Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While it is known that treatment with insulin-like growth factor I (IGF-I) stimulates growth of the fetal kidney, nothing is known about the short term or long term effects of IGF-I on fetal renal function. To investigate the acute effects of IGF-I on fetal renal function and on the activity of the fetal renin-angiotensin system, studies were carried out in 12 chronically catheterized fetal sheep aged 120 +/- 1 days, before and during a 4 h I.V. infusion of IGF-I at 80 ug h-1. Seven control fetuses were infused over the same period with vehicle (0.1% bovine serum albumin in 0.15 M saline). IGF-I infusion increased plasma IGF-I concentrations by about 80%. There was a small fall in arterial PO2 (P < 0.01), arterial PCO2 increased (P < 0.05), plasma lactate levels increased (P < 0.01) and arterial pH fell (P < 0.05). Fractional bicarbonate reabsorption increased and bicarbonate excretion decreased (P < 0.05). Infusions of IGF-I had no sustained effect on fetal arterial pressure. Glomerular filtration rate (GFR) did not change significantly during IGF-I infusion, but renal blood flow (RBF) fell (P < 0.05). Therefore filtration fraction relative to control values increased (P < 0.05), suggesting that efferent arteriolar vasoconstriction had occurred. IGF-I infusion led to an antidiuresis (P < 0.01), a rise in urinary osmolality (P < 0.05) and a fall in free water clearance (P < 0.01). Since fetal PO2 fell, it is probable that these effects were mediated by arginine vasopressin. The excretion rates of sodium, chloride and phosphate were all reduced by 4 h of infusion (P < 0.05), because their fractional reabsorption rates were all increased (sodium, P < 0.01; chloride, P < 0.01; and phosphate, P < 0.05). Plasma renin concentration increased by 275 +/- 52% during infusion of IGF-I (P < 0.005). Plasma renin activity also increased (P < 0.005), while circulating angiotensinogen concentrations fell (P < 0.05). In the adult, IGF-I increases both RBF and GFR, enhances tubular reabsorption and stimulates the renin-angiotensin system. In the fetus, however, it decreased RBF and had no effect on GFR, but was associated with enhanced tubular function and intense stimulation of renin secretion. Some of these effects of IGF-I on fetal renal function may be involved in maturation of the kidney in preparation for life after birth.
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PMID:Insulin-like growth factor I alters renal function and stimulates renin secretion in late gestation fetal sheep. 1120 73

Overexpression of the renin-angiotensin system is important in the pathogenesis of macroangiopathy (MA). Patients with diabetes with end-stage renal failure have elevated serum angiotensin-converting enzyme (ACE) activity compared with their nonuremic counterparts. Because their major cause of death is MA, the significance of serum ACE activity on outcome of this group of patients is studied. We performed a prospective cohort study of 49 patients with type 2 diabetes on continuous ambulatory peritoneal dialysis (CAPD) therapy. Baseline serum ACE activity was determined by a modified spectrophotometric method and followed up at a median of 34 months. The prevalence of MA (defined as ischemic heart disease, sudden cardiac arrest, stroke, or peripheral vascular disease) and all-cause mortality rates were studied. Risk for MA is associated with serum ACE activity (median with MA, 69.0 U/L [range, 46.0 to 100.1 U/L] versus without MA, 57.2 U/L [range, 36.3 to 81.0 U/L]; P = 0.02). At the end of follow-up, 48% of patients (24 of 49 patients) died, 70% of MA. The group that died had increased baseline serum ACE activity (nonsurvivors, 65.0 U/L [range, 33.5 to 100.0 U/L] versus survivors, 49.4 U/L [range, 36.4 to 86.5 U/L]; P < 0.05) and MA rates (nonsurvivors, 77% versus survivors, 36%; P < 0.01). Cox regression analysis performed with age, sex, mean blood pressure, body mass index, metabolic control, Kt/V, residual renal function, serum albumin level, and ACE activity showed that baseline serum ACE activity (P = 0.033) is an independent predictor for mortality in patients with type 2 diabetes on CAPD therapy. Among patients with type 2 diabetes on CAPD therapy, serum ACE activity is associated with risk for MA and is an independent predictor for mortality. Whether ACE inhibition will have a beneficial effect on the outcome of these patients needs further investigation.
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PMID:Prognostic role of serum ACE activity on outcome of type 2 diabetic patients on chronic ambulatory peritoneal dialysis. 1197 50

