About 25% of patients with IgA nephropathy (IgAN) progress to stage 5 chronic kidney disease (CKD) after years of evolution. Various tools have been developed in recent years designed to predict ...which of the patients will had poorer outcomes. The value of circulating galactosyl-deficient IgA1 (Gd-IgA1) has been related to a worse evolution of IgAN in several studies. There are also some publications that relate higher APRIL values with a worse evolution. Recently, a new method has been developed that allows measuring the value of circulating Gd-IgA1 in a simpler way than those previously available. The objective of this study is to analyze the influence of circulating Gd-IgA1, measured by this method, on the progression of IgAN.
Forty-nine patients with a diagnosis of IgAN demonstrated by renal biopsy were selected in our center, without having received prior immunosuppressive treatment, for whom frozen serum was available. The median follow-up was 4 years. Gd-IgA1 was measured by lectin-independent ELISA with the monoclonal antibody KM55 (IgA1 kit Cat. No. 30111694. IBL Int., Hamburg, Germany). Likewise, APRIL levels were also measured in these patients.
19 (38.8%) patients reached stage 5 CKD. The fourth quartile of circulating Gd-IgA1 was related to a higher cumulative risk of reaching stage 5 CKD in the Kaplan–Meier analysis (risk at the 5th year 39.4% vs. 24.3%, log rank p=0.019). The Gd-IgA1 value was related to an increased risk of CKD stage 5 (HR 1.147, 95% CI 1.035–1.270, p=0.009), regardless of glomerular filtration rate, proteinuria, the percentage of sclerosed glomeruli and the value of segmental sclerosis. We did not find significant differences in the APRIL values.
The value of circulating Gd-IgA1 measured by the monoclonal antibody KM55 is related to a worse evolution of patients with IgAN independently of other variables, so it could be included in the study of patients to improve the prediction of the risk of disease progression.
En torno al 25% de los pacientes con nefropatía IgA (NIgA) progresa hacia el estadio 5 de la enfermedad renal crónica tras años de evolución. En los últimos años se han desarrollado diversas herramientas diseñadas para predecir qué pacientes evolucionan peor. El valor de IgA1 galactosil-deficiente (Gd-IgA1) circulante se ha relacionado con una peor evolución de la NIgA en algunos estudios. También hay varios trabajos que relacionan valores más elevados de APRIL con una peor evolución. Recientemente se ha desarrollado un método que permite medir el valor de Gd-IgA1 circulante de una manera más sencilla que los previamente disponibles. El objetivo de este estudio es analizar la influencia de la Gd-IgA1 circulante, medida por este método, en la progresión de la NIgA.
Se seleccionaron 49 pacientes con diagnóstico de NIgA demostrado mediante biopsia renal en nuestro centro, sin haber recibido tratamiento inmunosupresor previo, de los que se dispusiera de suero congelado. La mediana de seguimiento fue de cuatro años. Se midió Gd-IgA1 mediante ELISA independiente de lectina con el anticuerpo monoclonal KM55 (IgA1 kit Cat. No 30111694. IBL Int., Hamburgo, Alemania). Así mismo también se midieron los niveles de APRIL en estos pacientes.
19 (38,8%) pacientes alcanzaron ERC estadio 5. El cuarto cuartil de Gd-IgA1 circulante se relacionaba con un mayor riesgo acumulado de llegar a ERC estadio 5 en el análisis de Kaplan–Meier (riesgo al 5 año 39,4% vs. 24,3%; log rank p=0,019). El valor de Gd-IgA1 se relacionaba con un mayor riesgo de ERC estadio 5 (HR 1,147; IC 95%: 1,035–1,270; p=0,009), independientemente del filtrado glomerular, la proteinuria, el porcentaje de glomérulos esclerosados y el valor de esclerosis segmentaria. No encontramos diferencias significativas en los valores de APRIL.
El valor de Gd-IgA1 circulante medido mediante el anticuerpo monoclonal KM55 se relaciona con una peor evolución de los pacientes con NIgA independientemente de otras variables, por lo que se podría incluir en el estudio de los pacientes para mejorar la predicción del riesgo de progresión de la enfermedad.
