Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy leading to end-stage renal disease in children and transplantation is complicated by recurrent disease in a significant percentage of children. Treatment of recurrent FSGS has included high-dose steroids, high-dose cyclosporine (CSA), plasmapheresis, and ACE inhibitors with mixed results. We have had a consistent approach using oral cyclophosphamide (CTX) to treat recurrent FSGS since 1982. Three patients with ESRD secondary to nephrotic syndrome had recurrent disease. Biopsies in all 3 were consistent with recurrent FSGS. Patients were begun on a 8-12 week course of 1-2 mg/kg/day of CTX and dosage was adjusted for WBC count. Azathioprine was with held during CTX. Patients' dosage at the end of 12 weeks ranged from 0.89-1.75 mg/kg/day. All patients tolerated CTX well. After 8-12 weeks of treatment, 2 patients with nephrotic syndrome normalized their serum albumin and had negative to trace protein on urinary dipstick. One patient with proteinuria decreased his protein excretion from 770 to 340 mg/m2/day. At follow-up at 8, 38, and 125 months post-transplant, these 3 patients have stable graft function and negative to trace protein on urinalysis. The patient followed for 125 months has had 2 additional relapses at 51 and 82 months post-transplant that were treated successfully with pulse intravenous steroids. Three pediatric patients with recurrent focal segmental glomerulosclerosis post-renal transplant were treated with oral CTX and had significant improvement in proteinuria and preservation of graft function. This suggests that oral CTX is a potentially effective and well-tolerated treatment for recurrent FSGS in children.
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PMID:Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: successful treatment with oral cyclophosphamide. 786 17

Elevated serum levels of the atherogenic and thrombogenic lipoprotein (a) (Lp(a)) have been recognized as a feature of the nephrotic syndrome associated hyperlipidaemia. To examine a possible relationship between serum Lp(a) concentration and proteinuria, serum albumin, or blood pressure, we studied nine patients with nephrotic-range proteinuria both at baseline and after various forms of antihypertensive and antiproteinuric treatment. In fixed order, patients received conventional antihypertensive treatment (either alpha-methyldopa or clonidine), subsequently ACE-inhibition therapy (lisinopril), ACE inhibition combined with an NSAID (indomethacin), and finally NSAID plus conventional antihypertensive therapy. Measurements were performed at the end of each 2-month study period. When compared to controls (n = 29), proteinuric patients before treatment showed increased levels of total cholesterol, very-low and low-density lipoprotein (VLDL+LDL) cholesterol, triglycerides and apolipoprotein B (apoB), while high-density lipoprotein (HDL) HDL cholesterol was lower. Lp(a) was significantly higher in patients (107 (95% CI: 55-208) mg/l) as compared to controls (25 (13-49) mg/l, P < 0.01). Conventional antihypertensive treatment did not reduce proteinuria, while Lp(a) remained unaffected. ACE-inhibitor treatment lowered proteinuria, raised serum albumin, while La(a) tended to fall (-11 +/- 8%). Addition of an NSAID induced a further fall in proteinuria and a rise in serum albumin. Lp(a) now fell by 40 +/- 5% from baseline values (P < 0.01). Both serum total, HDL and VLDL+LDL cholesterol fell significantly. Finally, during subsequent single therapy with NSAID most parameters, including proteinuria and Lp(a), returned towards values obtained during single therapy with ACE inhibiton.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Symptomatic antiproteinuric treatment decreases serum lipoprotein (a) concentration in patients with glomerular proteinuria. 805 29

