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Reliable models of renal failure in large animals are critical to the successful translation of the next generation of renal replacement therapies (RRT) into humans. While models exist for the induction of renal failure, none are optimized for the implantation of devices to the retroperitoneal vasculature. We successfully piloted an embolization-to-implantation protocol enabling the first implant of a silicon nanopore membrane hemodialyzer (SNMHD) in a swine renal failure model. Renal arterial embolization is a non-invasive approach to near-total nephrectomy that preserves retroperitoneal anatomy for device implants. Silicon nanopore membranes (SNM) are efficient blood-compatible membranes that enable novel approaches to RRT. Yucatan minipigs underwent staged bilateral renal arterial embolization to induce renal failure, managed by intermittent hemodialysis. A small-scale arteriovenous SNMHD prototype was implanted into the retroperitoneum. Dialysate catheters were tunneled externally for connection to a dialysate recirculation pump. SNMHD clearance was determined by intermittent sampling of recirculating dialysate. Creatinine and urea clearance through the SNMHD were 76-105 mL/min/m2 and 140-165 mL/min/m2, respectively, without albumin leakage. Normalized creatinine and urea clearance measured in the SNMHD may translate to a fully implantable clinical-scale device. This pilot study establishes a path toward therapeutic testing of the clinical-scale SNMHD and other implantable RRT devices.

Objective: This study aimed to assess the presence of elbow pain and its relationship with vascular access site for hemodialysis in end-stage renal disease patients. Methods:One-hundred and nine chronic end-stage renal disease patients over 18 years of age undergoing hemodialysis treatment were enrolled in the study. Patients who had undergone surgery of the upper extremity in the last three months and patients with cancer, chronic hearing loss, or neurologic diseases were excluded. Sociodemographic features were evaluated. The Beck Depression Inventory, the Nottingham Health Profile, the Disabilities of the Arm, Shoulder and Hand Score, and the Visual Analogue Scale were administered to all patients. Results:One-hundred and nine patients (38 women, 71 men) participated in the study. The mean age of the patients was 62.22 ± 11.64. The patients were grouped based on the presence of elbow pain into Group 1 (elbow pain positive, n=30) and Group 2 (elbow pain negative, n=79). There was a statistically significant difference between the groups in terms of vascular access site and elbow pain site (p=0.002). In addition, the patients with elbow pain were mostly women, and this result was statistically significant (p<0.05). Conclusions: According to the results of this study, there may be a relationship between elbow pain and hemodialysis vascular site., Objetivo: Este estudio tuvo como objetivo evaluar la presencia de dolor en el codo y su relación con el sitio del acceso vascular para hemodiálisis en pacientes con enfermedad renal terminal. Métodos: Participaron del estudio 109 pacientes mayores de 18 años con enfermedad renal crónica terminal en tratamiento de hemodiálisis. Se excluyeron los pacientes intervenidos quirúrgicamente en la extremidad superior en los últimos tres meses y los pacientes con cáncer, hipoacusia crónica o enfermedades neurológicas. Se evaluaron las características sociodemográficas. A todos los pacientes se les administró el Inventario de Depresión de Beck, el Perfil de Salud de Nottingham, la Puntuación de Discapacidades del Brazo, el Hombro y la Mano, y la Escala Visual Analógica. Resultados: Ciento nueve pacientes (38 mujeres, 71 hombres) participaron en el estudio. La edad media de los pacientes fue de 62,22 ± 11,64. Los pacientes se agruparon en función de la presencia de dolor en el codo en dos grupos: el Grupo 1 (dolor en el codo positivo, n=30) y el Grupo 2 (dolor en el codo negativo, n=79). Hubo una diferencia estadísticamente significativa entre los grupos en cuanto al sitio de acceso vascular y el sitio del dolor en el codo (p=0,002). Además, los pacientes con dolor en el codo eran en su mayoría mujeres, y este resultado fue estadísticamente significativo (p<0,05). Conclusiones: Según los resultados de este estudio, puede existir una relación entre el dolor del codo y el sitio vascular de hemodiálisis.

This study aimed to explore the lived experiences of patients receiving maintenance hemodialysis in Pakistan. Purposive sampling was used to recruit 24 patients and six healthcare professionals, each participated in a semi-structured interview. Interpretive Phenomenological Analysis was used to analyze interviews’ data. Two superordinate themes, “The experience of hemodialysis” and “The conceptualizations of hemodialysis” as well as six sub-themes were identified. The experience of hemodialysis was related to, the implications of HD procedure on everyday life, social, cognitive, emotional, financial, and occupational influences. While all participants recognized the importance of hemodialysis for their survival, their conceptualizations of the treatment varied. Despite facing multiple challenges, optimism and independence were observed among participants. Stigma related to hemodialysis, and role adaptation, which appear unique to the Pakistani context, highlight a need for tailored interventions designed to enhance and maintain the mental health of patients receiving hemodialysis in Pakistan.

Background Health-related quality of life (HRQOL) has a direct association with increased morbidity and mortality among end stage renal disease patients. Valid and reliable instruments to measure the HRQOL of patients with end stage renal disease are therefore required. This study aimed to translate, culturally adapt and evaluate the psychometric properties of the Amharic version of the Kidney Disease Quality of Life-36 (KDQOL-36) instrument in Ethiopian patients with end stage renal disease undergoing hemodialysis. Methods The KDQOL-36 instrument was developed for individuals with kidney disease who are being treated with dialysis and includes both generic and disease-specific components. The KDQOL-36 was translated to Amharic language and distributed to a cross-sectional sample of 292 hemodialysis patients. The psychometric evaluation included construct validity through corrected item-total correlation, confirmatory factor analysis and known group analysis. Convergent validity was evaluated by correlations between each of the three kidney disease targeted scales (symptoms/problems list, burden of kidney disease and effects of kidney diseases) and the European Quality of Life 5D-5L and Visual Analog Scales. Regarding reliability, internal consistency and test-retest reliability were assessed. Results Two hundred ninety-two patients with a mean age of 48 (SD +/- 14.7) completed the questionnaire. Corrected item- total correlation scores were > 0.4 for all items. Confirmatory factor analysis revealed a two chi(2) /df was 4.4, Root Mean Square Error of Approximation (RMSEA) = 0.108 (90% CI 0.064-0.095), Comparative Fit Index (CFI) = 0.922, Tucker Lewis Index (TLI) = 0.948 and Standardized Root mean-squared residual (SRMR) = 0.058) and three chi(2) /df = 3.1, RMSEA = 0.085 (90% CI 0.064-0.095), CFI = 0.854, TLI = 0.838 and SRMR = 0.067) factor models for the generic and disease specific components respectively. The mean scores of the three kidney disease targeted do

Background Health-related quality of life (HRQOL) has a direct association with increased morbidity and mortality among end stage renal disease patients. Valid and reliable instruments to measure the HRQOL of patients with end stage renal disease are therefore required. This study aimed to translate, culturally adapt and evaluate the psychometric properties of the Amharic version of the Kidney Disease Quality of Life-36 (KDQOL-36) instrument in Ethiopian patients with end stage renal disease undergoing hemodialysis. Methods The KDQOL-36 instrument was developed for individuals with kidney disease who are being treated with dialysis and includes both generic and disease-specific components. The KDQOL-36 was translated to Amharic language and distributed to a cross-sectional sample of 292 hemodialysis patients. The psychometric evaluation included construct validity through corrected item-total correlation, confirmatory factor analysis and known group analysis. Convergent validity was evaluated by correlations between each of the three kidney disease targeted scales (symptoms/problems list, burden of kidney disease and effects of kidney diseases) and the European Quality of Life 5D-5L and Visual Analog Scales. Regarding reliability, internal consistency and test-retest reliability were assessed. Results Two hundred ninety-two patients with a mean age of 48 (SD +/- 14.7) completed the questionnaire. Corrected item- total correlation scores were > 0.4 for all items. Confirmatory factor analysis revealed a two chi(2) /df was 4.4, Root Mean Square Error of Approximation (RMSEA) = 0.108 (90% CI 0.064-0.095), Comparative Fit Index (CFI) = 0.922, Tucker Lewis Index (TLI) = 0.948 and Standardized Root mean-squared residual (SRMR) = 0.058) and three chi(2) /df = 3.1, RMSEA = 0.085 (90% CI 0.064-0.095), CFI = 0.854, TLI = 0.838 and SRMR = 0.067) factor models for the generic and disease specific components respectively. The mean scores of the three kidney disease targeted do

