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)

Abnormal renal diseases including nephrotic syndrome and chronic renal failure are associated with hyperlipidemia, significance of abnormal lipid metabolism has been thought to be limited in some inherited renal diseases. However, recent studies have postulated that glomerulosclerosis is induced by hyperlipidemia and is in common with atherosclerosis. This involvement is found in the progressive renal disorders, e.g., focal glomerular sclerosis, diabetic nephropathy and glycogen storage disease. Interaction between macrophages and mesangial cells may play an important role in such conditions. This evidence is supported by experimental models with hyperlipidemia. On the other hand, discovery and new hereditary metabolic disorders, such as type III hyperlipoproteinemia and lipoprotein glomerulopathy, shows that apolipoprotein (apo) E abnormalities are responsible for the glomerular lesions. Especially, lipoprotein glomerulopathy has specific features different from those of lipid-induced renal diseases. In this disease, apo E Sendai which results from new substitution (Arginine 145-->Proline) may induce intraglomerular lipoprotein thrombi characteristic of lipoprotein glomerulopathy.
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PMID:Abnormal lipid metabolism and renal disorders. 916 48

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.
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PMID:Proteinuria in mild to moderate hypertension: results of the VA cooperative study of six antihypertensive agents and placebo. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. 918 Dec 78

Diabetic nephropathy is a major cause of illness and premature death in diabetic patients, largely through accompanying cardiovascular disease and end-stage renal failure. Proteinuria heralds the clinical nephropathy, and the worsening of proteinuria parallels the progression of renal disease towards chronic renal failure. A large body of evidence has accumulated that emphasizes the role of elevated blood pressure in the progression of renal disease, as well as the clear benefit of antihypertensive treatment. However, the choice of antihypertensive drug to protect renal function was less clear in the past. In earlier studies, a reduction in the rate of progressive renal failure in hypertensive subjects has been shown with diuretics, beta-blockers, and vasodilators. However, there is now increasing evidence that angiotensin converting enzyme (ACE) inhibitors and some calcium antagonists produce a more beneficial effect on nephropathy in terms of reducing proteinuria and slowing progression to renal failure. These drugs are attributed nephroprotective capacity beyond their systemic blood pressure lowering effects, and initial clinical trials with combinations have revealed additive nephroprotective effects. Finally, ACE-inhibitors and calcium antagonists have no adverse effects on glycemic control or lipid levels and may even improve insulin sensitivity. This further promotes these antihypertensives to first-line drugs when treating subjects at risk of metabolic disorders or people with diabetes.
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PMID:Protecting the residual renal function: which drugs of choice? 923 93

A very low protein diet (0.3 g/kg ideal body weight) supplemented with essential amino acids (or ketoanalogues) is seldom employed at present in chronic renal failure for fear of inducing protein deficiency, especially in patients who also have the nephrotic syndrome. Nevertheless, we have used this dietary regimen in predialysis patients for a number of years. We have shown that when these patients reach the end stage, they rarely exhibit hypoalbuminemia, in contrast to the reported 25-50% hypoalbuminemia at the onset of dialysis nationwide. Furthermore, their survival for the first 2 years on dialysis is much improved, in comparison with the national experience, adjusted for age, sex, and cause of renal disease. When nephrotic patients are given this regimen, they exhibit some improvement in parameters of the nephrotic state, but nevertheless progress to dialysis, provided their initial glomerular filtration rate (GFR) is < 30 ml/min. However, if their initial GFR is > 30 ml/min, they may show gradual but complete remission of the nephrotic syndrome, even when the underlying disease is diabetic nephropathy or focal segmental glomerulosclerosis. We conclude that this dietary regimen is not only safe in patients with renal failure, with or without the nephrotic syndrome, but may be of substantial benefit. The mechanism remains to be explained.
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PMID:Effects of a supplemented very low protein diet in predialysis patients on the serum albumin level, proteinuria, and subsequent survival on dialysis. 939 19