Phoneutria nigriventer venom was fractionated by gel filtration followed by ion-exchange chromatography from which 16 fractions (I-XVI) were obtained and assayed in rabbit skin in order to identify those responsible for the increased vascular permeability observed with the whole venom. The fractions, and control mediators (tissue kallikrein, bradykinin and histamine) were intradermally injected in male New Zealand white rabbits. Local oedema formation was measured as the local accumulation of i.v. injected 125I-human serum albumin into skin sites. Fraction XIII was the only fraction assayed which significantly induced oedema formation. Fraction XIII-induced oedema was greatly reduced by either the protease inhibitor aprotinin or the bradykinin B2 receptor antagonist D-Arg,[Hyp3,Thi5,8D-Phe7]-Bk, whereas the plasma kallikrein inhibitor soybean trypsin inhibitor failed to significantly affect this oedematogenic response. The kininase II inhibitor captopril markedly potentiated fraction XIII-induced oedema. Our results indicate that the increased vascular permeability induced by fraction XIII is due to local generation of kinins in response to tissue (but not plasma) kallikrein-kinin system activation.
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PMID:Activation of tissue kallikrein-kininogen-kinin system in rabbit skin by a fraction isolated from Phoneutria nigriventer (armed spider) venom. 831 Apr 40

Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of free cholesterol, and the distribution of cholesteryl ester among lipoproteins in plasma. Alterations in these processes may play a role in the lipoprotein abnormalities associated with glomerular proteinuria. The activities of LCAT and CETP were measured using excess exogenous substrate assays in nine patients with nephrotic-range proteinuria and in 18 matched controls. The proteinuria-lowering effect of four weeks of angiotensin converting enzyme (ACE) inhibition with enalapril was also studied. Plasma very low lipoprotein and low density lipoprotein (VLDL and LDL) cholesterol, triacylglycerol and apolipoprotein B levels were significantly elevated in the patients compared with controls. High density lipoprotein (HDL) total cholesterol, free cholesterol, cholesteryl ester and the free cholesterol/cholesteryl ester ratio in HDL were lower. Total plasma apolipoprotein A1 was normal. Plasma LCAT and CETP activities were elevated in the patients by 30% (P < 0.01) and by 39% (P < 0.01), respectively, and were both inversely related to serum albumin. VLDL and LDL cholesterol levels were positively related to LCAT and CETP activities, whereas the HDL free cholesterol content was inversely related to LCAT activity. ACE inhibition resulted in a 40% reduction of proteinuria, a partial normalization of LCAT activity, and a decrease in VLDL and LDL cholesterol. In conclusion, elevated activities of LCAT and CETP may provide a mechanism that contributes to the low proportion of cholesterol in HDL relative to that in VLDL and LDL, as well as to the compositional changes of HDL seen in glomerular proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of elevated lecithin: cholesterol acyltransferase and cholesteryl ester transfer protein activities in abnormal lipoproteins from proteinuric patients. 835 71

A progressive decline in glomerular function occurs in diabetic nephropathy. The predictive effects of progression promoters were examined in 182 non-insulin-dependent diabetic patients from a baseline serum creatinine concentration of 133 mumol/l. During a total of 605 person-years follow-up, 107 patients developed end-stage renal failure requiring dialysis. The rate of decline of renal function was highly variable. Urinary protein excretion was the strongest predictor correlated to the rate of decline, followed by diastolic and systolic blood pressure, total cholesterol and platelet count, while the protective effects were seen in serum albumin and haematocrit. Adjustment for urinary protein excretion revealed that diastolic blood pressure, familial predisposition to hypertension, serum albumin, and smoking were independent significant predictors. Angiotensin converting enzyme inhibitors (ACE-I) significantly retarded the development of end-stage renal failure compared to antihypertensives other than ACE-I (mostly nifedipine), and the effect was evident particularly in patients with proteinuria below the median (2.5 g/24 h) (presumably those who responded to ACE-I). A complex effect of proteinuria in association with blood pressure elevation, familial predisposition to hypertension, hypoalbuminaemia, and smoking may play an important role in the progression of nephropathy.
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PMID:Predictors of the progression of diabetic nephropathy and the beneficial effect of angiotensin-converting enzyme inhibitors in NIDDM patients. 911 17

