Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigation of renal biopsy specimens from 488 patients with diabetic glomerulosclerosis (DGS) of varying severity revealed the following: 1) The severity of DGS increases with the duration of the diabetes. 2) As the severity of DGS increases, it is complicated with increasing frequency by exudative changes, which correspond in detail to hyperperfusion lesions described in the literature. 3) As the severity of DGS increases, the severity of arteriolosclerosis and the incidence of nephrotic syndrome increase significantly. 4) The 5- and 10-year renal survival rates are highest for those diabetic patients in whom the tubules and renal cortical interstitium are of normal appearance. These survival rates are diminished if any of the following are present at the time of biopsy: a) interstitial fibrosis; b) hyperperfusion lesions; c) nephrotic syndrome; d) elevation of the serum creatinine concentration to more than 1.3 mg%. 5) No significant correlation was found between renal survival rate and age, sex, or type of diabetes. 6) The inflammation of the renal interstitium seen in diabetes does not differ from that seen in chronic glomerulonephritis. Monocytes, macrophages, T lymphocytes, fibroblasts and fibrocytes play the major role in this inflammation. This inflammatory process is considered to represent not pyelonephritis, but rather an auto-immune process. In other words, it is proposed that the diabetic kidney fails not only as a result of non-specific glomerular lesions (hyperperfusion lesions) but also because of non-specific tubulointerstitial changes, whereas diabetic glomerulosclerosis alone does not lead to chronic renal failure.
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PMID:The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis. 206 8

The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain to be established. However, there is now evidence that renal disease clusters in families and that genetic factors are of central importance in determining liability. A predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Genetically controlled hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. This suggestion derives from the observation that the fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first sign of renal damage is the appearance of microalbuminuria and of a small elevation in arterial pressure, changes associated with significant mesangial expansion. Microalbuminuria is associated with abnormalities of lipoprotein profiles possibly as a consequence of insulin-resistance-induced hyperinsulinemia. It could be postulated that the environmental changes brought about by diabetes lead in susceptible individuals to increased systemic and intraglomerular pressure on the one hand and mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities would further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered of reduction in renal function, more hypertension, more proteinuria, more glomerular obsolence, more hyperlipidemia and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Mechanisms of diabetic renal and cardiovascular disease. 207 90

Nonsteroidal anti-inflammatory drugs, especially indomethacin, have variable effects on proteinuria when used alone, but can dramatically reduce proteinuria if combined with diuretics and sodium restriction. Reduction of angiotensin II concentrations in plasma and kidney following angiotensin-converting enzyme inhibition also reduces proteinuria, not only in nephrotic conditions but also in diverse diseases, including diabetes mellitus, glomerulosclerosis following subtotal nephrectomy, and membranous nephropathy. The reduction of proteinuria appears independent of decrements in blood pressure since other hypotensive agents do not alter proteinuria in these conditions.
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PMID:Prostaglandins, angiotension II, and proteinuria. 211 84

Coexistent renal pathology with diabetic glomerulosclerosis was found in 38 of 136 (28%) consecutive renal biopsies performed primarily for proteinuria in individuals with diabetes mellitus. The histological lesions found were glomerulonephritis (14), focal tubulointerstitial disease (23), and amyloidosis (1). Significant microscopic haematuria was present in 66% of all patients and did not help to distinguish non-diabetic disease. The severity of diffuse diabetic glomerular disease was independently associated with duration of diabetes, raised plasma creatinine, the presence of hypertension, clinical retinopathy and neuropathy, but not with type of diabetes, degree of proteinuria or glycosylated haemoglobin at the time of biopsy. Diffuse interstitial fibrosis was related to the severity of glomerular disease and, if severe, also with a significantly (p less than 0.01) higher plasma creatinine. Coexisting renal disease was found to be associated with a significantly higher plasma creatinine (p less than 0.01) independent of the severity of diabetic glomerulopathy. Coexistent pathology is a not uncommon finding in renal biopsies from diabetic patients with proteinuria. These lesions and their underlying causes may not only influence the renal function and natural history of renal disease in diabetic individuals, but may also determine the response of proteinuria to therapy.
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PMID:A clinical-histological study of individuals with diabetes mellitus and proteinuria. 213 92

Three cases are presented in which biopsy-proven diabetic nephropathy was found in nephrotic patients with no prior history of diabetes. One patient presented with advanced retinopathy and end-stage renal disease (ESRD), another with retinopathy and mild renal insufficiency, and a third with mild renal insufficiency alone. In each case, biopsy showed diffuse and nodular glomerulosclerosis with no evidence of kappa or lambda light chains. The patients had normal fasting serum glucose values, and two had normal oral glucose tolerance tests. Twenty-three similar cases in the literature were reviewed, and in most, some evidence of diabetes or hyperglycemia was found; five cases remained in which there was no evidence of hyperglycemia at any time. The cases reviewed included a disproportionate number of men (65%) and blacks (42%). It is concluded that diabetic nephropathy may exist in the absence of detectable hyperglycemia in a small number of extraordinarily susceptible individuals. Men and blacks appear to be at increased risk.
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PMID:Diabetic nephropathy without hyperglycemia. 214 35

