Aproximación a la identificación de proteinas diferencialmente expresadas en enfermedades de depósito lisosomal.

CO-138 Introducción: Las esfingolipidosis son enfermedades de depósito lisosomal (EDL) caracterizadas por una alteración en el transporte y metabolización de lípidos en el lisosoma y su subsecuente acumulación en el interior de este orgánulo. Son enfermedades de baja prevalencia y mayoritariamente de herencia autosómica recesiva con una gran variabilidad clínica que provoca que, a pesar de poder diagnosticarse en edad pediátrica, hasta en un 40% el diagnóstico se demora hasta la edad adulta. La enfermedad de Gaucher (EG) es la más común entre las EDL, pero también se encuentran otras esfingolipidosis como el déficit de esfingomielinasa ácida (DEMA), la enfermedad de Niemann-Pick tipo C (NPC) en la que el acúmulo de esfingolípidos es secundario a la disfunción lisosomal, o el déficit de lipasa ácida lisosomal (DLAL). En todas ellas existe un importante componente inflamatorio que se traduce en algunos casos por el incremento de inmunoglobulinas o la presencia de gammapatías monoclonales. Se ha prestado poca atención y estudiado escasamente la distribución de las diferentes proteínas séricas en estas entidades. ..

Renal Transplantation in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Multicenter Experience

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of rapidly progressive glomerulonephritis resulting in end-stage renal disease (ESRD). The optimal timing of kidney transplantation (KTX) for ESRD as a result of AAV and the risk of AAV relapse after KTX are not well defined. We report our experience with AAV patients who underwent KTX at our institutions between 1996 and 2010. Median follow-up was 64 months

Stony Coral Tissue Loss Disease and Other Diseases Affect Adults and Recruits of Major Reef Builders at Different Spatial Scales in the Dominican Republic

Monitoring programs can help understand coral disease dynamics. Here, we present results from a national program in the Dominican Republic (DR) aimed at evaluating coral diseases 3 times a year following a nested spatial design. Prevalence of coral diseases in DR varied from sites to regions, suggesting that disease dynamics can be driven by local processes and/or across larger spatial scales. Three diseases were common: Dark Spot (DSD), Yellow Band (YBD) and Stony Coral Tissue Loss Disease (SCTLD). DSD and YBD were more prevalent across the western coast (north and south), whereas SCTLD was restricted for the study period to the northern coast. SCTLD has become endemic in the northwestern coast, epizootic in the northeastern, and absent in other sites across DR. SCTLD prevalence in the northwest was below 10% across sites, whereas in the northeast it varied from 2.13±3.69% (mean± sd) to 38.7±13.55% in Galeras and from 1.9±0.99% to 38.5±19.8% in Samaná. Over 10 coral species were affected by SCTLD in DR, with Pseudodiploria spp, Dendrogyra cylindrus, Eusmilia fastigiata, Siderastrea siderea, Montastraea cavernosa and Meandrina spp, being the most susceptible. We observed SCTLD affecting recruits and juvenile corals with 5% prevalence on average. Furthermore, we observed Oreaster reticulatus climbing on 1% healthy and 27% SCTLD P. strigosa colonies in Samaná. We conclude that SCTLD is a serious problem in DR, producing rapid loss of coral cover of major reef builders that are locally used for propagation efforts. This monitoring plan will provide future insights to design more effective disease responses

Low- and high-molecular-weight urinary proteins as predictors of response to rituximab in patients with membranous nephropathy: a prospective study

