Comparison of 3 anti-PLA2R inmmunoassaysfor the diagnosis of idiopathic membranous nephropathy in an european population. A pilot study.

Membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome. Renal biopsy is nowadays the gold standard for the diagnosis of MN. The presence of circulating PLA2R antibody is a very specific tool for the diagnosis of this disease, especially associated with primary or idiopathic MN (IMN), even though it can be also found in a small proportion of patients with secondary MN (SMN). This pilot study compares three different techniques for the detection of anti-PLA2R autoantibodies (immunofluorescence, ELISA immunoassay, and multiplex laser bead technology). Serum of 12 IMN and 9 SMN patients was obtained at diagnosis. Additionally, we employed serum samples of 15 healthy volunteers. From our patient cohort, we obtained a 7.75 RU/ml cut-off for the ELISA and 3104 MFI for the Luminex assays. The agreement between the three techniques improved considerably when applying the new cut-off points. As several authors have suggested, cut-offs may be calculated for each specific population instead of establishing global cut-off points. Patients with IMN showed significantly lower serum albumin levels and higher 24 h proteinuria compared to those with SMN. Analysis of ROC curves suggests that ELISA and LUMINEX assays are more useful than biochemical variables to differentiate patients with IMN and SMN. This pilot study contributes to confirming that the combination of ELISA and Luminex assays provide excellent sensitivity and specificity for the identification of IMN.

Nuevos retos en las nefritis tubulointersticiales inducidas por fármacos / New challenges in tubulointerstitial nephritis induced by drugs

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High levels of circulating TNFR1 increase the risk of all-cause mortality and progression of renal disease in type 2 diabetic nephropathy.

BACKGROUND: Several studies have demonstrated that levels of circulating inflammatory markers such as tumour necrosis factorα (TNFα), are associated with early progression of diabetic nephropathy (DN). The aim of this study was to investigate whether there is an association between circulating TNFα receptor and disease progression in patients with advanced type 2 DN and severe proteinuria. METHODS: Between 2006 and 2011, we measured levels of circulating soluble TNFα receptor 1 (TNFR1) and soluble TNFα receptor 2 (TNFR2) at baseline and 4 and 12 months in 101 patients included in a multicenter randomized controlled trial to compare the effect of optimal doses of renin-angiotensin system blockers in monotherapy or in combination (dual blockade) to slow progression of established type 2 DN. The primary composite endpoint was a >50% increase in baseline serum creatinine, end-stage renal disease, or death. RESULTS: The median follow-up was 32 months (IQR, 18-48), during which time 28 patients (22.7%) achieved the primary endpoint. The TNFR1 level, but not the TNFR2 level, was correlated with other inflammatory markers. Cox regression analysis showed that the highest TNFR1 levels (HR, 2.60; 95%CI, 1.11-86.34) and baseline proteinuria (HR 1.32; 95%CI 1.15-1.52) were associated with the primary endpoint. The mixed model analysis revealed that TNFR1 and the TNFR2 levels did not change after starting treatment with renin-angiotensin system blockers. CONCLUSIONS: Our results show that the highest levels of TNFR1 are independently associated with progression of renal disease and death in type 2 DN. The renin angiotensin blockers have no effect on these inflammatory markers.

Mantenimiento de la función renal residual en hemodiálisis: experiencia de 5 años de una pauta de diálisis incremental / Maintaining residual renal function in patients on haemodialysis: 5-year experience using a progressively increasing dialysis regimen

Introducción: A diferencia de los pacientes tratados con diálisis peritoneal, la programación de una dosis incremental de diálisis no se considera en el enfermo tratado con hemodiálisis (HD) periódica, ni tampoco es habitual tener en cuenta la función renal residual en el cálculo de la dosis total de diálisis, asumiéndose como tal la proporcionada exclusivamente por el aclaramiento del dializador. A partir del año 2006 decidimos establecer una pauta incremental de diálisis al inicio del tratamiento renal sustitutivo, valorando la posibilidad de comenzar con 2 HD/semana cuando el aclaramiento renal de urea fuera igual o superior a 2,5 ml/min. En el presente trabajo presentamos nuestra experiencia de los primeros 5 años de aplicación de esta pauta incremental de HD y su repercusión sobre la función renal residual. Metodología: Se han incluido a todos los enfermos que iniciaron tratamiento con HD periódica entre el 1/1/2006 y el 30/9/2010, y permanecieron en diálisis más de tres meses. El seguimiento de los enfermos finalizó el 31/12/2010 (fecha de cierre del estudio). Cuando un enfermo inicia HD se determina el aclaramiento de urea y creatinina con las concentraciones de urea y creatinina en una muestra de sangre obtenida antes de la diálisis y (..) (AU)

