Neutrophil Gelatinase-Associated Lipocalin Cutoff Value Selection and Acute Kidney Injury Classification System Determine Phenotype Allocation and Associated Outcomes.

Background: We explored the extent to which neutrophil gelatinase-associated lipocalin (NGAL) cutoff value selection and the acute kidney injury (AKI) classification system determine clinical AKI-phenotype allocation and associated outcomes. Methods: Cutoff values from ROC curves of data from two independent prospective cardiac surgery study cohorts (Magdeburg and Berlin, Germany) were used to predict Kidney Disease: Improving Global Outcome (KDIGO)- or Risk, Injury, Failure, Loss of kidney function, End-stage (RIFLE)-defined AKI. Statistical methodologies (maximum Youden index, lowest distance to [0, 1] in ROC space, sensitivity≍specificity) and cutoff values from two NGAL meta-analyses were evaluated. Associated risks of adverse outcomes (acute dialysis initiation and in-hospital mortality) were compared. Results: NGAL cutoff concentrations calculated from ROC curves to predict AKI varied according to the statistical methodology and AKI classification system (10.6-159.1 and 16.85-149.3 ng/mL in the Magdeburg and Berlin cohorts, respectively). Proportions of attributed subclinical AKI ranged 2%-33.0% and 10.1%-33.1% in the Magdeburg and Berlin cohorts, respectively. The difference in calculated risk for adverse outcomes (fraction of odds ratios for AKI-phenotype group differences) varied considerably when changing the cutoff concentration within the RIFLE or KDIGO classification (up to 18.33- and 16.11-times risk difference, respectively) and was even greater when comparing cutoff methodologies between RIFLE and KDIGO classifications (up to 25.7-times risk difference). Conclusions: NGAL positivity adds prognostic information regardless of RIFLE or KDIGO classification or cutoff selection methodology. The risk of adverse events depends on the methodology of cutoff selection and AKI classification system.

Contrast enhanced sonography shows superior microvascular renal allograft perfusion in patients switched from cyclosporine A to everolimus.

BACKGROUND: Real-time contrast enhanced sonography (CES) provides quantitative information on microvascular tissue perfusion in renal allografts. In contrast to calcineurin inhibitors, mammalian target of rapamycin inhibitors may have beneficial effects on renal microvascular tissue perfusion. There is no information on the microperfusion of renal allografts in patients receiving either mammalian target of rapamycin inhibitor or calcineurin inhibitor. METHODS: In a prospective randomized, clinical trial, renal parenchymal tissue perfusion of 24 stable renal allograft recipients was evaluated with CES. Eleven patients were kept on cyclosporine A (CsA); 13 were converted to everolimus (EVR). Measurements were made at the time of the switch from CsA to EVR, 8.21+/-6.36 months posttransplantation, and 21.2+/-6.57 months posttransplantation. In addition to laboratory and clinical parameters, Doppler indices and estimated glomerular filtration rate (eGFR) were measured. RESULTS.: After the switch from CsA to EVR, microvascular perfusion in the EVR-treated patients (Axbeta value at baseline 9.23+/-7.44 dB/sec, Axbeta value at time of follow-up 19.6+/-13.0 dB/sec, P=0.03) and the estimated GFR (81.2+/-20.3 and 96.9+/-22.6 mL/min, P=0.001) improved significantly. Microvascular perfusion (Axbeta 7.04+/-5.32 dB/sec and Axbeta 8.66+/-9.01 dB/sec, P=0.34) and the eGFR of the group continuing CsA treatment remained stable (78.5+/-25.9 and 73.2+/-37.3 mL/min, P=0.1). CONCLUSION: The study demonstrates that renal microperfusion visualized by CES based on microbubble contrast agent and concomitantly kidney function, improved significantly after the switch from CsA to EVR.

Low levels of prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central venous catheters.

BACKGROUND AND PURPOSE: Central venous catheters are frequently placed in intensive care medicine for multiple indications. The risk of severe bleeding after cannulation is considered to be increased in patients with abnormal coagulation, common in critically ill patients. PATIENTS AND METHODS: This open prospective trial, performed at two medical intensive care units and one hematology intermediate care ward, investigated whether insertion of a central venous catheter in patients with coagulopathy (prothrombin time or= 1.5] and/or platelets

Switch of immunosuppression from cyclosporine A to everolimus: impact on pulse wave velocity in stable de-novo renal allograft recipients.

BACKGROUND: Cardiovascular mortality is extraordinarily high in renal allograft recipients and accounts for almost half of all allograft losses. Whereas the immunosuppression with calcineurin inhibitors is associated with an increased cardiovascular risk, beneficial effects of mammalian target of rapamycin inhibitors on the vascular system are suspected. METHODS: In a randomized clinical trial, we evaluated the impact on pulse wave velocity (PWV) of a switch from cyclosporine A (CsA) to everolimus (EVR), 6 months after transplantation, in 27 stable de-novo renal allograft recipients. PWV was assessed before and after randomization to the different immunosuppressive protocols at 6 and 15 months post-transplantation, respectively. Seventeen out of 27 patients included in the analysis were switched to EVR; 10 out of 27 were kept on CsA. RESULTS: The switch of immunosuppressive therapy from CsA to EVR resulted in stable PWV (9.50+/-1.92 vs. 9.13+/-1.62 m/s, DeltaPWV= -0.37+/-1.14 m/s, P=0.16), whereas a significant increase of PWV (9.93+/-1.94 vs. 10.8+/-2.24 m/s, DeltaPWV=0.89+/-1.47 m/s, P=0.03) was observed in patients on continued CsA therapy. CONCLUSION: In renal allograft recipients, the prolonged treatment with CsA was associated with a significant increase of PWV whereas no further deterioration of large vessel compliance was observed in patients that were switched to EVR 6 months post transplantation. The cardiovascular risk profile in stable de-novo renal allograft recipients might therefore be positively impacted by an early switch of the primary immunosuppressive therapy from CsA to EVR.

Real-time contrast-enhanced sonography in renal transplant recipients.

Conventional colour Doppler ultrasonography (CDUS) is a well-established and the most frequently used imaging procedure to diagnose kidney allograft dysfunction. Unfortunately, this technique is limited to the estimation of the allograft perfusion in large arteries. Early diagnosis of vascular damage, i.e., chronic allograft nephropathy is essential for an early therapeutic intervention. CDUS is still limited in interpreting vascular integrity. In contrast-enhanced sonography (CES) is a feasible technique for quantitative analysis of kidney perfusion and early diagnosis of biopsy proven chronic allograft nephropathy. CES does not provide only quantitative information on microvascular perfusion of the renal allografts but also represents improved diagnostic significance compared with CDUS for the detection of chronic allograft nephropathy.

Color doppler ultrasonography in the diagnostic evaluation of renal allografts.

Color Doppler ultrasonography of large allograft vessels and renal parenchyma is established firmly in the diagnosis of renal allograft perfusion. While conventional color Doppler ultrasonography has proven itself to be an indispensable, rapid, highly valid and practicable method, e.g. in the diagnosis of allograft artery stenosis or allograft vein thrombosis, the diagnostic usefulness of this method with regard to allograft perfusion is considerably limited. With contrast-enhanced sonography, a simple and readily implementable method that enables the early diagnosis of chronic allograft nephropathy is now available. The timely diagnosis of vascular damage prior to a rise in S-creatinine offers the possibility of early therapeutic intervention and thus at least the potential for the improvement of allograft survival.