Urinary and Serum Biomarkers for Prediction of Acute Kidney Injury in Patients Undergoing Liver Transplantation.

Acute kidney injury (AKI) is a frequent and serious complication of orthotopic liver transplantation (OLT), with a significant impact on mortality, graft survival, and chronic kidney disease. Currently, the diagnosis of AKI is based on changes in serum creatinine, which is a late marker, usually rising when there is already significant damage to the renal parenchyma. During the last 2 decades, various biomarkers have been studied in many clinical situations, mostly after cardiac surgery, in drug-induced AKI, or in sepsis. The present article summarizes the data on those biomarkers that have been evaluated for the prediction of AKI in patients undergoing OLT.

Netrin-1 and semaphorin 3A predict the development of acute kidney injury in liver transplant patients.

Acute kidney injury (AKI) is a serious complication after liver transplantation. Currently there are no validated biomarkers available for early diagnosis of AKI. The current study was carried out to determine the usefulness of the recently identified biomarkers netrin-1 and semaphorin 3A in predicting AKI in liver transplant patients. A total of 63 patients' samples were collected and analyzed. AKI was detected at 48 hours after liver transplantation using serum creatinine as a marker. In contrast, urine netrin-1 (897.8 ± 112.4 pg/mg creatinine), semaphorin 3A (847.9 ± 93.3 pg/mg creatinine) and NGAL (2172.2 ± 378.1 ng/mg creatinine) levels were increased significantly and peaked at 2 hours after liver transplantation but were no longer significantly elevated at 6 hours after transplantation. The predictive power of netrin-1, as demonstrated by the area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 24 hours after liver transplantation was 0.66, 0.57 and 0.59, respectively. The area under the curve for diagnosis of AKI was 0.63 and 0.65 for semaphorin 3A and NGAL at 2 hr respectively. Combined analysis of two or more biomarkers for simultaneous occurrence in urine did not improve the AUC for the prediction of AKI whereas the AUC was improved significantly (0.732) only when at least 1 of the 3 biomarkers in urine was positive for predicting AKI. Adjusting for BMI, all three biomarkers at 2 hours remained independent predictors of AKI with an odds ratio of 1.003 (95% confidence interval: 1.000 to 1.006; P = 0.0364). These studies demonstrate that semaphorin 3A and netrin-1 can be useful early diagnostic biomarkers of AKI after liver transplantation.

[Wilms tumor as a novel model of angiogenesis in childood nephropathies]. / Guz Wilmsa jako model angiogenezy w nefropatiach wieku mlodzienczego.

Wilms tumor has a unique possibility of recapitulation within its substance different stages of renal development. Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) are regarded to play the crucial role in the process of simultaneous development of tubules and glomeruli in animal kidney. Neoangiogenesis, secondary to rearrangement of epithelial elements in Wilms tumor, may therefore follow the lack of glomeruli in this neoplasm. The aim of the present research was an immunohistochemical analysis of VEGF-C and VEGFR-2 expressions in Wilms tumor and an attempt of explanation of neovascularisation process in this malignancy. The study group was composed of 16 children diagnosed with Wilms tumor (stage III of clinical classification) hospitalised in Department of Paediatric Oncology, Hematology and Transplantology, University of Medical Sciences in Poznan. The indirect immunohistochemical assay with the use of monoclonal antibodies directed against VEGF-C and VEGFR-2 was employed. VEGF-C expression was detected within blastemal and hypocellular stromal components of Wilms tumor. On the other hand, immuno-reactivity of VEGFR-2 was established in dysplastic tubules in the closest proximity of VEGF-C positive parts of stromal origin. VEGF-C dependent neovascularisation in Wilms tumor may follow an adequate differentiation of already existing epithelial elements. It may also explain the process of glomeruli-dependent physiological development of kidney and, what is also probable, the phenomenon of neoangiogenesis described in individual childhood nephropathies.