Study On Clinical Characteristics And Prognosis Risk Factors Of Alamyloidosis

?Objective?Amyloidosis nephropathy?ANP?is a kidney disease caused by monoclonal immunoglobulins,accounting for 3.6%of secondary kidney disease.However,ANP is very difficult to diagnose and treat,and clinicians still lack sufficient knowledge about the disease.This study intends to summarize the clinical,pathological and prognostic characteristics of AL amyloidosis patients by retrospective cohort study,and to study the risk factors of all-cause mortality and progression to ESRD,aimed at providing a theoretical basis for clinical diagnosis and treatment.?Patients and Methods?Patients biopsied and diagnosed as AL amyloidosis in our center from 2012.01 to 2017.12 were enrolled.Criteria of enrollment:patients biopsied from January 2012 to December 2017 in the Department of Nephrology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine or those who diagnosed as AL-type amyloidosis by relecture of the result of pathology by the doctor in our center.Exclusion criteria:patients who were not regularly followed up after discharge and who died due to non-related factors of the disease.The study protocol was approved by the Ethics Committee of Ruijin Hospital affiliated to Jiaotong University School of Medicine and the patients were signed with informed consent.Methods:The clinical,pathological and prognostic data of the selected patients were collected,including 24-hour proteinuria,albuminemia,creatinine,hematuria,immunofixation electrophoresis,differential free light chain?FLC?,pathological data?amyloid deposition,renal tubular atrophy,renal interstitial fibrosis,etc?,bone marrow flow cytometry,minimal residual disease?MRD?,complications,renal function progression and remission,etc.;Endpoint:death or ESRD(eGFR<15 ml/min/1.73 m²).COX regression analysis was used to further explore risk factors for renal function progression and all-cause mortality.?Results?This study enrolled 96 patients.ANP patients account for 0.59%².18%of patients underwent renal biopsy.The ratio of male to female was 7:5,the median age was 58?35-74 years old?,and the number of patients over 60 years old was 38.5%.72.92%of patients with onset of nephrotic syndrome,24h protenuria6966.14±3390.17 mg/d,albuminemia 16.64±7.39 g/L,baseline serum creatinine72.71±17.69?mol/L,80.21%of patients with normal renal function.The?type was more prone to liver involvement than the?type?31.25%vs 8.33%,P=0.037?,and the alkaline phosphatase level was higher?84.50 IU/L vs 66.50 IU/L,P=0.032?;the 24-hour proteinuria was also more significant?7707.88±4256.88 mg/d vs5764.77±3054.04 mg/d,P=0.036?,the detection rate of?in blood/urine immunofixation electrophoresis was lower?12.50%-46.67%?,and the FLC ratio was more sensitive?100%?.There was no significant difference in clinical manifestations between patients with MM and non-MM.Alkaline phosphatase?HR:1.013,95%CI:1.002-1.024,P=0.020?,NT-proBNP?HR:1.001,95%CI:1.000-1.001,P=0.009?is the cause of all-cause death in patients.Risk factors,survival time was significantly lower in patients with cardiac amyloidosis?27.27 months vs 74.57 months,P<0.001?;baseline creatinine?HR:1.000,95%CI:0.994-1.007,P=0.940?,24-hour proteinuria?HR:1.000,95%CI:1.000-1.000,P=0.254?was not significantly associated with renal function progression in patients.The pathological manifestations of the patients were amyloid deposition mainly at mesangial area,with or without tubular atrophy and interstitial fibrosis.There was no significant correlation of amyloid deposition amount or location with both 24-hour proteinuria and with baseline creatinine levels.Creatinine levels were higher in patients with more severe tubular atrophy and interstitial fibrosis?r _S=0.456,P<0.05;r_S=0.453,P<0.05?.Pathological manifestations were not associated with prognosis and risk of progression to ESRD.The phenotype of all patients is CD138+CD38+CD19-CD45dim,and the expression of CD56,CD117 and CD81 is heterogeneous.There is no difference in terms of renal presentation between CD56+and CD56-patients while it remains uncertain if there is difference in the prognosis?32 months vs.18.5 months,P=0.05?.There is no significant difference in median survival and renal survival between CD117+patients and CD117-patients?20 months vs 23 months,P=0.45?.?Conclusion?The study found that patients with AL renal amyloidosis often have an onset of nephrotic syndrome,with appearance of multiple system involvement.NT-proBNP and PAL are major factors affecting the prognosis of patients.Thus,the evaluation of organ involvement deserves more attention.The clinical manifestations are not proportional to the extent of amyloid deposition in histopathology.Interstitial fibrosis and tubular atrophy are the main factors affecting renal function.CD138+CD38+CD19-is a specific immunophenotype of ANP patients.The expression of CD117,which varies among patients,shows no significance in predicting overall or renal prognosis.The significance of expression of CD56 remains unclear.