Background Health-related quality of life (HRQOL) has a direct association with increased morbidity and mortality among end stage renal disease patients. Valid and reliable instruments to measure the HRQOL of patients with end stage renal disease are therefore required. This study aimed to translate, culturally adapt and evaluate the psychometric properties of the Amharic version of the Kidney Disease Quality of Life-36 (KDQOL-36) instrument in Ethiopian patients with end stage renal disease undergoing hemodialysis. Methods The KDQOL-36 instrument was developed for individuals with kidney disease who are being treated with dialysis and includes both generic and disease-specific components. The KDQOL-36 was translated to Amharic language and distributed to a cross-sectional sample of 292 hemodialysis patients. The psychometric evaluation included construct validity through corrected item-total correlation, confirmatory factor analysis and known group analysis. Convergent validity was evaluated by correlations between each of the three kidney disease targeted scales (symptoms/problems list, burden of kidney disease and effects of kidney diseases) and the European Quality of Life 5D-5L and Visual Analog Scales. Regarding reliability, internal consistency and test-retest reliability were assessed. Results Two hundred ninety-two patients with a mean age of 48 (SD +/- 14.7) completed the questionnaire. Corrected item- total correlation scores were > 0.4 for all items. Confirmatory factor analysis revealed a two chi(2) /df was 4.4, Root Mean Square Error of Approximation (RMSEA) = 0.108 (90% CI 0.064-0.095), Comparative Fit Index (CFI) = 0.922, Tucker Lewis Index (TLI) = 0.948 and Standardized Root mean-squared residual (SRMR) = 0.058) and three chi(2) /df = 3.1, RMSEA = 0.085 (90% CI 0.064-0.095), CFI = 0.854, TLI = 0.838 and SRMR = 0.067) factor models for the generic and disease specific components respectively. The mean scores of the three kidney disease targeted do

Background Health-related quality of life (HRQOL) has a direct association with increased morbidity and mortality among end stage renal disease patients. Valid and reliable instruments to measure the HRQOL of patients with end stage renal disease are therefore required. This study aimed to translate, culturally adapt and evaluate the psychometric properties of the Amharic version of the Kidney Disease Quality of Life-36 (KDQOL-36) instrument in Ethiopian patients with end stage renal disease undergoing hemodialysis. Methods The KDQOL-36 instrument was developed for individuals with kidney disease who are being treated with dialysis and includes both generic and disease-specific components. The KDQOL-36 was translated to Amharic language and distributed to a cross-sectional sample of 292 hemodialysis patients. The psychometric evaluation included construct validity through corrected item-total correlation, confirmatory factor analysis and known group analysis. Convergent validity was evaluated by correlations between each of the three kidney disease targeted scales (symptoms/problems list, burden of kidney disease and effects of kidney diseases) and the European Quality of Life 5D-5L and Visual Analog Scales. Regarding reliability, internal consistency and test-retest reliability were assessed. Results Two hundred ninety-two patients with a mean age of 48 (SD +/- 14.7) completed the questionnaire. Corrected item- total correlation scores were > 0.4 for all items. Confirmatory factor analysis revealed a two chi(2) /df was 4.4, Root Mean Square Error of Approximation (RMSEA) = 0.108 (90% CI 0.064-0.095), Comparative Fit Index (CFI) = 0.922, Tucker Lewis Index (TLI) = 0.948 and Standardized Root mean-squared residual (SRMR) = 0.058) and three chi(2) /df = 3.1, RMSEA = 0.085 (90% CI 0.064-0.095), CFI = 0.854, TLI = 0.838 and SRMR = 0.067) factor models for the generic and disease specific components respectively. The mean scores of the three kidney disease targeted do

Background Health-related quality of life (HRQOL) has a direct association with increased morbidity and mortality among end stage renal disease patients. Valid and reliable instruments to measure the HRQOL of patients with end stage renal disease are therefore required. This study aimed to translate, culturally adapt and evaluate the psychometric properties of the Amharic version of the Kidney Disease Quality of Life-36 (KDQOL-36) instrument in Ethiopian patients with end stage renal disease undergoing hemodialysis. Methods The KDQOL-36 instrument was developed for individuals with kidney disease who are being treated with dialysis and includes both generic and disease-specific components. The KDQOL-36 was translated to Amharic language and distributed to a cross-sectional sample of 292 hemodialysis patients. The psychometric evaluation included construct validity through corrected item-total correlation, confirmatory factor analysis and known group analysis. Convergent validity was evaluated by correlations between each of the three kidney disease targeted scales (symptoms/problems list, burden of kidney disease and effects of kidney diseases) and the European Quality of Life 5D-5L and Visual Analog Scales. Regarding reliability, internal consistency and test-retest reliability were assessed. Results Two hundred ninety-two patients with a mean age of 48 (SD +/- 14.7) completed the questionnaire. Corrected item- total correlation scores were > 0.4 for all items. Confirmatory factor analysis revealed a two chi(2) /df was 4.4, Root Mean Square Error of Approximation (RMSEA) = 0.108 (90% CI 0.064-0.095), Comparative Fit Index (CFI) = 0.922, Tucker Lewis Index (TLI) = 0.948 and Standardized Root mean-squared residual (SRMR) = 0.058) and three chi(2) /df = 3.1, RMSEA = 0.085 (90% CI 0.064-0.095), CFI = 0.854, TLI = 0.838 and SRMR = 0.067) factor models for the generic and disease specific components respectively. The mean scores of the three kidney disease targeted do

Rapidly progressive immune complex-mediated glomerulonephritis (RPGNMN II) is a clinical syndrome characterized by severe deterioration of renal function associated with hematuria, edema, and oliguria. It is histologically characterized as a crescentic glomerulonephritis, with the presence of granular deposits on immunofluorescence. Although it is a rare condition, it is a potentially serious disease that may progress to chronic renal disease, therefore its early identificationis essential. Here we present a review of this form of glomerulonephritis, with emphasis on its etiology and the currently available therapeutic options., La glomerulonefritis rápidamente progresiva mediada por complejos inmunes (GMNRP II) es un síndrome clínico caracterizado por el rápido deterioro de la función renal asociado a hematuria, edemas y oliguria. Histológicamente se manifiesta como una glomerulonefritis crescéntica, con la presencia de depósitos granulares en la inmunofluorescencia. Aunque es una enfermedad rara, es grave y puede evolucionar a una enfermedad renal crónica, por lo cual es fundamental su identificación temprana. A continuación, se presenta una revisión sobre este tipo de glomerulonefritis, con énfasis en su etiología y en las opciones terapéuticas existentes en la actualidad.

Background: Lupus nephritis (LN) is a poor prognostic marker in children with Systemic Lupus Erythematosus (SLE). Treatment strategies are based on adult guidelines, involving multiple immunosuppressive agents. Aim(s): In children with LN at Monash Children's Hospital (MCH), to review induction treatment and immunosuppressive agents used compared to international guidelines, and to describe patient outcomes. Method(s): Retrospective chart review identified children diagnosed with SLE and LN at MCH from January 2002-June 2020. Demographic and clinical data were collected, including relapses or progression of LN and modalities of treatment. Result(s): Over the study period, 17 children with LN were treated at MCH. Data from 16 patients was available. 68.7% were female, with median age at diagnosis 12.5 years (range 8-17). 15 patients had LN at presentation: all had proteinuria (nephrotic range in 7), 14 had haematuria and no patient had renal impairment. All had systemic features, most commonly rash, fever and arthritis. 15 of 16 patients underwent renal biopsy, with proliferative LN in 66.6%. All patients received oral hydroxychloroquine and glucocorticoids. 81.2% received intravenous methylprednisolone and 75% commenced mycophenolate mofetil at induction. 8 of 15 had at least one further kidney biopsy, with a change in LN class observed in five patients. Three patients had progressive LN- requiring treatment with cyclophosphamide, rituximab and ultimately dialysis (median age 15, median time to dialysis 5 years). Excluding the 3 patients with end stage kidney disease, the median eGFR at last follow-up (median 2.25 years) was 108 mL/min/1.73 m2 (2 patients had an eGFR <90 mL/min/1.73 m2). Conclusion(s): Induction treatment of paediatric patients with LN at MCH aligned with recommendations of current international guidelines. End stage kidney disease developed in 18.7% of patients.

