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Advances in basic and clinical research have improved our understanding of the pathomechanisms underlying nephrotic syndrome caused by minimal change disease (MCD) and focal and segmental glomerulosclerosis (FSGS). These advances are reflected in the new 2021 KDIGO-Guidelines, which emphasize the clear distinction between primary, secondary and genetic causes. Proper classification is critical, as it directly affects the therapy of choice. While glucocorticoids still play a central in inducing remission in primary forms, calcineurin inhibitors, mycophenolate mofetil, cyclophosphamide and rituximab (off label) are viable adjuncts/alternatives to reduce or replace glucocorticoids in case of side effects or contraindications. Since SGLT-2-inhibitors have shown renoprotective effects in non-diabetic patients and may help to reduce proteinuria, they should be considered in all (adult) patients with chronic kidney disease, including MCD and FSGS patients. In the near future, Sparsentan, an endothelin type A and angiotensin receptor blocker may be added to the growing arsenal of proteinuria-reducing agents, with a phase 3 trail expected to be completed in late 2022. Finally, we recommend the inclusion of all MCD/FSGS patients in clinical registries (e. g. FOrMe Registry in Germany) to ensure adequate therapy and genetic testing if indicated. In addition, national registries are an invaluable source of clinical data that helps to refine our therapies towards individualized medicine.EINTEILUNG DER MINIMAL-CHANGE-DISEASE UND FOKALEN UND SEGMENTALEN GLOMERULOSKLEROSE: Das zunehmende Wissen über die verschiedenen Auslöser der MCD und FSGS spiegelt sich in den neuen KDIGO-Leitlinien wider, welche eine klare Einteilung der (MCD und) FSGS in primäre, sekundäre und genetische Ursachen vorsieht. Die korrekte Klassifizierung ist wichtig und hat eine direkte Auswirkung auf die Therapie. THERAPIE: Die Therapie besteht bei der primären MCD und FSGS weiterhin aus Steroiden oder – bei Nichtansprechen bzw. Kontraindikationen – aus Calcineurin-Inhibitoren, Mycophenolatmofetil oder Cyclophosphamid. Auch Rituximab findet in refraktären Fällen als „Off-Label“ Verwendung. Bei sekundären Formen wird die Grunderkrankung behandelt. AUSBLICK: Mit Sparsentan befindet sich ein neuer Wirkstoff in der klinischen Testung. Bereits jetzt können SGLT-2-Inhibitoren verschrieben werden, um einen eGFR-Verlust zu minimieren. Die zeitnahe (kinder-)nephrologische Anbindung von Patienten mit MCD/FSGS ist für das Outcome von großer Bedeutung. Durch das nationale FOrMe-Register stehen regionale Experten für die Behandlung der MCD und FSGS zur Verfügung.

Geriatric syndromes (GS) do not fit into discrete disease categories and are often underdiagnosed in hospitalized older adults. Geriatric resources (GR) are also not routinely collected in clinical settings, although this may potentiate the beneficial effects of clinical decisions. The prognostic relevance of GS and GR has never been systematically evaluated through clinical tools developed for clinical decision purposes. To ascertain the impact of common GS and GR on patients’ prognosis as assessed by means of the comprehensive geriatric assessment (CGA)-based Multidimensional Prognostic Index (MPI). One hundred and thirty-five hospitalized patients aged 70 years and older underwent a CGA evaluation with calculation of the MPI on admission and discharge. Accordingly, patients were subdivided in low (MPI-1, score 0–0.33), moderate (MPI-2, score 0.34–0.66), and severe (MPI-3, score 0.67–1)-risk of mortality at 1 month and 1 year. Nine GR and 17 GS were identified and collected accordingly. A lower number of GS and a higher number of GR were shown to be highly significantly correlated with a lower MPI, as well as years of education, grade of care, and number of medications independent of age, sex and number of GS or GR. Underweight and obesity according to the BMI were significantly correlated to higher number of GS. Patients with more GR had a significantly higher chance of being discharged home. The MPI evaluation together with GS and GR in acute care for older patients should be encouraged to improve clinical decision-making.

Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular scarring. Currently, no targeted treatment of FSGS is available. This lack of therapeutic strategies is explained by a limited understanding of the defects in podocyte cell biology leading to FSGS. To date, most studies in the field have focused on protein-coding genes and their gene products. However, more than 80% of all transcripts produced by mammalian cells are actually non-coding. Here, long non-coding RNAs (lncRNAs) are a relatively novel class of transcripts and have not been systematically studied in FSGS to date. The appropriate tools to facilitate lncRNA research for the renal scientific community are urgently required due to a row of challenges compared to classical analysis pipelines optimized for coding RNA expression analysis. Here, we present the bioinformatic pipeline CALINCA as a solution for this problem. CALINCA automatically analyzes datasets from murine FSGS models and quantifies both annotated and de novo assembled lncRNAs. In addition, the tool provides in-depth information on podocyte specificity of these lncRNAs, as well as evolutionary conservation and expression in human datasets making this pipeline a crucial basis to lncRNA studies in FSGS.

