In recent years, the significance of repeat kidney biopsy in the treatment of kidney disease has attracted increasing attention, and the significance of repeat kidney biopsy in the diagnosis and treatment of crescentic nephritis, lupus nephritis, refractory nephrotic syndrome and renal transplant rejection has been widely recognized [Wang, Haiyan], but reports on repeat kidney biopsy for anti-glomerular basement membrane antibody (Anti-GBM) disease There are not many reports on repeat renal biopsies for anti-glomerular basement membrane antibody (Anti-GBM) disease, which is a systemic disease mediated by Anti-GBM antibodies and can involve the kidneys, lungs, and central nervous system [1]. Most patients have acute nephritis, which has a poor prognosis [2.3] and often leads to end-stage renal failure and death within a short period of time. The literature confirms the efficacy of plasma exchange combined with high-dose hormone shock therapy, and early diagnosis and targeted treatment are essential to improve the prognosis. In this paper, we reviewed the clinical and pathological data of four patients treated with plasma exchange and hormone shock, two of whom had repeat renal biopsies, to investigate the significance of repeat renal biopsies in the diagnosis and treatment of anti-glomerular basement membrane antibody (Anti-GBM) disease. Case selection and methods I. Case selection: All four cases were inpatients of our hospital and were clearly diagnosed as Anti-GBM disease by renal biopsy. The diagnostic basis included acute glomerulonephritis and/or pulmonary hemorrhage, peripheral antibodies (+) and linear IgG deposition seen by immunofluorescence examination of renal tissue. Methods: 1. The determination of serum Anti-GBM was performed by indirect immunofluorescence method [4]; 2. ANCA was determined by indirect immunofluorescence method [5]; 3. Crescentic, sclerosing glomerular and interstitial tubular lesions were observed in the first and second renal biopsy pathology of four patients. Results The clinical and experimental-based findings of Anti-GBM disease are detailed in Tables 1, 2 and 3. 4 cases were male, and the mean age of onset was 29.00±9.38 years. Three cases had a history of upper respiratory tract infection before the onset of the disease. three cases had pulmonary damage, with pulmonary symptoms appearing earlier than renal damage, manifesting as severe hemoptysis. one case had central nervous system damage (manifesting as hydrocephalus due to midbrain conduit obstruction) during the course of the disease. Renal involvement was mainly manifested by visual or microscopic hematuria in 4 cases or massive proteinuria in 3 cases and progressive renal hypofunction in 3 cases. Table 2 and Table 3 show that the creatinine was significantly elevated in three patients at the time of consultation and developed progressively within a short period of time. Proteinuria was moderate to severe. All were non-selective proteinuria with a decrease in serum protein concentration. Serum immunoglobulin and complement C3 concentrations were within the normal range, and complement C4 concentrations were decreased in two cases. The histological changes in the kidney pathology of patients with Anti-GBM disease and the results of repeat renal biopsies are shown in Table 4. immune complex deposits were seen on the epithelial side of the basement membrane in four patients, and immunofluorescence examination revealed diffuse linear IgG deposits formed along the basement membrane of capillary trips, and IgM and IgA deposits were rare. The complement component was mainly C3 deposition without clear C4 and C1q deposition. Three of the patients presented with crescentic nephritis, and the percentage of crescentic glomeruli was above 80% before treatment. Repeat renal biopsies were performed 1-2 months after plasma exchange and high-dose methylprednisolone shock therapy. As seen in Table 4, the early stage was mostly cytogenic crescents with less fibrous crescents and glomerulosclerotic changes, while in the relatively late stage, the cytogenic crescents were converted to fibrinous crescents with significant global or (and) segmental glomerulosclerotic changes. Although plasma exchange and high-dose methylprednisolone shock therapy were effective, three of the patients with combined pulmonary hemorrhage resolved their pulmonary symptoms within one week with plasma exchange and methylprednisolone shock therapy. Case 2 had reappearance of pulmonary symptoms and radiographic features 2 weeks after discontinuation of plasma exchange therapy. Renal function improved significantly in two cases and did not worsen in one case. Follow-up showed that all cases entered irreversible renal failure between 2 months and 5 months after onset, including 2 patients with once-improved renal function who were treated with replacement therapy for irreversible renal failure between 6 months and 1 year and 5 months after discontinuation of plasma exchange and methylprednisolone shock, and case 2 died of central nervous system complications. The renal function of all four patients improved, with normalization of creatinine in cases 1, 2, 3, and 4. However, repeat renal biopsies showed that the renal biopsies of cases 1, 2, 3, and 4 still showed cellular crescent and cellular fibrous crescent, and a large number