Experience with abatacept in refractory lupus nephritis.

Lupus nephritis is a major cause of morbidity in patients with systemic lupus erythematosus. Responsiveness to treatment is crucial to avoid chronic kidney disease. New molecules have been developed in recent years to improve renal survival rates. Biological therapies as coadjutant to conventional induction treatment have been tested in randomized clinical trials with heterogeneous results. Like many others biologic therapies, Abatacept has not shown a clear benefit in the context of clinical trials. We present two cases of lupus nephritis patients in whom addition of abatacept resulted in complete remission of the renal disease. The first case described a 49-year-old male with class IV lupus nephritis with nephrotic range proteinuria and high immunological activity refractory to conventional treatment with cyclophosphamide and corticosteroids and multitarget therapy with tacrolimus, mycophenolate mofetil and prednisone. Several biological therapies (rituximab, belimumab and tocilizumab) were unsuccessfully tried, so that abatacept was added to his background multitarget therapy showing complete clinical response. The second case described a 52-year-old female with class IV lupus nephritis treated initially with conventional treatment with partial response. In successive renal flares with nephrotic proteinuria, she showed intolerance to rituximab and refractoriness to voclosporin. Finally, abatacept was added to her background therapy with MMF and PDN showing complete and maintained remission of the disease. In no case the use of abatacept was associated with serious adverse events. Based on our experience, abatacept should be considered as a safe rescue therapy in patients with refractory lupus nephritis and proteinuria with nephrotic range. In addition to this case, we reviewed the use of abatacept in lupus nephritis in the literature.

Sevelamer Use and Mortality in People with Chronic Kidney Disease Stages 4 and 5 Not on Dialysis.

Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.

Impact of dialysis modality on morbimortality of kidney transplant recipients after allograft failure. Analysis in the presence of competing events.

BACKGROUND AND OBJECTIVE: The number of patients who start dialysis due to graft failure increases every day. The best dialysis modality for this type of patient is not well defined and most patients are referred to HD. The objective of our study is to evaluate the impact of the dialysis modality on morbidity and mortality in transplant patients who start dialysis after graft failure. MATERIAL AND METHODS: A multicentre retrospective observation and cohort study was performed to compare the evolution of patients who started dialysis after graft failure from January 2000 to December 2013. One group started on PD and the other on HD. The patients were followed until the change of dialysis technique, retransplantation or death. Anthropometric data, comorbidity, estimated glomerular filtration rate (eGFR) at start of dialysis, the presence of an optimal access for dialysis, the appearance of graft intolerance and retransplantation were analyzed. We studied the causes for the first 10 hospital admissions after starting dialysis. For the statistical analysis, the presence of competitive events that hindered the observation of the event of interest, death or hospital admission was analyzed. RESULTS: 175 patients were included, 86 in DP and 89 in HD. The patients who started PD were younger, had less comorbidity and started dialysis with lower eGFR than those on HD. The mean follow-up was 34 ± 33 months, with a median of 24 months (IQR 7-50 months), Patients on HD had longer follow-up than patients on PD (35 vs. 18 months, p = < 0.001). The mortality risk factors were age sHR 1.06 (95% CI: 1.03-1.106, p = 0.000), non-optimal use of access for dialysis sHR 3.00 (95% CI: 1.507-5.982, p = 0.028) and the dialysis modality sHR (PD/HD) 0.36 (95% CI: 0.148-0.890, p = 0.028). Patients on PD had a lower risk of hospital admission sHR [DP/HD] 0.52 (95% CI: 0.369-0.743, p = < 0.001) and less probability of developing graft intolerance HR 0.307 (95% CI 0.142-0.758, p = 0.009). CONCLUSIONS: With the limitations of a retrospective and non-randomized study, it is the first time nationwide that PD shows in terms of survival to be better than HD during the first year and a half after the kidney graft failure. The presence of a non-optimal access for dialysis was an independent and modifiable risk factor for mortality. Early referral of patients to advanced chronic kidney disease units is essential for the patient to choose the technique that best suits their circumstances and to prepare an optimal access for the start of dialysis.

Impact of dialysis modality on morbimortality of kidney transplant recipients after allograft failure. Analysis in the presence of competing events. / Impacto de la modalidad de diálisis sobre la morbimortalidad tras el fracaso del injerto renal: análisis con eventos competitivos.

