IgG4-related kidney disease--an update

Abstract

Purpose of review: IgG4-related disease (IgG4-RD) is a recently recognized systemic inflammatory disorder that can affect most organs/tissues such as sarcoidosis. The kidney is a frequently affected organ with tubulointerstitial nephritis (TIN), the representative lesion of IgG4-RD. This review focuses on the latest knowledge of IgG4-related kidney disease (IgG4-RKD).

Recent findings: A wide range of renal manifestations of IgG4-RD, that is TIN, membranous glomerulonephritis (MGN) and other glomerular lesions, and pyelitis, are collectively referred to as IgG4-RKD. Clinically, decreased renal function, or characteristic imaging findings such as multiple low-density lesions on contrast-enhanced computed tomography or diffuse thickening of the renal pelvic wall, are typical presenting features. Although a rapid response to corticosteroid therapy is a very important feature of IgG4-TIN, in cases in which renal function is moderately to severely decreased before therapy, only partial recovery of renal function is obtained.

Summary: TIN with characteristic imaging findings is a typical manifestation of IgG4-RKD in the interstitium, while MGN is a representative manifestation of the glomerular lesions. Although IgG4 is a central feature of IgG4-RD, the recent discovery of IgG4-negative IgG4-RD raises questions about the causative role of the IgG4 molecule in this context.

Box 1

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FIGURE 1

A variety of patterns of multiple low-density lesions on contrast-enhanced computed tomography (CT). Upper: Contrast-enhanced CT scan shows bilateral diffuse patchy involvement. Middle: Contrast-enhanced CT scan shows multiple parenchymal low-density lesions including mass-like lesions protruding beyond the surface of the kidney (arrow). Lower: Contrast-enhanced CT scan shows a rim-like lesion of the kidney.

FIGURE 2

Typical histological features of IgG4-related tubulointerstitial nephritis. Upper: Histopathological examination in a patient with IgG4-related kidney disease (IgG4-RKD) shows plasma cell rich tubulointerstitial nephritis with different stages of fibrosis intermingled within different areas (periodic acid-methenamine-silver staining x100). Lower: Immunostaining for IgG4 shows many IgG4-positive plasma cells in the area of inflammation just outside the renal capsule, probably corresponding to the rim-like lesion of the kidney noted on imaging study (x400).

FIGURE 3

Longitudinal changes of imaging findings during corticosteroid therapy. Upper: Contrast-enhanced computed tomography (CT) scan before corticosteroid therapy shows multiple low-density lesions in the bilateral kidneys in a patient with IgG4-RKD. Middle: Two months after starting steroid therapy, contrast-enhanced CT scan shows complete recovery and disappearance of low-density lesions without atrophy in some areas of the kidney (arrow), while atrophic scarring starts to appear in other areas (arrowhead). Lower: Six years after therapy and still under steroid maintenance therapy, the area that showed early recovery maintains its normal appearance without atrophy (arrow), but the area where atrophic scarring started to appear shows progressive scarring with decreased enhancement (arrowhead) on contrast-enhanced CT scan.