Riesgo , Anemia , Deficiencias de Hierro , Anemia Ferropénica , Depresión/etiología , Adulto , Pruebas de Función Renal , Fatiga/etiología , Complicaciones Posoperatorias , Países Bajos , Anciano , Ansiedad/etiologíaRESUMEN
Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.
Asunto(s)
Glomerulonefritis Membranosa , Trasplante de Riñón , Recurrencia , Humanos , Glomerulonefritis Membranosa/etiología , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Adulto , Tasa de Filtración Glomerular , Fallo Renal Crónico/cirugía , Complicaciones Posoperatorias , Supervivencia de Injerto , Pruebas de Función Renal , Incidencia , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Tasa de SupervivenciaRESUMEN
Antibody-mediated rejection (ABMR) is a leading cause of graft failure. Emerging evidence suggests a significant contribution of natural killer (NK) cells to microvascular inflammation (MVI). We investigated the influence of genetically determined NK cell functionality on ABMR development and activity. The study included 86 kidney transplant recipients subjected to systematic biopsies triggered by donor-specific antibody detection. We performed killer immunoglobulin-like receptor typing to predict missing self and genotyped polymorphisms determining NK cell functionality (FCGR3AV/F158 [rs396991], KLRC2wt/del, KLRK1HNK/LNK [rs1049174], rs9916629-C/T). Fifty patients had ABMR with considerable MVI and elevated NK cell transcripts. Missing self was not related to MVI. Only KLRC2wt/wt showed an association (MVI score: 2 [median; interquartile range: 0-3] vs 0 [0-1] in KLRC2wt/del recipients; P = .001) and remained significant in a proportional odds multivariable model (odds ratio, 7.84; 95% confidence interval, 2.37-30.47; P = .001). A sum score incorporating all polymorphisms and missing self did not outperform a score including only KLRC2 and FCGR3A variants, which were predictive in univariable analysis. NK cell genetics did not affect graft functional decline and survival. In conclusion, a functional KLRC2 polymorphism emerged as an independent determinant of ABMR activity, without a considerable contribution of missing self and other NK cell gene polymorphisms.
Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Inflamación , Isoanticuerpos , Trasplante de Riñón , Células Asesinas Naturales , Donantes de Tejidos , Humanos , Células Asesinas Naturales/inmunología , Rechazo de Injerto/inmunología , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Donantes de Tejidos/provisión & distribución , Isoanticuerpos/inmunología , Pronóstico , Inflamación/inmunología , Estudios de Seguimiento , Supervivencia de Injerto/inmunología , Adulto , Factores de Riesgo , Microvasos/patología , Microvasos/inmunología , Genotipo , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/genética , Pruebas de Función Renal , Biomarcadores/análisis , Biomarcadores/metabolismoRESUMEN
Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.
Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Trasplante de Riñón , MicroARNs , Humanos , Trasplante de Riñón/efectos adversos , MicroARNs/genética , MicroARNs/sangre , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/etiología , Masculino , Citomegalovirus/genética , Persona de Mediana Edad , Femenino , Estudios de Seguimiento , Factores de Riesgo , Biomarcadores/sangre , Pronóstico , Rechazo de Injerto/etiología , Rechazo de Injerto/virología , Fallo Renal Crónico/cirugía , Complicaciones Posoperatorias/diagnóstico , Viremia/virología , Viremia/diagnóstico , Viremia/epidemiología , Adulto , Supervivencia de Injerto , Pruebas de Función RenalRESUMEN
Durable tolerance in kidney transplant recipients remains an important but elusive goal. We hypothesized that adding B cell depletion to T cell depletion would generate an immune milieu postreconstitution dominated by immature transitional B cells, favoring tolerance. The Immune Tolerance Network ITN039ST Research Study of ATG and Rituximab in Renal Transplantation was a prospective multicenter pilot study of live donor kidney transplant recipients who received induction with rabbit antithymocyte globulin and rituximab and initiated immunosuppression (IS) withdrawal (ISW) at 26 weeks. The primary endpoint was freedom from rejection at 52 weeks post-ISW. Six of the 10 subjects successfully completed ISW. Of these 6 subjects, 4 restarted immunosuppressive medications due to acute rejection or recurrent disease, 1 remains IS-free for over 9 years, and 1 was lost to follow-up after being IS-free for 42 weeks. There were no cases of patient or graft loss. CD19+ B cell frequencies returned to predepletion levels by 26 weeks posttransplant; immunoglobulin D+CD27--naïve B cells predominated. In contrast, memory cells dominated the repopulation of the T cell compartment. A regimen of combined B and T cell depletion did not generate the tolerogenic B cell profile observed in preclinical studies and did not lead to durable tolerance in the majority of kidney transplant recipients.