We studied the features of acute renal failure (ARF) in elderly patients treated in a hospital, without an intensive care unit, to identify etiological factors and establish adequate preventive measures and treatment. During twelve consecutive months we studied prospectively 99 patients with ARF diagnosed by conventional criteria, an incidence of 1,238 cases per million per year. ARF affected 1.78% of patients admitted to hospital. We analyzed age, sex, serum creatinine, diuresis, etiology, type of ARF, preexisting chronic diseases, treatment, complications and outcome. Preexisting chronic diseases were common, the most frequent being hypertension (54%) and diabetes (39%). Previous treatments for cardiovascular diseases were frequent (angiotensin-renin system blockade 35.4%, diuretics 50.5%). 79% of ARF arose in hospital, 21% outside hospital. ARF was pre-renal in 60%, renal in 31% and post-renal in 9%. 34.7% were caused by volume depletion, 23.4% by low cardiac output and 23.4% by infection. 44.4% of ARF patients had oliguria or anuria latrogenic factors contributed to the ethiology of ARF in 35.3% of patients. Hospital stay was doubled by ARF the presence of ARF and the mortality was 36.4%. The rate was higher in ARF arising in hospital than in ARF acquired before admission. Factors that had a significant influence on the mortality rate were comorbid conditions, oliguroanuria, ARF of renal origin and serum albumin. We conclude that ARF has a high incidence, morbidity and mortality in this elderly population. Volume depletion, associated cardiovascular pathology and pharmacological treatment are important etiological factors in those with ARF outside hospital. Adequate treatment of ARF and avoidance of nephrotoxic medications are necessary in hospital.
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PMID:[Characteristics of acute renal failure in elderly patients admitted to a small town hospital]. 1251 88

Malignant ascites occurs in association with a variety of neoplasms. It is a frequent cause of morbidity and presents significant problems for which there are no clear management guidelines. In this article we discuss various modalities which are available including diuretic therapy, paracentesis, peritoneovenous shunts and intraperitoneal chemotherapy. There are no randomized trials of diuretic drugs to assess their efficacy in malignant ascites. Phase II data suggest that they are effective in approximately one-third of patients with malignancy, and their efficacy may be determined by plasma renin/aldosterone concentrations. Paracentesis provides relief in up to 90% of patients; because of varying reports of hypovolaemia, some advocate simultaneous intravenous fluid infusion. Permanent percutaneous drains may prevent the need for repeated paracentesis, although there is potential for infection. A peritoneovenous shunt also prevents the need for repeated paracenteses, whilst maintaining normal serum albumin concentrations. Blockage occurs in 25% of shunts, which are contraindicated in the presence of heavily bloodstained ascites because of the risk of occlusion. The preclinical and clinical experience with anti-angiogenic agents such as the matrix metalloproteinase inhibitors and the VEGF antagonists suggests that these agents may have a role in the treatment of malignant ascites.
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PMID:The current and future management of malignant ascites. 1270 13

Recent immunosuppressive treatments for lupus nephritis have improved renal survival rate, however, there still exists lupus nephritis refractory to these treatments. Angiotensin receptor blockers (ARBs) are known not only to decrease blood pressure but also to have an independent renoprotecting effect by interrupting renin-angiotensin system. The aim of this study was to evaluate whether ARBs have an additive effect on refractory lupus nephritis. Enrolled in this trial were twelve patients with lupus nephritis who were diagnosed by renal biopsy and remained proteinuria despite corticosteroids and/or immunosuppressive treatments. ARB, losartan or candesartan, was administered for six months. Various clinical parameters were compared before and after ARB administration. Proteinuria decreased after ARB treatment in 83% of the patients and the median amount of proteinuria significantly decreased from 2530 mg/g Cr to 459 mg/g Cr (P = 0.03). In addition, serum albumin and cholesterol levels were significantly improved. Systolic blood pressure significantly decreased, but none had symptoms of hypotension. The antiproteinuric effect of ARB did not correlate with the reduction of blood pressure. Interestingly, higher total complement activity levels before ARB treatment were associated with a greater reduction of proteinuria. The addition of ARB would be a safe and effective treatment for lupus nephritis with persistent proteinuria despite corticosteroids and/or immunosuppressive treatments.
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PMID:Antiproteinuric effect of ARB in lupus nephritis patients with persistent proteinuria despite immunosuppressive therapy. 1586 15

