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Membranous nephropathy (MN) constitutes a major cause of nephrotic syndrome (NS) in adults. After kidney transplantation (KTx), both recurrent and de novo MN has been reported. In addition to PLA2R and THSD7A, recent identification of neural EGFL‐like‐1 protein, NELL1, as a potential disease antigen has enriched our understanding of MN pathogenesis. To date, NELL1‐positive MN has only been described in native kidneys, but never been diagnosed in renal allografts. We here report on a 56‐year‐old male kidney transplant recipient suffering from amyotrophic lateral sclerosis (ALS), who developed NS 25 years after KTx. Allograft biopsy revealed NELL1‐positive MN. Using specifically established immunoblotting techniques, we detected new‐onset NELL1‐IgG1, IgG3, and IgG4 antibodies in the patient´s serum correlating with the course of proteinuria. While primary renal disease was undetermined, MN recurrence seemed unlikely given the long‐time span since KTx. By clinical investigation of de novo etiologies, we did not detect an underlying malignancy. However, previous self‐medication with dimercaptopropane sulfonate (DMPS) and alpha lipoic acid (ALA) represented a potential trigger and cessation associated with partial remission of proteinuria. This report illustrates the first case of posttransplant NS due to NELL1‐positive MN. Monitoring NELL1 antibodies in the serum promise to be a non‐invasive diagnostic tool guiding disease management. This unique case of posttransplant membranous nephropathy associated with new‐onset NELL1‐IgG autoantibodies identifiable in both the patient's serum and the allograft tissue.

The identification and location of critical defects inside battery cells before the performance decreases or safety issues arise remain a challenge. This study compares two nondestructive testing methods for the 3D visualization of defects at different depths inside a pouch battery cell: scanning acoustic microscopy (SAM) and X‐ray computed tomography (CT). A manufactured pouch cell with eight electrode sheets is used for this investigation. SAM using a 15 MHz transducer in reflection mode can detect defects at depths of up to four electrode sheets with a lateral resolution of 150 μm in 2 min. CT can locate defects on all eight stacked electrode sheets inside the pouch cell. The CT measurements take about 12.5 h. Both methods can complement each other in detecting defects inside thin pouch cells as an end‐of‐line test after the production or for qualifying individual battery cells for second‐life applications. As an in‐line quality check, SAM has proven to be a cost‐effective and efficient method for detecting defects such as misalignment on stacked electrodes. Both methods have the potential to expand the portfolio of nondestructive quality assurance tests in the production of lithium‐ion battery cells. This contributes to increasing the safety and productivity of battery technology. Two nondestructive testing methods are used to locate defects within pouch cells: scanning acoustic microscopy (SAM) and X‐ray computed tomography (CT). SAM detects defects at depths of up to four electrode sheets in 2 min with a resolution of 150 μm. CT locates defects on all eight stacked electrode sheets in about 12 h with a resolution of 22 μm.

End-stage renal disease (ESRD) of undetermined etiology is highly prevalent and constitutes a significant clinical challenge, particularly in the context of kidney transplantation (KT). Despite the identification of numerous rare hereditary nephropathies over the last few decades, patients with undetermined ESRD are not being systematically investigated for rare genetic causes in clinical practice. To address this, we utilized mutation analysis in patients on the kidney transplant waitlist and scrutinized underlying renal diagnoses of 142 patients in a single center KT-waitlist. This cohort was stratified into 85 cases of determined and 57 cases of undetermined ESRD. The latter patients were analyzed by a renal gene panel for mutations in 209 genes associated with ESRD. The most likely genetic diagnoses in 12% of the tested individuals with undetermined ESRD were established. All of these patients showed mutations in genes encoding components of the glomerular filtration barrier. Taken together, hereditary nephropathies, including autosomal dominant polycystic kidney disease, were identified in 35 of the 142 patients of the waitlist cohort. By significantly increasing the proportion of hereditary diagnoses from 29 to 35 patients, the rate of undetermined ESRD significantly decreased from 57 to 51 patients. This study demonstrates the beneficial use of genetic diagnostics in significantly unraveling undetermined ESRD cases prior to KT. Thus, in the absence of renal histology or the presence of unspecific histological conditions, such as hypertensive nephrosclerosis, focal segmental glomerulosclerosis or thrombotic microangiopathy, genetic analysis may provide a robust and specific renal diagnosis and allow for optimizing pre- and post-KT management.