BACKGROUND: Myeloperoxidase ANCA-associated vasculitis is a major cause of ESKD. Efficacy of anti-CD20 mAb treatment was tested in a mouse model of the disease. METHOD(S): MPO immunization induced anti-MPO autoimmunity, and a subnephritogenic dose of sheep anti-mouse GBM globulin triggered GN. RESULT(S): Anti-CD20 mAb treatment increased the numbers and immunomodulatory capacity of MPO-specific T regulatory cells (Tregs) and attenuated T cell-mediated and humoral anti-MPO autoimmunity and GN. Disabling of Tregs negated the therapeutic benefit of anti-CD20 treatment. The mechanism of enhancement of Treg activity could be attributed to anti-CD20 mAb effects on inducing B cell apoptosis. Administering anti-CD20 mAb-induced apoptotic splenocytes to mice developing anti-MPO GN was as effective as anti-CD20 mAb treatment in inducing Tregs and attenuating both anti-MPO autoimmunity and GN. A nonredundant role for splenic macrophages in mediating the anti-CD20 mAb-induced immunomodulation was demonstrated by showing that administration of anti-CD20 mAb ex vivo-induced apoptotic splenocytes to unmanipulated mice attenuated autoimmunity and GN, whereas deletion of splenic marginal zone macrophages prevented anti-CD20 mAb-induced immunomodulation and treatment efficacy. Six days after administering anti-CD20 mAb to mice with murine anti-MPO GN, cell-mediated anti-MPO responses and GN were attenuated, and Tregs were enhanced, but ANCA levels were unchanged, suggesting humoral autoimmunity was redundant at this time point. CONCLUSION(S): Collectively, these data suggest that, as well as reducing humoral autoimmunity, anti-CD20 mAb more rapidly induces protective anti-MPO Treg-mediated immunomodulation by splenic processing of anti-CD20-induced apoptotic B cells.Copyright © 2021 by the American Society of Nephrology.

Background: Lupus nephritis (LN) is a poor prognostic marker in children with Systemic Lupus Erythematosus (SLE). Treatment strategies are based on adult guidelines, involving multiple immunosuppressive agents. Aim(s): In children with LN at Monash Children's Hospital (MCH), to review induction treatment and immunosuppressive agents used compared to international guidelines, and to describe patient outcomes. Method(s): Retrospective chart review identified children diagnosed with SLE and LN at MCH from January 2002-June 2020. Demographic and clinical data were collected, including relapses or progression of LN and modalities of treatment. Result(s): Over the study period, 17 children with LN were treated at MCH. Data from 16 patients was available. 68.7% were female, with median age at diagnosis 12.5 years (range 8-17). 15 patients had LN at presentation: all had proteinuria (nephrotic range in 7), 14 had haematuria and no patient had renal impairment. All had systemic features, most commonly rash, fever and arthritis. 15 of 16 patients underwent renal biopsy, with proliferative LN in 66.6%. All patients received oral hydroxychloroquine and glucocorticoids. 81.2% received intravenous methylprednisolone and 75% commenced mycophenolate mofetil at induction. 8 of 15 had at least one further kidney biopsy, with a change in LN class observed in five patients. Three patients had progressive LN- requiring treatment with cyclophosphamide, rituximab and ultimately dialysis (median age 15, median time to dialysis 5 years). Excluding the 3 patients with end stage kidney disease, the median eGFR at last follow-up (median 2.25 years) was 108 mL/min/1.73 m2 (2 patients had an eGFR <90 mL/min/1.73 m2). Conclusion(s): Induction treatment of paediatric patients with LN at MCH aligned with recommendations of current international guidelines. End stage kidney disease developed in 18.7% of patients.

AIM: Cardiovascular death is a leading cause of mortality in paediatric end stage kidney disease (ESKD). There is however little known about clinically relevant vascular disease in this population. We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to identify demographic or childhood risk factors for these endpoints, and whether vascular disease predicts mortality. METHOD(S): Data on Australian patients who commenced RRT at <18years of age from 1991-2017 was extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Multivariable competing risks regression was used to identify factors associated with vascular events. RESULT(S): A cohort of 1268 patients were followed up for a median of 10.31years. Vascular disease was reported in 5.4%, and vascular death in 4.1%. The cumulative incidence of any vascular event, i.e. disease or death, at 10 and 20years was 5.5% and 12.8% respectively. Childhood vascular events were associated with non-Caucasian, non-Indigenous ethnicity, and for the 804 patients followed-up after 18years of age, vascular events were associated with lack of childhood transplantation, longer childhood dialysis duration and Indigenous ethnicity. Vascular disease was only reported for 25.49% of patients who had a vascular death, and although a significant risk factor for mortality, it had limited ability to predict mortality. CONCLUSION(S): Cumulative incidence of vascular events is significant after commencing RRT during childhood and is associated with ethnicity, longer childhood dialysis duration and lack of childhood transplantation.Copyright This article is protected by copyright. All rights reserved.

Aim: We report the dietary habits of people with advanced CKD and their adherence to country specific Dietary Guidelines. Background(s): Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with advanced chronic kidney disease (CKD stage 4-5) is not well described. Method(s): Participants with CKD 4-5, receiving or planning dialysis commencement within 12-months, enrolled in the FAVOURED trial completed a lifestyle questionnaire at baseline on their dietary habits of key food groups including fruit, vegetables, chicken, meat, fish, and alcohol consumption. Result(s): Of 567 participants (mean age 54.8 +/- 14.3 years, 63% male), 538 (ANZ n = 386, Malaysian n = 152) completed the dietary and lifestyle questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% consumed >=2 serves/day of fruit and 61% ate >=2 serves/day of vegetables compared to 24% and 34% of Malaysians respectively (P < 0.0001). Only 4% of ANZ participants met Australian Dietary recommendations of 2 fruit and 5 vegetable serves/day. Fish consumption was higher in Malaysians with 83% consuming >=2 serves/week compared to 21% of ANZ participants (P < 0.0001). Red meat intake was significantly higher in ANZ participants however chicken consumption was similar; 48% consumed >2 chicken serves/week and 65% ate >2 serves/week of red meat compared to 43% and 15% of Malaysians, respectively. Nearly two thirds (62%) of participants in Malaysia and ANZ did not use added salt. Alcohol was consumed by 5% of Malaysians compared with 41% of ANZ participants. Conclusion(s): Significant regional variation in dietary intake for fruit, vegetables and animal protein are described which likely reflect cultural and economic differences. Barriers to meeting recommended dietary intakes requires further study.

Aim: We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to evaluate whether demographic or childhood clinical factors predict these endpoints, and whether vascular disease predicts mortality. Background(s): Cardiovascular death is a leading cause of mortality in paediatric end stage kidney disease (ESKD). There is however relatively little known about clinically relevant vascular disease in this population. Method(s): Data on Australian patients who commenced RRT at <18 years of age from 1991-2017 were extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). The association of variables with outcomes were evaluated using Fine and Gray competing risk models. Result(s): A cohort of 1268 patients were followed up for a median of 10.31 years. Vascular disease was reported in 5.4%, and vascular death in 4.1%. The cumulative incidence of any vascular event, i.e. disease or death, at 10 and 20 years was 5.5% and 12.8% respectively. Vascular events were predicted by non-Caucasian (especially Indigenous) ethnicity. For the 804 patients who were followed-up after 18 years of age, vascular disease was predicted by longer childhood dialysis duration and vascular mortality by lack of transplantation during childhood. Whilst vascular disease was only reported for 15.4% of patients who had a vascular death, it was predictive of mortality. Conclusion(s): Cumulative incidence of vascular events is significant after commencing RRT during childhood. Vascular events are associated with ethnicity, longer childhood dialysis duration and lack of transplantation during childhood.

