Hepatitis-B- und -C-assoziierte Glomerulonephritiden

Zusammenfassung: Virale Hepatitiden sind häufig mit extrahepatischen Manifestationen assoziiert. Bei der HepatitisB ist die membranöse Glomerulonephritis (GN) die häufigste histologische Diagnose. Im Rahmen der HepatitisC wird vorwiegend eine membranoproliferative GN mit oder ohne gemischte Kryoglobulinämie beobachtet. Eine zentrale pathogenetische Rolle spielen Immunkomplexe (virale Antigene, antivirale Antikörper, bei Kryoglobulinämie auch Rheumafaktoren). Diese Komplexe werden in der Niere abgelagert und aktivieren Komplement, was schließlich zum Nierenschaden führt. Therapeutisch zentral ist die antivirale Therapie mit dem Ziel der Antigenelimination. Im Falle der HepatitisB kann eine Therapie mit IFNα durchgeführt werden, alternativ mit Lamivudin. Eine immunsuppressive Therapie steht eher im Hintergrund. Bei der HepatitisC ist die Standardtherapie IFNα in Kombination mit Ribavirin. Bei einer zusätzlichen Kryoglobulinämie besteht die Alternative einer Therapie mit Rituximab, bei schwerem Verlauf mit Plasmapherese, Steroiden und Cyclophosphamid. Bei vollständiger Elimination der Virusreplikation ist die Prognose dieser sekundären GN günsti

C4d staining of renal allograft biopsies: a comparative analysis of different staining techniques

Background. Detection of C4d along peritubular capillaries (PTC) in renal allograft biopsies is an independent prognostic marker of poor long-term graft survival. It is typically associated with circulating donor-specific antibodies. Since only little information is available on the best technique to stain C4d, we compared the two methods most often used for detecting C4d in renal allograft specimens. Methods. We investigated the expression of C4d along PTC in 64 renal allograft biopsies using a monoclonal antibody (Quidel) and immunofluorescence for frozen (F-IF) and a polyclonal antibody (Biomedica) and immunohistochemistry for formalin-fixed and paraffin-embedded (P-IHC) tissue samples. We compared the staining extent (diffuse, focal, minimal, no staining) in frozen and paraffin sections and evaluated the intra- and inter-observer concordance rates using kappa statistics. In addition, we determined the inter-observer concordance in 240 paraffin-embedded biopsies of a multi-centre study. Results. The inter- and intra-investigator concordance rate (κ = 0.9) of analysing the C4d expression by F-IF was excellent. In contrast, the detection of C4d by P-IHC demonstrated a substantially lower prevalence and extent of C4d expression with a lower intra- and inter-observer concordance rate (κ = 0.3). Only 69% of diffuse and 13% of focal C4d-expressing cases were in line classified by F-IF and P-IHC. On average, the estimated area of C4d-positive PTC in the diffuse group was 36% lower by P-IHC than by F-IF. The inter-observer concordance rate in paraffin of the 64 renal biopsies and the multi-centre study was good, but not perfect (κ = 0.57 or 0.67). Conclusions. C4d staining determined on frozen tissue samples using F-IF with a monoclonal antibody appears to be better suited for diagnostic as well as research purposes. Future studies should correlate C4d staining patterns with circulating donor-specific antibodie

Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer

Objective: Prospective study to evaluate the feasibility of a preoperative bronchoscopic radioisotope application, followed by conventional sentinel lymph-node (SLN) identification and to investigate the occurrence and distribution of micrometastases in relation to SLN activity. Methods: Twenty patients with a mean age of 63 years and proven clinical stage T1-3 N0-1 non-small-cell lung cancer (NSCLC) were included. A dosage of 80 MBq radiolabeled technetium-99m nanocolloid was endoscopically administrated on intubated patients in the operation theatre. At thoracotomy, scintigraphic readings of both the primary tumor and hilar and mediastinal lymph-node stations were obtained with a hand-held gamma-counter. Patients underwent lung resection and mediastinal lymphadenectomy. Radiolabeled nodes were also examined separately on back-table. SLNs were defined as the hottest nodes or nodes with at least one-tenth of the radioactivity of the hottest nodes. SLNs pathologic assessment included standard examination using hematoxylin and eosin staining on step sections and immunohistochemistry (ICH) for cytokeratins. Results: Identification of SLNs was possible in 19/20 (95%) patients after bronchoscopic radioisotope application. In 7/19 (37%) patients, a unique SLN was identified, whereas in 12/19 (63%) patients, nodes from two different stations could be classified as SLNs. Metastatic nodal disease was found in 9/19 (47%) patients. ICH revealed micrometastases in 2/12 (17%) patients, initially classified nodal negative. Pathologic negative SLNs were a predictor for absence of metastatic nodal disease after mediastinal lymphadenectomy. No complication related to the procedure was observed. Conclusion: Our preliminary results suggest that preoperative bronchoscopic radioisotope injection for SLN identification is a safe and simple method, improving accuracy of SLN detection in comparison to intraoperative technique. The absence of metastases in the SLNs seems to predict a negative nodal status accuratel

Normal gas exchange after 30-h ischemia and treatment with phosphodiesterase inhibitor PDI747

Objective: Phosphodiesterases (PDEs) negatively regulate the concentrations of cAMP and/or cGMP, which act as downstream second messengers to the prostaglandins. PDE type-4 (PDE4) is selective for cAMP and is found in high concentrations in endothelial, epithelial, and different blood cells. The aim of this study was to evaluate if PDI747, a novel selective inhibitor of PDE4, can restore pretransplant cAMP levels and thereby posttransplant organ function after prolonged cold ischemia. Methods: Left lung transplantation was performed in pigs (25-31 kg). Donor lungs were flushed with low potassium dextran glucose (LPDG) solution only (control, n=5)or, in addition with 1 μmol of PDI747 (PDI747, n=5) and stored for 30 h at 1 °C. PDI747 animals further received a bolus of PDI747 (0.3 mg/kg) 15 min prior to reperfusion and a continuous infusion (0.3 mg/kg per hour) during the 5 h after reperfusion. After occlusion of the right pulmonary arteries and the right main bronchus, hemodynamic and gas exchange parameters and extravascular lung water (EVLW) levels of the transplanted lung were assessed. Results: Two control animals died of severe lung edema leading to heart failure (control, n=3). One animal in the treatment group was excluded due to a patent ductus arteriosus (PDI747, n=4). Gas exchange at the end of the experiment was restored to normal levels in the PDI747 group (Pa, o2 47.6±11.2 kPa, Pa,co2 6.4±1.8 kPa) but not in the control group (Pa, o2 7.7±2.9 kPa, Pa, co2 11.9±3.0 kPa, PPao2<0.0001, PPa, co2=0.06). Extravascular lung water (EVLW) was normal in the PDI747 group (8.5±1.1 ml/kg) and clearly elevated in the control group (16.2±5.6 ml/kg, P=0.007). Airway pressure in the PDI747 group was significantly lower than in the control group (7.8±0.5 cm H2O vs. 11.3±0.6 cm H2O, respectively, P<0.0001). The free radical mediated tissue injury measured by lipid peroxidation (TBARS) was significantly reduced (P=0.001) in the PDI747 group. Conclusions: With the inhibition of PDE4 with PDI747 we achieved normal gas exchange, no posttransplant lung edema, normal airway pressures, and a reduced free radical injury after 30 h of cold ischemi

Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome

Background Pulmonary-renal syndrome associated with anti-glomerular basement membrane (GBM) antibodies, also known as Goodpasture's syndrome, is a rare but acute and life-threatening condition. One third of patients presenting as anti-GBM antibody positive pulmonary-renal syndrome or rapidly progressive glomerulonephritis are also tested positive for anti-neutrophil cytoplasmic antibodies (ANCA). Whilst anti-GBM disease is considered a non-relapsing condition, the long-term course of double-positive patients is less predictable. Case Presentation We report a patient with such dual positivity, who presented with pulmonary hemorrhage, crescentic glomerulonephritis and membranous nephropathy. Plasmapheresis in combination with immunosuppresive therapy led to a rapid remission but the disease relapsed after two years. The serum of the patient was tested positive for antibodies to human lysosomal membrane protein 2 (hLAMP2), a novel autoantigen in patients with active small-vessel vasculitis (SVV). The anti-hLAMP2 antibody levels correlated positively with clinical disease activity in this patient. Conclusion We hypothesize that this antibody may indicate a clinical course similar to ANCA-associated vasculitis in double-positive patients. However, this needs to be confirmed on comprehensive patient cohorts