Background. Selective urinary biomarkers have been considered superior to total proteinuria in predicting response to treatment and outcome in patients with membranous nephropathy (MN). Methods. We prospectively tested whether urinary (U) excretion of retinol-binding protein (RBP), α1-microglobulin (α1M), albumin, immunoglobulinIgG and IgM and/or anti-phospholipase 2 receptor (PLA2R) levels could predict response to rituximab (RTX) therapy better than standard measures in MN. We also correlated changes in antibodies to PLA2R with these urinary biomarkers. Results. Twenty patients with MN and proteinuria (P) >5 g/24 h received RTX (375 mg/m2 × 4) and at 12 months, 1 patient was in complete remission (CR), 9 were in partial remission (PR), 5 had a limited response (LR) and 4 were non-responders (NR). At 24 months, CR occurred in 4, PR in 12, LR in 1, NR in 2 and 1 patient relapsed. By simple linear regression analysis, UIgG at baseline (mg/24 h) was a significant predictor of change in proteinuria at 12 months (Δ urinary protein) (P = 0.04). In addition, fractional excretion (FE) of IgG, urinary alpha 1 microglobulin (Uα1M) (mg/24 h) and URBP (μg/24 h) were also predictors of response (P = 0.05, 0.04, and 0.03, respectively). On the other hand, UIgM, FEIgM, albumin and FE albumin did not predict response (P = 0.10, 0.27, 0.22 and 0.20, respectively). However, when results were analyzed in relation to proteinuria at 24 months, none of the U markers that predicted response at 12 m could predict response at 24 m (P = 0.55, 0.42, 0.29 and 0.20). Decline in anti-PLA2R levels was associated with and often preceded urinary biomarker response but positivity at baseline was not a predictor of proteinuria response. Conclusions. The results suggest that in patients with MN, quantification of low-, medium- and high-molecular-weight urinary proteins may be associated with rate of response to RTX, but do not correlate with longer term outcomes

A rapid high-performance semi-automated tool to measure total kidney volume from MRI in autosomal dominant polycystic kidney disease.

OBJECTIVES: To develop a high-performance, rapid semi-automated method (Sheffield TKV Tool) for measuring total kidney volume (TKV) from magnetic resonance images (MRI) in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: TKV was initially measured in 61 patients with ADPKD using the Sheffield TKV Tool and its performance compared to manual segmentation and other published methods (ellipsoidal, mid-slice, MIROS). It was then validated using an external dataset of MRI scans from 65 patients with ADPKD. RESULTS: Sixty-one patients (mean age 45 ± 14 years, baseline eGFR 76 ± 32 ml/min/1.73 m2) with ADPKD had a wide range of TKV (258-3680 ml) measured manually. The Sheffield TKV Tool was highly accurate (mean volume error 0.5 ± 5.3% for right kidney, - 0.7 ± 5.5% for left kidney), reproducible (intra-operator variability - 0.2 ± 1.3%; inter-operator variability 1.1 ± 2.9%) and outperformed published methods. It took less than 6 min to execute and performed consistently with high accuracy in an external MRI dataset of T2-weighted sequences with TKV acquired using three different scanners and measured using a different segmentation methodology (mean volume error was 3.45 ± 3.96%, n = 65). CONCLUSIONS: The Sheffield TKV Tool is operator friendly, requiring minimal user interaction to rapidly, accurately and reproducibly measure TKV in this, the largest reported unselected European patient cohort with ADPKD. It is more accurate than estimating equations and its accuracy is maintained at larger kidney volumes than previously reported with other semi-automated methods. It is free to use, can run as an independent executable and will accelerate the application of TKV as a prognostic biomarker for ADPKD into clinical practice. KEY POINTS: • This new semi-automated method (Sheffield TKV Tool) to measure total kidney volume (TKV) will facilitate the routine clinical assessment of patients with ADPKD. • Measuring TKV manually is time consuming and laborious. • TKV is a prognostic indicator in ADPKD and the only imaging biomarker approved by the FDA and EMA

Autosomal dominant polycystic kidney disease: recent advances in clinical management

The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD) go back at least 500 years to the late 16th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21st century. In this commentary, we consider how clinical management is likely to change in the coming decade

The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta-analysis of European literature and prevalence evaluation in the Italian province of Modena suggest that ADPKD is a rare and underdiagnosed condition

ADPKD is erroneously perceived as a not rare condition, which is mainly due to the repeated citation of a mistaken interpretation of old epidemiological data, as reported in the Dalgaard's work (1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD in the general population is uncertain, with a wide range of estimations reported by different authors. In this work, we have performed a meta-analysis of available epidemiological data in the European literature. Furthermore we collected the diagnosis and clinical data of ADPKD in a province in the north of Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well as the main clinical characteristics of ADPKD in this region

Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

BACKGROUND: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. RESULTS: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. CONCLUSIONS: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival