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Cardiac surgery is associated with a high risk of postoperative acute kidney injury (AKI) and subsequent loss of kidney function. We explored the clinical utility of urinary dickkopf-3 (DKK3), a renal tubular stress marker, for preoperative identification of patients at risk for AKI and subsequent kidney function loss.This observational cohort study included patients who had cardiac surgery in a derivation cohort and those who had cardiac surgery in a validation cohort (RenalRIP trial). The study comprised consecutive patients who had elective cardiac surgery at the Saarland University Medical Centre (Homburg, Germany; derivation cohort) and those undergoing elective cardiac surgery (selected on the basis of a Cleveland Clinical Foundation score of 6 or higher) who were enrolled in the prospective RenalRIP multicentre trial (validation cohort) and who were randomly assigned to remote ischaemic preconditioning or a sham procedure. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3:creatinine) and postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria, and subsequent kidney function loss, as determined by estimated glomerular filtration rate, was assessed.In the 733 patient in the derivation cohort, urinary concentrations of DKK3 to creatinine that were higher than 471 pg/mg were associated with significantly increased risk for AKI (odds ratio [OR] 1·65, 95% CI 1·10-2·47, p=0·015), independent of baseline kidney function. Compared with clinical and other laboratory measurements, urinary concentrations of DKK3:creatinine significantly improved AKI prediction (net reclassification improvement 0·32, 95% CI 0·23-0·42, p0·0001). High urinary DKK3:creatinine concentrations were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (IQR 733-910). In the RenalRIP trial, preoperative urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with a significantly higher risk for AKI (OR 1·94, 95% CI 1·08-3·47, p=0·026), persistent renal dysfunction (OR 6·67, 1·67-26·61, p=0·0072), and dialysis dependency (OR 13·57, 1·50-122·77, p=0·020) after 90 days compared with DKK3:creatinine concentrations of 471 pg/mg or less. Urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with significantly higher risk for AKI (OR 2·79, 95% CI 1·45-5·37) and persistent renal dysfunction (OR 3·82, 1·32-11·05) only in patients having a sham procedure, but not remote ischaemic preconditioning (AKI OR 1·35, 0·76-2·39 and persistent renal dysfunction OR 1·05, 0·12-9·45).Preoperative urinary DKK3 is an independent predictor for postoperative AKI and for subsequent loss of kidney function. Urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective.No study funding.

Background The individual course of CKD may vary, and improved methods for identifying which patients will experience short-term eGFR loss are needed. Assessing urinary Dickkopf-3 (DKK3), a stress-induced tubular epithelia–derived profibrotic glycoprotein, may provide information about ongoing tubulointerstitial fibrosis and short-term eGFR loss. Methods To investigate urinary DKK3’s potential as a biomarker of short-term eGFR loss (over 12 months), we prospectively assessed eGFR and urinary DKK3 levels in patients with CKD of various etiologies at baseline and annual follow-ups. We also measured urinary DKK3 in a general population sample and patients with diagnostic kidney biopsies or IgA nephropathy under treatment. Results Median urinary DKK3-to-creatinine concentration at baseline was significantly higher in patients with CKD than the general population sample (431 versus 33 pg/mg). In the CKD cohort, having a urinary DKK3-to-creatinine level >4000 pg/mg was independently and significantly associated after multiple adjustments with mean annual decline in eGFR of 7.6% over 12 months. Urinary DKK3 significantly improved prediction of kidney function decline compared with eGFR or albuminuria alone. Urinary DKK3-to-creatinine levels were related to the extent of tubulointerstitial fibrosis in kidney biopsies. In patients with IgA nephropathy, a rise in urinary DKK3 was associated with significant eGFR decline within 6 months, whereas stable or decreasing urinary DKK3 indicated a more favorable course. Conclusions Urinary DKK3 levels identify patients at high risk for eGFR decline over the next 12 months regardless of the cause of kidney injury and beyond established biomarkers, potentially providing a tool to monitor CKD progression and assess effects of interventions.

