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ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis

BACKGROUND The phenotype of renal involvement in anti-neutrophil cytoplasmic antibodies (ANCA) vasculitis has a major influence on survival, and histological subgrouping of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate this histological subgrouping and to investigate the additional value of ANCA serotype in the prediction of renal outcome. METHODS Data were retrospectively collected from the time of diagnosis by systematic review of medical records from 136 patients with renal biopsies recruited to cohorts from the UK and Spain, over 15 years. The end point, renal survival, was the composite of end-stage renal disease (ESRD) or death from any cause. The occurrence of ESRD, Stage 4 Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease, was assessed separately, in order to establish a severity index risk of chronic kidney disease. RESULTS Renal survival at 5 years was 96% in the focal, 86% in the crescentic, 81% in the mixed and 61% in the sclerotic subgroups (P = 0.03). Myeloperoxidase (MPO)-ANCA was associated with more severe disease when compared with PR3-ANCA, as demonstrated by a lower frequency of focal and higher frequency of sclerotic subgroups, by more advanced interstitial fibrotic change and by lower glomerular filtration rate at diagnosis and worse renal function at 1 and 2 years. CONCLUSIONS We have confirmed the predictive value for renal survival of the ANCA vasculitis histology classification in a multi-centre study. We found a worse renal outcome in patients with tubulointerstitial fibrosis and atrophy. MPO-ANCA positive patients had a worse renal prognosis due to more severe glomerular injury. These results contribute to patient stratification in renal vasculitis for therapeutic, epidemiological and basic research.

Rapid calcitriol increase and persistent calcidiol insufficiency in the first 6 months after kidney transplantation.

IntroductionVitamin D deficiency or insufficiency is prevalent in kidney transplant recipients. Little is known about post-transplantation changes in vitamin D forms, which are essential for bone health and other health outcomes. The aim was to measure the levels of calcidiol and calcitriol during the first 6 months after kidney transplantation and examine their relation with other bone mineral metabolic parameters. Patients and methodsA prospective study was performed on 98 patients recruited between April 2010 and June 2011. Calcidiol and calcitriol levels were measured at baseline and at days 15, 30, 90, and 180 after kidney transplantation. ResultsSerum calcidiol levels remained persistently low: 14.3 (9–22) ng/ml at baseline and 16.3 (10.1–20.6) ng/ml at 6 months (P=0.641). At 6 months, calcidiol levels showed an inverse correlation with simultaneously measured parathyroid hormone levels. Calcidiol showed a trend to be higher in patients transplanted in spring but with no statistically significant difference. Calcitriol levels increased from 17 (13–23.7) pg/ml at baseline to 24 (16–32) pg/ml (P=0.002) in the first 2 weeks after transplantation and reached 37 (25–50) pg/ml (P=0.000) after 6 months. During the follow-up, calcitriol levels showed a significant inverse correlation with baseline fibroblast growth factor-23 levels. At month 6, calcitriol levels were inversely correlated with baseline fibroblast growth factor-23 levels and directly correlated with calcidiol levels. ConclusionIn most patients, calcidiol levels remain low 6 months after kidney transplantation, whereas calcitriol levels rapidly return to normal. Lower calcidiol blood levels promoted lower calcitriol blood levels and higher parathyroid hormone concentrations.

Histopathological evaluation of pretransplant donor biopsies in expanded criteria donors with high kidney donor profile index: a retrospective observational cohort study

There is no consensus on the allocation of renal transplants from expanded criteria donors (ECD). The Kidney Donor Profile Index (KDPI) is used without the need for pretransplant donor biopsies (PTDB). We explored whether PTDB based on Remuzzi Score (RS) allows identification of those marginal kidneys in the highest calculated KDPI risk group (>91%) that appropriate for single transplantation. A retrospective study was conducted of 485 consecutive kidneys procured from a single center and transplanted if the RS was ≤4. We compared 5‐year kidney and patients survival between KDPI groups and between RS <4 or =4 in the highest KDPI group. The median KDPI (interquartile range) was 71 (66–76) for KDPI <80% (n = 77), 86 (81–90) for KDPI 81–90% (n = 82), and 97 (94–100) for KDPI >91% (n = 205). Patient survival at 5 years was 85.7%, 85.3%, and 76.09% (P = 0.058) and death‐censored graft survival was 84.4%, 86.5%, 73.6% (P = 0.015), respectively for each KDPI group. In >91% calculated KDPI group, there were no differences in graft survival depending on the RS (<4 vs. =4) (P = 0.714). The implementation of PTDB based on RS used for allocation of organs with the highest KDPI range could support to the acceptance of suitable organs for single transplantation with good patient and graft survival rate.

