Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy. Background IgA nephropathy (IgAN) is the most common chronic glomerular disease in adults. End-stage renal disease (ESRD) develops in about 30% of the patients. Early intervention and consequent therapy may prevent or at least delay the development of ESRD in these patients. Up to now, the diagnosis could only be achieved with a renal biopsy. Methods The urine of 45 patients with IgAN was collected and screened for protein/polypeptide patterns with a novel high throughput method, capillary electrophoreses on-line coupled to a mass spectrometer (CE-MS). CE-MS allows the fast and accurate evaluation of up to 2000 polypeptides in one urine sample. The results in IgAN were compared to findings in 13 patients with membranous nephropathy (MN) and 57 healthy individuals. Results In the patients with IgAN, even when urinary protein excretion was within the normal range of regular tests, the polypeptide pattern in urine differed significantly from that of healthy controls and patients with MN, indicating a specific “IgAN” pattern of polypeptide excretion. Classification regarding discrimination of IgAN from healthy controls and from MN had a sensitivity of 100% and 77%, respectively. Specificity was 90% and 100%, respectively. Compared to patterns established earlier in patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or diabetic nephropathy (DN), sensitivity and specificity were 100%. Treatment of the patients was associated with changes of the pattern, possibly indicating a therapeutic effect. Conclusion Proteomic analysis with CE-MS coupling permits fast and accurate identification and differentiation of polypeptide patterns in the urine of patients with IgAN, allowing differentiation from healthy controls and, probably, other renal diseases.

Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes. Background Proteomics applied in large scale may provide a useful diagnostic tool. Methods We developed an online combination of capillary electrophoresis with mass spectrometry, allowing fast and sensitive evaluation of polypeptides found in body fluids. Utilizing this technology, polypeptide patterns from urine are established within 45 minutes. About 900 to 2500 polypeptides as well as their concentrations are detected in individual urine samples without the need for specific reagents such as antibodies. To test this method for clinical application, we examined spot urine samples from 57 healthy individuals, 16 patients with minimal change disease (MCD), 18 patients with membranous glomerulonephritis (MGN), and 10 patients with focal segmental glomerulosclerosis (FSGS). Results One-hundred seventy-three polypeptides were present in more than 90% of the urine samples obtained from healthy individuals, while 690 polypeptides were present with more than 50% probability. These data permitted the establishment of a “normal” polypeptide pattern in healthy individuals. Polypeptides found in the urine of patients differed significantly from the normal controls. These differences allowed the distinction of specific protein spectra in patients with different primary renal diseases. Abnormal pattern of proteins were found even in urine from patients in clinical remission. Conclusion The data indicate that capillary electrophoresis with mass spectrometry coupling provides a promising tool that permits fast and accurate identification and differentiation of protein patterns in body fluids of healthy and diseased individuals, thus enabling diagnosis based on these patterns.