Plasma lipoproteins (LP) may be identified on the basis of density properties or apolipoprotein (apo) composition. ApoB-containing LP occur in VLDL, IDL and LDL. There are several types of apoB-containing LP characterized by specific composition of minor apolipoproteins (apoC, apoE etc.) and lipid constituents (triglycerides and cholesterol), metabolic properties and relative atherogenicity. The alterations of lipoprotein metabolism in renal disease resulting in elevated levels of apoB-containing LP may be reflected in hyperlipidemia. Whereas nephrotic syndrome and heavy proteinuria are associated with increased formation of cholesterol-rich apoB-containing LP in LDL and VLDL, the characteristic feature in renal failure is the accumulation of intact or partially metabolised triglyceride-rich LP in IDL and VLDL. The potentially atherogenic apoB-containing LP have been linked to the pathogenic processes that result in progressive glomerular and interstitial lesions and ultimate loss of renal function. The mechanisms of injury are not fully understood. Receptor- and non-receptor mediated uptake of LP by mesangial cells may induce or accelerate proliferative and sclerotic processes in the glomerular mesangium that are analogous to atherosclerosis in the arterial wall. Changes in glomerular permeability can result in increased filtration of LP that may be internalized by tubular cells and elicit corresponding lesions in the interstitial tissues. The negative impact of proteinuria on the prognosis of renal disease could be mediated in part through an increased filtration of lipoproteins. Induction of hyperlipidemia accelerates glomerular and interstitial damage in experimental renal failure. This can be attenuated by treatment with hypolipemic agents. In patients, increased concentrations of apoB-containing LP are associated with more rapid progression of renal insufficiency in both primary renal disease and diabetic nephropathy. It is, however, presently not known to what extent treatment of the renal dyslipidemia can modify the progression of chronic renal failure. Experimental and clinical evidence suggest that apoB-containing LP may play a pathogenetic role in the progression of renal disease.
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PMID:Progression of renal failure: role of apolipoprotein B-containing lipoproteins. 940 33

A prospective study of all new cases of chronic renal failure (CRF) including inservice referrals was done at our hospital over a period of 1 year from May 1994 to April 1995. The diagnosis of CRF was based on clinical, laboratory, and radiological features. Kidney biopsies were done when indicated. The patients were subdivided into various etiologic groups of primary renal disease according to standard criteria. There were a total of 835 cases of CRF with a median age of 43 years (range 10 days to 90 years); 67.8% of them were men. Glomerulonephritis (28.6%), diabetic nephropathy (23.2%), and interstitial nephritis (16.5%) were the most common causes of CRF, followed by obstructive nephropathy (6.4%), benign nephrosclerosis (4.1%), and polycystic kidney disease (2%). However, in patients more than 40 years of age, diabetic nephropathy was the most common cause (36.8%). The cause of CRF was unknown in 16.2% of the cases. One hundred twenty-one patients (14.5%) had an acute deterioration of their underlying renal dysfunction at presentation. This was most commonly due to accelerated hypertension (26.1%), infection (22.4%), volume depletion (20.1%), and drugs (14.9%). Anti-inflammatory drugs were the most common drugs responsible for the acute decline in renal function. One year after their initial presentation, of the 512 patients (61.3%) with end stage renal disease, 12.5% had died, 17% had received a kidney allograft, 12.7% were on some form of maintenance dialysis, and 295 patients were lost to follow-up. Of the 323 patients with less severe illness, 7 died, 209 were on outpatient treatment, and 107 patients were lost to follow-up. We conclude that the pattern of CRF in India does not differ greatly from that in the developed countries. However, it carries a poorer prognosis due to late referral and limited availability and affordability of renal replacement therapy in India.
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PMID:Chronic renal failure in India. 941 33

Diabetic nephropathy is a major cause of chronic renal failure. The evidence available indicates that renal hemodynamics are altered in clinical and experimental diabetes mellitus. In these circumstances, an increased glomerular filtration rate (GFR) is associated with albuminuria and eventually with glomerulosclerosis. We studied the renal and hemodynamic effects of long-term treatment (5 months) using an angiotensin-converting enzyme inhibitor (trandolapril, 0.7 mg/g b.w. per day) and a calcium antagonist (verapamil, 20 mg/g b.w. per day), and the combination of the two (veratran) at the same dose, on streptozotocin-diabetic uninephrectomized rats. A moderate degree of hyperglycemia (2-4 g/l) was maintained with daily insulin. Mean arterial pressure (MAP) was measured monthly using the tail-cuff method. Determinations were made of urinary protein excretion, creatinine clearance, urinary electrolyte excretion and, at the end of treatment, renal and cardiac hypertrophy. MAP was similar in control and untreated diabetic rats. Trandolapril and veratran reduced MAP whereas verapamil alone had no effect on these animals. All groups showed a slight proteinuria that increased with verapamil treatment. The GFR of diabetic animals was higher than in the control group (mainly the first 2 months), except for veratran group, in which it was similar to the control value. Urinary electrolyte excretion increased in all diabetic groups with no significant differences among them. Veratran induced a protective effect against cardiac hypertrophy. None of the treatments affected renal hypertrophy. It is concluded that in a murine model of diabetes without hypertension or proteinuria, a combination of verapamil and trandolapril prevents hyperfiltration whereas verapamil alone increases proteinuria.
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PMID:Renal effects of antihypertensive therapy in uninephrectomized diabetic rats. 944 Jan 38