BACKGROUND AND OBJECTIVE: The number of patients who start dialysis due to graft failure increases every day. The best dialysis modality for this type of patient is not well defined and most patients are referred to HD. The objective of our study is to evaluate the impact of the dialysis modality on morbidity and mortality in transplant patients who start dialysis after graft failure. MATERIAL AND METHODS: A multicentre retrospective observation and cohort study was performed to compare the evolution of patients who started dialysis after graft failure from January 2000 to December 2013. One group started on PD and the other on HD. The patients were followed until the change of dialysis technique, retransplantation or death. Anthropometric data, comorbidity, estimated glomerular filtration rate (eGFR) at start of dialysis, the presence of an optimal access for dialysis, the appearance of graft intolerance and retransplantation were analysed. We studied the causes for the first 10 hospital admissions after starting dialysis. For the statistical analysis, the presence of competitive events that hindered the observation of the event of interest, death or hospital admission was analysed. RESULTS: 175 patients were included, 86 in DP and 89 in HD. The patients who started PD were younger, had less comorbidity and started dialysis with lower eGFR than those on HD. The mean follow-up was 34 ± 33 months, with a median of 24 months (IQR 7 - 50 months), Patients on HD had longer follow-up than patients on PD (35 vs. 18 months, p = < 0.001). The mortality risk factors were age sHR 1.06 (95% CI: 1.033 - 1.106, p = 0.000), non-optimal use of access for dialysis sHR 3.00 (95% CI: 1.507 - 5.982, p = 0.028) and the dialysis modality sHR (PD / HD) 0.36 (95% CI: 0.148 - 0.890, p = 0.028). Patients on PD had a lower risk of hospital admission sHR [DP / HD] 0.52 (95% CI: 0.369-0.743, p = < 0.001) and less probability of developing graft intolerance HR 0.307 (95% CI 0.142-0.758, p = 0.009). CONCLUSIONS: With the limitations of a retrospective and non-randomized study, it is the first time nationwide that PD shows in terms of survival to be better than HD during the first year and a half after the kidney graft failure. The presence of a non-optimal access for dialysis was an independent and modifiable risk factor for mortality. Early referral of patients to advanced chronic kidney disease units is essential for the patient to choose the technique that best suits their circumstances and to prepare an optimal access for the start of dialysis.

Recommendations for the use of everolimus in de novo kidney transplantation: False beliefs, myths and realities. / Recomendaciones para el uso de everolimus en trasplante renal de novo: falsas creencias, mitos y realidades.

The immunosuppressive combination most commonly used in de novo kidney transplantation comprises a calcineurin inhibitor (CI), tacrolimus, a mycophenolic acid derivative and steroids. The evidence which underlies this practice is based in the Symphony trial with controlled follow-up of one year, in which no comparator group included the combination CI-mTOR inhibitor. Different high-quality clinical trials support the use of everolimus as a standard immunosuppressive drug associated with reduced exposure of a CI in kidney transplantation. This combination could improve health related outcomes in kidney transplantation recipients. The present recommendations constitute an attempt to summarise the scientific evidence supporting this practice, discuss false beliefs, myths and facts, and offer specific guidelines for safe use, avoiding complications.

Recomendaciones para el uso de everolimus en trasplante renal de novo: falsas creencias, mitos y realidades / Recommendations for the use of everolimus in de novo kidney transplantation: False beliefs, myths and realities

La combinación inmunosupresora más utilizada en trasplante renal de novo incluye un inhibidor de calcineurina (IC), tacrolimus, un derivado del ácido micofenólico y esteroides. La evidencia que sustenta esta práctica se basa en el ensayo clínico Symphony, de evolución controlada durante un año, en el que no existía ningún grupo comparador con IC asociado a un inhibidor de mTOR. Diversos ensayos clínicos de alta calidad sustentan la indicación del uso de everolimus como inmunosupresor básico asociado a una exposición reducida de un IC en pacientes que reciben un trasplante renal. Esta combinación podría mejorar las expectativas de resultados en salud. Estas recomendaciones tratan de aportar la evidencia científica que apoya esta práctica, discuten las falsas creencias, mitos y realidades de la combinación y concretan pautas que permiten utilizarla con seguridad y evitar complicaciones (AU)