Eight-Year Experience with Nocturnal, Every-Other-Day, Online Haemodiafiltration

Background: New haemodialysis therapeutic regimens are required to improve patient survival. Longer and more frequent dialysis sessions have produced excellent survival and clinical advantages, while online haemodiafiltration (OL-HDF) provides the most efficient form of dialysis treatment. Methods: In this single-centre observational study, 57 patients on 4-5-hour thrice-weekly OL-HDF were switched to nocturnal every-other-day OL-HDF. Inclusion criteria consisted of stable patients with good prospects for improved occupational, psychological and social rehabilitation. The aim of this study was to report our 8-year experience with this schedule and to evaluate analytical and clinical outcomes. Results: Nocturnal, every-other-day OL-HDF was well tolerated and 56% of patients were working. The convective volume increased from 26.7 ± 2 litres at baseline to 46.6 ± 6.5 litres at 24 months (p < 0.01). Increasing the dialysis dose significantly decreased bicarbonate, blood-urea-nitrogen and creatinine values. Predialysis phosphate levels fell markedly with complete suspension of phosphate binders from the second year of follow-up. Although haemoglobin was unchanged, there was a 50.4% reduction in darbepoetin dose at 24 months and a significant decrease in the erythropoietin resistance index. Blood pressure significantly decreased in a few months. Antihypertensive medication requirements were decreased by 60% after 3 months and by 73% after 1 year and this difference was maintained thereafter. Conclusions: Nocturnal, every-other-day OL-HDF could be an excellent therapeutic alternative since it is well tolerated and leads to clinical and social-occupational rehabilitation with satisfactory morbidity and mortality. These encouraging results strengthen us to continue and invite other clinicians to join this initiative.

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy

ABSTRACT Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues. Renal toxicity has been described in several ICI but not with atezolizumab, an IgG1 monoclonal antibody targeting PD-L1 (programmed death ligand 1), approved by FDA as a second-line therapy for advanced urothelial carcinoma. Here we present a patient with a single kidney and metastatic renal cell carcinoma treated with atezolizumab and bevacizumab combination, with biopsy-proven acute interstitial nephritis, who had a complete resolution of renal dysfunction after steroid therapy.

Antiphospholipase 2 receptor antibody levels to predict complete spontaneous remission in primary membranous nephropathy

Abstract Background M-type phospholipase A2 receptor (APLA2R) is considered the major antigen involved in the pathogenesis of adult primary membranous nephropathy (MN), which is the leading cause of non-diabetic nephrotic syndrome. Antibodies to this antigen have been proved to be an excellent biomarker of disease activity in primary MN. In fact, preliminary data suggest that the higher the antibody level the more proteinuria, and that a decrease in antibody level precedes the remission of proteinuria, but more solid evidence is needed. Methods The present work aims to characterize the predictive value of the level of antibodies against PLA2R as a biomarker of disease course and treatment response in a well-defined cohort of 62 patients from University Hospitals Clinic of Barcelona and Josep Trueta in Girona. The primary outcome was the appearance of a spontaneous complete remission (CR), defined as induction of a CR without the use of immunosuppressive agents. Results In common with other reports, this work confirms that spontaneous CR is more frequent in patients with low titre of APLA2R at diagnosis, but strikingly, in this cohort we found that spontaneous CR was achieved in patients with APLA2R levels <40 UI/mL. Furthermore, spontaneous CR were less frequently observed in patients with proteinuria >8 g/day. Conclusions In conclusion, these findings point out the important role of APLA2R as a tool to predict the disease course and establish personalized therapeutic options at the moment of diagnosis of primary MN. Specifically, patients with low titre of APLA2R (<40 UI/mL) and proteinuria <4/day could obtain benefit of a longer period of follow-up with conservative treatment after diagnosis.

The utility of phospholipase A2 receptor autoantibody in membranous nephropathy after kidney transplantation

ABSTRACT Membranous nephropathy (MN) is estimated to cause end-stage renal disease in ∼ 5% of patients, in whom renal transplantation is the therapy of choice. Among patients receiving a transplant for MN, the disease will recur in the graft in 30–50%; among these, graft loss will occur in 50% within 10 years. Several studies have suggested that phospholipase A2 receptor autoantibody (aPLA2R) levels before transplantation might be useful in predicting recurrence, and their titration after transplantation is clinically relevant to assess the risk of recurrence and progression, to guide treatment indications and to monitor treatment response. In this review we describe the evolving role of aPLA2R as a biomarker in primary MN and its current usefulness in predicting recurrence of this autoimmune podocytopathy after renal transplantation.

Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia

INTRODUCTION In the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes. PATIENTS AND METHODS This is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014-2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed. RESULTS All patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose. CONCLUSION HCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.

Clinical impact of regional citrate anticoagulation in continuous renal replacement therapy in critically ill patients

Background Regional citrate anticoagulation (RCA) is being used increasingly in continuous renal replacement therapy (CRRT) as a safer alternative to heparin. However, complex metabolic control to avoid side effects have generated discrepancies about its introduction into everyday practice. We aimed to compare both anticoagulation techniques in terms of efficacy, safety and feasibility. Methods Observational retrospective study performed in 3 specialized ICUs in patients receiving CVVHDF with RCA between January 2013 and May 2016. Heparin-treated patients matched by age, sex and disease severity treated in the preceding year were selected as historic controls. Filter lifetime, number of filters used, haemorrhagic complications and metabolic complications were recorded. Results 54 patients (27 treated with RCA and 27 with heparin) were included in the study. Filter lifetimes in the first 72 hours were 55.1 ± 21.8 hours in the RCA group compared to 38.8 ± 24.8 hours in the heparin group, (p = 0.004). In addition, the number of filters used in the first 72 hours was significantly higher in the heparin group (2.4 ± 1.3 vs. 1.5 ± 0.7; p = 0.004). There was a trend toward a lower incidence of bleeding in the RCA group, with a significantly lower red blood cell transfusion rate (p = 0.027) in the citrate group. No clinically significant metabolic disturbances were observed in the RCA group. Regarding outcomes, there were no significant differences between groups. Conclusions These results suggest that the implementation of CVVHDF with RCA using concentrated citrate solutions prolongs filter lifetime, achieves a longer effective hemodiafiltration time and is a safe and feasible method.