Summary
Some Serratia entomophila isolates have been successfully exploited in biopesticides due to their ability to cause amber disease in larvae of the Aotearoa (New Zealand) endemic pasture pest, ...Costelytra giveni. Anti‐feeding prophage and ABC toxin complex virulence determinants are encoded by a 153‐kb single‐copy conjugative plasmid (pADAP; amber disease‐associated plasmid). Despite growing understanding of the S. entomophila pADAP model plasmid, little is known about the wider plasmid family. Here, we sequence and analyse mega‐plasmids from 50 Serratia isolates that induce variable disease phenotypes in the C. giveni insect host. Mega‐plasmids are highly conserved within S. entomophila, but show considerable divergence in Serratia proteamaculans with other variants in S. liquefaciens and S. marcescens, likely reflecting niche adaption. In this study to reconstruct ancestral relationships for a complex mega‐plasmid system, strong co‐evolution between Serratia species and their plasmids were found. We identify 12 distinct mega‐plasmid genotypes, all sharing a conserved gene backbone, but encoding highly variable accessory regions including virulence factors, secondary metabolite biosynthesis, Nitrogen fixation genes and toxin‐antitoxin systems. We show that the variable pathogenicity of Serratia isolates is largely caused by presence/absence of virulence clusters on the mega‐plasmids, but notably, is augmented by external chromosomally encoded factors.
We assessed the prevalence, awareness, treatment and control of hypertension in patients with moderate chronic kidney disease (CKD) under nephrological care in Germany. In the German Chronic Kidney ...Disease (GCKD) study, 5217 patients under nephrology specialist care were enrolled from 2010 to 2012 in a prospective observational cohort study. Inclusion criteria were an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min/1.73 m2. Office blood pressure was measured by trained study personnel in a standardized way and hypertension awareness and medication were assessed during standardized interviews. Blood pressure was considered as controlled if systolic < 140 and diastolic < 90 mmHg. In 5183 patients in whom measurements were available, mean blood pressure was 139.5 ± 20.4 / 79.3 ± 11.8 mmHg; 4985 (96.2%) of the patients were hypertensive. Awareness and treatment rates were > 90%. However, only 2456 (49.3%) of the hypertensive patients had controlled blood pressure. About half (51.0%) of the patients with uncontrolled blood pressure met criteria for resistant hypertension. Factors associated with better odds for controlled blood pressure in multivariate analyses included younger age, female sex, higher income, low or absent proteinuria, and use of certain classes of antihypertensive medication. We conclude that blood pressure control of CKD patients remains challenging even in the setting of nephrology specialist care, despite high rates of awareness and medication use.
Zu ihrer labormedizinischen Bestimmung am weitesten verbreitet sind die Modification of Diet in Renal Disease (MDRD) sowie die Chronic Disease Epidemiology Collaboration (CKD-EPI)-Formel. Die ...Quantifizierung der Albuminurie erfolgt im Spontanurin und wird als Albumin-Kreatinin-Ratio (ACR) in mg Albumin/g Kreatinin angegeben. Diese ist häufig dafür verantwortlich, dass eine renoprotektive Therapie mit Inhibitoren des Renin-Angiotensin-Aldosteron-Systems (RAAS) beendet wird. Hierzu wurden in den letzten Jahren neue, gut verträgliche orale Kaliumbinder (z. B. Patiromer und Natrium-Zirconium-Cyclosilicat) zur Dauertherapie zugelassen. 10% der erwachsenen Bevölkerung in Deutschland leidet an einer chronischen Nierenerkrankung Blutdrucksenkung Bis 2020 wurde bei CKD ohne Albuminurie ein Zielblutdruck von < 140/90 mmHg und ab einer Albuminurie von > 30 mg/d eine Blutdrucksenkung von < 130/80 mmHg empfohlen. Lipidmanagement Die ESC-Leitlinien stufen Patienten mit einer GFR von 30-70 ml/min (CKD Stadium 3) als Hochrisiko-Patienten, und mit einer GFR von 15-30 ml/min (CKD Stadium 4) als Höchstrisiko-Patienten ein und empfehlen die Senkung des LDL-Cholesterins auf Werte < 70 mg/dl bzw. Blockade des Renin-Angiotension-Aldosteron-Systems (RAAS): Die RAAS-Hemmung durch ACE-Hemmer oder Angiotensin-II-Rezeptorblocker (ARB) ist unverändert eine der wichtigsten Maßnahmen zur Reduktion der CKD-Progression. Thomas Sitter LMU Klinikum Medizinische Klinik und Poliklinik IV Nehrologisches Zentrum Campus Innenstadt Ziemssenstr. 5 D-80336 München thomas.sitter@med.uni-muenchen.de Fazit für die Praxis Die Einteilung der CKD in fünf Stadien beruht auf der von der Labormedizin kalkulierten eGFR und der im Spontanurin gemessenen Albumin/Kreatinin Ratio.
