Spectrum of Kidney Involvement in Patients with Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are characterized by a high prevalence of associated autoimmune manifestations. Kidney involvement has been rarely reported in MDS patients. We report on the spectrum of kidney pathological findings in MDS patients. We retrospectively identified MDS patients who had undergone a kidney biopsy between 2001 and 2019 in nine Swiss and French nephrology centres. Nineteen patients (median age 74 years [63-83]) were included. At the time of kidney biopsy, eleven (58%) patients had extra-renal auto-immune manifestations and sixteen (84%) presented with acute kidney injury. Median serum creatinine at diagnosis was 2.8 mg/dL [0.6-8.3] and median urinary protein to creatinine ratio was 1.2 g/g [0.2-11]. Acute tubulo-interstitial nephritis (TIN) was present in seven (37%) patients. Immunofluorescence study in one patient with acute TIN disclosed intense IgG deposits along the tubular basement membrane and Bowman's capsule. Other kidney pathological features included ANCA-negative pauci-immune necrotizing and crescentic glomerulonephritis (n = 3), membranous nephropathy (n = 2), IgA nephropathy (n = 1), IgA vasculitis (n = 1), immunoglobulin-associated membrano-proliferative glomerulonephritis type I (n=1), crescentic C3 glomerulopathy (n = 1), fibrillary glomerulonephritis (n = 1) and minimal change disease (n = 1). Eleven (58%) patients received immunosuppressive treatments, among whom one developed a severe infectious complication. After a median follow-up of 7 month [1-96], nine (47%) patients had chronic kidney disease stage 3 (n = 6) or 4 (n = 3) and five (26%) progressed to end-stage kidney disease. Three patients died. MDS are associated to several autoimmune kidney manifestations, predominantly acute TIN. MDS are to be listed among the potential causes of autoimmune TIN

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

How I diagnose and treat atypical hemolytic uremic syndrome.

Our understanding and management of atypical haemolytic uremic syndrome (HUS) has dramatically improved in the last decade. Atypical HUS has been established as a prototypic disease resulting from a dysregulation of the complement alternative C3 convertase. Subsequently, prospective non-randomized studies and retrospective series have shown the efficacy of C5 blockade in the treatment of this devastating disease. C5 blockade has become the cornerstone of the treatment of atypical HUS. This therapeutic breakthrough has been mitigated by persistent difficulties in the positive diagnosis of atypical HUS, and the latter remains, to date, a diagnosis by exclusion. Furthermore, the precise spectrum of complement-mediated renal thrombotic microangiopathy is still a matter of debate. Nevertheless, long-term management of atypical HUS is increasingly individualized and life-long C5 blockade is no more a paradigm that applies to all patients with this disease. The potential benefit of complement blockade in other forms of HUS, notably secondary HUS, remains uncertain

The Rational Use of Complement Inhibitors in Kidney Diseases.

The development of complement inhibitors represented one of the major breakthroughs in clinical nephrology in the last decade. Complement inhibition has dramatically transformed the outcome of one of the most severe kidney diseases, the atypical hemolytic uremic syndrome (aHUS), a prototypic complement-mediated disorder. The availability of complement inhibitors has also opened new promising perspectives for the management of several other kidney diseases in which complement activation is involved to a variable extent. With the rapidly growing number of complement inhibitors tested in a rapidly increasing number of indications, a rational use of this innovative and expensive new therapeutic class has become crucial. The present review aims to summarize what we know, and what we still ignore, regarding complement activation and therapeutic inhibition in kidney diseases. It also provides some clues and elements of thoughts for a rational approach of complement modulation in kidney diseases