Severity of Intrarenal Arterial Lesions Can Predict the Clinical Prognosis of Hepatitis B Virus-Associated Glomerulonephritis: A Retrospective Study

Abstract

Background: Intrarenal arterial lesions (IALs) have been studied in immunoglobulin A nephropathy and lupus nephritis, but this has not been reported in hepatitis B virus-associated glomerulonephritis (HBV-GN). This study aims to investigate the prevalence and the role of IALs in HBV-GN.

Methods: IALs were examined in kidney biopsy specimens from 205 patients with HBV-GN retrospectively. The severity of IALs and tubular interstitial lesions was scored semi-quantitatively. The severity of IALs was divided into 4 groups on the basis of ILA score, which were no IALs (Score 0), mild IALs (Score 1-2), moderate IALs (Score 3-4), and severe IALs (Score 5-10) groups. Survival analysis was performed using the Kaplan-Meier method between the severity of IALs and clinical events (doubling of serum creatinine [SCr], ESRD, and death due to the kidney disease).

Results: Among 205 patients with HBV-GN, 143 (69.8%) had IALs in their kidney biopsy specimens. IALs were mild in 28 (19.6%) patients, moderate in 101 (70.6%) patients, and severe in 14 (9.8%) patients. The severity of IALs was associated with high blood pressure (BP), high SCr, and severe tubulointerstitial injuries. The average follow-up time of these 205 HBV-GN patients was 94.2 ± 47.1 months, in which 46 cases had clinical event. The proportions of clinical events in no IAL, mild IAL, moderate IAL, and severe IAL groups were 9.7, 14.3, 25.7, and 71.4%, respectively. Event-free survival of patient in IAL group was significantly lower than that in the no IAL group (p = 0.000). Multivariate cox regression analysis indicated SCr (1.011, 1.007-1.016), hypertension (1.767, 1.004-3.108), and IAL (2.194, 1.062-4.530) were independent risk factors for clinical events after adjustment for age and gender. Event-free clinical survival in moderate and severe IAL groups was significantly lower than that in the no IAL group (p = 0.0111 and p = 0.0001, respectively). Besides, event-free renal survival in severe IAL group was significantly lower than that in moderate IAL group (p = 0.009). Multivariate cox regression analysis showed that the more severe the IALs, the higher the risk of the clinical event, with a hazard ratio of 2.284 for moderate IALs (1.085-4.907) and 3.315 for severe IALs (1.296-8.482).

Conclusions: Severity of IALs is associated with high BP, reduced renal function, and poor clinical prognosis in HBV-GN patients.

Keywords: Hepatitis B virus-associated glomerulonephritis; Intrarenal arterial lesion; Renal biopsy; Tubular interstitial injury.

Fig. 1

HBsAg and HBcAg deposition in renal tissue by immunohistochemical staining. a HBV-MPGN with HBsAg deposition in the mesangial area and afferent glomerular arteriole, but no obvious deposition in glomerular capillary loop (×400). b HBV-SGN with HBsAg deposition in sclerotic glomeruli and some intrarenal small artery walls (×200). c HBV-MsPGN with HBsAg deposition in interstitial arteriole walls (×200). d HBV-MPGN with HBsAg deposition in mesangial area, capillary loops, and the afferent artery (×400). e HBV-GN with HBsAg deposition in vasa recta (×400). f HBV-MPGN with HBcAg deposition in the mesangial area and glomerular capillary loop (×200). HBsAg, hepatitis B surface antigen; HBcAg, hepatitis B core antigen; HBV, hepatitis B virus; MPGN, membranoproliferative glomerulonephritis; SGN, sclerotic glomerulonephritis; MsPGN, mesangial proliferative glomerulonephritis; GN, glomerulonephritis.

Fig. 2

Pathological features of IALs in patients with HBV-GN. a Normal intrarenal arteriole in HBV-MsPGN. b Thickening of arterial wall in HBV-MN. c Fibrosis of arterial wall in HBV-SGN. d Arterial onion-skin change in HBV-MPGN. e Arterial hyaline change in HBV-MPGN. f Arterial hyaline change in HBV-MPGN. (a–e) PASM-Masson staining (f) PAS staining. (e, f) Panels were from same patient. Magnification ×200. IALs, intrarenal arterial lesions; HBV, hepatitis B virus; GN, glomerulonephritis; MsPGN, mesangial proliferative glomerulonephritis; MN, membranous nephropathy; MPGN, membranoproliferative glomerulonephritis; SGN, sclerotic glomerulonephritis; PSAM, periodic acid-silver methenamine; PAS, periodic acid-Schiff.

Fig. 3

SBP (a), DBP (b), and SCr (c) increase significantly in patients with severe IALs. d CKD stage constituent ratio in IAL groups with different severities. e Correlation between the severity of IALs and tubular interstitial lesions evaluated by Katafuchi scores. *p < 0.05, **p < 0.01, ***p < 0.001 versus no IAL; ^#p < 0.05, ^##p < 0.01 versus mild and moderate IALs. The Pearson correlation between IAL scores and mean Katafuchi scores is positive at 0.382, showing a significant positive linear relationship between the 2 variables with p = 0.000. Note: Since AKI can affect the SBP, DBP, SCr, and CKD stage, we analysed the data after excluding the AKI patients in (a–d) (n = 196). SBP, systolic blood pressure; DBP, diastolic blood pressure; SCr, serum creatinine; IALs, intrarenal arterial lesions; AKI, acute kidney injury.

Fig. 4

The Kaplan-Meier curves after adjustment for covariates (a) and cox regression analysis (b) of event-free survival based on the presence of IALs. Event defined as doubling of SCr, ESRD, and death due to the kidney disease (p < 0.001, χ² = 42.119, p = 0.000). Univariate analyses revealed that age, SCr, hypertension, and IALs were risk factors for clinical events (p < 0.05); multivariate cox regression analysis indicated that SCr, hypertension, and IALs were independent risk factors for the clinical events. IALs, intrarenal arterial lesions; SCr, serum creatinine.

Fig. 5

The Kaplan-Meier curves (a) and cox regression analysis (b) of event-free survival based on the severity of IALs. Log-rank analysis showed that there are significant differences in event-free survival between the severe IALs and no IALs (χ² = 20.6, p = 0.0001), the moderate IALs and no IALs (χ² = 6.456, p = 0.0111), and the moderate IALs and severe IALs (χ² = 6.829, p = 0.009). Univariate analyses revealed that age, SCr, hypertension, and IALs were risk factors for clinical events (p < 0.05); multivariate cox regression analysis indicated that only SCr and IALs were independent risk factors for the clinical events. Event defined as doubling of SCr, ESRD, and death due to the kidney disease. IALs, intrarenal arterial lesions; SCr, serum creatinine.