Asunto(s)
Suero Antilinfocítico , Rechazo de Injerto , Supervivencia de Injerto , Inmunosupresores , Trasplante de Riñón , Donadores Vivos , Rituximab , Humanos , Suero Antilinfocítico/uso terapéutico , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Adulto , Inmunosupresores/uso terapéutico , Estudios de Seguimiento , Proyectos Piloto , Supervivencia de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/inmunología , Pronóstico , Terapia de Inmunosupresión/métodos , Pruebas de Función Renal , Receptores de TrasplantesRESUMEN
Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.
Asunto(s)
Infecciones por Virus de Epstein-Barr , Rechazo de Injerto , Supervivencia de Injerto , Herpesvirus Humano 4 , Inmunosupresores , Trasplante de Riñón , Trastornos Linfoproliferativos , Complicaciones Posoperatorias , Donantes de Tejidos , Humanos , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/etiología , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/virología , Persona de Mediana Edad , Adulto , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Factores de Riesgo , Estudios de Seguimiento , Pronóstico , Rechazo de Injerto/etiología , Suero Antilinfocítico/efectos adversos , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Receptores de Trasplantes , Incidencia , Quimioterapia de Inducción/efectos adversos , Basiliximab , Alemtuzumab/efectos adversos , Pruebas de Función RenalRESUMEN
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.
Asunto(s)
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
OBJECTIVES: Accurate glomerular filtration rate (GFR) assessment is essential in critically ill patients. GFR is often estimated using creatinine-based equations, which require surrogates for muscle mass such as age and sex. Race has also been included in GFR equations, based on the assumption that Black individuals have genetically determined higher muscle mass. However, race-based GFR estimation has been questioned with the recognition that race is a poor surrogate for genetic ancestry, and racial health disparities are driven largely by socioeconomic factors. The American Society of Nephrology and the National Kidney Foundation (ASN/NKF) recommend widespread adoption of new "race-free" creatinine equations, and increased use of cystatin C as a race-agnostic GFR biomarker. DATA SOURCES: Literature review and expert consensus. STUDY SELECTION: English language publications evaluating GFR assessment and racial disparities. DATA EXTRACTION: We provide an overview of the ASN/NKF recommendations. We then apply an Implementation science methodology to identify facilitators and barriers to implementation of the ASN/NKF recommendations into critical care settings and identify evidence-based implementation strategies. Last, we highlight research priorities for advancing GFR estimation in critically ill patients. DATA SYNTHESIS: Implementation of the new creatinine-based GFR equation is facilitated by low cost and relative ease of incorporation into electronic health records. The key barrier to implementation is a lack of direct evidence in critically ill patients. Additional barriers to implementing cystatin C-based GFR estimation include higher cost and lack of test availability in most laboratories. Further, cystatin C concentrations are influenced by inflammation, which complicates interpretation. CONCLUSIONS: The lack of direct evidence in critically ill patients is a key barrier to broad implementation of newly developed "race-free" GFR equations. Additional research evaluating GFR equations in critically ill patients and novel approaches to dynamic kidney function estimation is required to advance equitable GFR assessment in this vulnerable population.