Many primary renal diseases are associated with marked proteinuria resistant to immunosuppressive therapy. Short-term treatment with angiotensin converting enzyme (ACE) inhibitors may decrease proteinuria in these patients, but the long-term effect of these agents on urinary protein excretion is not known. We conducted a double-blind, parallel-design, placebo-controlled study of 1 year duration to evaluate the efficacy of the new ACE inhibitor, perindopril, in reducing proteinuria in patients with nephrotic syndrome due to histologically proven membranous and membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Half of the patients treated with perindopril displayed a decrease in urinary protein excretion from 6.1 +/- 1.0 to 1.2 +/- 0.5 g/24 h, and a rise in serum albumin levels. In the placebo group, protein excretion increased modestly and serum albumin level did not change. There was no difference between the responders and nonresponders to perindopril in age, blood pressure, level of creatinine clearance or urinary sodium excretion. However, the degree of proteinuria before treatment with perindopril was significantly (p < 0.01) higher in the nonresponders. In 3 patients in whom the treatment with perindopril was extended for 18-24 months, urinary protein excretion remained below 1 g/24 h. The data show that perindopril: (1) is an effective agent in the treatment of proteinuria of primary renal diseases; (2) the effect is sustained for up to 2 years if the administration of the drugs is maintained, and (3) this action of perindopril does not depend on the level of sodium intake.
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PMID:Effect of angiotensin converting enzyme inhibition by perindopril on proteinuria of primary renal diseases. 942 47

The aim of the present study was to examine the association between 4-hour dialysate-to-plasma ratio of creatinine (D/PCr), erythropoietin (EPO) responsiveness [EPO (U/week)/hemoglobin (g/L)], and C-reactive protein (CRP). Subjects were 54 prevalent peritoneal dialysis (PD) patients [mean age: 58 years; 30 women, 24 men; 28 with diabetes; 15 on continuous ambulatory peritoneal dialysis (CAPD); 39 on continuous cycling peritoneal dialysis (CCPD); mean Kt/V: 2.44]. In 17 patients, CRP was elevated (> 15 mg/L), and in 39 patients, 4-hour D/PCr was high or high-average (> or = 0.65). Mean hemoglobin (Hb) was 115.5 +/- 12.9 g/L; median EPO dose was 2800 U/week, and median EPO/Hb was 24.5. A nonsignificant negative correlation was noted between CRP and hemoglobin (r = -0.25, p = 0.07), but no correlations were seen between CRP and 4-hour D/PCr, or hemoglobin and 4-hour D/PCr. No correlation was seen between EPO/Hb and 4-hour D/PCr or CRP. Multiple linear regression (stepwise, alpha = 0.05) was performed with outcome hemoglobin and independent variables EPO [U/week (forced in)], percent transferrin saturation [TSAT (forced in)], age, sex, diabetes mellitus, serum albumin, CRP, time on PD, 4-hour D/PCr, normalized protein catabolic rate (nPCR), ferritin, intact parathyroid hormone (iPTH), aluminum, and angiotensin converting enzyme inhibitor (ACEI) use. Serum albumin (1.27, p < 0.01) and diabetes mellitus (-6.69, p = 0.04) were the only significant predictors of hemoglobin. With serum albumin removed from the model, age (but not CRP) became significant. These results do not support an association between peritoneal transport and EPO responsiveness, mediated by inflammation. The association between serum albumin and hemoglobin appears to be confounded by age more than by inflammation.
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PMID:Inflammation, peritoneal transport, and response to erythropoietin in peritoneal dialysis patients. 1151 Feb 66

Hypotension associated with the rapid infusion of human serum albumin products was first recognised in Australasia in the early 1970s. An association with the angiotensin converting enzyme inhibitor class of drugs (ACE-I) followed, leading to a proposed mechanism involving bradykinin generation through pre-kallikrein activator (PKA) presence in the infused fluid. The newer generation albumin products (Albumex) contain very low concentrations of PKA and are generally thought safe to use in most patient populations. Anecdotal reports of paradoxical hypotension with rapid infusion of 4% albumin in our department led to an audit of practice over three months. Four out of 36 patients (11%) who received 4% albumin intravenously experienced paradoxical hypotension. Three of these patients were taking ACE-I preoperatively (P=0.04). There was no observed hypotension associated with intravenous infusion of crystalloid fluid. We believe 4% albumin should be used with caution, particularly in those patients receiving ACE-I preoperatively.
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PMID:Human serum albumin induced hypotension in the postoperative phase of cardiac surgery. 1177

