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Introduction: Diagnostic genomic sequencing is the emerging standard of care in nephrology. There is a growing need to scale up the implementation of genomic diagnostics nationally to improve patient outcomes. Methods: This pragmatic study provided genomic or genetic testing to patients with suspected monogenic kidney disease through a national network of kidney genetics clinics (KGCs). We sought to evaluate the experiences of implementing genomic diagnostics across Australia and associated diagnostic outcomes between 2013 and 2022. Results: We successfully established and expanded a nationwide network of 20 clinics as of 2022; concurrently developing laboratory, research, and education programs to scale the clinical application of genomics in nephrology. We report on an Australian cohort of 1506 kidney patients, of whom 1322 received their test results. We assessed barriers to implementation in the nephrology context, and where possible, applied real-time solutions to improve clinical processes over 10 years. Conclusion: Developing a multidisciplinary kidney genetics model across multiple health services nationally was highly successful. This model supported optimal care of individuals with monogenic kidney disease in an economically responsible way. It has continued to evolve with technological and service developments and is now set to scale further as genomic testing for kidney patients transitions to health care system funding.
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Urinary CXCL10 and metabolites are biomarkers independently associated with TCMR. We sought to test whether these biomarkers fluctuate in association with histological severity of TCMR over short time frames. Forty-nine pairs of renal biopsies obtained 1-3 months apart from 40 pediatric renal transplant recipients were each scored for TCMR acuity score (i + t; Banff criteria). Urinary CXCL10:Cr and TCMR MDS were obtained at each biopsy and were tested for association with changes between biopsies in acuity, estimated GFR (ΔeGFR), and 12-month ΔeGFR. Sequential biopsies were obtained 1.8 ± 0.8 months apart. Biopsy 1 was usually obtained under protocol (75%), and 62% percent had evidence of TCMR. Using each biopsy pair for comparison, ΔeGFR did not predict change in acuity. By contrast, change in acuity was significantly correlated with change in urinary CXCL10:Cr (ρ 0.45, P = .003) and MDS (ρ 0.29, P = .04) between biopsies. The 12-month ΔeGFR was not predicted by TCMR acuity or CXCL10:Cr at Biopsy 2; however, an inverse correlation was seen with urinary MDS (ρ -0.35; P = .02). Changes in eGFR correlate poorly with evolving TCMR acuity on histology. Urinary biomarkers may be superior for non-invasive monitoring of rejection, including histological response to therapy, and may be prognostic for medium-term function.
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Quimiocina CXCL10/orina , Rechazo de Injerto/diagnóstico , Trasplante de Riñón , Riñón/patología , Riñón/fisiopatología , Adolescente , Biomarcadores/orina , Biopsia , Estudios de Casos y Controles , Niño , Preescolar , Creatinina/orina , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/patología , Rechazo de Injerto/fisiopatología , Rechazo de Injerto/orina , Humanos , Lactante , Recién Nacido , Riñón/metabolismo , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Although the clinical benefit of interleukin-2-receptor antibody (IL-2RAb) induction in reducing the risk of acute rejection in adult kidney transplant recipients is well established, a similar benefit in pediatric recipients remains controversial. The aim of this study is to evaluate the efficacy of IL-2RAb in reducing acute rejection in pediatric and adolescent recipients aged 21 years or younger using Australia and New Zealand Dialysis and Transplant registry. METHODS: The association between IL-2RAb induction and risk of acute rejection was examined using adjusted logistic regression and propensity score analyses, whereby the associations between induction, graft loss, and incident cancer were examined using adjusted Cox regression analysis. RESULTS: There were 658 recipients followed up for a median of 5.5 years between 2001 and 2012. The use of IL-2RAb induction was associated with adjusted odds ratios of 0.61 (95% confidence interval [CI], 0.41-0.91; P = 0.007) for any rejection and 0.57 (95% CI, 0.35-0.92; P = 0.020) for early rejection occurring in the first 6 months after transplant. These associations were attenuated in the propensity score analysis but remained statistically significant with adjusted odds ratio of 0.65 (95% CI, 0.49-0.87) for any rejection and 0.64 (95% CI, 0.44-0.93) for early rejection. There were no associations between induction, graft loss, and incident cancer. CONCLUSIONS: Induction treatment of IL-2RAb in pediatric and adolescent kidney transplant recipients is associated with at least a 40% reduction in the odds of acute rejection, independent of age, era, immunological status, and initial immunosuppression.
