Renal biopsy is the gold standard for diagnosis of membranous nephropathy. Circulating PLA
R1 antibody found in 75% of patients with membranous nephropathy is very specific for the diagnosis of this ...disease. Therefore, the question arises whether PLA
R1-antibody-positive patients still need a diagnostic renal biopsy. In this study we investigated whether additional relevant information is obtained by performing renal biopsy in nephrotic patients, who are PLA
R1-antibody positive. A detailed analysis of renal biopsies, including immunohistochemistry and electron microscopy, was performed in 263 patients with biopsy-proven membranous nephropathy, of whom 194 patients were PLA
R1-antibody positive, to detect diagnostic features additional to membranous nephropathy. Twelve (6%) of the 194 PLA
R1-antibody-positive patients had a second relevant diagnosis in addition to membranous nephropathy: five (3%) patients had interstitial nephritis, in five (3%) other patients a diabetic nephropathy was diagnosed and two (1%) patients had IgA nephropathy. Patients with a second diagnosis in addition to membranous nephropathy had a significantly higher serum creatinine (p < 0.01) and lower eGFR (p = 0.04) compared to patients in whom only the diagnosis of membranous nephropathy was made. In 7 (10%) of 69 PLA
R1-antibody-negative patients, renal biopsies showed an additional diagnosis to membranous nephropathy: one (1%) case of IgA nephropathy, cholesterol emboli, IgG4-related disease, necrotising glomerulonephritis, thrombotic microangiopathy, interstitial nephritis and diabetic nephropathy each. The advantage of detecting an additional diagnosis to membranous nephropathy in 6% of PLA
R1-antibody-positive patients by renal biopsy has to be balanced to the potential risks and costs of the biopsy procedure. Renal biopsy is particularly relevant in patients presenting with impaired renal function and abnormalities in urinalysis going beyond proteinuria. Immunohistochemical staining for PLA
R1 was the only histomorphologic analysis allowing a reliable differentiation of PLA
R1-antibody-positive from PLA
R1-antibody-negative membranous nephropathy.
Circulating autoantibodies against the M-type phospholipase A
receptor 1 (PLA
R1) are important biomarkers in membranous nephropathy (MN), supporting the diagnosis and the clinical monitoring of ...patients. Standardized recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme-linked immunosorbent assay (ELISA) are widely established for the detection of anti-PLA
R1 autoantibodies (PLA
R1-ab). The RC-IFA provides higher sensitivity than the ELISA, but lacks exact graduated quantification of antibody levels. In this study, we evaluated the diagnostic performance of a novel PLA
R1-ab immunoassay based on chemiluminescence (ChLIA) by comparing it to RC-IFA and ELISA in samples from patients with MN with different diagnostic scenarios.
Serum samples from patients with biopsy-proven MN and disease controls were analyzed for PLA
R1-ab by ChLIA, ELISA, and RC-IFA.
The ChLIA demonstrated almost perfect agreement with RC-IFA for the identification of patients with PLA
R1-associated MN, while additionally allowing fine-graduated quantification of PLA
R1-ab levels. In patients with a relapse of MN, the ChLIA allowed an earlier detection of PLA
R1-ab recurrence by at least 3 months in 63% of cases compared with the ELISA.
The PLA
R1-ab ChLIA had the same excellent diagnostic performance as the RC-IFA and outperformed the ELISA in the diagnosis of MN and the early identification of relapses. It thus presents a favorable tool for accurate PLA
R1-ab assessment in routine diagnostic settings, while enabling fast processing and fully automated random-access implementation.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections represent a particular risk for several groups of patients with nephrological diseases. Patients on dialysis represent ...a particularly vulnerable group during the SARS-CoV‑2 pandemic. Initial data from international registries show a much higher mortality of dialysis patients with SARS-CoV‑2 infections. Because of the substantial differences between the healthcare systems, (state) preventive measures and treatment possibilities etc., in the different countries worldwide, local and national registry data cannot be easily transferred. In order to gain a reliable overview of the prevalence and mortality of dialysis patients with SARS-CoV‑2 infection in Germany, the German Society of Nephrology implemented a national registry for dialysis patients with a SARS-CoV‑2 infection. Within this framework a standardized collection of these data is carried out on a weekly basis, which should enable a real-time overview of the case numbers and perhaps the acquisition of new scientific knowledge. Particularly in the current phase of the pandemic (autumn 2020), which is accompanied by a multiplication of the numbers of daily new-onset cases within only a few weeks, such data are highly relevant for the estimation and adjustment of the personnel, structural and organizational needs as well as the capacities for the treatment of patients.
Zusammenfassung
Eine SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-Infektion stellt für mehrere nephrologische Patientengruppen ein besonderes Risiko dar. Im Rahmen einer Pandemie ...sind dialysepflichtige Patienten ein besonders vulnerables Patientenkollektiv. Erste internationale Daten weisen auf eine deutlich erhöhte Mortalität von dialysepflichtigen Patienten im Rahmen einer SARS-CoV-2-Infektion hin. Aufgrund der erheblichen Unterschiede zwischen den Gesundheitssystemen, (staatlichen) Präventionsmaßnahmen, Therapiemöglichkeiten etc. in den verschiedenen Ländern weltweit sind lokale oder nationale Registerdaten im internationalen Kontext nicht ohne Weiteres übertragbar. Um zuverlässige Daten zur Prävalenz und Mortalität der SARS-CoV-2-Infektion bei dialysepflichtigen Patienten in Deutschland zu erheben, wurde unter dem Schirm der Deutschen Gesellschaft für Nephrologie ein Register für Dialysepatienten mit einer SARS-CoV-2-Infektion entwickelt. In diesem Rahmen erfolgt eine wöchentliche standardisierte Datenerhebung, die einen zeitnahen Überblick über die Fallzahlen und ggf. die Gewinnung neuer wissenschaftlicher Erkenntnisse ermöglichen soll. Insbesondere in der aktuellen Phase der Pandemie (Herbst 2020), die mit einer Vervielfachung der Anzahl der täglich Neuerkrankten innerhalb weniger Wochen einhergeht, sind solche Daten für eine Einschätzung und Anpassung des personellen, strukturellen und organisatorischen Bedarfs sowie der Kapazitäten für die Behandlung dieser Patienten hoch relevant.
