Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study was designed to show whether there was any relation between muscle capillary basement membrane thickness, HLA-antigens, anti-insulin antibodies and proliferative retinopathy. Electron microscopic measurements of muscle capillary basement membrane thickness were performed on muscle biopsies from 15 insulin-dependent diabetics and severe proliferative retinopathy, 24 insulin-dependent diabetics with minimal retinopathy and 18 age- and sex matched non-diabetics. All the patients had had diabetes for 20 years or more. None had biochemical or clinical evidence of diabetic nephropathy. Basement membrane thickness was measured according to the methods of Siperstein and Williamson. Muscle capillary basement membrane thickening occurred in 32 of 39 diabetics, using the Siperstein method, but patients with proliferative retinopathy did not exhibit thicker basement membranes than patients with no or minimal changes in the retina. There were apparent differences in HLA-antigens between diabetics with and without proliferative retinopathy, but they did not reach statistical significance. There was no correlation between muscle capillary basement membrane thickness and the quantity of insulin antibodies. The results indicate that factors other than basement membrane thickening and genetic factors in the HLA-region, are responsible for the development of proliferative retinopathy.
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PMID:Basement membrane thickness, insulin antibodies and HLA-antigens in long standing insulin dependent diabetics with and without severe retinopathy. 48 71

One-hundred and seventy-two normotensive, insulin-dependent diabetic patients without clinical proteinuria (Albustix negative) were typed for the major histocompatibility complex class I (HLA-A, -B) and class II (HLA-DR) antigens. Urinary albumin excretion was measured as the albumin:creatinine ratio (UA/UC, mg/mmol) in an early morning sample. Patients expressing the HLA-A2 antigen had significantly higher UA/UC values than those not expressing the antigen. The observed ratio of geometric means was 1.77 (95 per cent confidence interval (CI) 1.18-2.67; p < 0.01); the relative risk of microalbuminuria (UA/UC > 3.0 mg/mmol) associated with expression of HLA-A2 was 2.52 (95 per cent CI 1.11-5.73; p < 0.05). There was no significant association between UA/UC and HLA-B8, -B15, -DR3, -DR4 or other antigens. Patients were re-studied after a mean period of 5.3 years: multiple linear regression analysis showed that the UA/UC at this time was positively related to the initial glycosylated haemoglobin level (p < 0.01) and expression of the HLA-A2 antigen (p < 0.05), but not to blood pressure or creatinine clearance. Fifteen patients developed macroalbuminuria at follow-up (UA/UC > 45.5 mg/mmol). Compared with a group matched for age, sex, duration of diabetes, and glycosylated haemoglobin who did not develop macroalbuminuria, macroalbuminuric patients had a higher frequency of HLA-A2 (p < 0.01). The odds ratio of progressing to macroalbuminuria associated with HLA-A2 had a 95 per cent CI of 1.71 to infinity. We conclude that an immunogenetic factor may play a role in the development of early diabetic nephropathy and that the risk associated with expression of the HLA-A2 antigen is independent of metabolic control and blood pressure.
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PMID:The immunogenetics of early nephropathy in insulin-dependent diabetes mellitus: association between the HLA-A2 antigen and albuminuria. 144 47

Recent data suggest genetic contributions to the microvascular complications of Type 1 (insulin-dependent) diabetes mellitus. Most research has focused on the HLA region, and the potential role of other genetic loci has not been adequately explored. We examined the possible relationship between DNA polymorphisms in the region 5' to the insulin gene on chromosome 11 and diabetic nephropathy. This was done by comparison of those diabetic patients homozygous for class 1 alleles at the 5' insulin gene polymorphism locus to 1/3 heterozygotes in a well-characterized series of 324 insulin-requiring diabetic patients from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Proteinuria (defined as greater than or equal to 0.3 g protein/l urine), was used as suggestive evidence for diabetic nephropathy. Hypertension, a frequent associated finding in diabetic patients with nephropathy, was defined as a blood pressure greater than 140/90 or a history of previous treatment of hypertension. The two genotypically defined groups did not differ from each other in regard to sex ratio, age at diagnosis, age at examination, duration of diabetes, body mass, HbAlc or C-peptide. The 1+1 group had a higher prevalence of proteinuria, 29% as compared to 16.2% in other genotypes (p less than 0.05). There was no significant difference in the frequency of hypertension between the two genotypic groups. This finding suggests that the 5' insulin gene polymorphism may be associated with risk for nephropathy, but the pathophysiologic mechanism remains unclear.
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PMID:The 5' insulin gene polymorphism and the genetics of vascular complications in type 1 (insulin-dependent) diabetes mellitus. 195 2

