Risk Factor For Diabetic Nephropathy Research Articles

Glomerular hyperfiltration in type I, type II, and secondary diabetes

Glomerular hyperfiltration, a risk factor for diabetic nephropathy, has been reported in type I insulin-dependent diabetics, but it is not clear if it occurs in other types of diabetes. To ascertain the prevalence of glomerular hyperfiltration in various types of diabetes, we measured glomerular filtration rate (GFR) in 158 diabetics (91 type I, 36 type II without insulin treatment, 20 type II with insulin treatment, and 11 subjects with diabetes secondary to chronic pancreatitis), and classified them as hyper-, normo-, or hypofiltration according to values measured in 36 age-match controls. After elimination of subjects with overt renal disease or hypertension, glomerular hyperfiltration was detected in 35% of the type I diabetics, 32% of the type II diabetics without insulin treatment, one subject with chronic pancreatitis, and one type II diabetics with insulin treatment. Glomerular hyperfiltration was associated with high blood glucose in type I, insulin-dependent diabetics, and with a high apolipoprotein B A1 ratio in type II, non-insulin-dependent diabetics without insulin treatment. In all subjects with glomerular hyperfiltration, GFR values and urinary albumin excretion were positively related ( r = 0.33; n = 34; p = 0.05). Glomerular hyperfiltration is detectable among all types of diabetics.

Kidney transplantation in Type 1 (insulin-dependent) diabetic patients

The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24-36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml.min-1 at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p = 0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p = 0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p = 0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerular hyperfiltration as a risk factor for diabetic nephropathy: Five-year report of a prospective study

Glomerular hyperfiltration as a risk factor for diabetic nephropathy: Five-year report of a prospective study

Cigarette smoking and glomerular filtration rate in insulin‐treated diabetics without manifest nephropathy

A sample of 120 insulin-treated diabetics, 20-40 years of age, with a glomerular filtration rate (GFR) exceeding -2 SD of the age-adjusted value and without albuminuria greater than 300 mg 24 h-1, and with a diastolic blood pressure not greater than 90 mmHg, were studied in order to evaluate the possible effect of smoking on glomerular filtration rate. The patients reported their smoking habits, use of oral snuff, use of alcohol, physical exercise and heredity for hypertension in a simple questionnaire. GFR was assessed with 51Cr-EDTA-clearance and glomerular hyperfiltration was defined as a value exceeding +2 SD of the age-adjusted normal value. We found a significantly higher prevalence of glomerular hyperfiltration in smokers than in non-smokers (41% vs. 18%), but no increased prevalence in users of oral snuff. In cigarette smokers a multivariate analysis revealed that GFR was positively related to body mass index (BMI), and negatively related to the number of cigarettes smoked per week and the mean blood pressure. In non-smokers GFR was dependent only on age. We conclude that in insulin-treated diabetics glomerular hyperfiltration is related to smoking, and that the GFR in smoking diabetics is directly dependent on the smoke doses. As glomerular hyperfiltration is regarded as a risk factor for diabetic nephropathy, our findings should be relevant to preventive measures in clinical work.

The prevalence of micro-albuminuria and glomerular hyperfiltration in young patients with IDDM

We have assessed the prevalence of two risk factors for diabetic nephropathy, i.e., micro-albuminuria and a raised glomerular filtration rate (GFR), in 127 insulin-dependent diabetic patients aged 13–36 years. Micro-albuminuria (albumin excretion rate (AER) 20–200 μg/min) was found in 46 subjects (36%) and GFR was elevated (>135 ml/min/1.73 m 2) in 43 (34%). The prevalence of supranormal GFR declined and that of micro-albuminuria rose progressively with the increasing duration of diabetes. While age and sex distribution were similar in subjects with and without raised AER, duration of diabetes was significantly longer, blood pressure (BP) was significantly greater and age of onset was lower in the microalbuminuric group. Blood pressure was significantly elevated only in the patients with AFR of 70–200 μg/min; there was a linear trend for BP to rise as AER increased. Stepwise logistic regression analysis indicated that duration of diabetes ( P < 0.0001), age of onset of diabetes ( P < 0.005) and current glycaemic control. (HbA 1) ( P < 0.01) were risk factors for micro-albuminuria. The association with a rising blood pressure appears to be secondary to the renal involvement. In this cross-sectional study an association of micro-albuminuria with a raised GFR could not be demonstrated.

Prior long term glycaemic control and insulin therapy in insulin-dependent diabetic adolescents with microalbuminuria

Adolescence seems to be a period of increased risk for the initiation of diabetic renal disease in insulin-dependent diabetic children. Poor glycaemic control is a risk factor for diabetic nephropathy. We have therefore evaluated prior long-term glycaemic control in 23 diabetic adolescents with microalbuminuria (albumin excretion rate (AER) 20–200 μg/min, median 39.0 μg/min) and in 23 matched diabetic controls with AER < 20 μg/min (median 9.3 μg/min). Glycaemic control was assessed by mean HbA 1 and clinic blood glucose levels over a period ranging from 12 to 84 months (median 48 months). Mean HbA 1 was 13.6 ± 2.0% in the microalbuminuric subjects, compared to 11.5 ± 2.2% in the controls ( P < 0.002); mean blood glucose levels were 13.5 ± 3.0 and 11.4 ± 3.0 mmol/l, respectively ( P < 0.02). There appeared to be a ‘threshold effect’ (mean HbA 1 > 12.0%), above which the development of microalbuminuria was more likely. More patients with microalbuminuria than controls had been treated with a single rather than twice-daily insulin injections ( P < 0.001), and glycaemic control was significantly worse in patients treated with one injection. We conclude that poor long term glycaemic control is a risk factor for microalbuminuria, and that improving control during childhood is likely to reduce the prevalence of later microalbuminuria. Two insulin injections, of combined intermediate and short-acting preparations, are more likely to provide better control than a single daily insulin dose.

HLA antigens and risk factors for nephropathy in Type 1 (insulin-dependent) diabetes mellitus

This study of risk factors for diabetic nephropathy in juvenile Type 1 (insulin-dependent) diabetes mellitus compares two carefully characterised groups of patients, one with proteinuria (n = 23), the other a control group (n = 24) with no evidence of nephropathy despite more than 25 years of diabetic life. No significant difference was observed between the groups in any HLA-A, -B or -DR antigen of Bf allotype. DR3 was present in 87% of patients with proteinuria and 75% of the diabetic control group; DR4 was present in 48% of patients with proteinuria and 63% of diabetic controls; BfFl was present in 17% of patients with nephropathy and 9% of the diabetic control group. Compared with the control group, patients with proteinuria had significantly higher mean diabetic-clinic blood glucose concentrations before the diagnosis of microvascular disease, a significantly earlier age at diagnosis of diabetes, and had more often been treated with once-daily as opposed to twice-daily insulin regimens. Susceptibility to nephropathy in Type 1 diabetes appears to be determined by the quality of metabolic control and age of onset of diabetes; although the number of subjects studied was relatively small no evidence was found of any influence of HLA or Bf phenotype.