Glomerulonephritis encompasses a group of diseases that are characterized by inflammatory glomerular processes and clinically usually present with a nephritic and / or a nephrotic syndrome, as well ...as a deterioration of the renal function. Often, the diseases are accompanied by arterial hypertension and severe edema. In many cases however, the clinical symptoms are very mild or missing in the early phase of disease and therefore lead to a delayed diagnosis only after an impairment of renal function has developed. Urinalysis shows abnormalities in the very early phases of glomerulonephritis and should be performed in all patients, as soon as any evidence of renal involvement is present. Glomerulonephritis may occur primarily in the glomeruli, or present as renal involvement in the context of systemic diseases, most often vasculitis. In some cases, a symptomatic therapy is sufficient, while in other patients, a glomerulonephritis may represent as a medical emergency, which should be immediately and aggressively treated in order to prevent loss of renal function. Here we summarize the most important entities of glomerulonephritis, focusing on the pathogenesis, diagnostic tools and treatment options. The primary goal is the early diagnosis and a targeted, effective treatment of these patients.
Eine SARS-CoV-2(„severe acute respiratory syndrome coronavirus 2“)-Infektion stellt für mehrere nephrologische Patientengruppen ein besonderes Risiko dar. Im Rahmen einer Pandemie sind ...dialysepflichtige Patienten ein besonders vulnerables Patientenkollektiv. Erste internationale Daten weisen auf eine deutlich erhöhte Mortalität von dialysepflichtigen Patienten im Rahmen einer SARS-CoV-2-Infektion hin. Aufgrund der erheblichen Unterschiede zwischen den Gesundheitssystemen, (staatlichen) Präventionsmaßnahmen, Therapiemöglichkeiten etc. in den verschiedenen Ländern weltweit sind lokale oder nationale Registerdaten im internationalen Kontext nicht ohne Weiteres übertragbar. Um zuverlässige Daten zur Prävalenz und Mortalität der SARS-CoV-2-Infektion bei dialysepflichtigen Patienten in Deutschland zu erheben, wurde unter dem Schirm der Deutschen Gesellschaft für Nephrologie ein Register für Dialysepatienten mit einer SARS-CoV-2-Infektion entwickelt. In diesem Rahmen erfolgt eine wöchentliche standardisierte Datenerhebung, die einen zeitnahen Überblick über die Fallzahlen und ggf. die Gewinnung neuer wissenschaftlicher Erkenntnisse ermöglichen soll. Insbesondere in der aktuellen Phase der Pandemie (Herbst 2020), die mit einer Vervielfachung der Anzahl der täglich Neuerkrankten innerhalb weniger Wochen einhergeht, sind solche Daten für eine Einschätzung und Anpassung des personellen, strukturellen und organisatorischen Bedarfs sowie der Kapazitäten für die Behandlung dieser Patienten hoch relevant.
Patients with primary membranous nephropathy (MN) who experience spontaneous remission of proteinuria generally have an excellent outcome without need of immunosuppressive therapy. It is, however, ...unclear whether non-nephrotic proteinuria at the time of diagnosis is also associated with good prognosis since a reasonable number of these patients develop nephrotic syndrome despite blockade of the renin-angiotensin system. No clinical or laboratory parameters are available, which allow the assessment of risk for development of nephrotic proteinuria. Phospholipase A.sub.2 Receptor antibodies (PLA.sub.2 R-Ab) play a prominent role in the pathogenesis of primary MN and are associated with persistence of nephrotic proteinuria. In this study we analysed whether PLA.sub.2 R-Ab levels might predict development of nephrotic syndrome and the clinical outcome in 33 patients with biopsy-proven primary MN and non-nephrotic proteinuria under treatment with blockers of the renin-angiotensin system. PLA.sub.2 R-Ab levels, proteinuria and serum creatinine were measured every three months. Nephrotic-range proteinuria developed in 18 (55%) patients. At study start (1.2#177;1.5 months after renal biopsy and time of diagnosis), 16 (48%) patients were positive for PLA.sub.2 R-Ab. A multivariate analysis showed that PLA.sub.2 R-Ab levels were associated with an increased risk for development of nephrotic proteinuria (HR = 3.66; 95%CI: 1.39-9.64; p = 0.009). Immunosuppressive therapy was initiated more frequently in PLA.sub.2 R-Ab positive patients (13 of 16 patients, 81%) compared to PLA.sub.2 R-Ab negative patients (2 of 17 patients, 12%). PLA.sub.2 R-Ab levels are associated with higher risk for development of nephrotic-range proteinuria in this cohort of non-nephrotic patients at the time of diagnosis and should be closely monitored in the clinical management.
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