Staphylococcal Infection-Related Glomerulonephritis With Cryoglobulinemic Features

Abstract

Introduction: Staphylococcal infection-related glomerulonephritis (GN) has been shown to represent a unique form of infection-related GN that contains IgA-dominant deposits and is often seen concurrently with the bacterial infection. Biopsies commonly reveal an endocapillary proliferative and/or exudative or mesangial proliferative GN. Rare cases have been reported to show cryoglobulin-like features, including hyaline pseudothrombi and wireloop deposits; however, detailed characterization of these cases is lacking.

Methods: The pathology archives from the University of Utah and Sharp Memorial Hospital were reviewed from January 2016 to September 2017 in search of cases with GN containing IgA-dominant deposits and features of cryoglobulinemia.

Results: Of 1965 native kidney biopsies, 5 showed IgA-dominant GN with cryoglobulinemic features. All patients had active staphylococcal infections at the time of biopsy. All presented with acute kidney injury (serum creatinine range: 1.7-6 mg/dl), and all had proteinuria and hematuria. All biopsies showed exudative GN, and 4 biopsies had focal crescents. All had focally prominent hyaline pseudothrombi with or without wireloop deposits, and all showed co-dominant staining for IgA and C3 on immunofluorescence microscopy. Serologic testing for cryoglobulinemia was performed in 3 patients and was transiently positive in 1 patient. Four patients required hemodialysis at last follow-up, whereas 1 patient returned to baseline kidney function.

Conclusion: IgA-dominant GN with cryoglobulinemic features is an uncommon but severe form of glomerular injury in patients with staphylococcal infections. Four of 5 patients had crescentic glomerular injuries, all of whom required hemodialysis at last follow-up. Patients with IgA-dominant GN with features of cryoglobulinemia should be evaluated for active staphylococcal infection.

Keywords: acute kidney injury; cryoglobulinemia; infection-related glomerulonephritis.

Figure 1

By light microscopy, all cases showed proliferative and exudative glomerulonephritis with focal features suggestive of cryoglobulinemia, including hyaline pseudothrombi. Patient #1 (a), patient #2 (b), patient #3 (c), and patient #5 (f) (arrows) and wireloop deposits (patient #4 [d]; circle). Cellular crescents (patient #3 [c], patient #5 [e]) were identified in 4 of 5 cases.

Figure 2

Immunofluorescence microscopy showed dominant or co-dominant staining in all cases for IgA (a) and C3 (b) (patient #2), including in hyaline pseudothrombi (IgA [c] and C3 [d]) (patient #1).

Figure 3

By electron microscopy, all patients had subendothelial and mesangial immune-type electron-dense deposits. One patient (patient #1) had subepithelial hump-like deposits (a) (arrowhead) and 1 patient (patient #2) had abundant subendothelial deposits with segmental duplication of the glomerular basement membrane (b; arrow). One patient (patient #3) had prominent intraluminal deposits on the sample for electron microscopy (c), and one (patient #4) demonstrated large subendothelial deposits corresponding to wireloop deposits on light microscopy (d).