In patients with chronic renal failure, cancer incidence is increased. This may be related to an elevated level of genomic damage, which has been demonstrated by micronuclei formation as well as by comet assay analysis. Advanced glycation end products (AGEs) are markedly elevated in renal failure. In the comet assay, the model AGEs methylglyoxal- and carboxy(methyl)lysine-modified bovine serum albumin (BSA) induced significant DNA damage in colon, kidney, and liver cells. The addition of antioxidants prevented AGE-induced DNA damage, suggesting enhanced formation of reactive oxygen species (ROS). The coincubation with dimethylfumarate (DMF), an inhibitor of NF-kappaB translocation, reduced the genotoxic effect, thereby underscoring the key role of NF-kappaB in this process. One of the genes induced by NF-kappaB is angiotensinogen. The ensuing proteolytic activity yields angiotensin II, which evokes oxidative stress as well as proinflammatory responses. A modulator of the renin-angiotensin system (RAS), the angiotensin II (Ang II) receptor 1 antagonist, candesartan, yielded a reduction of the AGE-induced DNA damage, connecting the two signal pathways, RAS and AGE signaling. We were able to identify important participants in AGE-induced DNA damage: ROS, NF-kappaB, and Ang II, as well as modulators to prevent this DNA damage: antioxidants, DMF, and AT1 antagonists.
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PMID:Genotoxicity of advanced glycation end products: involvement of oxidative stress and of angiotensin II type 1 receptors. 1603 94

Although hemodynamic and metabolic factors are individually implicated in the development of diabetic nephropathy, their interaction has not been defined clearly. In this study, the effects of angiotensin II (Ang II) and advanced glycation end products (AGE) both individually on each other are explored and compared. In the first study arm, Sprague-Dawley rats received a continuous infusion of AGE-modified rat serum albumin (RSA) or unmodified RSA for 4 wk with or without the angiotensin receptor type 1 antagonist valsartan. In the second arm, animals received a continuous infusion of Ang II (58.3 ng/kg per min) with or without the AGE inhibitor pyridoxamine. Components of the intrarenal renin-angiotensin system were measured using real time reverse transcription-PCR, immunohistochemistry, and standard angiotensin-converting enzyme (ACE) activity assays. Renal and serum AGE were quantified by immunohistochemistry, ELISA, and AGE-fluorescence. After an infusion of AGE-RSA, renal expression of angiotensinogen, ACE, renin, and angiotensin receptor type 1 were increased significantly (all P < 0.01), and ACE activity was elevated. This was associated with tubular and glomerular hypertrophy and AGE accumulation, which could be antagonized by valsartan. However, valsartan had no effect on increased filtration fraction associated with an AGE-RSA infusion. At the same time, an infusion of Ang II increased the serum and renal accumulation of AGE and advanced oxidation protein products and induced renal hypertrophy and salt retention that could be antagonized by pyridoxamine. However, pyridoxamine had no effect on renal vasoconstriction manifested by reduced renal blood flow. AGE and Ang II have overlapping activities in the kidney. The beneficial effects of blockade of either pathway underline the importance of this interaction in diabetic renal disease and the aging kidney.
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PMID:Interactions between renin angiotensin system and advanced glycation in the kidney. 1610 77