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Cuidados Críticos , Cistatina C , Tasa de Filtración Glomerular , Humanos , Cistatina C/sangre , Cuidados Críticos/métodos , Creatinina/sangre , Pruebas de Función Renal/métodos , Pruebas de Función Renal/normas , Biomarcadores/sangre , Enfermedad CríticaRESUMEN
RATIONALE & OBJECTIVE: Individuals with a low estimated glomerular filtration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause-specific mortality. STUDY DESIGN: Retrospective cohort study incorporating Mendelian randomization (MR). SETTING & PARTICIPANTS: Individual-level data from 436,214 White participants (54.3% female; aged 56.8±8.0 years) included in the UK Biobank. EXPOSURES: eGFR estimated using cystatin C (eGFRcyst). OUTCOMES: The outcomes of interest included all-cause mortality, cardiovascular mortality, cancer mortality, infection mortality, and other-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards analysis for the conventional observational analyses; linear and nonlinear MR analyses implemented using genetic allele scores as instrumental variables representing kidney function to estimate the effect of kidney function on the survival outcomes. RESULTS: During a median follow-up of 12.1 years, there were 30,489 deaths, 6,098 of which were attributed to cardiovascular events, 15,538 to cancer, 1,516 to infection, and 7,227 to other events. In the conventional observational analysis, eGFRcyst exhibited a nonlinear association with all the outcomes. MR analysis suggested that a genetically predicted lower eGFRcyst was linearly associated with a higher rate of cardiovascular mortality (HR, 1.43; 95% CI, 1.18-1.75) across the entire measurement range (every 10-mL/min/1.73m2 decrement). Nonetheless, no causal associations between eGFRcyst and all-cause mortality (HR, 1.07; 95% CI, 0.98-1.17) or any types of noncardiovascular mortality were detected. LIMITATIONS: Potential misclassification of the actual cause of death, a nonrepresentative sample, and potential error in the interpretation of the magnitude of associations generated in MR analyses. CONCLUSIONS: These findings suggest a potential causal association between low eGFR and cardiovascular mortality in the general population, but no causal relationship with all-cause mortality or noncardiovascular mortality was observed. Further studies in other populations are warranted to confirm these findings. PLAIN-LANGUAGE SUMMARY: This study investigated the existence of a causal relationship between lower kidney function and death of different causes. Using data from 436,214 people in the United Kingdom, we applied conventional statistical analyses and those incorporating genetic data to implement Mendelian randomization, an approach that estimates causal associations. The observational analysis showed a nonlinear association between kidney function and various types of mortality outcomes. However, Mendelian randomization analysis suggested a linear increase in the risk of cardiovascular mortality with lower kidney function, but no causal link between the level of kidney function and all-cause or noncardiovascular mortality was identified. Managing kidney health may help reduce cardiovascular mortality, but caution is needed in interpreting the magnitudes of these results. Further validation in other populations and in those with advanced kidney failure is needed.
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Causas de Muerte , Tasa de Filtración Glomerular , Análisis de la Aleatorización Mendeliana , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Retrospectivos , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/genética , Cistatina C/sangre , Reino Unido/epidemiología , Estudios de Cohortes , Anciano , Pruebas de Función RenalRESUMEN
The most commonly used equations to estimate glomerular filtration rate incorporate a binary male-female sex coefficient, which has important implications for the care of transgender, gender-diverse, and nonbinary (TGD) people. Whether "sex assigned at birth" or a binary "gender identity" is most appropriate for the computation of estimated glomerular filtration rate (eGFR) is unknown. Furthermore, the use of gender-affirming hormone therapy (GAHT) for the development of physical changes to align TGD people with their affirmed gender is increasingly common, and may result in changes in serum creatinine and cystatin C, the biomarkers commonly used to estimate glomerular filtration rate. The paucity of current literature evaluating chronic kidney disease (CKD) prevalence and outcomes in TGD individuals on GAHT makes it difficult to assess any effects of GAHT on kidney function. Whether alterations in serum creatinine reflect changes in glomerular filtration rate or simply changes in muscle mass is unknown. Therefore, we propose a holistic framework to evaluate kidney function in TGD people. The framework focuses on kidney disease prevalence, risk factors, sex hormones, eGFR, other kidney function assessment tools, and the mitigation of health inequities in TGD people.
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Tasa de Filtración Glomerular , Humanos , Masculino , Femenino , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/diagnóstico , Pruebas de Función Renal/métodos , Personas Transgénero , Creatinina/sangre , Salud HolísticaRESUMEN
BACKGROUND: Renal function after left renal vein (LRV) ligation following en bloc resection of segmental inferior vena cava (IVC) and right kidney is understudied. We assessed the impact of LRV ligation on postoperative renal function following en bloc resection of segmental IVC and right kidney. METHODS: We retrospectively reviewed 28 patients who underwent LRV ligation during en bloc resection of segmental IVC and right kidney. Patient demographics, tumor characteristics, intraoperative factors, complications, length of hospital and intensive care unit (ICU) stay, and patient survival were collected. Pre- and postoperative renal function was retrospectively analyzed. RESULTS: Twenty patients underwent robot-assisted surgery and eight patients underwent open surgery. The median operative time was 162 min and estimated blood loss was 350 mL. Ten patients had normal renal function and 12 patients had an initial increase in creatinine but improved gradually. Six patients developed acute renal failure; five patients gradually recovered in 5-32 days after temporary hemodialysis. Renal replacement therapy significantly correlated with maximal anterior-posterior diameter of the LRV (p = 0.001). Complications were observed in 11 cases, four of which were Clavien-Dindo grades I-II. Thirteen patients were alive with no recurrence, nine patients were alive with metastasis, and six cases died during the follow-up period. CONCLUSIONS: LRV ligation following en bloc resection of segmental IVC and right kidney is feasible, with no significant long-term impact on renal function. The maximum anterior-posterior diameter of the LRV is a reliable method for predicting renal replacement therapy in the absence of collateral circulation.
