How does HBV cause types of kidney disease?
The most common lesion seen worldwide with chronic HBV is MN. This lesion is a result of the formation of immune complexes in the sub-epithelial space of the basement membrane of the glomerulus forming “spikes” on electron microscopy similar to idiopathic MN, and demonstrates the classic “granular” immunofluorescence pattern with IgG and C3. The immune complex located in the sub-epithelial space most likely represents a sequential deposition of antigen followed by attachment by antibodies (as opposed to the circulating antigen–antibody complex being deposited in the sub-epithelial space). The only antigen that consistently fits the size limitation to deposit in this area of the basement membrane is HbeAg. Consistent with that observation is the fact that the vast majority of patients with chronic HBV who develop MN are positive for the HbsAg.
For HBV carriers who are HbsAg positive but HbeAg negative, the kidney lesion is usually not MN but MPGN, because the HbsAg is too large to deposit in the sub-epithelial space and is restricted to the sub-endothelial location. The subsequent local inflammation leads to cellular proliferation and histologically appears as Type I MPGN.
IgA nephropathy may result from three separate etiologies in HBV patients:
1. Since the liver is responsible for the metabolism of immunoglobulin A (IgA), in the presence of significant liver injury, the circulating levels of IgA increase and may deposit in the kidney. These complexes first embed in the mesangium, but may also be in the peripheral capillary loops. Clinically significant kidney disease from this “secondary” deposition of IgA in the glomeruli in any patient with liver disease regardless of etiology is extremely rare.
2. IgA antibodies have been shown to co-localize with HBV antigens in the mesangium, indicating HBV can directly cause IgA nephropathy.
3. Because HBV is present worldwide, especially in Asia where IgA is extremely prevalent, it is possible that HBV and IgA can occur independent of each other in certain populations.
Polyarteritis nodosa is a necrotizing vasculitis of medium-sized vessels that is not a direct form of glomerulonephritis. Rather, it affects the inflow circulation of the kidney and, as a result of fibrinoid necrosis and thrombosis of the larger muscular arteries of the kidney, there is severe hypertension, glomerular ischemia, and progressive kidney failure. The etiology for the vasculitis is the presence of HbsAg-antibody-immune complexes in the blood vessel walls, causing local complement activation and necrosis. The presence or absence of HbeAg is not important in the genesis of this lesion.
Finally, reports have shown a higher than expected incidence of FSGS in patients with chronic HBV. Because there are no immune complexes in the kidney with FSGS, it is not clear why this pathologic entity develops. Some studies have shown that HBV may enter and deposit in kidney tissue and through unknown mechanisms lead to FSGS.
