Urinary Proteomics in Kidney Transplantation

Although kidney transplantation is the best treatment option for end stage kidney disease, it is still associated with long-term graft failure. One of the greater challenges for transplant professionals is the ability to identify grafts with a high risk of failure before initial decline of eGFR with irreversible graft changes. Transplantation medicine is facing an emerging need for novel disease end point-specific biomarkers, with practical application in preventive screening, early diagnostic, and improved prognostic and therapeutic utility. The aim of our review was to evaluate the clinical application of urinary proteomics in kidney transplant recipients at risk for any type of future graft failure.

KDClassifier: Urinary Proteomic Spectra Analysis Based on Machine Learning for Classification of Kidney Diseases

BackgroundBy extracting the spectrum features from urinary proteomics based on an advanced mass spectrometer and machine learning algorithms, more accurate reporting results can be achieved for disease classification. We attempted to establish a novel diagnosis model of kidney diseases by combining machine learning with an extreme gradient boosting (XGBoost) algorithm with complete mass spectrum information from the urinary proteomics.MethodsWe enrolled 134 patients (including those with IgA nephropathy, membranous nephropathy, and diabetic kidney disease) and 68 healthy participants as a control, and for training and validation of the diagnostic model, applied a total of 610,102 mass spectra from their urinary proteomics produced using high-resolution mass spectrometry. We divided the mass spectrum data into a training dataset (80%) and a validation dataset (20%). The training dataset was directly used to create a diagnosis model using XGBoost, random forest (RF), a support vector machine (SVM), and artificial neural networks (ANNs). The diagnostic accuracy was evaluated using a confusion matrix. We also constructed the receiver operating-characteristic, Lorenz, and gain curves to evaluate the diagnosis model.ResultsCompared with RF, the SVM, and ANNs, the modified XGBoost model, called a Kidney Disease Classifier (KDClassifier), showed the best performance. The accuracy of the diagnostic XGBoost model was 96.03% (CI = 95.17%-96.77%; Kapa = 0.943; McNemar’s Test, P value = 0.00027). The area under the curve of the XGBoost model was 0.952 (CI = 0.9307-0.9733). The Kolmogorov-Smirnov (KS) value of the Lorenz curve was 0.8514. The Lorenz and gain curves showed the strong robustness of the developed model.ConclusionsThis study presents the first XGBoost diagnosis model, i.e., the KDClassifier, combined with complete mass spectrum information from the urinary proteomics for distinguishing different kidney diseases. KDClassifier achieves a high accuracy and robustness, providing a potential tool for the classification of all types of kidney diseases.