At present the pathogenesis of diabetic nephropathy remains unresolved. Clearly lack of insulin, with its associated disorders of carbohydrate, protein, and/or lipid metabolism, initiates the process which eventually leads to the characteristic histologic picture of diabetic nephropathy. The disturbance in cellular metabolism per se could directly injure the kidney by altering the energy needs of the cell or by leading to the accumulation of cellular toxins (ie, polyols) or by causing the deficiency of key cellular metabolites (ie, myoinositol). Elevation of the plasma glucose concentration enhances the glycosylation of proteins, which in turn can lead to glomerular basement membrane thickening, loss of charge selectivity, and direct cellular damage. The multiple disturbances in intermediary metabolism are associated with increased levels of and/or enhanced sensitivity to a variety of growth factors, including IGF-I and angiotensin, and this could lead to glomerular hypertrophy. An increase in the filtered load and subsequent reabsorption of electrolytes and metabolites also could contribute to renal hypertrophy. In all animal models of nephropathy, including diabetes, glomerular hypertrophy has been shown to be the best correlate of glomerular sclerosis, proteinuria, and progressive renal deterioration. The potential mechanisms by which glomerular hypertrophy can lead to renal histologic damage were discussed previously. By increasing the luminal diameter, glomerular hypertrophy also would be expected to augment wall tension and thereby increase intraglomerular pressure. Derangements in cellular metabolism or altered sensitivity to angiotensin also can directly elevate the intraglomerular pressure and lead to structural renal damage. In this schema, elevated intraglomerular pressure is but one of many pathogenic factors that contribute to the development of diabetic glomerulopathy and albuminuria. The precise role of increased glomerular pressure in the evolution of diabetic nephropathy remains uncertain at present. In rats, severe diabetic nephropathy can occur without an increase in Pgc, while in humans, hyperfiltration does not appear to be a predictor of proteinuria and renal dysfunction. Lastly, it is likely that a variety of other factors, including the coagulation system, plasma/cell lipid levels, prostaglandins, etc, also play a role in the pathogenesis of diabetic nephropathy. According to the outline presented in Figure 1, it is unlikely that any single factor will be sufficient to explain the development of diabetic glomerulosclerosis. Ultimately, the origin of diabetic nephropathy in IDDM must be traced to insulin lack, with its associated derangements in cellular metabolism. Therefore, the importance of tight glucose control should not be underemphasized.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hyperfiltration and diabetic nephropathy: is it the beginning? Or is it the end? 219 Feb 80

Kidney disease, characterized by proteinuria and glomerular lesions, is a common complication of spontaneous diabetes mellitus in many animal species. It occurs in animals with hypoinsulinemia, hyperinsulinemia, or impaired glucose tolerance. The renal functional and structural abnormalities in spontaneously diabetic animals resemble human diabetic nephropathy in many respects. Mesangial expansion and glomerular basement membrane thickening, two structural hallmarks of diabetic glomerulopathy in humans, are the most frequently encountered lesions in animals. In addition, a nodular form of mesangial expansion that resembles but is not identical with human nodular glomerulosclerosis or the Kimmelstiel-Wilson lesion has been observed in some animal models. Other abnormalities, such as exudative hyaline lesions and arteriolar hyalinosis, have also been noted occasionally in other models. Although diabetic animals may develop kidney disease that resembles human diabetic nephropathy, no single animal model develops renal changes identical to those seen in humans. Nonetheless, animal models with spontaneous diabetic kidney disease may be useful for investigating the mechanisms of development of diabetic nephropathy and the effects of various treatment modalities on the progression of renal disease.
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PMID:Animal models of spontaneous diabetic kidney disease. 219 83

The natural history of renal lesions in nonobese diabetic mice was assessed. This strain develops a spontaneous overt insulin-dependent diabetes that has a female predominance and an autoimmune pathogenesis. We compared mice that had a normal glucose tolerance test with mice that had a diabetes of 2 to 15 weeks' duration. The glomerular surface area was increased in all diabetic mice regardless of the duration of hyperglycemia. There was an increase in the albumin/creatinine ratio in the urine of diabetic mice. Finally, nonobese diabetic mice all showed mesangial sclerosis that was more pronounced in the diabetic mice. This suggests that this strain is susceptible to glomerulosclerosis and that the occurrence of hyperglycemia results in an increase of glomerular size, mesangial sclerosis, and proteinuria, soon after glycosuria is first demonstrated.
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PMID:Glomerular lesions in nonobese diabetic mouse: before and after the onset of hyperglycemia. 219 27

Ten patients with insulin-dependent diabetes mellitus not associated with any signs of diabetic nephropathy were examined for the reserves of filtration renal function and early morphological alterations in organ tissues. The reserves of filtration were detected under the conditions of acute oral administration of protein (1.5 g/kg) as difference between the initial and stimulated levels of glomerular filtration (GF). Two groups of patients were distinguished: group I included patients with preserved filtration reserves (increment of GF amounted to 35%), group II included patients with no filtration reserves (reduction of GF was 20%). Both the groups differed significantly only in the initial level of GF (120 and 209 ml/min, respectively) and in the degree of morphological changes in the glomeruli: group I manifested minimum structural changes, group II showed the commencing diabetic glomerulosclerosis characterized by pronounced injury to the manubrium of the glomeruli. Therefore, the lack of filtration reserves in diabetes mellitus patients suggests the presence of the commencing diabetic glomerulonephritis even with the lack of the clinical signs of renal injury, which does not require the resorting to organ biopsy. The primary injury to the manubrium of the glomeruli is likely to be related to a high gradient of intraglomerular hydrostatic pressure, resulting in hyperfiltration.
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PMID:[The functional kidney reserves of diabetics]. 233 4

Nodular mesangial glomerulosclerosis is considered to be the specific renal lesion of diabetes mellitus, and typical histological lesions in non-diabetic patients have been reported only occasionally. A similar lesion has recently been described in patients suffering from light chain disease. We report on two patients without manifest diabetes and without light chain disease, showing progressive impairment of renal function and typical nodular mesangial glomerulosclerosis.
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PMID:Nodular mesangial glomerulosclerosis in patients without manifest diabetes mellitus. 238 7


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