Urinary biomarkers of IgA nephropathy and other IgA-associated renal diseases

Abstract

IgA nephropathy is the most common primary glomerulonephritis and is a frequent cause for chronic kidney disease in children and young adults. Glomerular deposition of IgA also characterizes other renal disorders, including Henoch-Schoenlein purpura nephritis and immune-complex glomerulonephritis afflicting patients with liver disease due to chronic infection with the hepatitis C virus. Several treatment options are often considered, with the goal to prevent end-stage renal failure. Unfortunately, the diagnosis currently requires an invasive procedure, a renal biopsy. Because of the inherent risks, repetitive renal biopsy is frequently foregone as a means to monitor the clinical course or response to treatment. Recent advances in the analysis of the urinary proteome suggest that the excreted polypeptides include disease-specific patterns. We review recent studies of the various techniques for the identification and validation of such urinary biomarkers of IgA-associated glomerulonephritides. Currently, capillary electrophoresis coupled with mass spectrometry (MS) offers the greatest promise. To date, it seems more likely that disease-specific urinary polypeptide biomarkers are comprised of a panel of several distinct and well-defined peptides rather than a single molecule. Even most patients in clinical remission with normal clinical testing (dipstick urinalysis and quantitative proteinuria) were correctly classified by the pattern of polypeptides identified by capillary electrophoresis coupled with MS. With confirmation and refinement, such urinary testing may provide a tool for the diagnosis and monitoring of patients with IgA-associated renal diseases that is more sensitive than current standard clinical testing and far less risky than renal biopsy.

IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1

“…(A) Gene transcriptional levels of specific glycosyltransferases were quantitated by real-time RT-PCR, normalized to β-actin, and compared between patients (n = 11; black bars) and controls (n = 11; white bars) using the E-method (55) We determined the levels of IgA and Gal-deficient IgA1 in the urine samples from the 22 IgAN and healthy control subjects by capture ELISA and expressed the data relative to urinary creatinine concentration (51). The findings were confirmed by Western blotting with α chain-specific antibody (52,53). The levels of urinary IgA and Gal-deficient IgA1 were higher in the IgAN patients than in the healthy controls (P < 0.05 and P < 0.01, respectively; Table 1).…”

Mini-review: emerging roles of microRNAs in the pathophysiology of renal diseases

“…Global analysis of renal miRNA expression has also identified several miRNAs related to immunological and pathological changes that might contribute to the development or progression of IgA nephropathy (137). Additionally, urinary levels of several miRNAs are significantly altered in IgA nephropathy patients and have the potential to be used as biomarkers for diagnostic purposes (58,104,137).…”

Uromodulin and α₁-Antitrypsin Urinary Peptide Analysis to Differentiate Glomerular Kidney Diseases

“…Urine is one of the most amenable fluids in clinical proteomics, because it can be obtained noninvasively, allowing one to identify GKD-related markers [12,13,14,15,16,17,18,19,20,21,22]. Profiling methods are gaining popularity in the quest for new putative biomarkers for glomerular disorders [23,24,25,26,27,28,29,30,31]. …”