Die Bestimmung des Kreatinins im Serum ist die häufigste Methode zur Evaluation der Nierenfunktion im klinischen Alltag. See PDF. Kreatinin-Blinder-Bereich Einschätzung der Nierenfunktion mit ...Kalkulationsalgorithmen Da eine zuverlässige Einschätzung der Nierenfunktionen nur mit Blick auf das Serumkreatinin oft nicht möglich ist, wird mittlerweile von vielen Fachgesellschaften darauf hingewiesen, Kreatinin nicht als einzigen Parameter heranzuziehen 1. Stadieneinteilung der chronischen Nierenerkrankung (CKD) abhängig von der eGFR Mod. nach 6 Stadium eGFR (ml/min) Beschreibung G1 ≥ 90 GFR normal oder hoch G2 60-89 GFR leicht verringert (relativ im Vergleich zu jungen Erwachsenen) G3a 45-59 GFR leicht bis moderat verringert G3b 30-44 GFR moderat bis stark verringert G4 15-29 GFR stark verringert G5 < 15 Nierenversagen MDRD-Formel Die MDRD-Formel stammt aus der Modification of Diet in Renal Disease Study 3.
Background. Chronic inflammatory disorders or infections represent a major cause of hyporesponsiveness to recombinant human erythropoietin (rHuEpo). To test the hypothesis that dialysate‐related ...cytokine induction alters the response to rHuEpo, we conducted a prospective study with matched pairs of chronic haemodialysis patients. We compared the effect of two dialysis fluids, differing in their microbiological quality, on the rHuEpo therapy. Methods. Thirty male patients with end‐stage renal disease maintained on regular haemodialysis were assigned either to a group treated with conventional (potentially microbiologically contaminated) dialysate (group I) or to a group treated with online‐produced ultrapure dialysate (group II). Randomization was stratified according to the maintenance dose of rHuEpo necessary to maintain a target haemoglobin level of 10–10.5 g/dl. Patients were followed for 12 months. Kt/V was calculated by the formula of Daugirdas. Haemoglobin levels were measured weekly and serum ferritin concentrations were determined at 6‐week intervals. C‐reactive protein (CRP) and interleukin‐6 (IL‐6) was measured by an ELISA at the start of the study and after 3, 6 and 12 months. Results. In group I, continuous use of bicarbonate dialysate did not change the rHuEpo dosage given to achieve the target haemoglobin level and was associated with elevated surrogate markers (CRP, IL‐6) of cytokine‐induced inflammation. The switch from conventional to online‐produced ultrapure dialysate in group II resulted in a lower bacterial contamination with a significant decrease of CRP and IL‐6 blood levels. It was accompanied by a significant and sustained reduction of the rHuEpo dosage, which was required to correct the anaemia. Using multiple regression analysis, IL‐6 levels are shown to have a strong predictive value for rHuEpo dosage in both groups. Conclusions. Our data demonstrate that dialysate‐related factors such as low bacterial contamination can induce the activation of monocytes, resulting in elevated serum levels of IL‐6. Dialysate‐related cytokine induction might diminish erythropoiesis. The use of pyrogen free ultrapure dialysate resulted in a better response to rHuEpo. Not only would it save money, but it would also help to maintain an optimal haemoglobin level without further increase in rHuEpo dosage.
Local B-cell infiltrates play a role in tissue fibrosis, neolymphangiogenesis, and renal allograft survival. We sought to characterize the B-cell infiltrates, factors involved in B-cell recruitment, ...and lymphangiogenesis in renal interstitial injury (ie, acute and chronic interstitial nephritis and chronic IgA nephropathy). CD20-positive B cells formed a prominent part of the interstitial infiltrating cells. Together with CD3-positive T cells, the CD20-positive B cells formed larger nodular structures. CD10-positive pre-B cells were rare, and the majority were mature CD27-positive B cells. Proliferating B cells were detected within nodular infiltrates. The level of mRNA expression of the chemokine CXCL13 was increased and correlated with CD20 mRNA in the tubulointerstitial space. CXCL13 protein was predominantly found at sites of nodular infiltrates, in association with CXCR5-positive B cells. Furthermore, sites of chronic interstitial inflammation were associated with a high number of lymphatic vessels. B-cell infiltrates form a prominent part of the interstitial infiltrates both in primary interstitial lesions and in IgA nephropathy. CXCR5-positive B cells might be recruited via the chemokine CXCL13 and seem to contribute to the formation of intrarenal lymphoid follicle-like structures. These might represent an intrarenal immune system.
Oxalosis is a metabolic disorder characterized by deposition of oxalate crystals in various organs including the kidney. Whereas primary forms result from genetic defects in oxalate metabolism, ...secondary forms of oxalosis can result from excessive intestinal oxalate absorption or increased endogenous production, e.g. after intoxication with ethylene glycol.
Here, we describe a case of acute crystal-induced renal failure associated with excessive ingestion of rhubarb in a type 1 diabetic with previously normal excretory renal function. Renal biopsy revealed mild mesangial sclerosis, but prominent tubular deposition of oxalate crystals in the kidney. Oxalate serum levels were increased.
Acute secondary oxalate nephropathy due to excessive dietary intake of oxalate may lead to acute renal failure in patients with preexisting renal disease like mild diabetic nephropathy. Attention should be payed to special food behaviors when reasons for acute renal failure are explored.
Mesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. ...Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity.
By modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-α and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-β1.
TIMP-1-GPI stimulated rapid and efficient in vitro wound closure. The agent enhanced mesothelial cell proliferation and migration and was bioactive in the nanogram range. The application of TIMP-1-GPI may represent a new approach for limiting or repairing damaged mesothelium.
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