BACKGROUND: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas. METHOD(S): As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT). RESULT(S): Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups. CONCLUSION(S): These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

BACKGROUND: Myeloperoxidase ANCA-associated vasculitis is a major cause of ESKD. Efficacy of anti-CD20 mAb treatment was tested in a mouse model of the disease. METHOD(S): MPO immunization induced anti-MPO autoimmunity, and a subnephritogenic dose of sheep anti-mouse GBM globulin triggered GN. RESULT(S): Anti-CD20 mAb treatment increased the numbers and immunomodulatory capacity of MPO-specific T regulatory cells (Tregs) and attenuated T cell-mediated and humoral anti-MPO autoimmunity and GN. Disabling of Tregs negated the therapeutic benefit of anti-CD20 treatment. The mechanism of enhancement of Treg activity could be attributed to anti-CD20 mAb effects on inducing B cell apoptosis. Administering anti-CD20 mAb-induced apoptotic splenocytes to mice developing anti-MPO GN was as effective as anti-CD20 mAb treatment in inducing Tregs and attenuating both anti-MPO autoimmunity and GN. A nonredundant role for splenic macrophages in mediating the anti-CD20 mAb-induced immunomodulation was demonstrated by showing that administration of anti-CD20 mAb ex vivo-induced apoptotic splenocytes to unmanipulated mice attenuated autoimmunity and GN, whereas deletion of splenic marginal zone macrophages prevented anti-CD20 mAb-induced immunomodulation and treatment efficacy. Six days after administering anti-CD20 mAb to mice with murine anti-MPO GN, cell-mediated anti-MPO responses and GN were attenuated, and Tregs were enhanced, but ANCA levels were unchanged, suggesting humoral autoimmunity was redundant at this time point. CONCLUSION(S): Collectively, these data suggest that, as well as reducing humoral autoimmunity, anti-CD20 mAb more rapidly induces protective anti-MPO Treg-mediated immunomodulation by splenic processing of anti-CD20-induced apoptotic B cells.Copyright © 2021 by the American Society of Nephrology.

AIM: Cardiovascular death is a leading cause of mortality in paediatric end stage kidney disease (ESKD). There is however little known about clinically relevant vascular disease in this population. We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to identify demographic or childhood risk factors for these endpoints, and whether vascular disease predicts mortality. METHOD(S): Data on Australian patients who commenced RRT at <18years of age from 1991-2017 was extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Multivariable competing risks regression was used to identify factors associated with vascular events. RESULT(S): A cohort of 1268 patients were followed up for a median of 10.31years. Vascular disease was reported in 5.4%, and vascular death in 4.1%. The cumulative incidence of any vascular event, i.e. disease or death, at 10 and 20years was 5.5% and 12.8% respectively. Childhood vascular events were associated with non-Caucasian, non-Indigenous ethnicity, and for the 804 patients followed-up after 18years of age, vascular events were associated with lack of childhood transplantation, longer childhood dialysis duration and Indigenous ethnicity. Vascular disease was only reported for 25.49% of patients who had a vascular death, and although a significant risk factor for mortality, it had limited ability to predict mortality. CONCLUSION(S): Cumulative incidence of vascular events is significant after commencing RRT during childhood and is associated with ethnicity, longer childhood dialysis duration and lack of childhood transplantation.Copyright This article is protected by copyright. All rights reserved.

Aim: To examine prescriber characteristics and reasoning for selection of stroke prevention therapy for dialysis patients with atrial fibrillation (AF). Background(s): Warfarin therapy in dialysis patients with AF remains controversial especially for primary stoke prevention. Method(s): Utilising scanned medical records, dialysis patients with AF at Monash Health were identified. Patient demographics, therapeutic agent for AF, prescriber characteristics and reasoning were then assessed. Result(s): Of 575 dialysis patients, 100 (17.4%) were identified as having AF. Of those, 31 patients received warfarin, 46 received antiplatelet therapy, 21 did not receive stroke prevention therapy and 2 received other forms of stroke prevention therapy (clexane non-dialysis days, apixaban). Of the 31 patients on warfarin, 15 were placed on warfarin for primary prevention, 13 for secondary prevention and 3 were unknown. The AF cohort was generally older compared to the cohort without AF (71.9 vs 61.2 years, p < 0.001). Demographically, patient subgroups on warfarin, antiplatelet agents and no stroke prevention therapy were similar. 16 of 31 patients were commenced on warfarin by cardiology, predominantly for primary stroke prevention (81%). Neurology commenced warfarin in 9 of 31 patients, in all instances for secondary stroke prevention (100%). 16 patients were previously on warfarin. Most cases of warfarin cessation were instigated by nephrology (63%) with major reasons including conflicting evidence regarding warfarin use in dialysis patients, bleeding complications, bleed risk greater than stroke risk, and dialysis commencement. Conclusion(s): Further research is required to provide an evidence-based approach to primary stroke prevention therapy in dialysis patients with AF. Presently, with limited evidence and differences in clinical practice between the various specialties, a multidisciplinary approach is necessary for the individualized management of AF in dialysis patients.

Aim: We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to evaluate whether demographic or childhood clinical factors predict these endpoints, and whether vascular disease predicts mortality. Background(s): Cardiovascular death is a leading cause of mortality in paediatric end stage kidney disease (ESKD). There is however relatively little known about clinically relevant vascular disease in this population. Method(s): Data on Australian patients who commenced RRT at <18 years of age from 1991-2017 were extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). The association of variables with outcomes were evaluated using Fine and Gray competing risk models. Result(s): A cohort of 1268 patients were followed up for a median of 10.31 years. Vascular disease was reported in 5.4%, and vascular death in 4.1%. The cumulative incidence of any vascular event, i.e. disease or death, at 10 and 20 years was 5.5% and 12.8% respectively. Vascular events were predicted by non-Caucasian (especially Indigenous) ethnicity. For the 804 patients who were followed-up after 18 years of age, vascular disease was predicted by longer childhood dialysis duration and vascular mortality by lack of transplantation during childhood. Whilst vascular disease was only reported for 15.4% of patients who had a vascular death, it was predictive of mortality. Conclusion(s): Cumulative incidence of vascular events is significant after commencing RRT during childhood. Vascular events are associated with ethnicity, longer childhood dialysis duration and lack of transplantation during childhood.

Aim: We report the dietary habits of people with advanced CKD and their adherence to country specific Dietary Guidelines. Background(s): Dietary management plays an important role in patients with kidney failure. Current dietary habits of Australians and New Zealanders (ANZ) and Malaysians with advanced chronic kidney disease (CKD stage 4-5) is not well described. Method(s): Participants with CKD 4-5, receiving or planning dialysis commencement within 12-months, enrolled in the FAVOURED trial completed a lifestyle questionnaire at baseline on their dietary habits of key food groups including fruit, vegetables, chicken, meat, fish, and alcohol consumption. Result(s): Of 567 participants (mean age 54.8 +/- 14.3 years, 63% male), 538 (ANZ n = 386, Malaysian n = 152) completed the dietary and lifestyle questionnaire. Dietary fruit and vegetable intakes were higher in ANZ participants; 49% consumed >=2 serves/day of fruit and 61% ate >=2 serves/day of vegetables compared to 24% and 34% of Malaysians respectively (P < 0.0001). Only 4% of ANZ participants met Australian Dietary recommendations of 2 fruit and 5 vegetable serves/day. Fish consumption was higher in Malaysians with 83% consuming >=2 serves/week compared to 21% of ANZ participants (P < 0.0001). Red meat intake was significantly higher in ANZ participants however chicken consumption was similar; 48% consumed >2 chicken serves/week and 65% ate >2 serves/week of red meat compared to 43% and 15% of Malaysians, respectively. Nearly two thirds (62%) of participants in Malaysia and ANZ did not use added salt. Alcohol was consumed by 5% of Malaysians compared with 41% of ANZ participants. Conclusion(s): Significant regional variation in dietary intake for fruit, vegetables and animal protein are described which likely reflect cultural and economic differences. Barriers to meeting recommended dietary intakes requires further study.

