Kidney Involvement in Hypocomplementemic Urticarial Vasculitis Syndrome-A Case-Based Review

Abstract

Hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome, is a rare small vessel vasculitis associated with urticaria, hypocomplementemia and positivity of anti-C1q antibodies. In rare cases, HUVS can manifest as an immune-complex mediated glomerulonephritis with a membranoproliferative pattern of injury. Due to the rarity of this disorder, little is known about the clinical manifestation, pathogenesis, treatment response and outcome of such patients. We describe here three cases of HUVS with severe renal involvement. These patients had a rapidly progressive form of glomerulonephritis with severe nephrotic syndrome against a background of a membranoproliferative pattern of glomerular injury with extensive crescent formation. Therefore, these patients required aggressive induction and maintenance immunosuppressive therapy, with a clinical and renal response in two patients, while the third patient progressed to end-stage renal disease. Because of the rarity of this condition, there are few data regarding the clinical presentation, pathology and outcome of such patients. Accordingly, we provide an extensive literature review of cases reported from 1976 until 2020 and place them in the context of the current knowledge of HUVS pathogenesis. We identified 60 patients with HUVS and renal involvement that had adequate clinical data reported, out of which 52 patients underwent a percutaneous kidney biopsy. The most frequent renal manifestation was hematuria associated with proteinuria (70% of patients), while one third had abnormal kidney function on presentation (estimated glomerular filtration (GFR) below 60 mL/min/1.73 m²). The most frequent glomerular pattern of injury was membranoproliferative (35%), followed by mesangioproliferative (21%) and membranous (19%). Similar to other systemic vasculitis, renal involvement carries a poorer prognosis, but the outcome can be improved by aggressive immunosuppressive treatment.

Keywords: anti-C1q antibodies; crescentic glomerulonephritis; hypocomplementemic urticarial vasculitis syndrome (HUVS); kidney involvement; nephrotic syndrome.

Figure 1

(A) Immunofluorescence. Moderate staining for IgG in the mesangium and along the glomerular capillary walls. (B) Immunofluorescence. Minimal staining for C3 in the mesangium and along the glomerular capillary walls. (C) Light microscopy (Toluidin Blue). Glomerulus with a membranoproliferative pattern of injury, fibrinoid necrosis and a fibro-cellular crescent. (D) Light microscopy (Toluidin Blue). Glomeruli showing a membranoproliferative pattern with diffuse lobular accentuation (mesangial expansion with hypercellularity, endocapillary hypercellularity and fibrous crescents). There is also moderate tubular atrophy and interstitial fibrosis. (E,F) Electron microscopy. There are subendothelial, unstructured, electron-dense deposits. Podocytes show diffuse foot process effacement. Additionally, there is severe endothelial injury with swollen glomerular endothelial cells and loss of fenestrations.

Figure 2

(A) Immunofluorescence. Moderate staining for IgG in the mesangium and along the glomerular capillary walls. (B) Immunofluorescence. Moderate staining for C3 in the mesangium and along the glomerular capillary walls. (C) Light microscopy (PAS staining). Glomeruli showing a membranoproliferative pattern with diffuse lobular accentuation (mesangial expansion with hypercellularity, endocapillary and extra-capillary hypercellularity). There is also moderate tubular atrophy and interstitial fibrosis and arteriosclerosis. (D) Light microscopy (Masson staining). Glomerulus with a membranoproliferative pattern of injury and a fibro-cellular crescent. Additionally, there is mesangial expansion due to accumulation of extracellular matrix, consistent with lesions of class II diabetic nephropathy (E) Electron microscopy. Podocytes showing diffuse foot process effacement. Additionally, there are swollen glomerular endothelial cells with loss of fenestrations and glomerular basement membrane thickening (460 nm). (F) Electron microscopy. Podocytes showing diffuse foot process effacement. There is also severe endothelial injury and endocapillary hypercellularity.

Figure 3

Urticarial-like exanthema (case 3).

Figure 4

Possible pathogenetic roles of anti-C1q antibody (anti-C1q-AB) in hypocomplementemic urticarial vasculitis syndrome (HUVS).