Introduction: In contrast to patients treated with peritoneal dialysis, those on periodical haemodialysis (HD) do not receive programmed progressive increases in dialysis dosage, nor is residual renal function taken into account in the calculation of the total dialysis prescription; rather, only dialyser clearance is factored into the equation. In 2006, we decided to establish a progressively increasing dialysis regimen at the start of renal replacement therapy, evaluating the possibility of starting with 2 sessions of HD/week when renal clearance of urea was equal to or greater than 2.5ml/min. This study summarises our experience during the first 5 years of application of this progressively increasing HD prescription and its repercussions on residual renal function. Methods: We included all patients who started periodical HD between 1/1/2006 and 30/9/2010 and remained on dialysis for more than three months. The follow-up period ended on 31/12/2010 (study end date). When a patient started HD, urea and creatinine clearance levels were measured based on urea and creatinine concentrations in blood samples taken before dialysis and in urine samples taken 24 hours prior to starting the first dialysis session of the week. If urea clearance was equal to or greater than 2.5ml/min, 2 sessions of HD per week were applied, as long as the patient's clinical situation allowed for it (according to the criteria of the attending physician). Residual renal function was analysed every 2 months until diuresis was less than 100ml/day, which is considered to be basically null. We evaluated the decrease in residual renal function, calculating the rate of decrease in (..) (AU)

Maintaining residual renal function in patients on haemodialysis: 5-year experience using a progressively increasing dialysis regimen.

INTRODUCTION: In contrast to patients treated with peritoneal dialysis, those on periodical haemodialysis (HD) do not receive programmed progressive increases in dialysis dosage, nor is residual renal function taken into account in the calculation of the total dialysis prescription; rather, only dialyser clearance is factored into the equation. In 2006, we decided to establish a progressively increasing dialysis regimen at the start of renal replacement therapy, evaluating the possibility of starting with 2 sessions of HD/week when renal clearance of urea was equal to or greater than 2.5 ml/min. This study summarises our experience during the first 5 years of application of this progressively increasing HD prescription and its repercussions on residual renal function. METHODS: We included all patients who started periodical HD between 1/1/2006 and 30/9/2010 and remained on dialysis for more than three months. The follow-up period ended on 31/12/2010 (study end date). When a patient started HD, urea and creatinine clearance levels were measured based on urea and creatinine concentrations in blood samples taken before dialysis and in urine samples taken 24 hours prior to starting the first dialysis session of the week. If urea clearance was equal to or greater than 2.5 ml/min, 2 sessions of HD per week were applied, as long as the patient's clinical situation allowed for it (according to the criteria of the attending physician). Residual renal function was analysed every 2 months until diuresis was less than 100ml/day, which is considered to be basically null. We evaluated the decrease in residual renal function, calculating the rate of decrease in glomerular filtration (ml/min/month) and 24-hour diuresis (ml/month) in patients receiving 2 and 3 HD sessions per week. In January 2010, we took a cross-sectional sample, evaluating glomerular filtration and how this value was associated with various clinical and laboratory parameters in patients receiving 2 or 3 dialysis sessions per week. RESULTS: During the study period, 95 patients were included in the study, 41 of which (43%) started with 2 HD sessions per week, and 54 (57%) with 3 sessions per week. The mean time that patients remained on the 2HD sessions/week regimen was 11.1 ± 7.2 months (range: 2-25 months). Of the 41 patients that started with 2 HD sessions/week, 10 received a transplant while on the treatment regimen, 1 was transferred to peritoneal dialysis, 6 recovered renal function and were able to abandon dialysis treatment, 15 were switched to the 3 HD sessions/week regimen, and 9 continued on the 2 HD sessions/week regimen at the time the study ended. Of the 15 patients that were switched to the 3 HD sessions/week regimen, 4 received transplants, 3 died, and the remaining 8 continued on HD until the end of the study. A Kaplan-Meier survival analysis revealed that patients who started on the 2 HD sessions/week regimen had a greater survival rate (log-rank: 3.964; P=.04). Losses in both glomerular filtration rate and 24-hour diuresis were lower in patients on the 2 HD sessions/week regimen: 0.22 ± 0.36 ml/min/month vs 0.89 ± 1.26 ml/min/month for glomerular filtration (P=.001), and 90.59 ± 132 ml/month vs 206.23 ± 286 ml/month for 24-hour diuresis (P=.001), respectively. In the cross-sectional sample taken in January 2010, 17 patients were on the 2 HD sessions/week regimen and 47 were on the 3 HD sessions/week regimen. Serum concentrations of ß2-microglobulin were significantly lower in the 2 HD sessions/week group (19.7 ± 5 vs 38.3 ± 13; P=.000). The mean haemoglobin concentration was similar between the two groups, with a significantly lower dose required of erythropoietin in patients on the 2 HD sessions/week regimen (7058 ± 3749 units/week vs 12 553 ± 10 826 units/week; P=.037). CONCLUSION: In select populations, the start of HD can be administered on a progressively increasing dosage, starting with two sessions/week. In our experience, this is a safe prescription that probably contributes to preserving residual renal function.