RESUMO
The study was a retrospective study. The clinical data of 866 patients with IgA nephropathy (IgAN) in Beijing Anzhen Hospital, Capital Medical University from March 2010 to March 2021 were analyzed, to investigate the clinical pathology and renal prognosis of IgAN patients with intrarenal arteriolosclerosis, and to preliminarily explore whether abnormal activation of complement system is involved in the injury of arteriolosclerosis. The patients were divided into renal arteriolar lesions group and non-renal arteriolar lesions group according to the renal histopathology, and the differences of clinical pathological manifestations, prognosis between the two groups were compared. The results showed that, compared with the non-renal arteriolar lesions group ( n=236), IgAN patients in the renal arteriolar lesions group ( n=630) had higher proportions of hypertension and malignant hypertension, higher levels of urinary albumin-creatinine ratio, 24-hour urine protein quantification and serum uric acid, lower estimated glomerular filtration rate, and more severe MEST-C lesions of the Oxford classification (all P < 0.05). Cox regression analysis results showed that intrarenal arteriolosclerosis was the independent risk factor affecting the progression of IgAN to ESRD ( HR=6.437, 95% CI 2.013-20.585, P=0.002). Renal histopathology showed that the deposition of complement C3c on the wall of intrarenal arterioles in the renal arteriolar lesions group ( n=98) was stronger than that in non-renal arteriolar lesions group ( n=18, P < 0.05). IgAN patients with renal arteriolosclerosis present with serious clinical and pathological manifestations, and renal prognosis. Abnormal activation of complement system may be involved in the pathogenesis of intrarenal arteriolosclerosis.
RESUMO
Objective:To investigate the role of complement activation in the pathogenesis of primary malignant hypertension (MHT) with nephrosclerosis complicated with severe cardiorenal injury.Methods:Data of MHT patients with nephrosclerosis proven by biopsy from January 2010 to December 2020 in the Beijing Anzhen Hospital, Capital Medical University were retrospectively analyzed. The expressions of complement-related component C4d, C1q, complement factor H-related protein 5, C3c and C5b-9 were detected by immunohistochemical staining. According to whether the patients were complicated with acute heart failure (AHF) and/or acute kidney injury (AKI), they were divided into severe cardiorenal injury group and non-severe cardiorenal injury group. The differences of clinicopathological data between the two groups were compared. According to the degree of C4d deposition in renal tissues, patients were divided into C4d diffused deposition group and non-C4d diffused deposition group. The severity of cardiorenal injury and the pathological characteristics of thrombotic microangiopathy in renal tissues were compared between the two groups.Results:A total of 33 patients were enrolled in this study, of which 17 cases (51.5%) were complicated with severe cardiorenal injury; AHF occurred in 16 patients (48.5%), AKI occurred in 8 patients (26.7%), and AHF and AKI were combined in 7 patients (21.2%). Compared with non-severe cardiorenal injury group, patients in severe cardiorenal injury group had higher levels of baseline lactate dehydrogenase [326.0 (217.0, 366.0) IU/L vs 197.0 (165.0, 220.0) IU/L, Z=37.000, P=0.002] and hemoglobin [(143.6±24.0) g/L vs (106.4±24.7) g/L, t=38.500, P<0.001], lower levels of 12 h urinary incontinence osmolality [400.0 (342.5, 504.0) mmol/L vs 476.0 (432.3, 616.5) mmol/L, Z=72.000, P=0.021] and serum albumin [(36.2±9.4) g/L vs (43.2±6.2) g/L, t=6.423, P=0.017], and thicker left ventricular posterior wall [(14.0±2.1) mm vs (12.1±1.1) mm, t=6.552, P=0.018]. The immunohistochemical results of kidney tissue showed that the proportions of C4d and C5b-9 diffused deposition in severe cardiorenal injury group were significantly higher than those in non-severe cardiorenal injury group (5/16 vs 0/15, P=0.043; 12/16 vs 5/15, P=0.032). Compared with non-C4d diffused deposition group, C4d diffused deposition group had higher incidence of AHF (5/5 vs 10/26, P=0.018), poorer heart function, more severe ventricular remodeling, and shorter history of hypertension [2.0 (0, 12.0) months vs 48.0 (9.5, 84.0) months, Z=22.500, P=0.022]. Conclusions:The incidence of severe cardiorenal injury in MHT patients with nephrosclerosis is about 51.5%. The proportion of diffuse deposition of complement activated components in renal tissues in patients with severe cardiorenal injury is higher than that in patients with non-severe cardiorenal injury. Overactivation of complement may be involved in the pathogenic process of severe heart and kidney injury caused by MHT.