TIMP-2 and IGFBP7 in human kidney biopsies in renal disease

ABSTRACT Background Tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are markers of tubular stress and urinary [TIMP-2]*[IGFBP7] is an established biomarker for risk assessment of acute kidney injury. There are no studies of expression profiles or localization of these markers in human renal tissue with confirmed renal disease. Methods We analysed 37 kidney biopsies of patients with renal disease and 10 non-diseased control biopsies for TIMP-2 and IGFBP7 expression using immunohistochemistry. Changes in glomerular morphology were evaluated by a semi-quantitative glomerulosclerosis score (GSI) and tubular interstitial changes were graded by the tubular injury score (TSI) using periodic acid–Schiff-stained paraffin sections. Interstitial fibrosis and tubular atrophy (IF/TA) were graded according to the Banff classification. Urinary [TIMP-2]*[IGFBP7] was collected at the time of biopsy. Results TIMP-2 and IGFBP7 had significantly greater expression in kidney biopsies from patients with renal disease compared with control tissue, especially in the tubular compartment. Here, IGFBP7 was detected in proximal and distal tubules while TIMP-2 was predominantly localized in the collecting ducts. Renal injury significantly correlated with staining intensity for TIMP-2 and IGFBP7: GSI weakly correlated with glomerular TIMP-2 (r = 0.36) and IGFBP7 (r = 0.35) and TSI correlated with tubular TIMP-2 (r = 0.41) and IGFBP7 (r = 0.43). Urinary [TIMP-2]*[IGFBP7] correlated weakly with the histopathological damage score but not with glomerular and tubular expression. Conclusion Our findings underline the role of TIMP-2/IGFBP7 as an unspecific marker of renal injury that is already in use for early detection of acute kidney injury. </jats:sec

Effects of anisotropy on the geometry of tracer particle trajectories in turbulent flows

Using curvature and torsion to describe Lagrangian trajectories gives a full description of these as well as an insight into small and large time scales as temporal derivatives up to order 3 are involved. One might expect that the statistics of these properties depend on the geometry of the flow. Therefore, we calculated curvature and torsion probability density functions (PDFs) of experimental Lagrangian trajectories processed using the Shake-the-Box algorithm of turbulent von Kármán flow, Rayleigh-Bénard convection and a zero-pressuregradient boundary layer over a flat plate. The results for the von-Kármán flow compare well with experimental results for the curvature PDF and numerical simulation of homogeneous and isotropic turbulence for the torsion PDF. For the experimental Rayleigh-Bénard convection, the power law tails found agree with those measured for von-Kármán flow. Results for the logarithmic layer within the boundary layer differ slightly, we give some potential explanation below. To detect and quantify the effect of anisotropy either resulting from a mean flow or large-scale coherent motions on the geometry or tracer particle trajectories, we introduce the curvature vector. We connect its statistics with those of velocity fluctuations and demonstrate that strong large-scale motion in a given spatial direction results in meandering rather than helical trajectories

Effects of anisotropy on the geometry of tracer particle trajectories in turbulent flows

Using curvature and torsion to describe Lagrangian trajectories gives a full description of these as well as an insight into small and large time scales as temporal derivatives up to order 3 are involved. One might expect that the statistics of these properties depend on the geometry of the flow. Therefore, we calculated curvature and torsion probability density functions (PDFs) of experimental Lagrangian trajectories processed using the Shake-the-Box algorithm of turbulent von K\'arm\'an flow, Rayleigh-B\'enard convection and a zero-pressure-gradient turbulent boundary layer over a flat plate. The results for the von K\'arm\'an flow compare well with previous experimental results for the curvature PDF and numerical simulation of homogeneous and isotropic turbulence for the torsion PDF. Results for Rayleigh-B\'enard convection agree with those obtained for K\'arm\'an flow, while results for the logarithmic layer within the boundary layer differ slightly, and we provide a potential explanation. To detect and quantify the effect of anisotropy either resulting from a mean flow or large-scale coherent motions on the geometry or tracer particle trajectories, we introduce the curvature vector. We connect its statistics with those of velocity fluctuations and demonstrate that strong large-scale motion in a given spatial direction results in meandering rather than helical trajectories

Under-recognition of Acute Kidney Injury after Cardiac Surgery in the ICU Impedes Early Detection and Prevention

Background: Acute kidney injury (AKI) is associated with high morbidity and mortality; therefore, prevention is important. The aim of this study was to systematically assess AKI incidence after cardiac surgery as documented in clinical routine compared to the real incidence because AKI may be under-recognized in clinical practice. Further, its postoperative management was compared to Kidney Disease: Improving Global Outcomes (KDIGO) recommendations because recognition and adequate treatment represent the fundamental cornerstone in the prevention and management of AKI. Methods: This retrospective single-center study included n = 100 patients who underwent cardiac surgery with cardiopulmonary bypass. The coded incidence of postoperative AKI during intensive care unit stay after surgery was compared to the real AKI incidence. Furthermore, conformity of postoperative parameters with KDIGO recommendations for AKI prevention and management was reviewed. Results: We found a considerable discrepancy between coded and real incidence, and conformity with KDIGO recommendations was found to be relatively low. The coded incidence was significantly lower (n = 12 vs. n = 52, p < 0.05), representing a coding rate of 23.1%. Regarding postoperative management, 90% of all patients had at least 1 episode with mean arterial pressure <65 mm Hg within the first 72 h. Furthermore, regarding other preventive parameters (avoiding hyperglycemia, stopping angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, avoiding contrast media, and nephrotoxic drugs), only 10 patients (20.8%) in the non-AKI group and in 5 (9.6%) subjects in the AKI group had none of all the above potential AKI-promoting factors. Conclusions: AKI recognition in everyday clinical routine seems to be low, especially in lower AKI stages, and the current postoperative management still offers potential for optimization. Possibly, higher AKI awareness and stricter postoperative management could already achieve significant effects in prevention and treatment of AKI

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Ost- und Süd-Afrika

von Moritz SchanzIn Fraktu