Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension is both an exacerbating factor for, and a consequence of, diabetic renal disease. In diabetic patients, hypertension is associated with increased total body sodium secondary to impaired renal excretion, and increased vascular reactivity, notably to catecholamines and angiotensin II. The mechanisms causing these changes are discussed. Control of hypertension will slow the progression of diabetic renal disease and the inexorable decline in GFR. A number of studies now suggest that in proteinuric IDDM and NIDDM patients angiotensin converting enzyme inhibitors (ACE-I) may have additional reno-protective effects in addition to their hypotensive action. In addition ACE-I will reduce proteinuria and delay the onset of diabetic nephropathy in normotensive microalbuminuric IDDM and NIDDM patients. Use of ambulatory blood pressure monitoring indicates that such patients may not be truly 'normotensive'. On-going studies seem to suggest that the most reno-protective blood pressure is the lowest one achievable, as long as the patient remains asymptomatic. Further studies are required to assess the impact of blood pressure control, and especially ACE-I, on the incidence of end-stage renal failure. In addition, more direct comparisons between different pharmacological agents in early diabetic renal disease would be useful.
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PMID:The management of hypertension in diabetes: with special reference to diabetic kidney disease. 873 20

Microalbuminuria (MA) is a term used for urinary albumin excretion between 20 and 200 micrograms/min. or 30-300 mg/24 h. This definition is not used by all authors. In addition, various methods may influence the results. The significance of MA concerns the prognosis in diabetics. For the juvenile type 1 diabetes nephropathy is the most important complication. In adult type 2 diabetics the prognosis concerns mainly cardiovascular death. The excess mortality to be attributed to MA is several fold in type 1 diabetes, less in the adult onset type variety. MA is the expression of an incipient general disease of blood vessels touching as much the kidney as the heart. According to the presence or absence of other vascular damage. MA develops toward nephropathy or cardiovascular complications. The features leading to or worsening MA are elevated blood pressure, poor glucose control, elevated lipoproteins, diminished insulin sensitivity and probably smoking. Retinopathy is an indicator for particularly sensitive patients responding with the development of MA upon only mildly elevated blood pressure or poor metabolic control. The prevalence of MA is close to 20% for both types of diabetes. Non-diabetic persons under 60 years of age exhibit MA in 2-10%, the elderly in 20-30%. For non-diabetic persons with hypertension MA is reported to be present in 19%. Over a time span of 5 years, 19% of type 1 patients with MA develop proteinuria of more than 300 mg/24 hours. In a third of cases albumin excretion normalises. In the remaining half a small progression of MA occurs. For type 2 patients the increased mortality risk is restricted to the first 5 years, thereafter the survival curves return to those of patients without MA. In these patients the excess mortality is already present at albumin excretion rates above 10 micrograms/min. Higher values have, therefore, to be considered pathological. For the treatment of the syndrome ACE-inhibitors and ev. Ca-antagonists (with the exception of dihydropyridine, nifedipine) are recommended. They reduce albumin excretion by 50%. In a single study (yet) with type 1 diabetes mortality also was reduced by 40-50%. This would imply that the excess mortality could be halved in patients undergoing this treatment.
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PMID:[Microalbuminuria in diabetes mellitus--illness or symptom?]. 873 41

The kidneys play an important role in the development of cardiovascular risk factors. It is well known that heavy proteinuria can induce hyperlipidemia, the uric acid is elevated in some renal deficiencies and that hypertension develops in most end stage renal diseases. In prehypertensive states, specially in subjects with a family history of hypertension, some hemodynamic changes take place, characterized by an increase in renal vasoconstriction with a reduction in renal plasma flow and an elevation of sodium reabsorption. The mechanisms for these alterations are not well understood, but an increase in intracytosolic calcium in vascular smooth muscle cells, a reduction in vasodilatory substances such as nitric oxide and an increased sympathetic nervous activity have been proposed. In normotensive subjects with two hypertensive parents a reduction in sodium diet, an increase in protein intake or in arginine diet could prevent established essential hypertension from developing. In borderline hypertension an early therapy with low doses of calcium antagonists, ACE inhibition or diuretics could be indicated.
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PMID:Can the kidney prevent cardiovascular diseases? 874 38

