Relationship Between Plasma Fibrinogen And Prognosis Of Type 2 Diabetes With Chronic Kidney Disease

Objective:Several studies have found that plasma fibrinogen(Fib)is often elevated in type 2 diabetes mellitus(T2DM),but its correlation with the clinicopathological manifestations and prognosis of chronic kidney disease(CKD)in type 2 diabetes are not fully understood.Our study aims to investigate the relationship between plasma Fib levels and clinicopathological profile,renal prognosis in T2 DM patients with CKD(patients with glomerular disease confirmed by renal biopsy),to early identify high-risk patients with high likelihood of progression to end-stage renal disease.Methods:We conducted a retrospective cohort study,including a total of 277 T2 DM patients with CKD(defined as biopsy proven glomerular disease),from 2011 to 2020.The patients were classified into diabetic nephropathy(DN)(145 cases)and non-diabetic renal disease(NDRD)(132 cases),according to the pathological findings.T2 DM patients with CKD,DN patients as well as NDRD patients,were divided into 4 groups(Q1,Q2,Q3,and Q4),based on quartiles of plasma Fib levels.The endpoint is defined as progression to endstage renal disease or requiring renal replacement therapy.T2 DM patients with CKD,DN patients,NDRD patients were further divided into 2 subgroups,depends on whether endpoint was met.Cox regression analysis was used to evaluate the effect of plasma Fib level on the renal prognosis of T2 DM patients with CKD and DN patients.Results:1.The analysis after grouping T2 DM patients with CKD based on plasma Fib level in quartiles,demonstrated that,the groups with higher plasma Fib levels tend be associated with longer duration of diabetes,higher 24-hour urinary protein,total cholesterol,triglyceride levels,and lower albumin levels.2.Cox regression analysis showed that lower plasma fibrinogen level is independently associated with a higher risk of progression to end-stage renal disease in T2 DM patients with CKD(HR,natural log-transformed plasma Fib per 1 SD is 2.91;95% CI,1.43 to 5.93,P=0.003),after adjusting for sex,age,24-hour urinary protein,and serum creatinine level.Compared with Q1,the HR values for Q2,Q3 and Q4 were 2.68(95% CI 1.23-5.84,P=0.013),3.08(95% CI 1.42-6.68,P=0.004),and 2.51(95% CI 1.15-5.50,P=0.021),respectively.3.In order to predict the risk of disease progression into end-stage renal disease in T2 DM patients with CKD,a prediction model was built including gender,age,duration of diabetes,hypertension,24-hour urinary protein,serum creatinine level,and pathological factors etc.The AUC area of the model was increased by 0.01 after adding ln(plasma Fib),with the specificity at 80%,the sensitivity at 79.2%,and the cut-off value at 0.37(P<0.05).The same analysis was also conducted in DN patients,the AUC area was increased by 0.03,with the specificity at 54.90%,the sensitivity at 85.5%,and the cut-off value at 0.37 after the addition of Fib,comparing to the simple inclusion of traditional risk factors(P<0.05).Conclusion:1.The clinical data of T2 DM patients with CKD,DN patients and NDRD patients have different characteristics in different quartile groups of plasma Fib,but all of them show aggravated proteinuria with increasing plasma Fib.2.Plasma Fib is an independent risk factor for progression to end-stage renal disease in T2 DM patients with CKD,and the addition of Plasma Fib to the traditional prediction models improves the predictive power.