Aim: We aimed to describe the trends in incidence, aetiology, renal replacement therapy (RRT) modality and access to transplant among Aboriginal and Torres Strait Islander children and young adults (ACYA) residing in Australia. Background(s): Details of the paediatric end stage kidney disease population in Australia and New Zealand have been published previously. There is, however, paucity of studies exploring the trends in RRT modality and access to transplant among ACYA residing in Australia. Method(s): Data on Australian patients who commenced RRT at <=24 years of age from 1961-2017 was extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). The incidence and prevalence rates were restricted from 1997 to 2017 due to unavailability of Aboriginal status specific census data prior to 1997. Result(s): A total of 3629 children and young adults received RRT during the observation period, including 178 (4.9%), who identified as ACYA and 3451 (95.1%) other children and young adults (OCYA). Compared with OCYA, incident rates have risen among ACYA group since 2000 with the biggest rise for young adults aged 20-24 years. Fewer ACYA received a kidney transplant compared to OCYA cohort (56.2% versus 89.3%, p < 0.001). Only 6 (3.4%) ACYA received pre-emptive kidney transplant versus 580 (16.8%) OCYA (p < 0.001). Living related donor transplants were less common among ACYA than OCYA (10.7% versus 35.9%, p < 0.001). Conclusion(s): Our study shows rising incident rates and poorer access to kidney transplantation among ACYA in Australia. The reasons for this health care disparity and barriers to transplantation need to be explored further and require addressing.

BACKGROUND: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas. METHOD(S): As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT). RESULT(S): Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups. CONCLUSION(S): These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Health Services Research and Policy, 2019, End stage renal disease (ESRD) is a condition characterized by severely diminishing function of the kidneys; it is the only condition that qualifies an individual to receive Medicare benefits regardless of their age. In January 2011, Medicare launched a bundled prospective payment system (PPS) to help reduce escalating costs. Additionally, the ESRD Quality Improvement Program (QIP) was enacted in 2011 to promote high-quality services and is tied to a portion of payments to dialysis facilities. This study aimed to examine the impact of the 2011 Medicare dialysis payment reform (the new Medicare bundled payment and quality improvement program) on care practices and health outcomes for ESRD patients on dialysis. Secondary aims determined the potential different impacts of Medicare payment reform on processes of care and risk-adjusted outcomes among dialysis facilities with different organizational characteristics (i.e. profit status, chain affiliation and size) and with different pre-reform total staffing and registered nurse staffing patterns. This study used United States Renal Data System (USRDS), the Centers for Medicare and Medicaid Services’ (CMS) Facility Compare and QIP Results, and the Agency for Healthcare Research and Quality’s Area Health Resource File. To account for the unmeasured policy effect, a difference-in-difference (DID) framework was implemented and used general estimating equations to test all hypotheses. The result of the principle aim of interest of percentage of primary Medicare payers does not explain the differences among hemodialysis facilities after the Medicare reform. The study findings for the secondary and tertiary aims are also primarily statistically insignificant. Despite the lack of statistical significance, health outcomes are improving among hemodialysis patients after the Medicare reform. But, there is an increasing trend in hospitalizations due to infections and fractures.

BackgroundCardiovascular disease is the major cause of mortality in end stage renal disease (ESRD) patients on dialysis and myocardial infarction constitutes almost 20% of such deaths. We assessed the trends, characteristics and in-hospital outcomes in patients with ESRD.MethodsWe used national inpatient sample (NIS) to identify patients with ESRD presenting with ST-segment elevation myocardial infarction (STEMI) for calendar years 2012-2016. Multiple logistic regression analysis and propensity matched data was used to compare outcomes for the purpose of our study.ResultsPatients on dialysis who presented with STEMI were less likely to be treated with emergent reperfusion therapies including percutaneous coronary intervention, bypass graft surgery and thrombolytics with in first 24 h. In propensity-matched cohort, the mortality was nearly double in patients who have ESRD compared to patients without ESRD (29.7% vs. 15.9%, p < 0.01). In-patient morbidity such as utilization of tracheostomy, mechanical ventilation and feeding tubes was also more prevalent in propensity matched ESRD cohort. In multivariate regression analysis, ESRD remains a strong predictor of increased mortality in STEMI patients (OR 2.65, 95% CI, 2.57-2.75, p < 0.01).ConclusionOur study showed low utilization of evidence-based prompt reperfusion therapies in ESRD patients with STEMI along with concomitant increased poor outcomes and resource utilization. Future research specifically targeting this extremely high-risk patient population is needed to identify the role of prompt reperfusion therapies in improving outcomes in these patients.

Radiologic imaging techniques, such as F-18-fluorodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT), provide diagnostic value in a variety of diseases. In cases of suspected infection, FDG PET/CT can find areas of fluorodeoxyglucose metabolism, correlating with local acute inflammation. The following case involves a man with end-stage renal disease (ESRD), who presented with symptoms of infection and positive blood cultures with high suspicion of arteriovenous fistula as the source of infection. The patient also had two central lines that could be a site of infection. Concerns for patient's persistent positive blood cultures necessitated FDG PET/CT to confirm site of infection. Confirming active infection and the source of infection guides therapeutic measures and eliminates concern for other disease etiologies common in patients with ESRD.

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies.

BackgroundMortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) remains exceptionally high. While traditional risk factors such as obesity are paradoxically associated with better survival, nontraditional risk factors including cachexia increase the likelihood of poor outcomes. There is accumulating evidence that the endocannabinoid (ECB) system plays a major role in energy preservation and storage, factors which can prevent the deleterious effects of cachexia. Hence, in this study, we evaluated the association of circulating ECB levels with mortality in MHD patients.MethodsSerum concentrations of anandamide (AEA) and 2-arachidonoyl-sn-glycerol (2-AG), major ECB ligands, were measured in MHD patients. Their correlation with various clinical/laboratory indices and association with 12-month all-cause mortality were examined.ResultsSerum 2-AG levels positively correlated with body mass index, serum triglycerides and body anthropometric measures. Meanwhile, serum AEA levels correlated positively with serum interleukin-6, and negatively with serum very low-density lipoprotein levels. While increased serum 2-AG levels were associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.52, 95% CI 0.28-0.98), there was no clear association between serum AEA levels and mortality (HR 0.91, 95% CI 0.48-1.72).ConclusionsIn MHD patients, the circulating levels of ECB ligand, 2-AG, may play an important role in determining body mass and risk of mortality. These observations were unique to 2-AG as similar findings were not obtained with serum AEA. Future studies need to investigate the mechanisms responsible for these associations and examine the modulation of the ECB system as a potential target for therapy in ESRD.

BackgroundMortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) remains exceptionally high. While traditional risk factors such as obesity are paradoxically associated with better survival, nontraditional risk factors including cachexia increase the likelihood of poor outcomes. There is accumulating evidence that the endocannabinoid (ECB) system plays a major role in energy preservation and storage, factors which can prevent the deleterious effects of cachexia. Hence, in this study, we evaluated the association of circulating ECB levels with mortality in MHD patients.MethodsSerum concentrations of anandamide (AEA) and 2-arachidonoyl-sn-glycerol (2-AG), major ECB ligands, were measured in MHD patients. Their correlation with various clinical/laboratory indices and association with 12-month all-cause mortality were examined.ResultsSerum 2-AG levels positively correlated with body mass index, serum triglycerides and body anthropometric measures. Meanwhile, serum AEA levels correlated positively with serum interleukin-6, and negatively with serum very low-density lipoprotein levels. While increased serum 2-AG levels were associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.52, 95% CI 0.28-0.98), there was no clear association between serum AEA levels and mortality (HR 0.91, 95% CI 0.48-1.72).ConclusionsIn MHD patients, the circulating levels of ECB ligand, 2-AG, may play an important role in determining body mass and risk of mortality. These observations were unique to 2-AG as similar findings were not obtained with serum AEA. Future studies need to investigate the mechanisms responsible for these associations and examine the modulation of the ECB system as a potential target for therapy in ESRD.

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION(S): Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.Copyright © 2019 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

Background: Current guidelines favor fistulas over catheters as vascular access. Yet, the observational literature comparing fistulas to catheters has important limitations and biases that may be difficult to overcome in the absence of randomization. However, it is not clear if physicians would be willing to participate in a clinical trial comparing fistulas to catheters. Objective(s): We also sought to elicit participants' opinions on willingness to participate in a future trial regarding catheters and fistulas. Design(s): We created a three-part survey consisting of 19 questions. We collected demographic information, respondents' knowledge of the vascular access literature, appropriateness of current guideline recommendations, and their willingness to participate in a future trial. Setting(s): Participants were recruited from Canada, Europe, Australia, and New Zealand. Participant(s): Participants include physicians and trainees who are involved in the care of end-stage renal disease patients requiring vascular access. Measurements: Descriptive statistics were used to describe baseline characteristics of respondents according to geographic location. We used logistic regression to model willingness to participate in a future trial. Method(s): We surveyed nephrologists from Canada, Europe, Australia, and New Zealand to assess their willingness to participate in a randomized trial comparing fistulas to catheters in incident hemodialysis patients. Result(s): Our results show that in Canada, 86 % of respondents were willing to participate in a trial (32 % in all patients; 54 % only in patients at high risk of primary failure). In Europe and Australia/New Zealand, the willingness to participate in a trial that included all patients was lower (28 % in Europe; 25 % in Australia/New Zealand), as was a trial that included patients at high risk of primary failure (38 % in Europe; 39 % in Australia/New Zealand). Nephrologists who have been in practice for a few years, saw a l

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION(S): Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.Copyright © 2019 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

Background: Acute kidney injury (AKI) is a common complication of hospital admission, and survivors are at increased future risk of major adverse kidney events (MAKE), including chronic kidney disease (CKD), end-stage kidney disease (ESKD) and death. High-risk patients may benefit from specialist follow-up; however, the factors associated with increased risk have not been reported. Method(s): We conducted a retrospective study of all adult patients admitted with AKI to a single centre between 1 January 2012 and 31 December 2016. Cox regression models were performed to examine the primary outcome, which was the development of a MAKE in the first year following hospital discharge. The secondary outcomes (CKD, ESKD, and death) were studied using Cox and competing risk regression analyses. Candidate predictor variables included patient demographics, comorbidities, and laboratory values available at the time of hospital discharge. Result(s): Of 2,101 patients included in the study, 767 patients (37%) developed a MAKE within the first year. MAKE occurred more frequently in patients who were older (HR 1.02 95% CI 1.01-1.02) and in those with a history of chronic heart failure (HR 1.41 95% CI 1.19-1.67), liver disease (HR 1.68 95% CI 1.39-2.03), and either non-metastatic (HR 1.44 95%CI 1.14-1.82) or metastatic (HR 2.26 95% CI 1.80-2.83) malignancy. They were also more common in patients with a greater severity of AKI (stage 2 HR 1.38 95% CI 1.16-1.64; stage 3 HR 1.62 95% CI 1.31-2.01) and in those with a higher serum creatinine level at discharge (HR 1.01 95% CI 1.00-1.01). Female sex (SHR 1.54 95% CI 1.27-1.88) and hypertension (SHR 1.28 95% CI 1.04-1.58) were additional risk factors for the development of CKD. Conclusion(s): A significant number of patients with AKI will develop a MAKE within the first year. Clinical variables available at the time of discharge could be used to stratify risk and identify patients who may benefit from specialist follow up. (Figure Presente

Background: Acute kidney injury (AKI) is a common consequence of acute illness and is associated with high morbidity and mortality. Robust estimates of the long-term outcomes of AKI, using consensus definitions of exposure, are needed to inform clinical practice and guide optimal allocation of healthcare resources. Method(s): A systematic search was performed through EMBASE, MEDLINE, and grey literature sources to identify cohort studies reporting an association between AKI and chronic kidney disease (CKD), end-stage kidney disease (ESKD) or death. All studies published between 2004 and 2018 involving hospitalised adults were eligible if they defined AKI according to consensus definitions (RIFLE, AKIN, or KDIGO), included a non-AKI control group, and followed patients for at least 1 year. Risk of bias was assessed using the Newcastle-Ottawa Scale. Random effects meta-analysis was used to combine adjusted hazard ratios between studies. Subgroup, sensitivity and meta-regression analyses were performed to investigate potential sources of heterogeneity. Result(s): The systematic search retrieved 6369 citations, of which 81 studies comprising more than 2 million participants were eligible for inclusion. One-third of studies were in cardiovascular surgery patients and one-third were performed in Europe. Reporting of methods was incomplete in many studies. The most common sources of bias were poor representativeness of patient cohorts, and insufficient duration and completeness of follow up. Funnel plot asymmetry reflected a lack of small studies with negative effects. AKI was associated with a significantly increased risk of death across all subgroups: angiography (HR 3.07, 95%CI 2.12-4.46), cardiovascular surgery (HR 1.75, 95%CI 1.55-1.98), intensive care (HR 1.47, 95%CI 1.32-1.65), and hospital (HR 1.41, 95%CI 1.26-1.56). The risk of death increased from stage 1 (HR 1.35, 95%CI 1.27-1.44) to stage 3 (HR 2.76, 95%CI 2.28-3.35). AKI was associated with increased risks of

BACKGROUND: Home haemodialysis (HHD) is utilised significantly less often than facility haemodialysis globally with few exceptions despite being associated with improved survival, and better quality of life. Previously, HHD was exclusively offered to younger patients with few comorbidities. However, with the increasing burden of end-stage kidney disease (ESKD) alongside an ageing population, increasing numbers of older patients are being treated with HHD. This study aims to re-evaluate survival and related outcomes in the context of this epidemiological shift. METHOD(S): A matched cohort design was used to compare all-cause mortality, transplantation, average biochemical values and graft survival 6months post-transplant between HHD and facility haemodialysis patients. 181 HHD patients from a major hospital network were included, with 413 facility haemodialysis patients from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) matched by age, gender, and cause of ESKD. Survival analysis and competing risks analysis (for transplantation) were performed. RESULT(S): After adjusting for BMI, smoking status, racial group, and comorbidities, HHD was associated with significantly reduced risk of death compared to facility HD patients (HR=0.47, 95% CI 0.30-0.74). Transplantation rates were comparable, with high rates of graft survival at 6months in both groups. Haemoglobin, calcium, and parathyroid hormone levels did not vary significantly. However, home HD patients had significantly lower phosphate levels. CONCLUSION(S): In this study, improved survival outcomes were observed in patients on home compared to facility dialysis, with comparable rates of transplantation, graft survival and biochemical control.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Background Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. Studies investigating the disproportionate burden of cardiovascular disease have occurred predominantly in the peripheral vasculature, often used noninvasive imaging modalities, and infrequently recruited patients receiving dialysis. This study sought to evaluate invasive coronary dynamic vascular function in patients with end-stage renal failure (ESRF). Patients and methods Patients referred for invasive coronary angiography prior to renal transplantation were invited to participate. Control patients were recruited in parallel. Baseline characteristics were obtained. Coronary diameter (via quantitative coronary angiography) and coronary blood flow (via Doppler Flowire) were measured; macrovascular endothelial-dependent and independent effects were evaluated in response to intracoronary acetylcholine infusion (10-7 and 10-6 mol/l) and intracoronary glyceryl trinitrate, respectively. Microvascular function was evaluated by response to adenosine and expressed as coronary flow velocity reserve. Mean values were compared. Results Thirty patients were evaluated: 15 patients with ESRF (mean age 52.1 +/- 9, male 73%) and 15 control patients (mean age 53.3 +/- 13, male 60%). Comorbidity profile, aside from ESRF, was well matched. Baseline coronary blood flow was similar between groups (101.6 +/- 10.3 vs. 103.4 +/- 9.1 ml/min, P = 0.71), as was endothelial-dependent response to acetylcholine (159.1 +/- 16.9 vs. 171.1 +/- 16.8 ml/min, P = 0.41). Endothelial-independent response to glyceryl trinitrate was no different between groups (14.3 +/- 3.1 vs. 13.1 +/- 2.3%, P = 0.73. A significantly reduced coronary flow velocity reserve was observed in the ESRF cohort compared to controls (2.34 +/- 0.4 vs. 3.05 +/- 0.3, P = 0.003). Conclusion Patients with ESRF had preserved endothelial-dependent function however compared to controls, demonstrated significantly attenuated microvasc