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Neoplasias Renales , Venas Renales , Vena Cava Inferior , Humanos , Vena Cava Inferior/cirugía , Vena Cava Inferior/patología , Masculino , Femenino , Venas Renales/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Ligadura , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Anciano , Estudios de Seguimiento , Adulto , Tasa de Supervivencia , Nefrectomía/métodos , Complicaciones Posoperatorias , Pronóstico , Riñón/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Pruebas de Función Renal , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patologíaRESUMEN
Accurately measuring renal function is crucial for pediatric patients with kidney conditions. Traditional methods have limitations, but dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides a safe and efficient approach for detailed anatomical evaluation and renal function assessment. However, motion artifacts during DCE-MRI can degrade image quality and introduce misalignments, leading to unreliable results. This study introduces a motion-compensated reconstruction technique for DCE-MRI data acquired using golden-angle radial sampling. Our proposed method achieves three key objectives: (1) identifying and removing corrupted data (outliers) using a Gaussian process model fitting with a k -space center navigator, (2) efficiently clustering the data into motion phases and performing interphase registration, and (3) utilizing a novel formulation of motion-compensated radial reconstruction. We applied the proposed motion correction (MoCo) method to DCE-MRI data affected by varying degrees of motion, including both respiratory and bulk motion. We compared the outcomes with those obtained from the conventional radial reconstruction. Our evaluation encompassed assessing the quality of images, concentration curves, and tracer kinetic model fitting, and estimating renal function. The proposed MoCo reconstruction improved the temporal signal-to-noise ratio for all subjects, with a 21.8% increase on average, while total variation values of the aorta, right, and left kidney concentration were improved for each subject, with 32.5%, 41.3%, and 42.9% increases on average, respectively. Furthermore, evaluation of tracer kinetic model fitting indicated that the median standard deviation of the estimated filtration rate ( σ F T ), mean normalized root-mean-squared error (nRMSE), and chi-square goodness-of-fit of tracer kinetic model fit were decreased from 0.10 to 0.04, 0.27 to 0.24, and, 0.43 to 0.27, respectively. The proposed MoCo technique enabled more reliable renal function assessment and improved image quality for detailed anatomical evaluation in the case of bulk and respiratory motion during the acquisition of DCE-MRI.
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Medios de Contraste , Riñón , Imagen por Resonancia Magnética , Movimiento (Física) , Humanos , Imagen por Resonancia Magnética/métodos , Medios de Contraste/química , Riñón/diagnóstico por imagen , Riñón/fisiología , Procesamiento de Imagen Asistido por Computador/métodos , Pruebas de Función Renal/métodos , Masculino , Femenino , Artefactos , Relación Señal-RuidoRESUMEN
Owing to the increasing prevalence of diabetic mellitus, diabetic kidney disease (DKD) is presently the leading cause of chronic kidney disease and end-stage renal disease worldwide. Early identification and disease interception is of paramount clinical importance for DKD management. However, current diagnostic, disease monitoring and prognostic tools are not satisfactory, due to their low sensitivity, low specificity, or invasiveness. Magnetic resonance imaging (MRI) is noninvasive and offers a host of contrast mechanisms that are sensitive to pathophysiological changes and risk factors associated with DKD. MRI tissue characterization involves structural and functional information including renal morphology (kidney volume (TKV) and parenchyma thickness using T1- or T2-weighted MRI), renal microstructure (diffusion weighted imaging, DWI), renal tissue oxygenation (blood oxygenation level dependent MRI, BOLD), renal hemodynamics (arterial spin labeling and phase contrast MRI), fibrosis (DWI) and abdominal or perirenal fat fraction (Dixon MRI). Recent (pre)clinical studies demonstrated the feasibility and potential value of DKD evaluation with MRI. Recognizing this opportunity, this review outlines key concepts and current trends in renal MRI technology for furthering our understanding of the mechanisms underlying DKD and for supplementing clinical decision-making in DKD. Progress in preclinical MRI of DKD is surveyed, and challenges for clinical translation of renal MRI are discussed. Future directions of DKD assessment and renal tissue characterization with (multi)parametric MRI are explored. Opportunities for discovery and clinical break-through are discussed including biological validation of the MRI findings, large-scale population studies, standardization of DKD protocols, the synergistic connection with data science to advance comprehensive texture analysis, and the development of smart and automatic data analysis and data visualization tools to further the concepts of virtual biopsy and personalized DKD precision medicine. We hope that this review will convey this vision and inspire the reader to become pioneers in noninvasive assessment and management of DKD with MRI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.