Intrarenal Arterial Lesions Are Associated with Higher Blood Pressure, Reduced Renal Function and Poorer Renal Outcomes in Patients with IgA Nephropathy

Abstract

Background/Aims: Arterial fibrotic intimal thickening and arteriolar hyaline are considered common pathological features in immunoglobulin A nephropathy (IgAN), whereas little is known about the acute pathological manifestations of endothelial cell injury. The aim of this study was to investigate characteristics of intrarenal arterial lesions and to estimate their prognostic values in patients with IgAN. The primary renal endpoint was a 50% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD). Methods: Various renal arterial lesions (arterial fibrotic intimal thickening, arteriolar hyaline, arteriolar endotheliocyte swelling, arteriolar inflammatory cell infiltration, and arteriolar thrombosis) in 1683 patients with IgAN were reviewed and reclassified using a semi-quantitative scoring system. Their correlations with clinical features, pathological characteristics, and renal outcomes were evaluated. Results: The prevalence of intrarenal arterial lesions was up to 72.2% in IgAN patients. There were 978 patients (58.1%) with arterial fibrotic intimal thickening, 350 patients (20.8%) with arteriolar hyaline, 432 patients (25.7%) with arteriolar endotheliocyte swelling, 356 patients (21.2%) with arteriolar inflammatory cell infiltration and 43 patients (2.6%) with arteriolar thrombosis. Arterial fibrotic intimal thickening and arteriolar hyaline were strongly associated with higher mean arterial pressure (MAP) and reduced eGFR (P < 0.001) but were not related to proteinuria at the time of renal biopsy. In contrast, arteriolar endotheliocyte swelling and arteriolar thrombosis were correlated with heavier proteinuria as well as higher MAP and reduced eGFR. During follow-up, patients with vascular lesions received more renin-angiotensin system (RAS) blockade and less glucocorticoid and showed poorer renal outcomes. Univariate Cox model showed that the presence of renal vascular lesions [hazard ratio (HR) = 25.01, 95% confidence interval (CI): 6.19 to 101.03, P < 0.001] was a risk factor for renal outcomes. However, in multivariable Cox analysis, which included clinical factors and the Oxford-MEST-C, vascular lesions were not significantly associated with an increased risk of renal failure. Remarkably, the impact of vascular lesions on the survival from ESRD or 50% reduction in renal function was eliminated by the use of RAS blockade after adjustment for eGFR, proteinuria, and MAP. Conclusion: Our study demonstrates the high prevalence of vascular lesions, including the chronic and acute arterial pathological changes, in patients with IgAN. The presence of vascular lesions is associated with higher MAP, reduced eGFR and poorer renal outcomes, which could be influenced by the RAS blockade treatment.

Complement-mediated microangiopathy in IgA nephropathy and IgA vasculitis with nephritis

“…This higher prevalence may be explained-at least in part-by the fact that El Karoui et al re-examined the renal biopsies with the specific aim of identifying microangiopathic lesions, as well as the fact that patients were selected from an active hypertensive clinic. Although the patients in our cohort did not come from a hypertension clinic, we re-examined at least four different biopsy sections from each patient and found that 23% of biopsies with IgA nephrtopathy had microangiopathy with or without thrombosis, which is higher than we had expected based on other studies [4,[29][30][31]. Thus, our findings indicate that microangiopathy may be underdiagnosed in clinical practice, which is an important point given our finding that microangiopathy is clinically relevant-specifically, we found that patients with microangiopathy had a higher prevalence of hypertension, a higher number of chronic lesions, and poorer renal outcome compared to patients without microangiopathy.…”

Severity of arterial and/or arteriolar sclerosis in IgA nephropathy and the effects of renin–angiotensin system inhibitors on its prognosis

“…Kaneko et al reported that AH was associated with renal prognosis on univariate and multivariate analyses, considering other MEST‐C scores, but not with clinical findings or RASI [ 5 ]. Zhang et al reported that AAS was associated with renal prognosis on univariate analysis, and that RASI prevented ESRD in patients with vascular lesions, including AAS and acute arterial lesions, such as arteriolar endothelial swelling, inflammatory cell infiltration, and thrombosis [ 18 ]. These previous reports support the hypothesis and results of this investigation.…”

Arteriolar C4d in IgA Nephropathy: A Cohort Study

“…17,28 However, vascular lesions, such as arterial intima fibrosis, arteriolar hyalinosis, and microangiopathy, have recently been shown to be associated with worse outcome. 18,23,25 In particular, microangiopathic lesions have been proposed to be incorporated in the classification. 22,23 Interestingly, C4d has been shown to be a reliable general marker for thrombotic microangiopathy in various kidney diseases, 24 including IgAN.…”

“…15 The vascular compartment is neglected by the Oxford pathologic classification because its significance in predicting kidney outcomes is uncertain. [16][17][18][19] Nevertheless, the impact of risk factors for vascular disease on the progression of IgAN has been shown in numerous studies. 5,[19][20][21] Additionally, microangiopathic lesions in IgAN biopsy specimens have been associated with worse prognosis.…”