Diabetic nephropathy is the single most common cause of end-stage renal disease in the United States. Recently, several major therapeutic interventions have been developed and demonstrated to slow or halt the progression of renal failure in patients with diabetes and diabetic kidney disease. The Diabetes Control and Complications Trial demonstrated that microalbuminuria developed in fewer patients in the intensive blood sugar control group than in the conventional therapy group. Similarly, the risk of developing proteinuria was reduced by intensive blood sugar control. Multiple studies have demonstrated that in patients with insulin-dependent diabetes and proteinuria, lowering the systemic blood pressure slows the rate of decline in renal function and improves patients' survival. In the recently completed trial of ACE inhibition in diabetic nephropathy, ACE inhibitors were specifically shown to decrease dramatically the risk of doubling of serum creatinine or reaching a combined outcome of end-stage renal disease or death. In studies in small numbers of patients with insulin-dependent diabetes and established diabetic nephropathy, dietary protein restriction has also been demonstrated to slow the rate of decline of renal function. New potential interventions currently undergoing study include the use of aldose reductase inhibitors, the use of drugs that prevent the formation of advanced glycosylation end-products, and the use of angiotensin II receptor antagonists. Thus, several established benefits have recently been demonstrated to help prevent the development of or slow the progression of diabetic nephropathy, including blood pressure control, blood sugar control, and treatment with ACE inhibitors. Dietary protein restriction may also be of benefit. Multiple new interventions are undergoing clinical trials currently.
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PMID:Medical management of nephropathy in type I diabetes mellitus: current recommendations. 874 76

Hypertension is a common finding in patients with renal parenchymatous diseases. Development of hypertension causes increased proteinuria, decline in glomerular filtration rate and reduced life span in experimental models of glomerulonephritis. Hypertension has been shown to reduce glomerular filtration rate in man. It is therefore important to treat hypertension. The blood pressure should be reduced to about 140/80 mm Hg. Reduction of glomerular capillary pressure, inhibition of glomerular permeability, renal hypertrophy and inhibition of mesangial metabolism are the main mechanisms of renal protection during antihypertensive therapy. Autoregulation of the renal blood flow probably has an impact on these mechanisms. Impaired autoregulation is found in kidneys with low glomerular filtration rate and during treatment with calcium channel blockers. Alpha receptor blockers, angiotensin converting enzyme inhibitors (ACE-) and angiotensin II receptor blockers do not interfere with autoregulation. All types of antihypertensive drugs provide similar renal protection when the glomerular filtration rate is reduced. When calcium channel blockers are used in kidneys with normal or slightly reduced function, either blood pressure should be kept strictly at normal levels or these type of drugs should be combined with ACE inhibitors or angiotensin II receptor blockers.
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PMID:[Treatment of hypertension in renal parenchymal diseases]. 876 45

