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Minimal change variants: Mesangial proliferation; IgM nephropathy; C1q nephropathy

Alain Meyrier, MD
Gerald B Appel, MD
Section Editors
Richard J Glassock, MD, MACP
Fernando C Fervenza, MD, PhD
Deputy Editor
Albert Q Lam, MD


In addition to minimal change disease (MCD), three other disorders usually present with the nephrotic syndrome and may also show only minor changes on light microscopy: idiopathic mesangial proliferative glomerulonephritis; IgM nephropathy; and C1q nephropathy. These disorders may represent variants of MCD or focal segmental glomerulosclerosis (FSGS), but some clinicians and pathologists believe that they are separate conditions.

The nosology of IgM and C1q nephropathy is particularly unsettled. However, clinicopathologic findings suggest forms of idiopathic nephrotic syndrome that, in terms of prognosis and treatment options, are closer to FSGS than to MCD.


Focal (involving less than 50 percent of glomeruli on light microscopy) or diffuse mesangial cell proliferation (involving more than 50 percent of glomeruli on light microscopy) is a relatively nonspecific response to glomerular injury. This pattern can be seen in a variety of diseases including lupus nephritis, IgA nephropathy, and mild postinfectious glomerulonephritis [1]. In addition, there is a seemingly idiopathic form in which there are either no immune deposits (in contrast to the IgA or IgG deposits in the above disorders) or focal or diffuse IgM-containing deposits in the mesangial areas. Patients with this glomerulopathy tend to present in one of two ways: with hematuria; or, more commonly, with proteinuria that is often in the nephrotic range [2,3]. Most publications dealing with the latter involve childhood idiopathic nephrotic syndrome with focal segmental glomerulosclerosis (FSGS) on renal biopsy [4].

Hematuria — Some patients with mesangial proliferative glomerulonephritis present with episodes of gross hematuria [5] or with microscopic hematuria that may be detected on a routine examination [2,3]. These findings may follow a nonstreptococcal upper respiratory infection [6], a pattern that resembles that of IgA nephropathy (see "Glomerular disease: Evaluation and differential diagnosis in adults"). The hematuria often resolves spontaneously, although persistent microscopic hematuria may be seen [2]. The renal prognosis in these patients is almost always excellent [2,7].

Nephrotic syndrome — Approximately 3 to 5 percent of patients with idiopathic nephrotic syndrome have mild diffuse mesangial cell proliferation but not FSGS on light microscopy [2,8,9]. Electron microscopy usually demonstrates relatively diffuse foot process fusion, suggesting that this disorder may be part of the minimal change disease (MCD)-FSGS spectrum. The observations that more than one-half of patients respond initially to prednisone and that nonresponders at eight weeks are often in remission at one year are also consistent with a relation to these disorders [2,8-10]. It has been suggested, for example, that mesangial proliferative glomerulonephritis is a more severe form of MCD in which the initial injury is greater, leading to mesangial dysfunction and a slower rate of recovery [8].

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Literature review current through: Oct 2017. | This topic last updated: Jan 13, 2016.
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