| Backgroud:Amyloidosis is a systemic disease caused by the deposition of amyloid protein in multiple organs such as kidney,heart and skin.And it is secondary to a variety of diseases,such as plasma cell disease,chronic inflammatory disease and gene mutation.It’s reported that 36 human proteins are associated with amyloidosis,including immunoglobulin light chain(AL),serum amyloid A(AA),and transthyretin(ATFR),in which the AL and AA amyloidosis are most common forms.The clinical manifestations of amyloidosis are diverse in different systems,including heart failure,massive proteinuria,edema,skin ecchymotic papules,hepatosplenomegaly,and tongue hypertrophy.And the one of most frequented organs is kidney,which can lead to proteinuria,edema,and renal failure.Studies have shown that the clinical manifestations may be related to the location and mode of amyloid deposition.Glomerular deposition is mainly manifested as severe nephrotic syndrome with volume overload;while patients with tubulointerstitial or vascular deposition usually show lower proteinuria and progressive renal damage.The severity and prognosis of clinical manifestations may be closely related to the degree of amyloidosis deposition.While the incidence of amyloidosis has increased significantly in recent years,it is necessary to further confirm the correlation between pathological changes,clinical characteristics and the prognosis of amyloidosis nephropathy,and to identify the risk factors affecting the prognosis of patients with amyloidosis.Objective:1.To determine the epidemiological and pathological features of renal amyloidosis in Shandong province;2.To investigate the correlation between clinical features and pathological changes in patients with renal amyloidosis;3.To study the different clinical manifestations and prognostic characteristics of renal amyloidosis and other organs amyloidosis,and to find the risk factors affecting the prognosis of patients with amyloidosis.Methods:1.184 patients with renal amyloidosis were underwent pathological analysis of renal biopsy in the Department of Pathology,Shandong University School of Medicine from February 2000 to February 2020.They were from 17 prefectural tertiary hospitals and 15 secondary hospitals in Shandong Province.We evaluated their pathological sections and reports again,and conducted the histopathological classification,score and grade according to the histopathological classification criteria of renal amyloidosis,renal histopathological change scoring criteria and renal amyloid prognosis score and grade.And we analyzed the correlation between pathological changes and clinical characteristics of amyloidosis nephropathy.2.71 renal amyloidosis patients were diagnosed by renal biopsy at the Nephrology Department of Shandong Provincial Hospital from February 2000 to February 2020.We selected their clinical and pathological data,and analyzed their clinical and pathological features.3.175 patients who visited Shandong Provincial Hospital from February 2000 to February 2020 and were definitely diagnosed with amyloidosis were selected as the study subjects.Inclusion criteria:1.The pathological diagnosis of amyloidosis;2.Patients in our hospital or other hospital have complete case data;Exclusion criteria:1.Patients with severe cardiovascular and cerebrovascular diseases,malignant tumors,end-stage renal disease;2.Do not cooperate with the follow-up.Clinical datas of the patients were collected and followed up.The follow-up time ranged from definite diagnosis to patient death or clinical follow-up.The endpoint was patient death.The patients’ prognosis(cure,remission,no improvement,progression,death)was clarified,and factors that may affect the prognosis were collected.Results:1.Patients with renal amyloidosis account for 1.30%of renal biopsies in Shandong Province,China.Amyloid is mainly deposited in the glomerular mesangial area(91.85%),capillary wall(10.33%),and interstitial small vessel wall(53.8%).And the depositions in the subendothelium(2.17%),tubules(3.26%),or renal interstitium(4.89%)are mild.In our study,181 patients(98.37%)had amyloid deposition in glomeruli and 117 patients in blood vessels.There were 163 patients associated with varying degrees of tubular atrophy and renal interstitial fibrosis,of which 92.02%(150/163)had local changes.And 173 patients(94.02%)had renal tissue associated with inflammatory cell infiltration,in which 41 patients had massive or diffuse infiltration,and the rest had scattered or diffuse infiltration.There were 139 patients with glomerulosclerosis,and 132 patients with sclerosis proportion≤50%.According to the renal amyloid prognostic score and grading principles,there were 19(10.33%),125(67.93%),and 40(21.74%)patients