Previous studies have indicated that angiotensin II (Ang II) concentrations in renal interstitial fluid are much higher than plasma levels. In the present study, we performed experiments to explore renal interstitial fluid concentrations of Ang I and Ang II further and to determine whether these levels are altered by acute arterial infusion of an ACE inhibitor (enalaprilat) or by volume expansion. Microdialysis probes (molecular weight cutoff point: 30 000 Da) were implanted in the renal cortex of anesthetized rats and were perfused at a rate of 2 microL/min. Using relative equilibrium rates, the basal renal interstitial fluid Ang II concentration averaged 3.07+/-0.43 nmol/L, a value much higher than the plasma Ang II concentration of 107+/-8 pmol/L (n=7). Interstitial fluid Ang I concentrations (0.84+/-0.04 nmol/L) were consistently lower than the Ang II concentrations but higher than the plasma Ang I concentrations (112+/-14 pmol/L). Intra-arterial infusion of enalaprilat (7.5 micromol/kg/min, n=5) for 120 minutes resulted in a significant decrease in mean arterial pressure (from 114+/-4 to 68+/-4 mm Hg) along with reductions in plasma and renal ACE activity (by -99% and -52%, respectively). Enalaprilat resulted in a significant increase in plasma Ang I from 133+/-21 to 1167+/-328 pmol/L and a decrease in plasma Ang II from 110+/-12 to 67+/-9 pmol/L. During enalaprilat infusion, interstitial fluid concentration of Ang I was significantly increased from 0.78+/-0.06 to 0.97+/-0.08 nmol/L; however, Ang II concentrations were not altered significantly (3.67+/-0.28 versus 3.67+/-0.25 nmol/L). Acute volume loading with Ringer's solution containing 1% bovine serum albumin at a rate of 150 microL/min for 2 hours (6% to 7% of body weight) lowered plasma concentrations of Ang I from 110+/-23 to 16+/-2 pmol/L and Ang II from 100+/-23 to 36+/-6 pmol/L; however, renal interstitial fluid concentrations of Ang I and Ang II were not altered significantly during volume expansion (Ang I, from 0.77+/-0.05 to 0.69+/-0.03 nmol/L; Ang II, from 3.76+/-0.43 to 3.59+/-0.39 nmol/L, n=5). These data indicate that renal interstitial fluid concentrations of Ang I and Ang II are substantially higher than the corresponding plasma concentrations. Furthermore, the fact that the high interstitial fluid concentrations of Ang II are not responsive to acute ACE inhibition or volume expansion suggests the compartmentalization and independent regulation of renal interstitial fluid Ang II.
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PMID:Renal interstitial fluid concentrations of angiotensins I and II in anesthetized rats. 1179 91

Hypocalcemic toxicity accounts for the most common adverse effects of therapeutic plasma exchange. The symptoms can be related to a fall in plasma ionized calcium. Citrate-based anticoagulants, notably sodium citrate and ACD formula A, have been indicated as the major cause of hypocalcemic toxicity, but colloid replacement fluids containing human serum albumin are also at fault. Recognition of the signs and symptoms of hypocalcemic toxicity is important because several clinical measures are available to deal with them and to ensure patient comfort. A typical reactions, characterized by flushing and hypotension during plasma exchange, have been attributed to the effects of angiotensin converting enzyme inhibitors. Both exchange and adsorption apheresis procedures can result in atypical reactions in patients who have been taking this class of drugs within 48 to 72 hours of an apheresis procedure. These reactions are less common than hypocalcemic toxicity, but can be prevented by paying attention to detail.
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PMID:Hypocalcemic toxicity and atypical reactions in therapeutic plasma exchange. 1183 18


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