| Part one: A comparison study of clinical features and prognosis in patients with nodular and diffuse diabetic nephropathyObjective: To retrospectively investigate two types of diabetic nephropathy and compared their clinical features and prognosis. One is diffuse glomerulosclerosis (DIF), the other is nodular glomerulosclerosis (NOD).Methods: One hundred and twenty-four patients with biopsy-proven 58 DIF and 66 NOD were enrolled in this study. All patients satisfied the following entry criteria: urine protein excretion ≥500mg/24h or albumin excretion ≥300mg/24h, serum creatine ≤3mg/dl or glomerular filtration rates (GFR) ≥30ml/min. They were diagnosed diabetes mellitus according to the criteria of the World Health Organization(WHO) report of 1985 .Data as duration of diabetes and hypertention, body mass index(BMI), diabetic retinopathy, plasma glycosylated hemoglobin, albumin, triglyceride, cholesterol, creatinine and proteinuria, urine NAG enzyme, urine osmolity, clearance rate(Ccr) were determined. All the patients were visited by letters, telephone call or out-patient clinic. The deadline date of follow-up visit was July 2004. The follow up time was from 3 to 108 months, average 36 months. Results: 1)Compared with the DIF patients, the NOD patients had longer duration of diabetic mellitus(l 19± 8.5 &52+ 8.9m, p<0.01), more severe proteinuria(4.20± 3.3 & 1.79± 2.0 g/24h, p<0.01), lower Ccr (46.1± 25.0& 68.4+ 28.2 ml/min), 2) In the NOD cases, there were 90% presented diabetic retinopathy, in the DIF cases, while only 14% in the DIF cases. 3) In our cases, 26(21.0%) patients died during the follow-up visit, including 18 NOD cases and 8 DIF cases. The main causes of death were end-stage renal failure (73.1%), others were cardiovascular events (15.4%), tumor (7.7%), and hyperthyroidism (3.8%). In the DIF patients, the 5 year renal and patient survival rate was 78% and 81% respectively, in the NOD patients, the 5 year renal and patient survival rate was 24% and 41%, respectively. However, the 5 year renal andpatient survival rate of NOD subjects was significantly lower than that of DIF subjects (p<0.01).Conclusion: The NOD subjects had longer diabetic duration, more severe renal damage, and poorer prognosis, furthermore, these patients had higher risk to develop diabetic retinopathy. It was suggested that DIF maybe the earlier stage of NOD.Part two: Analysis of prognostic factors in patients with type 2 diabetic nephropathyObjective: To investigate the prognostic factors in patients with type 2 DN. Methods: 153 DN patients who underwent renal biopsy in our Research Institute of Nephrology were retrospectively reviewed (December 1992—April 2004) and the univariate and multivariate analysis were used to determinne the prognostic factors. All patients satisfied the following entry criteria: urine protein excretion >500mg/24h or albumin excretion >300mg/24h, serum creatine <3mg/dl or glomerular filtration rates (GFR) >30ml/min. Pathological changes included mild mesengium hyperplasia, diffuse glomerulosclerosis and nodular glomerulosclerosis. All patients were diagnosed diabetes mellitus according to the criteria of the World Health Organization (WHO) report of 1985.Results: There were 105 males(68.6%)and 48 females(31.4%), with an average age of 53 years (ranged from 26 to 75) , the average duration of diabetes was 93 months. There were 32 cases(20.9%) died during the follow-up visit, the main causes of death was end-stage renal disease(21 cases, 65.6%), the other causes of death were cardiovascular disease(6 cases, 18.8%), cerebrovascular disease(l cases, 3.1%), tumor(3 cases, 9.4%) and hyperthyroidism(l cases, 3.1%). The overall survival rates of these patients at 1 year and 5 year were 93.8% and 36.7% respectively. The median renal survival time of these patients was 69 months, the renal survival rates at 1 year and 5 year were 88.6% and 13.2% respectively. Kaplan-Meier estimates showed that gender, diabetes duration, diabetic retinopathy, control of blood pressure, body mass index, plasma cholesterol, proteinuria, plasma albumin, nodular glomerularlesion were the predictors of survival. Multivariate analysis showed that only diabetes duration, diabetic retinopathy, proteinuria and control of blood pressure were independent prognostic factors.Conclusion: Diabetes duration, diabetic retinopathy, proteinuria and control of blood pressure were independent prognostic factors in DN patients.Part three: The relationship between glucose transporter gene polymorphisms and clinical features and prognosis in diabetic nephropathyObjective: To analyze the relationship between glucose transporter-1 (GLUT1) gene polymorphisms and clinical features and prognosis in diabetic nephropathy. Methods: One hundred and two diabetic nephropathy patients (67 males, 35 females) were retrospectively reviewed (June 1996- July 2001). All patients satisfied the following entry criteria: urine protein excretion >500mg/24h or albumin excretion >300mg/24h, serum creatine <3mg/dl or glomerular filtration rates (GFR) >30ml/min. All patients were diagnosed diabetes mellitus according to the criteria of the World Health Organization (WHO) report of 1985 . 74 cases underwent renal biopsy during hospital stay. The control group includes 124 normal subjects (58 males, 66 females). The GLUT1 genotype was analyzed by PCR-RFLP in all these subjects. Data as age, duration of diabetes, plasma glycosylated hemoglobin, albumin, triglyceride, cholesterol, creatinine and proteinuria, urine NAG enzyme, urine osmolity, clearance rate(Ccr) were determined. 61 DN patients were followed up for 1-7 years. Results: 1) The frequencies of Xbal(+) and Xbal(-) allele were 79% and 21% respectively in normal subjects, and were 72% and 28% respectively in DN patients, the frequence of Xbal(-) allele was significantly higher in DN patients than in normal subjects (p<0.05) , 2) There was no significant difference of clinical feature in different GLUT1 genotype (p>0.05) , 3) There was no significant difference of frequences of GLUT1 genotype in patients with diffuse glomerulosclerosis(DIF) and nodular glomerulosclerosis (NOD) (p>0.05) , 4) The average renal survival time of...
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