Renal Histologic Changes And Cadiovascular Calcification In Patients With Diabetic Nephropathy

With the rapid economic development and behavioural changes,the increasing incidence of diabetes mellitus,especially type 2 diabetes mellitus(T2DM),is becoming a major threat to public health in China.Diabetic nephropathy(DN)is a common microvascular complication of diabetes and also one of the leading causes of end-stage renal disease.DN may severely impact the patients’ quality of life and impose an enormous burden on public health resources.Clinically,albuminuria and serum creatinine remain the major diagnostic and prognostic biomarkers of DN,despite low specificity and sensitivity.Pathologic changes provide a logical structure for clarify a diagnosis and predict the prognosis,and improve clinical management and efficiency.However,a uniform pathologic classification for DN was lacking.In 2010,a new pathologic classification was launched on behalf of the Renal Pathology Society,which divide DN into four hierarchical glomerular lesions with a separate evaluation for degrees of interstitial and vascular involvement.The classification attracted much attention since published,but its value in clinical practice remains unknown.Until now,several studies have attempted to establish the relationship between the classification system and clinical findings from small samples,but their conclusions were conflicting.Our aim was to evaluate the relationship between clinical and histological findings and validate the predictive power of the new classification in 396 T2DM patients,who were biopsy-confirmed DN and examined in a long-term follow-up.Cardiovascular disease is the leading cause of death among patients with diabetes and chronic kidney disease(CKD).Cardiovascular calcification and cardiovascular disease interact as both cause and effect.The existence and severity of cardiovascular calcification is a strong predictor of cardiovascular events and mortality.Previous study has identified diabetes as a risk factor of cardiovascular calcification,recently,the influence of Chronic Kidney Disease-Mineral and Bone Disorder on the life expectancy and the quality of life in CKD patients has attracted more and more attention.So far systemic research about calcification in patients with DN and renal dysfunction is extremely rare.In this study,we observed the distribution and severity of cardiovascular calcification in DN patients wtih renal dysfunction(CKD stages 2-5 and non-dialysis),and evaluated its risk factorsPart One:Renal Histologic Changes And The Outcome In Patients With Diabetic NephropathyObjective:The progression of diabetic nephropathy is frequently determined by clinical parameters;however,the predictive value of histologic lesions remains largely unknown.Our aim was to evaluate the relationship between histologic changes and renal outcome in patients with type 2 diabetes mellitus.Methods:396 patients with type 2 diabetes mellitus and biopsy-proven diabetic nephropathy who received follow-up for at least one year were recruited.The severity of different histologic lesions was assessed using the pathologic classification established by the Renal Pathology Society.Some common pathologic changes of DN were also examined.Renal outcomes were defined by progression to end-stage renal disease and doubling of serum creatinine.The influence of histologic findings on renal outcomes was assessed using univariate and multivariate Cox regression.Results:Among 396 enrolled patients,53 patients were included in class I,87 in class Ⅱa,32 in class Ⅱb,168 in classⅢ,and 56 in class Ⅳ based on the criteria of the pathological classification.Patients of different glomerular classifications had 5-year renal survival rates of 100%(class Ⅰ),90.1%(class Ⅱa),75.4%(class Ⅱb),39.0%(class Ⅲ)and 15.3%(class Ⅳ).A univariate Cox regression showed that the severity of glomerular and interstitial lesions had a significant impact on renal outcomes(p<0.001).Scores of vascular lesions demonstrated no association with renal outcomes(p>0.05).A multivariate COX analysis demonstrated that the glomerular classes and scores of interstitial fibrosis and tubular atrophy were significantly associated with renal outcomes when adjusting for baseline proteinuria,mean arterial pressure and estimated glomerular filtration rate(p<0.05).The glomerular and interstitial lesions correlated significantly among each other.However,in several patients,the severity of interstitial lesions did not correlate with glomerular lesions.Patients with nodule lesions,glomerular microaneurysms,atubular glomeruli,segmental sclerosis,hyaline caps,fibrinoid exudation,foam cells within loops,glomerular inflammation,crescents and segmental endothelial proliferation had a worse renal outcome.Crescent is an independent risk factor for renal survivalConclusion:These findings indicated that the severity of glomerular and interstitial lesions was significantly associated with renal outcomes in patients with diabetic nephropathy,whereas the current vascular indexes did not have any impact on renal outcomes,suggesting a nesscerry to redefine them.The glomerular and interstitial lesions correlated significantly among each other.However,in several patients,the severity of interstitial lesions did not correlate with glomerular lesions.Besides,crescent is an independent risk factor for renal survival.Part Two:Prevalence And Feature of Cardiovascular Calcification In Diabetic Nephropathy PatientsObjective:To evaluate the distribution of cardiovascular calcification and its risk factors in diabetic nephropathy patients with renal dysfunction.Methods:Two hundred seventy diabetic nephropathy patients with decreased renal function(CKD stages 2-5 and non-dialysis)were enrolled into this cross-sectional study.Coronary calcification score was detected by spiral computed tomography,abdominal aortic calcification score was detected by abdominal lateral radiographs,and the valve calcification was examined by cardiac ultrasound.Information about mineral disorder was collected.Related risk factors for cardiovascular calcification were evaluated by Logistic regression.Results:There were 40 patients in CKD stage 2(14.8%),121 in stage 3(44.8%),63 in stage 4(23.2%)and 46 in stage 5(17.0%).With the progression of CKD stages,serum phosphorus level increased gradually,serum calcium level decreased,while the intact parathyroid hormone level increased and 25-Hydroxyvitamin D level decreased(P<0.01).The total calcification prevalence was 70.3%in these patients,and the prevalence of coronary calcification,abdominal aortic calcification and valve calcification was 55.1%,43.4%and 23.9%,respectively.The total calcification prevalence in CKD stages 2-5 was 72.5%,73.6%,66.7%and 63.0%,respectively.The incidence of cardiovascular calcification was associated with age,duration of diabetes,duration of hypertension,history of cardiovascular diseases and the present of carotid artery plaque.No significant correlations were observed between calcification and sex,dyslipidemia,serum phosphorus and calcium,intact parathyroid hormone or stages of CKD.Among these,age,history of cardiovascular diseases and the present of carotid artery plaque were independent risk factors for coronary and abdominal aortic calcification,while age was the only independent risk factor for the valve calcification.Conclusion:The prevalence of cardiovascular calcification was high in diabetic nephropathy patients with renal dysfunction,even in early stage of CKD(stage 2)when mineral disorder was not obvious.The incidence of cardiovascular calcification was associated with traditional cardiovascular risk factors but not mineral disorder or stages of CKD.