Between December 1966 and April 1978, 265 uremic patients with type I diabetes received primary renal allografts at the University of Minnesota. One hundred of the diabetic patients were alive with a functioning graft 10 years after transplantation. The actual 10-year patient and primary graft functional survival rates overall were 40% and 32%, respectively. For recipients of HLA-identical sibling (n = 45), mismatched living-related (n = 121), and cadaver donor grafts (n = 99), the actual 10-year patient survival rates were 64%, 33%, and 36%, respectively, and the actual 10-year graft functional survival rates were 62%, 28%, and 22%, respectively. The differences in patient and graft survival rates between HLA-identical graft recipients and recipients of mismatched related and cadaver grafts were significant (P less than 0.001). Of the 100 patients who survived into a second decade, at 15 years posttransplant 51% were alive, and 41% had functioning grafts. For recipients of HLA-identical sibling, mismatched living-related donor grafts, and cadaver donor grafts who survived 10 years, 47%, 57%, and 43%, respectively, were alive at 15 years, and 31%, 45%, and 43%, respectively, had functioning grafts. For recipients who made it to the second decade, patient and primary graft survival rates thereafter were not statistically different by donor source. Twenty-three patients died in the second decade after transplantation, 10 of cardiovascular disease. Twenty-five patients lost graft function in the second decade, 19 from death with a functioning graft. In regard to diabetic complications, recurrence of diabetic nephropathy was common, but only two patients lost graft function solely for this reason. In 21 patients (42 eyes) followed prospectively for 10 years, visual acuity deteriorated in 26%, was stable in 64%, and improved in 10% of eyes. Neurophysiological test results indicated that correction of uremia does not stop the progression of diabetic neuropathy in recipients of kidney transplants alone. Even without cyclosporine, nearly two-thirds of recipients of HLA-identical kidney grafts, more than one-quarter of recipients of mismatched living-related donor grafts, and more than one-fifth receiving cadaver grafts enjoyed an extension of life for more than 10 years.
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PMID:Long-term survival following kidney transplantation in 100 type I diabetic patients. 264 18

Both early onset and late onset type II diabetes were present in one family of nine siblings. The three early onset type II diabetic siblings showed severe microvascular complications: proliferative retinopathy, diabetic nephropathy, and peripheral neuropathy. Early onset type II diabetes was not associated with any particular HLA haplotype. Early onset type II diabetes could be considered a clinical and genetic disease entity different from MODY type diabetes.
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PMID:Severe microvascular disease in type II diabetes of early onset. A family study. 275 Apr 46

The state of the complement system was studied in 91 patients with insulin dependent and in 47 patients with non-insulin dependent diabetes. A study was made of the quantity of hemolytically effective molecules of some components C2, C4, C3, C5 of classic and factors B and D of alternative pathway of activation. Complement components were studied for control in 51 healthy blood donors. Antigens B8 and B18 of the HLA-histocompatibility system were studied in parallel in 24 patients and 21 donors. A significantly raised level of components C3 and C4, factors B and D was revealed in the patients with insulin dependent diabetes as compared to the controls (p less than 0.05). In non-insulin dependent diabetes C4, factors B and D were significantly raised and the level of C5 was lowered (p less than 0.05). In the patients with insulin dependent diabetes having antigens B18 the level of C3 was raised and the level of C4 was lowered as compared to the controls. The level of factors B and D was also lower than that in the diabetic patients. An analysis of the content of the complement components in 31 diabetic patients with diabetic nephropathy indicated a decrease in the levels of components C3 and C5 and an increase in the content of C4 (p less than 0.001) as compared to the normal. Diabetes was accompanied by considerable variations as compared to normal values characterizing the state of the complement system and reflecting, to a certain extent, the main features of the pathogenesis of disease.
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PMID:[Levels of various components of the classical and alternative pathways of complement activation in diabetes mellitus patients]. 347 6