of interstitial inflammatory cells still infiltrated, suggesting the need for continued plasma exchange and high-dose methylprednisolone shock therapy or cytotoxic drug therapy. The follow-up results also showed that two of the four patients progressed to chronic renal failure, suggesting the need for continued treatment in this group of patients. Treatment and prognosis of patients with Anti-GBM disease Discussion There is a large amount of literature on Anti-GBM disease both in China and abroad (Zhao Minghui and Yao Xiaodan), but there are few reports on repeat renal biopsies for Anti-GBM disease. Anti-glomerular basement membrane antibody (Anti-GBM) disease is a systemic disease mediated by Anti-GBM antibodies, and its circulating Anti-GBM antibodies are usually of the IgG class, which uniquely target the Good Pusture (GP) antigen determinant cluster of collagen IV, as GP antigens are not only present not only in the glomerular basement membrane, but also in the tubular basement membrane, Bowmam’s capsule wall, alveolar basement membrane, placental vasculature and cerebral choroidal vascular basement membrane of collagen IV molecules, but the antigenic determinant clusters are not equally exposed, so that clinically they mostly present as renal and pulmonary and central nervous system involvement, but also as central nervous system involvement. Among them, acute progressive nephritis is the prominent manifestation in most patients, often leading to death in end-stage renal failure within a short period of time [1.2.3]. The characteristic pathological changes of the disease are linear IgG deposits along the glomerular capillary collaterals. Early diagnosis and targeted treatment are essential to improve the prognosis. In this paper, three of the four patients with Anti-GBM disease had pulmonary involvement, and the pulmonary lesions were mostly seen before the renal involvement, and all cases had elevated blood pressure. Early renal involvement was characterized by acute hyperalgesia, edema and moderate to severe proteinuria and hematuria with decreased serum protein concentration. Typical nephrotic syndrome is less common in only 1 of 4 cases, and acute hyperalgesia is seen in 3 cases within a short period of time after the onset of the disease. These clinical manifestations were similar to those reported in the early literature. Case 2 had a relapse after discontinuation of plasma exchange and methylprednisolone shock therapy, with manifestations such as hydrocephalus and less severe renal impairment. Positive peripheral blood Anti-GBM antibodies are an important diagnostic basis for the disease. 3 of the 4 cases were positive for Anti-GBM antibodies and 1 was negative, which may be related to the indirect immunofluorescence detection method (1), and in China, Zhao Minghui reported a 97% positive rate for Anti-GBM antibodies in peripheral blood. The cause of Anti-GBM antibody production reported in the literature is uncertain. In this paper, three patients presented with symptoms of viral or bacterial infection of the upper respiratory tract before the onset of the disease, suggesting that viral or bacterial infection may be an important causative factor (8.9). There may be a correlation between serum Anti-GBM antibody titers and disease activity. Three patients in this group had a gradual decrease in serum Anti-GBM antibody titers after treatment, and their condition improved, especially the early remission of pulmonary symptoms. The results of renal biopsy and repeat renal biopsy showed that the characteristic renal histological change of Anti-GBM disease was massive crescent formation, and three of the four cases were crescentic nephritis, but not all cases of Anti-GBM showed crescentic nephritis and acute progressive nephritis, and the percentage of crescentic glomeruli in case 2 was 100%, but there were only mild renal function changes throughout the course of the disease. The early stage of the disease was dominated by cytogenic crescents, and repeat renal biopsies showed that the cytogenic crescents could be converted to fibrinous crescents within a short period of time, while global or segmental sclerosis of the glomeruli and chronic fibrosis of the renal tubules developed. Repeat renal biopsies showed a significant downward trend in the proportion of glomeruli with crescent formation after treatment, and a significant decrease in CD4+ and CD8+ in renal tissue. Early plasma exchange and methylprednisolone shock therapy can control the progression of Anti-GBM disease and relieve lung and kidney damage, but relapse is possible after stopping treatment, and the results of repeat renal biopsies indicate that the renal lesions of Anti-GBM disease cannot be judged by clinical renal function alone, and repeat renal biopsies are needed to decide whether to discontinue or further treatment. Although the incidence of Anti-GBM is low, its onset is unique, its clinical course is rapid, early diagnosis is difficult, and the prognosis is serious; early plasma exchange and methylprednisolone shock can receive good remission effect, and repeat renal biopsy is important in guiding treatment and determining prognosis; repeat renal biopsy in patients with improved clinical renal function indicates that there are still active lesions, and further active treatment is still needed.