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Anticuerpos/uso terapéutico , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/uso terapéutico , Quimioterapia de Inducción , Subunidad alfa del Receptor de Interleucina-2/antagonistas & inhibidores , Trasplante de Riñón , Adolescente , Factores de Edad , Anticuerpos/efectos adversos , Australia , Distribución de Chi-Cuadrado , Niño , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Humanos , Inmunosupresores/efectos adversos , Quimioterapia de Inducción/efectos adversos , Quimioterapia de Inducción/mortalidad , Subunidad alfa del Receptor de Interleucina-2/inmunología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Modelos Lineales , Modelos Logísticos , Masculino , Análisis Multivariante , Nueva Zelanda , Oportunidad Relativa , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To describe, from a patient perspective, factors leading to suboptimal management of individuals with rheumatic fever (RF) and rheumatic heart disease (RHD) among members of the Kimberley population. METHOD: Qualitative in-depth semistructured and repeated interviews of seven Kimberley patients, or parents of children, with rheumatic fever and/or rheumatic heart disease, during 1998. RESULTS: Participants showed variable levels of understanding about RF/RHD, often relating to the need for secondary prophylaxis. Compliance with medication was closely linked with positive patient-staff interactions. From the perspective of health care, living in a remote location was frequently described as a negative influence. Participants desire more accessible and culturally appropriate opportunities for learning about their disease. CONCLUSIONS: Participants focused on issues closely related to effective and ineffective management of RF/RHD. The lessons learned are indicators for health staff attempting to improve the quality of management that people receive.
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Actitud Frente a la Salud/etnología , Nativos de Hawái y Otras Islas del Pacífico/etnología , Calidad de la Atención de Salud , Fiebre Reumática/etnología , Cardiopatía Reumática/etnología , Servicios de Salud Rural/normas , Adolescente , Adulto , Niño , Diversidad Cultural , Femenino , Encuestas de Atención de la Salud , Conocimientos, Actitudes y Práctica en Salud , Accesibilidad a los Servicios de Salud/normas , Humanos , Masculino , Área sin Atención Médica , Narración , Nativos de Hawái y Otras Islas del Pacífico/educación , Evaluación de Necesidades , Educación del Paciente como Asunto/normas , Relaciones Profesional-Paciente , Investigación Cualitativa , Fiebre Reumática/terapia , Cardiopatía Reumática/terapia , Encuestas y Cuestionarios , Australia OccidentalRESUMEN
OBJECTIVE: To evaluate the quality of management of Kimberley patients with rheumatic fever (RF) and rheumatic heart disease (RHD). METHODS: A retrospective analysis of medical records for 215 residents of the Kimberley region of Western Australia, diagnosed with RF or RHD during the years 1982 to 1996. RESULTS: Among patients prescribed intramuscular penicillin for secondary prophylaxis, 67% of prescribed doses were given, with individuals receiving 8-100% of doses prescribed. Of patients recommended visiting specialist or echocardiographic review, 78% and 64% attended respectively. Only 34% of patients with RHD in 1996 were recommended dental review in 1996 or 1997. Appropriate blood testing occurred in 34% of the months in which people had anticoagulant prescribed. CONCLUSIONS: A clinical audit can be used to evaluate the management received by this population and hence identify areas to improve management. We found much room for improvement if optimal clinical outcomes are to be obtained.