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk

Akute/subakute Niereninsuffizienz: Leitsymptome: Akuter Anstieg des Serumkreatinins und/oder Oligurie/Anurie

Eine Niereninsuffizienz kann akut auftreten, sich aber auch über Wochen und Monate entwickeln. Die Unterscheidung in eine akute, subakute oder chronische Form ist nicht immer eindeutig.Mischformen wie z.B. eine akute Exazerbation einer chronischen Niereninsuffizienz sind nicht selten. Wichtig ist es, eine akute Niereninsuffizienz zu erkennen und zu wissen, welche diagnostischen Massnahmen ergriffen werden müssen. Dazu wird ein Algorithmus vorgeschlagen. Eine akut auftretendeNiereninsuffizienz kann von Symptomen wie Flankenschmerzen oder einem Hautausschlag begleitet sein, die auf die Ursache hinweisen, oder von Symptomen wie Ödeme und Hypertonie, die eine Folge der Niereninsuffizienz sind. Bei einem subakuten Verlauf können Symptome auch völlig fehlen, und die Diagnose wird zufällig gestellt

Proliferation capacity of the renal proximal tubule involves the bulk of differentiated epithelial cells

We investigated the proliferative capacity of renal proximal tubular cells in healthy rats. Previously, we observed that tubular cells originate from differentiated cells. We now found 1) by application of bromo-deoxyuridine (BrdU) for 14 days and costaining for BrdU, and the G(1)-phase marker cyclin D1 that the bulk of cells in the S3 segment of juvenile rats were involved in proliferation; 2) that although the proliferation rate was about 10-fold higher in juvenile rats compared with adult rats, roughly 40% of S3 cells were in G(1) in both groups; 3) that after a strong mitotic stimulus (lead acetate), proliferation was similar in juveniles and adults; 4) that there was a high incidence of cyclin D1-positive cells also in the healthy human kidney; and 5) by labeling dividing cells with BrdU for 2 days before the application of lead acetate and subsequent costaining for BrdU and cell cycle markers, that, although a strong mitotic stimulus does not abolish the period of quiescence following division, it shortens it markedly. Thus the capacity of the proximal tubule to rapidly recruit cells into division relies on a large reserve pool of cells in G(1) and on the shortening of the obligatory period of quiescence that follows division

Verkalkt

Eine 73-jährige Patientin wurde zur Abklärung einer akuten Niereninsuffizienz zugewiesen. Die Nierenbiopsie zeigte eine Phosphatnephropathie. Wir identifizierten Colophos®, ein phosphathaltiges Abführmittel, das die Patientin einen Tag vor Diagnose der akuten Niereninsuffizienz erhalten hatte, als Verursacher. In der Folge verschlechterte sich die Nierenfunktion weiter, besserte danach jedoch wieder. Die meisten Fälle der akuten Phosphatnephropathie sind mit der Einnahme von phosphathaltigen Abführmitteln assoziiert. In einer Minderheit der Fälle kann ein irreversibler tubulo-interstitieller Schaden daraus resultieren, der eine terminale Niereninsuffizienz zur Folge hat. = A 73-year-old woman was referred due to an acute and progressive worsening of a previously mildly impaired kidney function of unknown origin. The kidney biopsy showed a phosphate nephropathy. We identified Colophos®, a phosphate-containing purgative as the causing agent, which the patient had received for bowel cleansing for a colonoscopy one day before the detection of the acute kidney failure. During the following months the kidney function initially declined further and then improved. Most cases of phosphate nephropathy are associated with the ingestion of phosphate-containing purgatives. Persons at risk are women, elderly persons, patients with impaired kidney function, hypertension, and dehydration. The consequence is sometimes an irreversible tubulointerstitial injury that can lead to end-stage renal disease in a minority of the cases