with grade Ⅰ,Ⅱ,and Ⅲ renal amyloidosis,respectively.Pathological grade is positively correlated with glomerular amyloid deposition classification(r=0.534,P<0.001),glomerular(r=0.497,P<0.001)and vascular(r=0.442,P<0.001)amyloid deposition degree,tubular atrophy and interstitial fibrosis(r=0.689,P<0.001),interstitial inflammation(r=0.603,P<0.001),and glomerulosclerosis degree(r=0.475,P<0.001).And it is positively correlated with creatinine(r=0.275,P=0.038)and urea nitrogen(r=0.409,P=0.002),negatively correlated with glomerular filtration rate(r=-0.292,P=0.028).It indicates that the severity of pathological grading is related to the degree of renal damage.There are significant differences in creatinine(t=7.601,P<0.001)and glomerular filtration rate(t=6.786,P<0.001)between different groups of tubular atrophy and interstitial fibrosis.Similarly,it is positively correlated with creatinine(r=0.384,P=0.003)and urea nitrogen(r=0.398,P=0.002);negatively correlated with glomerular filtration rate(r=-0.472,P<0.001),so that with the aggravation of tubular atrophy and interstitial fibrosis,the renal function injury is also more severe.2.We studied 71 patients with renal amyloidosis in the Department of Nephrology,Shandong Provincial Hospital,with mean age of 57.24±9.86.The main manifestations were proteinuria(95.78%),edema(87.32%).There are 50.70%patients with nephrotic syndrome,and some patients have hematuria(23.94%),renal impairment(35.21%),and other manifestations of extrarenal tissue involvement.Male patients have older age(t=2.960,P=0.004)and higher hemoglobin(t=2.005,P=0.049)than female patients.Hemoglobin(t=-2.295,P=0.028)and serum calcium levels(t=-2.172,P=0.033)were significantly lower in renal insufficiency group,and other renal function parameters such as urea nitrogen(t=5.215,P<0.001),cystatin C(t=4.054,P=0.001),β2-microglobulin(r=7.669,P<0.001),and uric acid(t=4.025,P<0.001)were significantly higher.Meanwhile,the degree of glomerular amyloid deposition(t=5.359,P=0.040),and tubular atrophy>10%(t=5.079,P=0.024)is more severe in renal insufficiency group.3.Amyloidosis is most likely to involve the kidney(42.86%)and heart(21.71%),causing edema,proteinuria,chest tightness,asthma,hypotension,skin ecchymosis and itching.Ordinal logistic regression analysis of different treatment groups shows that older age(P=0.001,OR=1.055,95%CI=1.021,1.090),cardiac involvement(P=0.001,OR=5.376,95%CI=2.059,14.041)and renal involvement(P=0.007,OR=2.907,95%CI=1.340,6.297)induce worse treatment effect.However,the treatment of hormone+immunosuppressive agents,hemodialysis,chemotherapy,ASCT or surgery(P<0.001,OR=0.135,95%CI=0.056,0.322)lead to converse effect.Multivariate Cox regression analysis shows that older age(P=0.001,HR=1.049,95%CI=1.020,1.078),hypotension(P=0.020,HR=2.431,95%CI=1.149,5.141),cardiac involvement(P<0.001,HR=6.556,95%CI=3.401,12.640),multiple organ involvement(P=0.026,HR=2.315,95%CI=1.107,4.840),lower ALB(P=0.012,HR=2.477,95%CI=1.219,5.034),lower eGFR(P=0.010,HR=2.215,95%CI=1.205,4.070),higher BNP(P=0.012,HR=3.962,95%CI=1.357,11.574),and higher cTnT(P=0.041,HR=2.872,95%CI=1.042,7.915)were risk factors of prognosis and mortality.Meanwhile,the effective treatments(hormone+immunosuppressive agents or hemodialysis or chemotherapy or ASCT or surgery)(P=0.007,HR=2.567,95%CI=1.291,5.103)can reduce the risk of death.Conclusions:1.Amyloidosis nephropathy is common in middle-aged and older-aged males,and mainly involved glomerular and small vessel walls.It’s mostly accompanied by mild tubular atrophy and renal interstitial fibrosis,interstitial inflammatory cell infiltration,and glomerular sclerosis.The degree of renal function damage of patients is related to the pathological grade,which is the same trend as renal tubule atrophy and interstitial fibrosis.The more severe the pathological grade and the degree of tubular atrophy and interstitial fibrosis,the more severe the renal function damage.2.Main clinical symptoms of amyloidosis nephropathy are proteinuria,edema and hematuria,renal impairment.The degree of glomerular amyloid deposition and tubular atrophy>10%is more significant in Patients with renal insufficiency.3.With the increase of age,the involvement of heart or kidney,the therapeutic effect will become worse;while patients receiving hormones+immunosuppressive agents or hemodialysis or chemotherapy or ASCT or surgery have better therapeutic effect.Older age,hypotension,cardiac involvement,multiple organ involvement,lower ALB and eGFR,higher BNP and cTnT are risk factors for prognosis and mortality;while treatments with hormones+immunosuppressive agents,hemodialysis,chemotherapy,ASCT or surgery can reduce the risk of death. |
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