Improved patient survival and rehabilitation have been continuously reported over the last decade for diabetics in irreversible kidney failure. There have, however, been no controlled prospective trials of the relative merits of CAPD, maintenance hemodialysis, or kidney transplantation in the uremic diabetic. As a generalization, younger, more rehabilitatable diabetics have been offered a kidney transplant, while older, often sicker diabetics have been relegated to CAPD, leaving most diabetics in the subset managed by maintenance hemodialysis. Treatment preference has reasonably been based on a team's experience and available facilities. Furthermore, nonuniform criteria for patient selection, and timing of the onset of uremia therapy, preclude direct comparisons between series of treated diabetics. While survival of diabetics treated with maintenance hemodialysis or peritoneal dialysis has improved substantially in recent years, survival and rehabilitation after kidney transplantation are superior to other forms of uremia therapy. Cumulative data suggest that a treated uremic diabetic patient has a 50% chance of living 3 years on hemodialysis, a 50% chance of surviving 5 years if he receives a well functioning cadaveric kidney transplant, and an even longer anticipated survival of 50% for 7.5 years if transplanted with a well-functioning living-related kidney. Even better results may be attainable with kidneys from HLA-identical siblings, particularly when transplanted early and employing cyclosporine rather than azathioprine, thereby allowing reduction of steroid dosage to minimal levels. Kidney transplantation, when judiciously undertaken by a team skilled in overall diabetic management, is the treatment of choice for the uremic diabetic. Dialytic therapy, however, has appreciable value, not only as an alternative in patients in whom transplantation is contraindicated, or for whom a kidney is not available, but as life-sustaining therapy while awaiting surgical intervention. No matter how treated, diabetic nephropathy need no longer be viewed as a disease of desperation. Unfortunately, proffering a substitute for the diabetic patient's own renal function does not, in and of itself, diminish progression of preexisting multisystem micro- and macrovascular disease. Implantation of a functioning kidney transplant in a failing diabetic with the renal-retinal syndrome provides a firm base upon which, with careful attention to regulation of blood glucose, reduction of hypertensive blood pressure, and provision of emotional support, a new, tenuous life may be built.
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PMID:Treatment of the uremic diabetic. 388 74

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.
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PMID:HLA antigens and risk factors for nephropathy in type 1 (insulin-dependent) diabetes mellitus. 659 Apr 2

We have studied the histocompatibility (HLA) antigens A and B in 99 insulin dependent diabetics (IDDN) with terminal uremia due to diabetic nephropathy and in 96 insulin dependent diabetic patients (IDD) without clinically detectable kidney disease. The two groups were matched for duration of disease and other clinical features. The frequencies of the HLA antigens B8, B15, B18 and B8/B15 were significantly increased in both groups and B7 and B12 were decreased. There were no significant differences between the two groups. These results contrast with previously described similar studies of HLA and diabetic proliferative retinopathy. In these studies B7 was significantly less common in patients with proliferative retinopathy as compared with patients without proliferative retinopathy and B15 was more common in a subset of patients with proliferative retinopathy. The differences between the two studies may reflect sample bias or a genetic difference between the two types of diabetic microangiopathy.
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PMID:Is diabetic microangiopathy genetically heterogeneous? HLA and diabetic nephropathy. 694 52

During the period 1969 to 1978 survival of recipients of 1st cadaveric renal grafts improved. This improvement occurred in spite of a sharp increase in high risk patients accepted for transplantation, including patients with high age, diabetic nephropathy and advanced arteriosclerotic disease. In the same period 1st graft survival decreased. The declining graft prognosis was related to the acceptance of 3-4 HLA-A and B incompatible grafts from 1973 onwards. Grafts with 0-2 incompatibilities had a stable survival during the whole 10-years period. The group of patients receiving grafts with 3-4 incompatibilities, however, included significantly more patients with diabetic nephropathy and age above 55 years. Further analysis demonstrated that the inferior graft prognosis was caused by a combined effect of HLA-mismatched grafts and the number of high risk patients. The distribution of antibodies at retransplantation (2nd graft) was similar whether the lost 1st graft was compatible for 0-2 or 3-4 HLA antigens. Also the prognosis of retransplantation was similar in the two groups.
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PMID:The effect of 3-4 HLA-A and -B antigen mis-matched cadaveric kidney transplants on graft and patient survival. 701 40


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