Während Autobiographien auf dem literarischen Markt immer noch als authentische Zeugnisse gelebten Lebens gehandelt werden, hatte sich bereits die lebensphilosophisch-hermeneutische Forschung im Gefolge Diltheys und im Blick auf den Goetheschen Prototyp Dichtung und Wahrheit auf die höhere, die ‚symbolische‘ Wahrheit der Autobiographie verständigt. Im Laufe des 20. Jahrhunderts verabschiedete sich die kritische Autobiographieforschung von der autobiographischen ‚Wahrheit‘ zugunsten des Authentizitätskriteriums der ‚Wahrhaftigkeit‘ und richtete ihre kritische Aufmerksamkeit zum einen auf die ‚Identität‘ und ‚Individualität‘ des Autobiographen / der Autobiographin und zum anderen auf den Kunstcharakter der Autobiographie. Die poststrukturalistische Toterklärung des Subjekts und der dem sprachlichen Zeichen seit den 60er Jahren des 20. Jahrhunderts diagnostizierte Bedeutungsverlust entzogen der Autobiographie schließlich die Referenz, um sie im dekonstruktiven Verständnis als eine rhetorische Falle zu beschreiben. Erst im Zuge der performativen Wende ist es möglich geworden, Zeichenhaftigkeit und Referenz im sprachlichen Setzungsakt selbst zusammenzudenken. Ausgangs- und Bezugspunkt ist in dieser Perspektive nicht mehr die außersprachliche Wirklichkeit oder die Authentizität des historisch Geschehenen, sondern die sprachliche Erzeugung von Lebensrealität als geschichtlicher oder auch politischer Vorgang.

Quercetin (QC), a polyphenolic compound widely distributed in fruits and vegetables has recently gained interest due to its cisplatin (CP) sensitizing properties in cancer cells. It is currently unknown, whether quercetin also increases the susceptibility of the kidneys to cisplatin toxicity. We studied the effects of various bioflavonoids on CP toxicity in an in vitro model of cultured tubular epithelial cells (LLC-PK1). Viability of LLC-PK1 cells, as assessed by lactate dehydrogenase (LDH) release and MTT-test, was affected by CP (100-400 microM) in a time and dose dependent fashion. Pretreatment of cells with QC for 3 h significantly reduced the extent of cell damage. The protective activity of QC was concentration dependent, starting at 10-25 microM and reaching a plateau between 50 and 100 microM. Other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations (100-500 microM). Quercetin itself showed some intrinsic cytotoxicity at concentrations exceeding 75 microM. Our data indicate that quercetin reduces cisplatin toxicity in cultured tubular epithelial cells. The exact mechanism of protection is unclear, though scavenging of free oxygen radicals may play an important role.

Novel tracers for the diagnosis of malignant disease with PET and PET/CT are being developed as the most commonly used 18F deoxyglucose (FDG) tracer shows certain limitations. Employing radioactively labelled glutamate derivatives for specific imaging of the truncated citrate cycle potentially allows more specific tumour imaging. Radiation dosimetry of the novel tracer BAY 85-8050, a glutamate derivative, was calculated and the effective dose (ED) was compared with that of FDG. Five healthy volunteers were included in the study. Attenuation-corrected whole-body PET/CT scans were performed from 0 to 90 min, at 120 and at 240 min after injection of 305.0 ± 17.6 MBq of BAY 85-8050. Organs with moderate to high uptake at any of the imaging time points were used as source organs. Total activity in each organ at each time point was measured. Time–activity curves (TAC) were determined for the whole body and all source organs. The resulting TACs were fitted to exponential equations and accumulated activities were determined. OLINDA/EXM software was used to calculate individual organ doses and the whole-body ED from the acquired data. Uptake of the tracer was highest in the kidneys due to renal excretion of the tracer, followed by the pancreas, heart wall and osteogenic cells. The mean organ doses were: kidneys 38.4 ± 11.2 μSv/MBq, pancreas 23.2 ± 3.8 μSv/MBq, heart wall 17.4 ± 4.1 μSv/MBq, and osteogenic cells 13.6 ± 3.5 μSv/MBq. The calculated ED was 8.9 ± 1.5 μSv/MBq. Based on the distribution and dose estimates, the calculated radiation dose of BAY 85-8050 is 2.67 ± 0.45 mSv at a patient dose of 300 MBq, which compares favourably with the radiation dose of FDG (5.7 mSv).