The molecular mechanisms of inflammation and scarring in the kidneys of immunoglobulin A nephropathy

Abstract

Kidney biopsy is the cornerstone for the diagnosis of immunoglobulin A nephropathy (IgAN). The immunofluorescence technique evidences the IgA deposits in the glomeruli; the routine histology shows degree of active and chronic renal lesions. The spectrum of renal lesions is highly variable, ranging from minor or no detectable lesions to diffuse proliferative or crescentic lesions. Over the past three decades, renal transcriptomic studies have been performed on fresh or frozen renal tissue, and formalin-fixed paraffin-embedded kidney tissue specimens obtained from archival histological repositories. This paper aims to describe (1) the transcriptomic profiles of the kidney biopsy and (2) the potential urinary biomarkers that can be used to monitor the follow-up of IgAN patients. The use of quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), microarrays and RNA-sequencing (RNA-seq) techniques on renal tissue and separated compartments of the nephron such as glomeruli and tubule-interstitium has clarified many aspects of the renal damage in IgAN. Recently, the introduction of the single-cell RNA-seq techniques has overcome the limitations of the previous methods, making that it is possible to study the whole renal tissue without the dissection of the nephron segments; it also allows better analysis of the cell-specific gene expression involved in cell differentiation. These gene products could represent effective candidates for urinary biomarkers for clinical decision making. Finally, some of these molecules may be the targets of old drugs, such as corticosteroids, renin–angiotensin–aldosterone blockers, and new drugs such as monoclonal antibodies. In the era of personalized medicine and precision therapy, high-throughput technologies may better characterize different renal patterns of IgAN and deliver targeted treatments to individual patients.

Detection of N‑glycoprotein associated with IgA nephropathy in urine as a potential diagnostic biomarker using glycosylated proteomic analysis

“…IgAN accounts for ~40% of all native-kidney biopsies in Japan, 25% in Europe and 12% in the United States ( 56 , 57 ). Currently, the gold standard for the diagnosis of IgAN remains renal biopsy, which, as an invasive diagnostic method, has numerous limitations and may lead to multiple complications ( 58 , 59 ). Traditional clinicopathological indicators remain inadequate to predict the diagnosis, progression and prognosis of IgAN, such as blood pressure, albuminuria and hematuria.…”

Kidney and urine cell transcriptomics in IgA nephropathy and lupus nephritis: a narrative review

“…Transcriptomic studies of fresh whole renal tissue and microdissected glomeruli and tubulointerstitium, performed on kidney biopsies from IgAN patients, have been described in a recent narrative review [ 13 ]. The translational aspect of kidney transcriptomics has been limited to a few recent publications (Table 1 ), where the research has advanced from transcriptomics of kidney tissue to the detection of protein markers in urine samples or a transcriptomic pattern in urinary cells.…”

IgA nephropathy: a perspective for 2021

“…Following IgA and/or IgA-containing immune complex deposition in the glomerular mesangium, it is important to understand the local responses that generate tissue injury as these may direct novel therapeutic approaches. The role of complement activation is covered by Nicholas Medjeral-Thomas, H. Terence Cook and Matthew C. Pickering [6], and the downstream molecular mechanisms for inflammation and scarring reviewed by Paolo Schena [7].…”