Diabetic Nephropathy Guideline Adherence Assessment And Disease Prediction

Part Ⅰ Influence of guidelines for diabetic nephropathy on clinical outcomes: a guideline adherence studyBackground: The rapid development of digital information technology provides rich medical data to support clinical research.Diabetic nephropathy(DN),a common chronic disease,is the main cause of end-stage kidney disease(ESKD).To slow down the development of DN,several versions of clinical guidelines have been developed in China and abroad.The significance and value of clinical guidelines can only be demonstrated by their wide dissemination and implementation,but in clinical practice,it is unclear whether the treatment of DN patients complies with the guidelines and its impact on prognosis.Objective: To evaluate the adherence of Chinese DN patients to domestic and international guidelines in terms of antihyperglycemic,antihypertensive,and lipid-lowering treatments,and to investigate the impact of guideline adherence on short-term clinical parameter control and longterm renal prognosis.Methods: Patients with DN diagnosed by renal biopsy from 2003 to 2018 were collected retrospectively.Each visit of the patient was taken as a sample.The samples were categorized into adherent and nonadherent according to whether the prescription was in compliance with the medication regimen and drug contraindications recommended by the American Diabetes Association(ADA)and Chinese guidelines.The proportion of the adherence sample was calculated for antihyperglycemic,antihypertensive,and lipid-lowering treatments.Clinical parameter control was compared after 3–6 months of therapy between two groups by generalized estimating equation models(GEE).At the patient level,the degree of guideline adherence for each patient was quantified and the impact of guideline adherence on ESKD was assessed using a time-dependent Cox model.Results: A total of 1,128 DN patients(15,374 visit samples)were included.Adherence to domestic and international guidelines was similar for Chinese DN patients.Among them,the guideline adherence rate of antihyperglycemic therapy was the highest,with 72.87% and 68.15% of samples meeting ADA and Chinese guidelines,respectively.Adherence to guidelines for lowering blood pressure and lipids was low.The GEE model results indicated adherence was more likely to have good glycated hemoglobin(Hb A1c)control(ADA: OR 1.46,95%CI 1.12-1.88;Chinese guideline: OR 1.42,95%CI 1.09-1.85)and good blood pressure control(ADA: OR 1.35,95%CI 1.03-1.78;Chinese guideline: OR 1.39,95%CI 1.08-1.79)compared with nonadherence.The improvement of patient’s adherence showed the potential to reduce ESKD risk.Conclusion: Guideline-concordant treatment improves clinical outcomes in patients with DN,contributing to better control of glycated hemoglobin and blood pressure levels and having the potential to reduce the risk of ESKD.However,guideline adherence in Chinese DN patients still needs to be improved in clinical practice.Part Ⅱ Causal relationship between body mass index and risk of diabetic nephropathy: a Mendelian randomization studyBackground: With the increasing awareness of health care in the population,various guidelines emphasize the importance of strengthening lifestyle interventions for disease prevention and treatment.Previous epidemiological studies have suggested that obesity is associated with an increased risk of diabetic nephropathy(DN),but some studies have also suggested that a higher body mass index(BMI)is a protective factor for renal function deterioration in patients with type 2 diabetes.The inconsistent findings may be attributed to the influence of potential confounding factors and reverse causality.The emergence of a large amount of medical data,including genetic data,has driven the emergence of Mendelian randomization studies that can reflect the true causal relationship between obesity and DN.Objective: To explore the causal effect of body mass index(BMI)on DN and kidney traits in type 2 diabetes by a two-sample Mendelian randomization analysis.Methods: A total of 56 genetic variants were selected as instrumental variables for BMI in 158,284 participants from Bio Bank Japan,and their effects on DN risk,estimated glomerular filtration rate(e GFR),and proteinuria were estimated in 3972 individuals with type 2 diabetes.Then,sex-stratified MR analysis was performed between BMI and DN.We selected generalized summary Mendelian randomization(GSMR)analysis as the primary method and six other robust methods to test MR assumptions.Results: BMI was causally related to DN risk and e GFR levels.One standard deviation increase in BMI was causally associated with a 2.76-fold increase in DN risk(OR,3.76;95% CI,1.88–7.53;P < 0.001),and a 29% decrease in e GFR levels(OR,0.71;95% CI,0.59–0.86;P < 0.001).However,BMI was not causally associated with proteinuria(P = 0.22).Sex-stratified analyses indicated the causal effect of BMI on DN was stronger in women(OR,14.81;95% CI,2.67–82.05;P = 0.002)than in men(OR,3.48;95% CI,1.18–10.27;P = 0.02).Sensitivity analyses did not show evidence for violation of the MR assumptions.Conclusions: Mendelian randomization analysis showed that higher BMI levels were causally associated with increased risk of DN and decreased e GFR levels.Moreover,compared to men,the risk of DN in women was more likely to be influenced by BMI levels.Part Ⅲ Impact of longitudinal changes in clinical parameters on clinical outcomes in patients with diabetic nephropathy: a trajectory analysis studyBackground: Clinical guidelines emphasize aggressive control of disease marker levels to slow the progression of diabetic nephropathy(DN).However,the levels of these clinical indicators are susceptible to various factors,including medication type and disease progression,and often fluctuate over the long-term course of DN patients.The single measurement used in previous studies provides limited information.The development of digital medicine provides an opportunity to record complete information on disease dynamics for each patient,providing data to assess the impact of longitudinal changes in disease indicators on clinical outcomes in DN.Objective: To evaluate the relationship between the trajectory of clinical parameters over time and the risk of end-stage kidney disease(ESKD)in DN patients.Methods: Patients with DN diagnosed by renal biopsy were retrospectively collected.Latent class mixed model was used to identify distinct trajectories for parameters in the first 2 years from enrollment,including Hb A1 c,systolic blood pressure,low-density lipoprotein,proteinuria,and uric acid.Patients with similar trajectories were fitted together in one group.The Cox proportional risk model was further applied to analyze the association of parameters’ baseline and different trajectory groups with ESKD occurrence and to compare the role of each parameter on the ESKD risk.Results: Higher baseline levels of proteinuria,LDL cholesterol,and uric acid are associated with an increased risk of ESRD in patients with DN.The longitudinal trajectory of each parameter divided the population into 3-4 subgroups.Among the longitudinal trajectories of proteinuria,the risk of ESKD was highest in participants with rising proteinuria trajectory group(PRO-Class 3),which was 8.29 fold higher risk(95% CI 4.81-14.28,P<0.001)compared to the low-stable trajectory group(PRO-Class1)after adjusting for confounding factors.There was no statistical difference in the risk of ESKD among distinct trajectory groups for Hb A1c(P> 0.05).Trajectories for LDL-C,SBP,and UA all indicated that participants with higher trajectories were associated with a higher risk of ESKD.Notably,among several clinical parameters,the trajectory of proteinuria was most closely associated with increased risk of ESKD,followed by LDL-C.Conclusion: Continuous control of proteinuria and LDL-C levels plays an important role in improving the renal prognosis of patients with DN,which provides an important reference value for the focus of treatment in clinical practice.