Injury of the renal tubulointerstitial compartment is recognized to play an important role in hypertension. Its damage may in turn, impair the activity of vasodepressor systems, like the kallikrein-kinin, in blood pressure regulation. The overload proteinuria model induces tubulointerstitial injury with activation of the renin-angiotensin system, but renal kallikrein and the development of hypertension have not received special attention. Sprague-Dawley rats received seven intraperitoneal doses of bovine serum albumin (BSA) 2 g/day under normosodic diet and were hydrated ad libitum. A second group received a high potassium diet to stimulate kallikrein production during the previous four weeks and while under BSA administration. A third one received potassium and BSA in the same schedule, but with the kinin B2 receptor antagonist, HOE140, added during the protein load phase. A control group received seven saline injections. Kallikrein protein was detected by immune labeling on renal sections and enzymatic activity in the urine. The BSA group showed massive proteinuria followed by intense tubulointerstitial damage. Blood pressure increased after the third dose in BSA animals, remaining elevated throughout the experiment, associated with significant reductions in renal expression and urinary activity of kallikrein, compared with controls. An inverse correlation was found between blood pressure and immunohistochemistry and urinary activity of kallikrein. Potassium induced a significant increase in both urinary activity and renal kallikrein expression, associated with significant reduction in blood pressure. The HOE140 antagonist blunted the antihypertensive effect of kallikrein stimulation in proteinuric rats. Loss of renal kallikrein, produced by tubulointerstitial injury, may participate in the pathogenesis of the hypertension observed in this model.
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PMID:Modulation of renal kallikrein by a high potassium diet in rats with intense proteinuria. 1637 23

Proteinuria (albuminuria) reflects dysfunction of the glomerular permeability barrier in which inflammatory cytokines play a key role. Pentoxifylline (PTX) is a phosphodiesterase inhibitor that possesses potent anti-inflammatory and immunomudulatory effects. This study evaluated the effectiveness of PTX to reduce proteinuria and inflammatory mediators in patients with proteinuric primary glomerular diseases. Seventeen patients with primary glomerular diseases, a persistent spot proteinuria exceeding 1.5 g/g creatinine (Cr) and a glomerular filtration rate between 24 and 115 ml/min/1.73 m(2) were treated with PTX 400 mg twice daily for 6 months. Before and after the treatment, serum Cr, plasma renin activity and aldosterone concentrations, plasma and urinary tumor necrosis factor (TNF)-alpha, interleukin-1beta and monocyte chemoattractant protein (MCP)-1, as well as urinary protein and Cr were measured. PTX significantly reduced urinary protein excretion, along with an increase of serum albumin. A significant correlation existed between the basal urinary protein/Cr and the basal urinary MCP-1/Cr ratios. PTX lowered the urinary MCP-1/Cr ratio, and the percent reduction of urinary protein/Cr ratio correlated directly with the precent decrease of urinary MCP-1/Cr ratio after PTX treatment. There was no significant change in blood pressure, renal function, biochemical parameters, plasma renin activity and aldosterone concentrations, or plasma TNF-alpha and MCP-1 levels during the study. In conclusion, administration of PTX 800 mg per day is safe and effective for reducing proteinuria in patients with proteinuric primary glomerular diseases. This beneficial effect occurs in close association with a reduction of urinary MCP-1 excretion.
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PMID:Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. 1654 Oct 21

The effect of telmisartan on ambulatory blood pressure, plasma neurohormonal parameters, and oxidation of serum albumin has not been investigated in hemodialysis (HD) patients. Thirteen hypertensive HD patients were treated with 40 mg telmisartan once daily, and 24-h ambulatory blood pressure monitoring was performed after 0, 4, and 8 weeks of treatment. Plasma renin activity, plasma aldosterone concentration (PAC), brain natriuretic peptide (BNP) level, and serum oxidized albumin level were determined at the same time points. Serum telmisartan concentration was also measured at 4 and 8 weeks. Telmisartan significantly reduced systolic blood pressure and diastolic blood pressure (both awake and sleeping) after 4 weeks, and these pressures showed a further significant decrease after 8 weeks. Plasma levels of aldosterone, BNP, and serum oxidized albumin were markedly decreased after 4 weeks and these lower levels were maintained at 8 weeks. The trough serum telmisartan concentration was not significantly different at 8 weeks compared with 4 weeks. Throughout the treatment period, there were no significant adverse effects. Telmisartan effectively lowers blood pressure and reduces PAC, BNP, and oxidative stress and is safe and well-tolerated by HD patients. A long-term study in a large population is required to determine the influence of telmisartan therapy on cardiovascular mortality and morbidity in HD patients.
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PMID:Effect of telmisartan on ambulatory blood pressure monitoring, plasma brain natriuretic peptide, and oxidative status of serum albumin in hemodialysis patients. 1667 38


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