Several observations question the role of blood pressure and renal hemodynamic changes in the long-term antiproteinuric effect of ACE inhibition. To differentiate blood pressure and renal effects in the initial antiproteinuric response, the placebo-controlled acute effects of the ACE inhibitor enalaprilat (10 mg i.v.) on blood pressure, renal hemodynamics, and proteinuria were compared with those of nitroprusside in nine patient with non-diabetic proteinuria. In addition, we studied whether an exogenous angiotensin II infusion reverse the initial enalaprilat-induced antiproteinuric response. Enalaprilat and nitroprusside reduced MAP by -11.3 +/- 2.4% and -14.1 +/- 2.3%, respectively, whereas only enalaprilat showed renal hemodynamic effects, reflected by an increase in ERPF of 18.4 +/- 5.4% and a decrease in FF of -17.1 +/- 2.6%. Despite the contrasting renal hemodynamic profiles, enalaprilat (-10.6 +/- 4.8%) and nitroprusside (-12.8 +/- 5.1% equally decreased proteinuria. Exogenous infusion of angiotensin II completely reversed the blood pressure reduction and renal efferent vasodilatation induced by enalaprilat. proteinuria also increased by 13.1 +/- 7.8% to placebo level, albeit statistically non-significant. We conclude that the initial antiproteinuric effect of ACE inhibition appears to be mediated by blood pressure reduction and does not require its specific renal hemodynamic effect. Further studies should clarify whether the renal efferent vasodilatation during ACE inhibition is required to gradually induce renal structural changes that prevent the abundant passage of proteins.
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PMID:Blood pressure reduction initiates the antiproteinuric effect of ACE inhibition. 877 Sep 65

Since the renin angiotensin system (RAS) is established as an important factor in renal disease progression, we determined whether RAS alleles that have been linked to variability in outcome in several cardiovascular diseases also affect progression of IgA nephropathy. These genetic variants include: (1) angiotensin I converting enzyme deletion polymorphism in intron 16 (ACE I/D), reported to be associated with increased risk of myocardial infarction as well as left ventricular hypertrophy; (2) a point mutation in the angiotensinogen (Agt) gene resulting in a methionine to threonine substitution at residue 235 (M235T), reported to be associated with hypertension in Caucasians; and (3) an angiotensin receptor type I (ATR) A to C transition at bp 1166 (A1166C) which shows synergy with the deleterious effects of the ACE DD genotype in myocardial infarction. We examined these polymorphisms by PCR amplification of genomic DNA samples from 64 Caucasian patients in the USA (age 6 to 83 years) with biopsy-proven IgA nephropathy whose renal status was followed for an average of almost seven years. Patients who presented with and maintained normal serum creatinine (Cr, < 1.5 mg/dl), had ACE genotype frequencies of II:35%, ID:61%, DD:4%. By contrast, in patients with progression (initially normal Cr increased to a mean of 4.5 +/- 0.86 mg/dl), ACE genotype frequencies were II:22%, ID:44%, DD:33% (P = 0.057 by Fishers's exact test, vs. non-progressors). The association of the DD genotype with progression was even more striking when patients with other risk factors (hypertension and/or heavy proteinuria) were excluded. In this subgroup, the genotype frequencies in patients with stable creatinine versus those with deterioration in renal function was 53%, 47%, and 0% versus 0%, 40%, and 60%, respectively, for II, ID, and DD genotypes (P = 0.009 by Fisher's exact test, progressors vs. non-progressors). Further, sequence analysis of the I gene polymorphism revealed a potential 13 bp silence motif. Neither the Agt 235T nor the ATR A 1166C gene variants, however, was associated with deterioration of renal function. Taken together, these results indicate that, although polymorphism in each of the three genes in the RAS system has been linked to cardiovascular diseases, only the ACE I/D polymorphism is associated with progressive deterioration in renal function in IgA nephropathy. Since previous observations link ACE polymorphism with ACE activity, these findings imply a widespread importance of ACE in modulating destructive processes in different organs.
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PMID:Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy. 882 46

