Recent advances in the understanding of immune-mediated nephrotic syndrome: diagnostic and prognostic implications

Abstract

Glomerular diseases with severe defects in glomerular permeability give rise to heavy proteinuria and can present as nephrotic syndrome. There are many different causes of the nephrotic syndrome and a renal biopsy is nearly always needed to elucidate the underlying disease. During the last decade, substantial advances have occurred in the understanding of the pathophysiological mechanisms involved in immune-mediated glomerular diseases. Here, we review the diagnostic and prognostic implications of recent progress on the understanding of membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, amyloidosis, IgA nephropathy and membranoproliferative glomerulonephritis.

Keywords:

• amyloidosis
• diagnostics
• focal segmental glomerulosclerosis
• IgA nephropathy
• membranoproliferative glomerulonephritis
• membranous nephropathy
• minimal change disease
• nephrotic syndrome
• prognostics

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Circulating anti-phospholipase A2 receptor (PLA2R) antibodies and glomerular PLA2R1 antigen deposits are specific for idiopathic membranous nephropathy and can aid in the differentiation between idiopathic and secondary membranous nephropathy.

• Serum levels of anti-PLA2R antibodies better categorize patients into different groups with (potential) prognostic and therapeutic implications.

• Circulating soluble urokinase-type plasminogen activator receptor levels cannot be used to differentiate primary from secondary focal segmental glomerulosclerosis or other renal diseases.

• Urinary CD80 is a promising diagnostic and prognostic biomarker of minimal change disease.

• Renal amyloidosis is mostly due to either AL or AA, which can be diagnosed by renal immunofluorescence and staining for serum amyloid A protein. Other amyloidogenic proteins are rare and need a more extensive work-up.

• Serum levels of galactose-deficient IgA1 and autoantibodies directed against these molecules may better categorize patients into different groups with potential prognostic and therapeutic implications.

• Membranoproliferative glomerulonephritis (MPGN) can be classified into either immunoglobulin-mediated or complement-mediated disease based on immunofluorescence microscopy. Further subdivision of immunoglobulin-mediated MPGN into a predominant IgM and/or a predominant IgG staining may potentially guide the further work-up.

• Serum measurement of complement components should be performed in all patients with MPGN.

• Serum and/or urine electrophoresis is indicated in all patients with MPGN, even in the absence of monoclonal glomerular deposits.

Notes