The tubular system of the kidneys is a complex series of morphological and functional units orchestrating the content of tubular fluid as it flows along the nephron and collecting ducts. Renal tubules maintain body water, regulate electrolytes and acid-base balance, reabsorb precious organic solutes and eliminate specific metabolites, toxins and drugs. In addition, decisive mechanisms to adjust blood pressure are governed by the renal tubules. Genetic as well as acquired disorders of these tubular functions may cause serious diseases that manifest both in childhood and adulthood. This review addresses a selection of tubulopathies and the underlying pathomechanisms, while highlighting the important differences in pediatric and adult nephrology care. These range from rare monogenic conditions such as nephrogenic diabetes insipidus, cystinosis and Bartter syndrome that present in childhood to the genetic and acquired tubular pathologies causing hypertension or nephrolithiasis that more prevalent in adults. Both pediatric and adult nephrologists must be aware of these conditions and the age-dependent manifestations that warrant close interaction between the two subspecialties.

Congenital anomalies of the kidney and urinary tract (CAKUT) represent the most common cause of chronic kidney failure in children. Despite growing knowledge of the genetic causes of CAKUT, the majority of cases remain etiologically unsolved. Genetic alterations in roundabout guidance receptor 1 (ROBO1) have been associated with neuronal and cardiac developmental defects in living individuals. Although Slit-Robo signaling is pivotal for kidney development, diagnostic ROBO1 variants have not been reported in viable CAKUT to date. By next-generation-sequencing methods, we identified six unrelated individuals and two non-viable fetus with biallelic truncating or combined missense and truncating variants in ROBO1. Kidney and genitourinary manifestation included unilateral or bilateral kidney agenesis, vesicoureteral junction obstruction, vesicoureteral reflux, posterior urethral valve, genital malformation, and increased kidney echogenicity. Further clinical characteristics were remarkably heterogeneous, including neurodevelopmental defects, intellectual impairment, cerebral malformations, eye anomalies, and cardiac defects. By in silicoanalysis, we determined the functional significance of identified missense variants and observed absence of kidney ROBO1 expression in both human and murine mutant tissues. While its expression in multiple tissues may explain heterogeneous organ involvement, variability of the kidney disease suggests gene dosage effects due to a combination of null alleles with mild hypomorphic alleles. Thus, comprehensive genetic analysis in CAKUT should include ROBO1 as a new cause of recessively inherited disease. Hence, in patients with already established ROBO1-associated cardiac or neuronal disorders, screening for kidney involvement is indicated.

The causal structure of the recent loop quantum gravity black hole collapse model [J. G. Kelly et al., Classical Quant. Grav. 38, 04LT01 (2021)] is analyzed. As the spacetime is only approximately diffeomorphism invariant up to powers of ℏ, it is not straightforwardly possible to find global conformally compactified coordinates or to construct the Penrose diagram. Therefore, radial ingoing and outgoing light rays are studied to extract the causal features and sketch a causal diagram. It was found that the eternal metric [J. G. Kelly et al., Phys. Rev. D 102, 106024 (2020)], which is the vacuum solution of the collapse model, has a causal horizon. However, in the collapsing case, light rays travel through matter to causally connect the regions inside and outside the horizon--the causal horizon is not present in the collapsing scenario. It is worked out that this is related to the shock wave and spacetime discontinuity, which allows matter traveling superluminally along a spacelike trajectory from the vacuum point of view, but remaining timelike from the matter perspective. The final causal diagram is a compact patch of a Reissner-Nordström causal diagram. Further, possibilities of a continuous matter collapse with only timelike evolution are studied. It is found that the time-reversed vacuum metric is also a solution of the dynamical equations, and a once continuously differentiable matching of the vacuum spacetime across the minimal radius is possible. This allows an everywhere continuous and timelike collapse process at the cost of an infinite extended causal diagram. This solution is part of an infinitely extended eternal black hole solution with a bounce, whose global extension is constructed. Due to the analysis of radial light rays, it is possible to sketch causal diagrams of these spacetimes. [ABSTRACT FROM AUTHOR]