The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Abstract Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV

New Short Tandem Repeat-Based Molecular Typing Method for Pneumocystis jirovecii Reveals Intrahospital Transmission between Patients from Different Wards.

Pneumocystis pneumonia is a severe opportunistic infection in immunocompromised patients caused by the unusual fungus Pneumocystis jirovecii. Transmission is airborne, with both immunocompromised and immunocompetent individuals acting as a reservoir for the fungus. Numerous reports of outbreaks in renal transplant units demonstrate the need for valid genotyping methods to detect transmission of a given genotype. Here, we developed a short tandem repeat (STR)-based molecular typing method for P. jirovecii. We analyzed the P. jirovecii genome and selected six genomic STR markers located on different contigs of the genome. We then tested these markers in 106 P. jirovecii PCR-positive respiratory samples collected between October 2010 and November 2013 from 91 patients with various underlying medical conditions. Unique (one allele per marker) and multiple (more than one allele per marker) genotypes were observed in 34 (32%) and 72 (68%) samples, respectively. A genotype could be assigned to 55 samples (54 patients) and 61 different genotypes were identified in total with a discriminatory power of 0.992. Analysis of the allelic distribution of the six markers and minimum spanning tree analysis of the 61 genotypes identified a specific genotype (Gt21) in our hospital, which may have been transmitted between 10 patients including six renal transplant recipients. Our STR-based molecular typing method is a quick, cheap and reliable approach to genotype Pneumocystis jirovecii in hospital settings and is sensitive enough to detect minor genotypes, thus enabling the study of the transmission and pathophysiology of Pneumocystis pneumonia

Transmission map of the 10 patients in whom the <i>P</i>. <i>jirovecii</i> genotype 21 was detected.

<p>The date corresponds to the time at which the patient was present in the hospital and is delineated as a circle. Colored circles show <i>P</i>. <i>jirovecii</i> exposure of a given patient on a given day. Color coding distinguishes the different groups of patients (purple for patients 01–03, blue for patients 04–06 and turquoise for patients 07–10). The red bar corresponds to transmission between two groups of patients. Colored bars show the transmission routes.</p

Summary of genotype categories for <i>P</i>. <i>jirovecii</i> samples.

<p>Summary of genotype categories for <i>P</i>. <i>jirovecii</i> samples.</p

Distribution of the different alleles in the 106 samples tested for the intronic (A), exonic (B) and intergenic (C) markers.

<p>Distribution of the different alleles in the 106 samples tested for the intronic (A), exonic (B) and intergenic (C) markers.</p

Characteristics of the STR markers and primers used in this study.

<p>Characteristics of the STR markers and primers used in this study.</p

Discriminatory power of the assay for genotyping <i>P</i>. <i>jirovecii</i>.

<p>Discriminatory power of the assay for genotyping <i>P</i>. <i>jirovecii</i>.</p

Minimum spanning tree analysis of 61 genotypes from 55 samples harboring a unique genotype (one allele per marker) or multiple genotypes (multiple alleles in one marker).

<p>The number of allelic mismatches among STR profiles was used as distance. Each circle corresponds to one genotype (Gt), with its arbitrary number indicated next to it. The size of the circle is correlated with the number of isolates possessing the corresponding Gt, from one (smallest circle) to nine (Gt21). Dark, dashed and thin connecting bars corresponds to one, 2 or >2 different markers observed between linked genotypes. Gray zones surrounding some groups of circles indicate that these profiles belong to the same genetic cluster, meaning that they have a single allelic mismatch with at least one other member of the group. Cluster 2, which was significantly associated with renal transplant recipients, is shown by a dashed line. The color of the circles indicates the underlying disease of the patient in whom this specific genotype was recovered (Green, HIV patient; Red, hematology patient; Purple, renal transplant recipient; Yellow, other cause of immunosuppression).</p