Background: Point-of-care ultrasound (POCUS) has been used in various vascular access contexts; however, to date, it has not been widely adopted in haemodialysis clinics. People with end-stage kidney disease receiving haemodialysis require an arteriovenous fistula (AVF), arteriovenous graft (AVG), or central venous access device (CVAD) in order to access their blood for therapy/treatment. Cannulation issues, such as haematoma and extravasation, related to AVFs and AVGs are common. This pilot and feasibility study will assess the feasibility of a randomised controlled trial aimed at evaluating whether POCUS-guided cannulation results in more successful and accurate AVF needle placement than the standard practice of blind cannulation. Method(s): A controlled, random order crossover design will be used to evaluate two clinical conditions: (1) POCUSguided cannulation and (2) standard practice of blind cannulation, when used by haemodialysis nurses. The feasibility of conducting this type of trial for these two clinical conditions will be assessed through recruitment, retention, and attrition rates; perceptions of acceptability; implementation measures; and assessment of methods of data collection. Clinical outcomes to be assessed are overall cannulation success on first attempt, accuracy of needle tip placement, number of extravasations, procedural time, and patient and nurse perceptions. The setting is a 16-chair dialysis unit in regional Australia. Participants will include adult haemodialysis patients with an AVF in situ for greater than 2 months and haemodialysis-trained registered nurses working full- or part-time. Clinical outcomes will be analysed using generalised linear mixed models. Feasibility data will be reported using descriptive statistics. Qualitative audio data will be digitally recorded, transcribed verbatim, and analysed using thematic analysis. Discussion(s): Point-of-care ultrasound for cannulation has the potential to promote high-quality, safe nur

Purpose of reviewChronic kidney disease (CKD) is associated with the development of mineral and bone disorders (MBD), including renal osteodystrophy (ROD). ROD is a global disorder of bone strength that is associated with an increased fracture risk. The use of bisphosphonates for fracture risk reduction in CKD remains controversial. This review provides a synopsis of the state-of-the literature regarding the safety and potential antifracture benefits of bisphosphonates in CKD patients.Recent findingsIn preclinical studies of animals with CKD 3-4 and evidence of CKD-MBD, bisphosphonates resulted in changes in bone quality that improve bone strength. Bone turnover was generally reduced to a similar extent in animals with and without CKD. Post hoc analyses of randomized trials in patients with CKD 3-4 reported increases in bone mineral density (BMD) and fracture reduction that were similar in patients with and without CKD. There are no primary clinical trial data in patients with CKD-MBD.SummaryIn patients with CKD without evidence of CKD-MBD, the use of bisphosphonates should follow general population guidelines. The lack of data for patients with CKD 4-5D and evidence of CKD-MBD makes treatment decisions challenging. Clinical studies are urgently needed to provide data on the safety and antifracture benefits of bisphosphonates in these cohorts.Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Background: Current guidelines favor fistulas over catheters as vascular access. Yet, the observational literature comparing fistulas to catheters has important limitations and biases that may be difficult to overcome in the absence of randomization. However, it is not clear if physicians would be willing to participate in a clinical trial comparing fistulas to catheters. Objective(s): We also sought to elicit participants' opinions on willingness to participate in a future trial regarding catheters and fistulas. Design(s): We created a three-part survey consisting of 19 questions. We collected demographic information, respondents' knowledge of the vascular access literature, appropriateness of current guideline recommendations, and their willingness to participate in a future trial. Setting(s): Participants were recruited from Canada, Europe, Australia, and New Zealand. Participant(s): Participants include physicians and trainees who are involved in the care of end-stage renal disease patients requiring vascular access. Measurements: Descriptive statistics were used to describe baseline characteristics of respondents according to geographic location. We used logistic regression to model willingness to participate in a future trial. Method(s): We surveyed nephrologists from Canada, Europe, Australia, and New Zealand to assess their willingness to participate in a randomized trial comparing fistulas to catheters in incident hemodialysis patients. Result(s): Our results show that in Canada, 86 % of respondents were willing to participate in a trial (32 % in all patients; 54 % only in patients at high risk of primary failure). In Europe and Australia/New Zealand, the willingness to participate in a trial that included all patients was lower (28 % in Europe; 25 % in Australia/New Zealand), as was a trial that included patients at high risk of primary failure (38 % in Europe; 39 % in Australia/New Zealand). Nephrologists who have been in practice for a few years, saw a l

BACKGROUND: Home haemodialysis (HHD) is utilised significantly less often than facility haemodialysis globally with few exceptions despite being associated with improved survival, and better quality of life. Previously, HHD was exclusively offered to younger patients with few comorbidities. However, with the increasing burden of end-stage kidney disease (ESKD) alongside an ageing population, increasing numbers of older patients are being treated with HHD. This study aims to re-evaluate survival and related outcomes in the context of this epidemiological shift. METHOD(S): A matched cohort design was used to compare all-cause mortality, transplantation, average biochemical values and graft survival 6months post-transplant between HHD and facility haemodialysis patients. 181 HHD patients from a major hospital network were included, with 413 facility haemodialysis patients from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) matched by age, gender, and cause of ESKD. Survival analysis and competing risks analysis (for transplantation) were performed. RESULT(S): After adjusting for BMI, smoking status, racial group, and comorbidities, HHD was associated with significantly reduced risk of death compared to facility HD patients (HR=0.47, 95% CI 0.30-0.74). Transplantation rates were comparable, with high rates of graft survival at 6months in both groups. Haemoglobin, calcium, and parathyroid hormone levels did not vary significantly. However, home HD patients had significantly lower phosphate levels. CONCLUSION(S): In this study, improved survival outcomes were observed in patients on home compared to facility dialysis, with comparable rates of transplantation, graft survival and biochemical control.Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Introduction: The association between acute kidney injury (AKI) and an increased risk of early morbidity and mortality is well established. However, the impact of AKI on long-term outcomes is less clear. Objective(s): To determine the long-term risk of death, chronic kidney disease (CKD), and end stage kidney disease (ESKD) in critically ill patients with AKI. Method(s): A literature search was performed through EMBASE, MEDLINE, and grey literature sources to identify cohort studies reporting an association between AKI and at least one of the outcomes of interest. All studies published between 2004 and 2017 involving critically ill adults were considered eligible if they defined AKI according to consensus definitions (RIFLE, AKIN, or KDIGO), included a non-AKI control group, and followed patients for at least 1 year. Exclusion criteria included solid organ transplant recipients and patients with AKI "syndromes". Risk of bias was assessed by the Newcastle- Ottawa Scale and random effects meta-analysis was used to compare the risk estimates between studies. Result(s): The search retrieved 3435 citations, of which 57 underwent full-text review. Eighteen studies comprising 92,218 patients met the inclusion criteria. The most common sources of bias were poor representativeness of patient cohorts, and insufficient follow up. Across the 10 studies examining mortality, AKI was associated with a significantly increased risk of death (HR 1.71, 95% CI 1.43-2.04), which progressively increased with AKI stage, although heterogeneity was high (I2 84.5%). There was also an association between AKI and ESKD (HR 5.18, 95% CI 3.14-8.53) and a non-significant increased risk of CKD (HR 5.72, 95% CI 0.62-52.67). Conclusion(s): Despite high heterogeneity between studies, AKI was associated with inferior long-term survival and an increased risk of adverse renal outcomes. Strategies to identify patients at greatest risk are required, to ensure appropriate long-term care is coordinated for t