En torno al 25% de los pacientes con nefropatía IgA (NIgA) progresa hacia el estadio 5 de la enfermedad renal crónica tras años de evolución. En los últimos años se han desarrollado diversas ...herramientas diseñadas para predecir qué pacientes evolucionan peor. El valor de IgA1 galactosil-deficiente (Gd-IgA1) circulante se ha relacionado con una peor evolución de la NIgA en algunos estudios. También hay varios trabajos que relacionan valores más elevados de APRIL con una peor evolución. Recientemente se ha desarrollado un método que permite medir el valor de Gd-IgA1 circulante de una manera más sencilla que los previamente disponibles. El objetivo de este estudio es analizar la influencia de la Gd-IgA1 circulante, medida por este método, en la progresión de la NIgA.
Se seleccionaron 49 pacientes con diagnóstico de NIgA demostrado mediante biopsia renal en nuestro centro, sin haber recibido tratamiento inmunosupresor previo, de los que se dispusiera de suero congelado. La mediana de seguimiento fue de cuatro años. Se midió Gd-IgA1 mediante ELISA independiente de lectina con el anticuerpo monoclonal KM55 (IgA1 kit Cat. No 30111694. IBL Int., Hamburgo, Alemania). Así mismo también se midieron los niveles de APRIL en estos pacientes.
19 (38,8%) pacientes alcanzaron ERC estadio 5. El cuarto cuartil de Gd-IgA1 circulante se relacionaba con un mayor riesgo acumulado de llegar a ERC estadio 5 en el análisis de Kaplan-Meier (riesgo al 5 año 39,4% vs. 24,3%; log rank p = 0,019). El valor de Gd-IgA1 se relacionaba con un mayor riesgo de ERC estadio 5 (HR 1,147; IC 95%: 1,035-1,270; p = 0,009), independientemente del filtrado glomerular, la proteinuria, el porcentaje de glomérulos esclerosados y el valor de esclerosis segmentaria. No encontramos diferencias significativas en los valores de APRIL.
El valor de Gd-IgA1 circulante medido mediante el anticuerpo monoclonal KM55 se relaciona con una peor evolución de los pacientes con NIgA independientemente de otras variables, por lo que se podría incluir en el estudio de los pacientes para mejorar la predicción del riesgo de progresión de la enfermedad.
About 25% of patients with IgA nephropathy (IgAN) progress to stage 5 chronic kidney disease (CKD) after years of evolution. Various tools have been developed in recent years designed to predict which of the patients will had poorer outcomes. The value of circulating galactosyl-deficient IgA1 (Gd-IgA1) has been related to a worse evolution of IgAN in several studies. There are also some publications that relate higher APRIL values with a worse evolution. Recently, a new method has been developed that allows measuring the value of circulating Gd-IgA1 in a simpler way than those previously available. The objective of this study is to analyze the influence of circulating Gd-IgA1, measured by this method, on the progression of IgAN.
Forty-nine patients with a diagnosis of IgAN demonstrated by renal biopsy were selected in our center, without having received prior immunosuppressive treatment, for whom frozen serum was available. The median follow-up was 4 years. Gd-IgA1 was measured by lectin-independent ELISA with the monoclonal antibody KM55 (IgA1 kit Cat. No. 30111694. IBL Int., Hamburg, Germany). Likewise, APRIL levels were also measured in these patients.
19 (38.8%) patients reached stage 5 CKD. The fourth quartile of circulating Gd-IgA1 was related to a higher cumulative risk of reaching stage 5 CKD in the Kaplan–Meier analysis (risk at the 5th year 39.4% vs. 24.3%, log rank p=0.019). The Gd-IgA1 value was related to an increased risk of CKD stage 5 (HR 1.147, 95% CI 1.035–1.270, p=0.009), regardless of glomerular filtration rate, proteinuria, the percentage of sclerosed glomeruli and the value of segmental sclerosis. We did not find significant differences in the APRIL values.
The value of circulating Gd-IgA1 measured by the monoclonal antibody KM55 is related to a worse evolution of patients with IgAN independently of other variables, so it could be included in the study of patients to improve the prediction of the risk of disease progression.
Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance ...immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus. We performed a prospective study including 54 consecutive KTx. Blood TTV load was measured by an in-house PCR at months 1 and 3. Together with doses and trough blood levels of tacrolimus and MPA, we calculated the coefficient of variability (CV), time in therapeutic range (TTR) and concentration/dose ratio (C/D) of tacrolimus, and the MPA-area under the curve (AUC-MPA) at the third month. TTV load at the first and third month discriminated those patients at risk of developing opportunistic infections between months 1 and 3 (AUC-ROC 0.723, 95%CI 0.559-0.905,
= 0.023) and between months 3 and 6 (AUC-ROC 0.778, 95%CI 0.599-0.957,
= 0.028), respectively, but not those at risk of acute rejection. TTV load did not relate to mean tacrolimus blood level, CV, TTR, C/D and AUC-MPA. To conclude, although TTV is a useful marker of net immunosuppressive status after KTx, it is not related to exposure to maintenance immunosuppression.
Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel ...biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49-16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (
= 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2-8.8),
= 0.021 and high risk tertiles HR 4.3 95%CI (1.65-11.54),
= 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09,
= 0.039) and 3-year mortality (ΔAUC = 0.11,
= 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates.
Kidney transplantation is the preferred therapeutic option for end-stage renal disease; however, the alloimmune response is still the leading cause of renal allograft failure. To better identify ...immunologic disparities in order to evaluate HLA compatibility between the donor and the recipient, the concept of eplet load has arisen. Regular kidney function monitoring is essential for the accurate and timely diagnosis of allograft rejection and the appropriate treatment. Donor-derived cell-free DNA (dd-cfDNA) has been proposed as a potential biomarker of acute rejection and graft failure in kidney transplantation. The proportion of plasma dd-cfDNA was determined in forty-two kidney patients at 1 month after transplantation. A total of eleven (26.2%) patients had a dd-cfDNA proportion of ≥1.0%. The only pretransplant variable related to dd-cfDNA > 1.0% was the HLA class II eplet mismatch load, mainly the HLA-DQB1 eplet mismatch load. Furthermore, dd-cfDNA was able to discriminate the patients with antibody-mediated rejection (AbMR) (AUC 87.3%), acute rejection (AUC 78.2%), and troubled graft (AUC 81.4%). Increased dd-cfDNA levels were associated with kidney allograft deterioration, particularly rejection, as well as a greater HLA class II eplet mismatch load. Consequently, combining dd-cfDNA determination and HLA eplet mismatch load calculation should improve the assessment of the risk of short- and long-term allograft damage.
El incremento en el número de pacientes en lista de espera de trasplante renal ha llevado a intentar aumentar el número de posibles donantes incorporando candidatos que anteriormente no se habrían ...considerado óptimos, incluyendo entre estos a los donantes de pacientes de asistolia (DA) y aquellos con criterios «expandidos» (DCE). Los receptores de injertos de DA controlada (DAc) sufren más función retrasada del injerto, pero presentan una evolución a largo plazo equiparable a los de donantes de muerte encefálica, lo que ha permitido un aumento en el número de trasplantes de DAc en distintos países en los últimos años. De forma paralela, el uso de DAc con criterios expandidos (DAc/DCE) se ha incrementado en los últimos años en diferentes países, permitiendo acortar la lista de espera del trasplante renal. El uso de estos injertos, aunque se relaciona con una mayor frecuencia de función retrasada del injerto, ofrece supervivencias del injerto a largo plazo similares o solo ligeramente inferiores a las de los donantes de muerte encefálica con criterios expandidos. Distintos estudios han observado que los receptores de injertos DAc/DCE tienen peor función renal que los DAc/estándar y que los donantes de muerte encefálica/DCE. La mortalidad asociada al trasplante de injertos de DAc/DCE se relaciona principalmente con la elevada edad del receptor. Los pacientes que reciben un trasplante renal de DAc/≥ 60 años presentan mejor supervivencia que los que continúan en la lista de espera, aunque este hecho no se ha demostrado en los receptores de DAc/> 65 años. La utilización de este tipo de órganos debe llevar pareja la optimización de los tiempos quirúrgicos y el menor tiempo de isquemia fría posible.