The immunosuppressive combination most commonly used in de novo kidney transplantation comprises a calcineurin inhibitor (CI), tacrolimus, a mycophenolic acid derivative and steroids. The evidence which underlies this practice is based in the Symphony trial with controlled follow-up of one year, in which no comparator group included the combination CI-mTOR inhibitor. Different high-quality clinical trials support the use of everolimus as a standard immunosuppressive drug associated with reduced exposure of a CI in kidney transplantation. This combination could improve health related outcomes in kidney transplantation recipients. The present recommendations constitute an attempt to summarise the scientific evidence supporting this practice, discuss false beliefs, myths and facts, and offer specific guidelines for safe use, avoiding complications (AU)

Impacto de la modalidad de diálisis sobre la morbimortalidad tras el fracaso del injerto renal: análisis con eventos competitivos / Impact of dialysis modality on morbimortality of kidney transplant recipients after allograft failure. Analysis in the presence of competing events

ANTECEDENTES Y OBJETIVO: El número de personas que inician diálisis por el fracaso del injerto aumenta cada día. La modalidad de diálisis mejor para este tipo de pacientes no está bien definida y la mayoría de ellos son derivados a hemodiálisis (HD). El objetivo de nuestro estudio es evaluar el impacto de la modalidad de diálisis sobre la morbilidad y la mortalidad en individuos trasplantados que inician este procedimiento tras el fracaso del injerto. MATERIAL Y MÉTODOS: Estudio multicéntrico retrospectivo observacional y de cohortes que compara la evolución de los pacientes que inician diálisis tras el fracaso del injerto, desde enero del año 2000 a diciembre del 2013. Un grupo lo hace en diálisis peritoneal (DP) y otro en HD. Se realizó un seguimiento a los pacientes hasta el cambio de técnica de diálisis, retrasplante o fallecimiento. Se analizaron datos antropométicos, comorbilidad, el filtrado glomerular (FG) con el que iniciaban la diálisis, la presencia de un acceso óptimo para esta, la presencia de intolerancia al injerto y el retrasplante. Estudiamos el motivo de los 10 primeros ingresos hospitalarios tras el inicio de la diálisis. Para el análisis estadístico, se tuvo en cuenta la presencia de eventos competitivos que dificultaran la aparición del evento de interés, muerte o ingreso hospitalario. RESULTADOS: Se incluyeron 175 pacientes. En DP 86 y 89 en HD. Los individuos que iniciaron DP eran más jóvenes, tenían menor comorbilidad y lo hacían con FG más bajos que los de HD. El seguimiento medio fue de 34 ± 33 meses, con una mediana de 24 (IQR siete a 50 meses), siendo mayor en los pacientes en HD que en los de DP (35 vs. 18 meses, p = < 0,001). Los factores de riesgo que influyeron en la mortalidad fueron la edad (coeficiente del sub Hazard Ratio [sHR] 1,06 (IC 95%: 1,033 a 1,106, p = 0,000), el uso no óptimo del acceso (sHR 3,00 (IC 95%: 1,507 a 5,982, p = 0,028) y el tipo de diálisis, la DP sHR[DP/HD] 0,36 (IC 95%: 0,148 a 0,890, p = 0,028). Los pacientes en DP tenían menos riesgo de un ingreso hospitalario sHR[DP/HD] 0,52 (IC 95%: 0,369 a 0,743, p = < 0,001) y menos probabilidad de desarrollar una intolerancia al injerto HR 0,307 (IC 95% 0,142 a 0,758, p = 0,009). CONCLUSIONES: Con las limitaciones de un estudio retrospectivo y no randomizado, es la primera vez a nivel nacional que se demuestra que la DP en términos de supervivencia es mejor que la HD cuando fracasa el injerto durante el primer año y medio en diálisis. La presencia de un acceso no óptimo para este procedimiento es un factor de riesgo de mortalidad independiente y modificable. La remisión precoz de los pacientes a las unidades de enfermedad renal crónica avanzada (ERCA) es fundamental para que estos elijan la técnica que más se adapte a sus circunstancias y preparar un acceso óptimo para el inicio de diálisis