We have encountered a 49-year-old female with persistent proteinuria and hematuria. Blood pressure, renal function, physical findings and chest X-p showed no abnormality, but blood tests disclosed mild thrombocytopenia, elevated serum ACE activity, serum lysozyme activity and serum IgA concentration. Abdominal echography and CT revealed multiple nodules in her spleen. In order to make a definite diagnosis and exclude the possibilities of malignant lymphoma or metastatic malignant tumor, splenectomy, and open renal biopsy were performed at the same time. On histological examinations, light microscopic appearance of the spleen was characterized by non-caseating granulomas compatible with sarcoidosis. Renal biopsy specimen showed diffuse proliferative glomerulonephritis with positive staining of IgA predominantly located in the mesangial area, compatible with IgA nephropathy. The present case may provide suggestive evidence for a link between sarcoidosis and IgA nephropathy in the pathogenesis. IgA nephropathy complicated by sarcoidosis is rare, and thus is of particular interest because common immunological abnormalities might be considered in the disease process of both diseases. We feel that despite a low index of suspicion, physicians must be alert to the possibility of IgA nephritis associated with sarcoidosis. The literature is reviewed regarding the relationship between IgA nephropathy and sarcoidosis.
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PMID:[Sarcoidosis representing multiple splenic nodules in a patient with IgA nephropathy]. 885 36

ACE inhibitors effectively reduce systemic vascular resistance in patients with hypertension, heart failure or chronic renal disease. This antihypertensive efficacy probably accounts for an important part of their long term renoprotective effects in patients with diabetic and non-diabetic renal disease. The renal mechanisms underlying the renal adverse effects of ACE inhibitors--intrarenal efferent vasodilation with a consequent fall in filtration pressure--are held to be involved in their renoprotective effects as well. The fall in filtration pressure presumably contributes to the antiproteinuric effect as well as to long term renoprotection. The former is suggested by the positive correlation between the fall in filtration fraction and the reduction in proteinuria found during ACE inhibition. The latter is suggested by the correlation between the (slight) reduction in glomerular filtration rate at onset of therapy and a more favourable course of renal function in the long term. Such a fall in filtration rate at the onset of ACE inhibitor treatment is reversible after withdrawal, and can be considered the trade-off for long term renal protection in patients with diabetic and nondiabetic chronic renal disease. In conditions in which glomerular filtration is critically dependent on angiotensin II-mediated efferent vascular tone (such as a post-stenotic kidney, or patients with heart failure and severe depletion of circulating volume), ACE inhibition can induce acute renal failure, which is reversible after withdrawal of the drug. Systemic and renal haemodynamic effects of ACE inhibition, both beneficial and adverse, are potentiated by sodium depletion. Consequently, sodium repletion contributes to the restoration of renal function in patients with ACE inhibitor-induced acute renal failure. Our the other hand, co-treatment with diuretics and sodium restriction can improve therapeutic efficacy in patients in whom the therapeutic response of blood pressure or proteinuria is insufficient. Patients at the greatest risk for renal adverse effects (those with heart failure, diabetes mellitus and/or chronic renal failure) also can expect the greatest benefit. Therefore, ACE inhibitors should not be withheld in these patients, but dosages should be carefully titrated, with monitoring of renal function and serum potassium levels.
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PMID:ACE inhibitors and the kidney. A risk-benefit assessment. 887 74

It has been considered unlikely that patients with insulin-dependent diabetes and diabetic nephropathy with nephrotic range proteinuria can substantially reduce proteinuria and continue for many years without further loss of renal function. We present a patient who had the diagnosis of insulin-dependent diabetes made at age 15, had his first of 6 laser treatments for proliferative and hemorrhagic retinopathy at age 27 and was found to have nephrotic range proteinuria and edema with hypertension at age 29, when results of a renal biopsy were typical of diabetic nephropathy. Ten years later, with the last 5.5 years on ACE inhibitors, proteinuria has been < 0.65 g/24 h for 2 years and recently 0.22 g, serum creatinine is unchanged at 90 to 102 mu mol/l, DTPA GFR is 104 ml/min and retinopathy has remained stable without laser therapy for 7 years. Blood pressure on clinic visits has averaged 126/74 for the last 8 years. This duration of stable renal function and the major decrease in proteinuria after being in the neprotic range is very rare in reports, if not unique.
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PMID:Stable renal function in insulin-dependent diabetes mellitus 10 years after nephrotic range proteinuria. 890 67


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