The increase in the number of patients on the kidney transplant waiting list has led to an attempt to increase the number of potential donors by incorporating candidates that previously would not have been considered optimal, including donors after cardiac death (DCD) and those with “expanded” criteria (ECD). Recipients of controlled DCD (cDCD) grafts suffer more delayed graft function (DGF), but have a long-term evolution comparable to those of brain-dead donors, which has allowed an increase in the number of cDCD transplants in different countries in recent years. In parallel, the use of cDCD with expanded criteria (cDCD/ECD) has increased in recent years in different countries, allowing the waiting list for kidney transplantation to be shortened. The use of these grafts, although associated with a higher frequency of DGF, offers similar or only slightly lower long-term graft survival than those of brain death donors with expanded criteria. Different studies have observed that cDCD/ECD graft recipients have worse kidney function than cDCD/standard and brain death/ECD. Mortality associated with cDCD/ECD graft transplantation mostly relates to the recipient age. Patients who receive a cDCD/≥60 graft have better survival than those who continue on the waiting list, although this fact has not been demonstrated in recipients of cDCD/>65 years. The use of this type of organ should be accompanied by the optimization of surgical times and the shortest possible cold ischemia.
SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant recipients ...(KT) were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country. This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT.
Epidemiology of hyperkalemia in chronic kidney disease Belmar Vega, Lara; Galabia, Emilio Rodrigo; Bada da Silva, Jairo ...
Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia,
2019 May - Jun, 20190501, Letnik:
39, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Hyperkalaemia is a significant electrolyte imbalance in chronic kidney disease (CKD). Renin-angiotensin-aldosterone system inhibitors (RAASi) have beneficial cardio-renal properties, although they ...can often cause hyperkalaemia.
To examine the prevalence of hyperkalaemia in CKD, identify factors associated with its appearance and the relationship between hyperkalaemia and mortality.
Retrospective observational study on patients with CKD in the period 1971-2017. The population was categorised into 3groups: Group 1, patients with CKD without renal replacement therapy; Group 2, patients on haemodialysis; and Group 3, patients on continuous ambulatory peritoneal dialysis.
A total of 2,629 patients were evaluated. The prevalence observed in the different groups was: 9.6%, 16.4% and 10.6%, respectively. Risk factors related to the appearance of hyperkalaemia in the CKD group were glomerular filtration rate (GFR) (P<.001), plasma creatinine (P<.001), plasma sodium (P<.001), haemoglobin (P=.028), diastolic blood pressure (P=.012), intake of ACE inhibitors and/or angiotensin ii receptor blockers (P=.008), treatment with metformin (P<.001) and diabetes (P=.045). Treatment with RAASi significantly increased hyperkalaemia as GFR decreased, as well as in patients with diabetes or heart failure.
Hyperkalaemia is a frequent metabolic alteration in CKD patients that increases in the presence of drugs with beneficial cardio-renal properties (RAASi), which means that patients often lose the benefit associated with these drugs. New, recently-appearing non-absorbable compounds, which bind to potassium in the gastrointestinal tract, enhancing faecal excretion and thus maintaining the cardio-renal benefit of the RAASi, could be relevant in the progress of patients with CKD.
Immunosuppression withdrawal after graft failure seems to favor sensitization. A high percentage of calculated panel-reactive antibody (cPRA) and the development of de novo donor specific antibodies ...(dnDSA) indicate human leukocyte antigen (HLA) sensitization and may hinder the option of retransplantation. There are no established protocols on the immunosuppressive treatment that should be maintained after transplant failure. A retrospective analysis including 77 patients who lost their first renal graft between 1 January 2006-31 December 2015 was performed. Two sera were selected per patient, one immediately prior to graft loss and another one after graft failure. cPRA was calculated by Single Antigen in all patients. It was possible to analyze the development of dnDSA in 73 patients. By multivariate logistic regression analysis, the absence of calcineurin inhibitor (CNI) at 6 months after graft failure was related to cPRA > 75% (OR 4.8, CI 95% 1.5-15.0,
= 0.006). The absence of calcineurin inhibitor (CNI) at 6 months after graft loss was significantly associated with dnDSA development (OR 23.2, CI 95% 5.3-100.6,
< 0.001). Our results suggest that the absence of CNI at the sixth month after graft loss is a risk factor for sensitization. Therefore, maintenance of an immunosuppressive regimen based on CNI after transplant failure should be considered when a new transplant is planned, since it seems to prevent HLA allosensitization.