Background Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. Studies investigating the disproportionate burden of cardiovascular disease have occurred predominantly in the peripheral vasculature, often used noninvasive imaging modalities, and infrequently recruited patients receiving dialysis. This study sought to evaluate invasive coronary dynamic vascular function in patients with end-stage renal failure (ESRF). Patients and methods Patients referred for invasive coronary angiography prior to renal transplantation were invited to participate. Control patients were recruited in parallel. Baseline characteristics were obtained. Coronary diameter (via quantitative coronary angiography) and coronary blood flow (via Doppler Flowire) were measured; macrovascular endothelial-dependent and independent effects were evaluated in response to intracoronary acetylcholine infusion (10-7 and 10-6 mol/l) and intracoronary glyceryl trinitrate, respectively. Microvascular function was evaluated by response to adenosine and expressed as coronary flow velocity reserve. Mean values were compared. Results Thirty patients were evaluated: 15 patients with ESRF (mean age 52.1 +/- 9, male 73%) and 15 control patients (mean age 53.3 +/- 13, male 60%). Comorbidity profile, aside from ESRF, was well matched. Baseline coronary blood flow was similar between groups (101.6 +/- 10.3 vs. 103.4 +/- 9.1 ml/min, P = 0.71), as was endothelial-dependent response to acetylcholine (159.1 +/- 16.9 vs. 171.1 +/- 16.8 ml/min, P = 0.41). Endothelial-independent response to glyceryl trinitrate was no different between groups (14.3 +/- 3.1 vs. 13.1 +/- 2.3%, P = 0.73. A significantly reduced coronary flow velocity reserve was observed in the ESRF cohort compared to controls (2.34 +/- 0.4 vs. 3.05 +/- 0.3, P = 0.003). Conclusion Patients with ESRF had preserved endothelial-dependent function however compared to controls, demonstrated significantly attenuated microvasc

Background: Point-of-care ultrasound (POCUS) has been used in various vascular access contexts; however, to date, it has not been widely adopted in haemodialysis clinics. People with end-stage kidney disease receiving haemodialysis require an arteriovenous fistula (AVF), arteriovenous graft (AVG), or central venous access device (CVAD) in order to access their blood for therapy/treatment. Cannulation issues, such as haematoma and extravasation, related to AVFs and AVGs are common. This pilot and feasibility study will assess the feasibility of a randomised controlled trial aimed at evaluating whether POCUS-guided cannulation results in more successful and accurate AVF needle placement than the standard practice of blind cannulation. Method(s): A controlled, random order crossover design will be used to evaluate two clinical conditions: (1) POCUSguided cannulation and (2) standard practice of blind cannulation, when used by haemodialysis nurses. The feasibility of conducting this type of trial for these two clinical conditions will be assessed through recruitment, retention, and attrition rates; perceptions of acceptability; implementation measures; and assessment of methods of data collection. Clinical outcomes to be assessed are overall cannulation success on first attempt, accuracy of needle tip placement, number of extravasations, procedural time, and patient and nurse perceptions. The setting is a 16-chair dialysis unit in regional Australia. Participants will include adult haemodialysis patients with an AVF in situ for greater than 2 months and haemodialysis-trained registered nurses working full- or part-time. Clinical outcomes will be analysed using generalised linear mixed models. Feasibility data will be reported using descriptive statistics. Qualitative audio data will be digitally recorded, transcribed verbatim, and analysed using thematic analysis. Discussion(s): Point-of-care ultrasound for cannulation has the potential to promote high-quality, safe nur

Background: Acute kidney injury (AKI) is a common complication of hospital admission, and survivors are at increased future risk of major adverse kidney events (MAKE), including chronic kidney disease (CKD), end-stage kidney disease (ESKD) and death. High-risk patients may benefit from specialist follow-up; however, the factors associated with increased risk have not been reported. Method(s): We conducted a retrospective study of all adult patients admitted with AKI to a single centre between 1 January 2012 and 31 December 2016. Cox regression models were performed to examine the primary outcome, which was the development of a MAKE in the first year following hospital discharge. The secondary outcomes (CKD, ESKD, and death) were studied using Cox and competing risk regression analyses. Candidate predictor variables included patient demographics, comorbidities, and laboratory values available at the time of hospital discharge. Result(s): Of 2,101 patients included in the study, 767 patients (37%) developed a MAKE within the first year. MAKE occurred more frequently in patients who were older (HR 1.02 95% CI 1.01-1.02) and in those with a history of chronic heart failure (HR 1.41 95% CI 1.19-1.67), liver disease (HR 1.68 95% CI 1.39-2.03), and either non-metastatic (HR 1.44 95%CI 1.14-1.82) or metastatic (HR 2.26 95% CI 1.80-2.83) malignancy. They were also more common in patients with a greater severity of AKI (stage 2 HR 1.38 95% CI 1.16-1.64; stage 3 HR 1.62 95% CI 1.31-2.01) and in those with a higher serum creatinine level at discharge (HR 1.01 95% CI 1.00-1.01). Female sex (SHR 1.54 95% CI 1.27-1.88) and hypertension (SHR 1.28 95% CI 1.04-1.58) were additional risk factors for the development of CKD. Conclusion(s): A significant number of patients with AKI will develop a MAKE within the first year. Clinical variables available at the time of discharge could be used to stratify risk and identify patients who may benefit from specialist follow up. (Figure Presente

Background: Acute kidney injury (AKI) is a common consequence of acute illness and is associated with high morbidity and mortality. Robust estimates of the long-term outcomes of AKI, using consensus definitions of exposure, are needed to inform clinical practice and guide optimal allocation of healthcare resources. Method(s): A systematic search was performed through EMBASE, MEDLINE, and grey literature sources to identify cohort studies reporting an association between AKI and chronic kidney disease (CKD), end-stage kidney disease (ESKD) or death. All studies published between 2004 and 2018 involving hospitalised adults were eligible if they defined AKI according to consensus definitions (RIFLE, AKIN, or KDIGO), included a non-AKI control group, and followed patients for at least 1 year. Risk of bias was assessed using the Newcastle-Ottawa Scale. Random effects meta-analysis was used to combine adjusted hazard ratios between studies. Subgroup, sensitivity and meta-regression analyses were performed to investigate potential sources of heterogeneity. Result(s): The systematic search retrieved 6369 citations, of which 81 studies comprising more than 2 million participants were eligible for inclusion. One-third of studies were in cardiovascular surgery patients and one-third were performed in Europe. Reporting of methods was incomplete in many studies. The most common sources of bias were poor representativeness of patient cohorts, and insufficient duration and completeness of follow up. Funnel plot asymmetry reflected a lack of small studies with negative effects. AKI was associated with a significantly increased risk of death across all subgroups: angiography (HR 3.07, 95%CI 2.12-4.46), cardiovascular surgery (HR 1.75, 95%CI 1.55-1.98), intensive care (HR 1.47, 95%CI 1.32-1.65), and hospital (HR 1.41, 95%CI 1.26-1.56). The risk of death increased from stage 1 (HR 1.35, 95%CI 1.27-1.44) to stage 3 (HR 2.76, 95%CI 2.28-3.35). AKI was associated with increased risks of

Purpose of reviewChronic kidney disease (CKD) is associated with the development of mineral and bone disorders (MBD), including renal osteodystrophy (ROD). ROD is a global disorder of bone strength that is associated with an increased fracture risk. The use of bisphosphonates for fracture risk reduction in CKD remains controversial. This review provides a synopsis of the state-of-the literature regarding the safety and potential antifracture benefits of bisphosphonates in CKD patients.Recent findingsIn preclinical studies of animals with CKD 3-4 and evidence of CKD-MBD, bisphosphonates resulted in changes in bone quality that improve bone strength. Bone turnover was generally reduced to a similar extent in animals with and without CKD. Post hoc analyses of randomized trials in patients with CKD 3-4 reported increases in bone mineral density (BMD) and fracture reduction that were similar in patients with and without CKD. There are no primary clinical trial data in patients with CKD-MBD.SummaryIn patients with CKD without evidence of CKD-MBD, the use of bisphosphonates should follow general population guidelines. The lack of data for patients with CKD 4-5D and evidence of CKD-MBD makes treatment decisions challenging. Clinical studies are urgently needed to provide data on the safety and antifracture benefits of bisphosphonates in these cohorts.Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.