OBJECTIVES The Multidimensional Prognostic Index (MPI) is a prognostic tool-amongst others-validated for mortality, length of hospital stay (LHS) and rehospitalisation risk assessment. Like the Comprehensive Geriatric Assessment (CGA), the MPI is usually obtained at hospital admission and discharge, not during the hospital stay. The aim of the present study was to address the role of an additional CGA-based MPI measurement during hospitalisation as an indicator of "real-time" in-hospital changes. STUDY DESIGN AND MAIN OUTCOME MEASURES Two-hundred consecutive multimorbid patients (128 M, 72 F, median age 75 (78-82)) admitted to an internal medicine ward of a German metropolitan university hospital prospectively underwent a CGA and a prognosis calculation using the MPI on admission and discharge. Seven to 10 days later, an intermediate assessment (IA) was performed for patients needing a longer stay. RESULTS The median LHS was 10 (6-19) days. As expected, patients who received an IA had poorer prognosis as measured by higher MPI values (P = .037) and a worse functional status at admission than patients who had a shorter stay (P = .025). In case of prolonged hospitalisation, significant changes in the MPI were detected between admission and IA, both in terms of improvement and deterioration (P

Idiopathic nephrotic syndrome is the most frequent glomerular disease in children in most parts of the world. Children with steroid-sensitive nephrotic syndrome (SSNS) generally have a good prognosis regarding the maintenance of normal kidney function even in the case of frequent relapses. The course of SSNS is often complicated by a high rate of relapses and the associated side effects of repeated glucocorticoid (steroid) therapy. The following recommendations for the treatment of SSNS are based on the comprehensive consideration of published evidence by a working group of the German Society for Pediatric Nephrology (GPN) based on the systematic Cochrane reviews on SSNS and the guidelines of the KDIGO working group (Kidney Disease - Improving Global Outcomes). Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05135-3.

The multidimensional prognostic index (MPI) is a validated, sensitive, and specific prognosis estimation tool based on a comprehensive geriatric assessment (CGA). The MPI accurately predicts mortality after 1 month and 1 year in older, multimorbid patients with acute disease or relapse of chronic conditions. To evaluate whether the MPI predicts indicators of healthcare resources, i.e. grade of care (GC), length of hospital stay (LHS) and destination after hospital discharge in older patients in an acute medical setting. In this study 135 hospitalized patients aged 70 years and older underwent a CGA evaluation to calculate the MPI on admission and discharge. Accordingly, patients were subdivided in low (MPI‑1, score 0–0.33), moderate (MPI-2, score 0.34–0.66) and high (MPI-3, score 0.67–1) risk of mortality. The GC, LHS and the discharge allocation were also recorded. The MPI score was significantly related to LHS (p = 0.011) and to GC (p

The misuse of insulin for performance enhancement in sport or as toxic agent has frequently been reported in the past. In contrast to synthetic insulin analogues, the administration of recombinant human insulin is hardly recognized by mass spectrometry. The present study was designed to uncover the misuse of recombinant human insulin for doping control purposes as well as for forensic applications. It is hypothesized that an altered metabolite profile of circulating insulin prevails after subcutaneous administration due to exposure of insulin to epidermal proteases. In vitro experiments with skin tissue lysates (S9 fraction and microsomes), different biological fluids (urine, serum, plasma) and recombinant human insulin were performed and the deriving metabolites were characterized by liquid chromatography coupled to high resolution mass spectrometry (HRMS). Afterwards, authentic blood samples of patients suffering from diabetes mellitus and a control group of healthy humans were analysed. Therefore, a method using protein precipitation, ultrafiltration and antibody-coated magnetic beads for purification with subsequent separation by nano-scale liquid chromatography coupled a Q Exactive mass spectrometer was applied. Several metabolites of insulin with C-terminally truncated sequences of the B-chain (and A-chain in minor extent) were identified within this study. Here, the DesB30 human insulin represents the major metabolite in all experiments. This metabolite is frequently found in urine samples due to degradation processes and, thus, disqualifies this matrix for the intended purposes. In contrast, blood samples do commonly not contain DesB30 insulin, which was corroborated by data obtained from the control group. In post-administration blood samples, minute but distinct amounts (approx. 50 pg mL(-1)) of DesB30 insulin were found and suggest the use of this analyte as potential marker for subcutaneous human insulin administration, supporting the attempts to uncover illicit recombinant human insulin administrations.

Bioactive peptides with an approximate molecular mass of 2-12 kDa are of considerable relevance in sports drug testing. Such peptides have been used to manipulate several potential performance-enhancing processes in the athlete's body and include for example growth hormone releasing hormones (sermorelin, CJC-1293, CJC-1295, tesamorelin), synthetic/animal insulins (lispro, aspart, glulisine, glargine, detemir, degludec, bovine and porcine insulin), synthetic ACTH (synacthen), synthetic IGF-I (longR(3) -IGF-I) and mechano growth factors (human MGF, modified human MGF, 'full-length' MGF). A combined initial test method using one analytical procedure is a desirable tool in doping controls and related disciplines as requests for higher sample throughput with utmost comprehensiveness preferably at reduced costs are constantly issued. An approach modified from an earlier assay proved fit-for-purpose employing pre-concentration of all target analytes by means of ultrafiltration, immunoaffinity purification with coated paramagnetic beads, nano-ultra high performance liquid chromatography (UHPLC) separation, and subsequent detection by means of high resolution tandem mass spectrometry. The method was shown to be applicable to blood and urine samples, which represent the most common doping control specimens. The method was validated considering the parameters specificity, recovery (11-69%), linearity, imprecision (25%), limit of detection (5-100 pg in urine, 0.1-2 ng in plasma), and ion suppression. The analysis of administration study samples for insulin degludec, detemir, aspart, and synacthen provided the essential data for the proof-of-principle of the method.