BACKGROUND AND OBJECTIVE: The number of patients who start dialysis due to graft failure increases every day. The best dialysis modality for this type of patient is not well defined and most patients are referred to HD. The objective of our study is to evaluate the impact of the dialysis modality on morbidity and mortality in transplant patients who start dialysis after graft failure. MATERIAL AND METHODS: A multicentre retrospective observation and cohort study was performed to compare the evolution of patients who started dialysis after graft failure from January 2000 to December 2013. One group started on PD and the other on HD. The patients were followed until the change of dialysis technique, retransplantation or death. Anthropometric data, comorbidity, estimated glomerular filtration rate (eGFR) at start of dialysis, the presence of an optimal access for dialysis, the appearance of graft intolerance and retransplantation were analysed. We studied the causes for the first 10 hospital admissions after starting dialysis. For the statistical analysis, the presence of competitive events that hindered the observation of the event of interest, death or hospital admission was analysed. RESULTS: 175 patients were included, 86 in DP and 89 in HD. The patients who started PD were younger, had less comorbidity and started dialysis with lower eGFR than those on HD. The mean follow-up was 34 ± 33 months, with a median of 24 months (IQR 7 - 50 months), Patients on HD had longer follow-up than patients on PD (35 vs. 18 months, p = < 0.001). The mortality risk factors were age sHR 1.06 (95% CI: 1.033 - 1.106, p = 0.000), non-optimal use of access for dialysis sHR 3.00 (95% CI: 1.507 - 5.982, p = 0.028) and the dialysis modality sHR (PD / HD) 0.36 (95% CI: 0.148 - 0.890, p = 0.028). Patients on PD had a lower risk of hospital admission sHR [DP / HD] 0.52 (95% CI: 0.369-0.743, p = < 0.001) and less probability of developing graft intolerance HR 0.307 (95% CI 0.142-0.758, p = 0.009). CONCLUSIONS: With the limitations of a retrospective and non-randomized study, it is the first time nationwide that PD shows in terms of survival to be better than HD during the first year and a half after the kidney graft failure. The presence of a non-optimal access for dialysis was an independent and modifiable risk factor for mortality. Early referral of patients to advanced chronic kidney disease units is essential for the patient to choose the technique that best suits their circumstances and to prepare an optimal access for the start of dialysis

Acute rejection and late renal transplant failure: risk factors and prognosis.

BACKGROUND: Acute rejection episodes are a major determinant of renal allograft survival, and the improvement of the transplantation results in the last two decades is largely due to a progressive decrease in the incidence of acute rejection. These results are explained by the incorporation of new immunosuppressive agents since the introduction of cyclosporine. Because the detrimental effect of acute rejection on graft survival is not limited to the early post-transplant period, we have focused on the impact of acute rejection episodes on late transplant failure in patients with the graft functioning 1 year after transplantation. METHODS: We have retrospectively analysed in 3365 renal transplants performed in adults in Spain during 1990, 1994 and 1998 the incidence and severity of the acute rejection episodes, their risk factors, and their influence on graft and patient survival. RESULTS: The incidence of rejection episodes in the whole series was 32.5%, decreasing in 1998 (25.1%) compared with the previous years (38%) (P<0.0001). Corticoid-resistant rejection episodes also decreased from 8% in 1990 and 1994 to 3.4% in 1998 (P<0.0001). Multivariate analysis showed that patients < 60 years old (P<0.0001), sensitized recipients (P = 0.038), patients with delayed graft function (P<0.0001), cytomegalovirus infection (P = 0.0060), and those transplanted in 1990 or 1994 (P<0.0001) had an increased incidence of rejection episodes. In the univariate analysis, induction treatment with antilymphocyte globulines or OKT3 (P = 0.0002), and traumatic donor death (P = 0.042) were associated with a lower incidence of acute rejection. In the univariate analysis of the transplants performed in 1998, addressed to evaluate the effect of the new immunosuppressive agents, treatment with mycophenolate mofetil (P<0.0001) or tacrolimus (P = 0.0067), but not with anti-IL2 antibodies reduced the incidence of acute rejection. Patients with rejection episodes had an increased risk of late graft failure (Cox proportional hazards model, P<0.0001), which was homogeneous in the three periods analysed, with no effect on patient survival (P = 0.13). CONCLUSIONS: Despite a decreased incidence and severity of acute rejections in 1998, compared with the previous years, acute rejection still remains a powerful risk factor for late transplant failure.