Abstract
Diabetic nephropathy, hypertension, and glomerulonephritis are the most common causes of chronic kidney diseases (CKD). Since CKD of various origins may not become apparent until kidney function is significantly impaired, a differential diagnosis and an appropriate treatment are needed at the very early stages. Conventional biomarkers may not have sufficient separation capabilities, while a full-proteomic approach may be used for these purposes. In the current study, several machine learning algorithms were examined for the differential diagnosis of CKD of three origins. The tested dataset was based on whole proteomic data obtained after the mass spectrometric analysis of plasma and urine samples of 34 CKD patients and the use of label-free quantification approach. The k-nearest-neighbors algorithm showed the possibility of separation of a healthy group from renal patients in general by proteomics data of plasma with high confidence (97.8%). This algorithm has also be proven to be the best of the three tested for distinguishing the groups of patients with diabetic nephropathy and glomerulonephritis according to proteomics data of plasma (96.3% of correct decisions). The group of hypertensive nephropathy could not be reliably separated according to plasma data, whereas analysis of entire proteomics data of urine did not allow differentiating the three diseases. Nevertheless, the group of hypertensive nephropathy was reliably separated from all other renal patients using the k-nearest-neighbors classifier “one against all” with 100% of accuracy by urine proteome data. The tested algorithms show good abilities to differentiate the various groups across proteomic data sets, which may help to avoid invasive intervention for the verification of the glomerulonephritis subtypes, as well as to differentiate hypertensive and diabetic nephropathy in the early stages based not on individual biomarkers, but on the whole proteomic composition of urine and blood.
Highlights
Chronic kidney disease (CKD) is a supra-nosological concept that unites all patients with signs of kidney damage and/or a decrease in their function [1]
We introduce a new approach to the differential diagnosis of CKDs of different origins, such as diabetic nephropathy, chronic glomerulonephritis and hypertensive nephropathy, which is based on large proteomics data sets obtained by mass spectrometry of blood plasma and urine, by means of several models of machine learning
Plasma and urine samples were collected from 15 patients with diabetic nephropathy, from 14 patients with glomerulonephritis, from 5 patients with hypertensive nephropathy, and from 14 healthy volunteers
Summary
Chronic kidney disease (CKD) is a supra-nosological concept that unites all patients with signs of kidney damage and/or a decrease in their function [1]. No obvious clinical symptoms appear in early stage disease until severe damage has occurred [2]. The need for early diagnosis of CKD is obvious. Diagnosis of the disease causing the damage is paramount in all cases of the CKD presence [3,4,5]. Serum creatinine (Scr), and renal histopathology are commonly used to diagnose CKD and determine its different stages. Kidney biopsy for histopathology may be an invasive and painful procedure, it is considered as the gold standard for the diagnosis of renal disease [7]. Bleeding and other surgical complications may follow this procedure. To reduce these risks, it could be safer to use alternative techniques
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