Diabetic nephropathy is one of the main causes of chronic renal failure in developed countries. The genesis and development of diabetic nephropathy is associated in both types of diabetes with a more rapid progression of other secondary complications and an increased mortality, in particular cardiovascular mortality. The main causes of development of diabetic nephropathy are prolonged hyperglycaemia along with a so far not elucidated inborn disposition. The course of diabetic nephropathy is characterized more clearly in type 1 diabetes. The clinically manifest stage is already irreversible and in the course of years it develops into chronic renal failure. Preventive and curative measures include maintenance of optimal metabolic control, systematic control of blood pressure, in particular by ACE-inhibitors, and a reduction of protein intake. Systematic multidisciplinary collaboration in care for patients with diabetic nephropathy helps to prevent the progression of other secondary complications such as diabetic foot and diabetic retinopathy. At present in the Czech Republic dialysis methods substituting renal function are available to practically all patients with diabetic nephropathy. As regards survival time and quality of life the optimal method of renal function replacement for patients in the terminal stage of diabetic nephropathy is transplantation.
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PMID:[Care of patients with diabetic nephropathy]. 947 80

Glomerulosclerosis and tubulointerstitial fibrosis are common morphological correlates of many end-stage kidneys. There is ample evidence that transforming growth factor-beta (TGF-beta) plays a major role in these alterations by directly stimulating synthesis of many extracellular matrix components and reducing collagenase production, finally leading to renal scarring. Although many factors may induce TGF-beta expression in the kidney, one very interesting aspect is the link between angiotensin II (ANG II) and TGF-beta. Originating from observations in vascular smooth muscle cells, there are now several additional studies showing that ANG II stimulates TGF-beta expression in the kidney. Although cell culture studies have convincingly demonstrated that the vasoactive peptide directly stimulates transcription as well as bioactivation of TGF-beta, the in vivo evidence is more indirect. Nevertheless, there are several pathophysiological situations including unilateral ureteral obstruction, chronic cyclosporin A nephrotoxicity, various models of hypertension, and probably diabetic nephropathy in which ANG II-mediated TGF-beta induction has been demonstrated to play an important role in the progression of the disease. The fascinating aspect of this relationship between ANG II and TGF-beta is the fact that hemodynamic changes as well as structural changes are linked together generating a unifying model of progression of chronic renal failure with ANG II as the key player. Angiotensin-converting enzyme (ACE) inhibitor and the more recently introduced AT1-receptor blocker may be potential drugs to interfere with this ANG II-mediated TGF-beta expression. Therefore, these drugs should not only be considered as antihypertensive medications, but should rather be viewed as renoprotective substances influencing renal remodeling by preventing local TGF-beta expression.
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PMID:Link between angiotensin II and TGF-beta in the kidney. 952 2

Two patients with non-insulin-dependent diabetes mellitus (NIDDM) and moderate chronic renal failure experienced a worsening of glycaemic control when recombinant human erythropoietin (r-HuEPO) was introduced, leading to insulin therapy. A 71-year-old woman with a 20-year history of NIDDM had presented histologically documented diabetic nephropathy for 2 years during which glucose control was stabilized by a diet and glibenclamide 10 mg. In the 6 months following introduction of r-HuEPO, hyperglycaemic symptoms developed, and HbA1C increased from 8.9% to 12.3%. During this period, no intercurrent events occurred, except epistaxis due to accelerated hypertension one month after r-HuEPO was started. A 62-year-old man had a 15-year history of NIDDM, with proliferative retinopathy, macroproteinuria and chronic renal failure for 4 years. The day after the first injection of r-HuEPO, capillary glucose level rose dramatically. In both of these cases, antihypertensive treatment was increased and insulin introduced. The role of r-HuEPO in hyperglycaemia was probable in the first case and highly probable in the second. Reports about the effects of r-HuEPO on glucose metabolism in uraemic patients are conflicting. Short- and long-term effects can differ, although long-term benefit is likely. The fact that our patients were not dialized may have been important. Clinicians should be aware that glucose control may deteriorate with r-HuEPO, requiring some uraemic NIDDM patients to undergo insulin therapy.
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PMID:Erythropoietin can deteriorate glucose control in uraemic non-insulin-dependent diabetic patients. 953 11


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