UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A choice of many antihypertensive strategies is now offered for the treatment of the hypertensive patient with renal insufficiency. Angiotensin-converting enzyme (ACE) inhibitors appear to be the drugs of choice since they not only lower blood pressure but also reduce some important risk factors that may cause progressive loss of renal function, such as intraglomerular hypertension, angiotensin II (Ang II)-induced glomerular growth, proteinuria and hyperlipidemia. Indeed, several clinical studies now show that ACE inhibitors offer renal protection beyond the lowering of systemic blood pressure. The new class of Ang II receptor antagonists and its first representative losartan has not yet been tested clinically for its renal protective efficacy. The first signs, however, look promising, since losartan appears to induce changes in several identified risk factors to the same extent as ACE inhibitors, such as renal vasodilation, and a fall in proteinuria and serum lipids. The challenge will be to discover the differences between ACE inhibitors and Ang II receptor antagonists and to use them to the future advantage of the renal patient.
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PMID:Losartan in patients with renal insufficiency. 766 17

This study examined the mechanisms by which angiotensin II (Ang II) receptor blockade improves glomerular barrier function in rats with reduced nephron number. Proteinuria was measured at four weeks after 5/6 renal ablation, and rats were then divided into a group which received the Ang II receptor blocker MK954 and a group which received no treatment. Studies performed one week later showed that Ang II receptor blockade reduced proteinuria without altering GFR in renal ablated rats. Micropuncture studies showed that Ang II blockade reduced both mean arterial pressure (142 +/- 7 mm Hg, ablation without treatment; 105 +/- 2 mm Hg, ablation with treatment) and glomerular transcapillary pressure (54 +/- 3 mm Hg, ablation without treatment; 43 +/- 1 mm Hg, ablation with treatment). Dextran sieving studies showed that untreated rats developed a size-selective defect characterized by increased transglomerular passage of neutral dextrans with radii 54 to 76 A and a charge-selective defect characterized by an increased transglomerular passage of anionic dextran sulfate with a radius of approximately 18 A. Ang II blockade reduced fractional clearance values for large neutral dextrans near to values observed in normal rats but had no effect on the fractional clearance of dextran sulfate (0.68 +/- 0.11, ablation without treatment; 0.66 +/- 0.08, ablation with treatment; 0.46 +/- 0.05, normal rats). These findings indicate that reducing Ang II activity improves size-selectivity without affecting charge-selectivity in injured remnant glomeruli.
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PMID:Effects of angiotensin II receptor blockade on remnant glomerular permselectivity. 768 77

The interaction of the endogenous vasoconstrictors endothelin (ET), angiotensin II (Ang II) and catecholamines with the kallikrein-kinin-, prostaglandin and renin-aldosterone systems in the pathogenesis of acute renal failure (ARF) is still to be defined. In 18 anesthesized pigs the influence of i.v. bolus applications of ET (2 micrograms/kg), Ang II (10 micrograms/kg) and norepinephrine (NE; 20 micrograms/kg) on hemodynamics, plasmatic coagulation and fibrinolysis system, prostaglandins and renal function was studied. ET induced a biphasic change in blood pressure, starting with an initial short-lasting reduction followed by a long-lasting elevation of systolic and diastolic blood pressure. Endothelin bolus resulted in a significant increase of 6-keto-PGF1 alpha, PGE2 and TXB2 plasma levels (P < 0.05 against preinjection values), whereas prostaglandins remained unchanged in the Ang II and NE groups. There was a distinct correlation between the plasma ET and 6-keto-PGF1 alpha levels (r = 0.82). In contrast to Ang II or NE, ET induced a shortening of the activated partial thromboplastin time (aPTT) and increase of antithrombin III levels (ATIII), fibrin monomers (FM), prekallikrein (PKK) and factor VIII activity at the beginning. Finally a pronounced decrease of ATIII, FM and PKK occurred, indicating a consumptive coagulopathy. At the end of the experiment, elevated plasma renin activity and pCO2, significantly decreased creatinine clearance, blood pH, pO2, base excess, HCO3-, oxygen saturation (P < 0.01), a distinct glomerular proteinuria, and a final anuria were observated. These results reveal that ET activates the plasmatic coagulation system and induces an ARF accompanied by impairment of pulmonary function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of endothelin on hemodynamics, prostaglandins, blood coagulation and renal function. 775 79

Angiotensin II (AII) appears essential in remnant kidney models of renal injury in rats, and renal injury was reduced by angiotensin-converting enzyme inhibitor (ACEI). To determine whether this is due to AII blockade or other actions of ACEI, we studied a nonpeptide AII type 1 receptor antagonist and an ACEI in partially nephrectomised spontaneously hypertensive rats (SHR). Thirty SHR underwent surgery and were divided into three equal groups: Control, TCV (0.5 mg/kg/day TCV-116), and CAP (30 mg/kg/day captopril). All SHR received a 5%-NaCl diet. Systolic blood pressure (SBP) and urinary protein were measured at 2-week intervals. Serum total protein, albumin, urea nitrogen, and creatinine were determined at week 8. Glomerular filtration rate (GFR) and renal blood flow (RBF) were measured at weeks 4 and 8. Renal injury was evaluated histopathologically. TCV and CAP reduced SBP at week 2 and proteinuria at week 8. GFR and RBF fell in all groups, but decreases were not significant in treated SHR and histopathological changes were significantly ameliorated. All blockade by TCV or CAP reduces renal injury in salt-loaded SHR with partial renal ablation. AII is essential in remnant kidney models of renal injury, and AII blockade is essential in renal protection by ACEI.
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PMID:Nonpeptide angiotensin II type 1 receptor antagonist prevents nephrosclerosis in hypertensive rats. 788 4

To prevent drug accumulation and adverse effects the dose of hydrophilic angiotensin-converting enzyme (ACE) inhibitors, e.g. lisinopril, must be reduced in patients with renal failure. To obtain a rational basis for dose recommendations, we undertook a prospective clinical trial. After 15 days of lisinopril treatment pharmacokinetic and pharmacodynamic parameters were determined in patients with advanced renal failure (n = 8; endogenous creatinine clearance [CLCR]: 18 ml.min-1.1.73 m-2) and in healthy subjects with normal renal function (n = 16; CLCR: 107 ml.min-1.1.73 m-2). The volunteers received 10 mg lisinopril once daily, the daily dose in patients (1.1-2.2 mg) was adjusted to the individual CLCR according to the method of Dettli [13]. After 15 days of lisinopril treatment the mean maximal serum concentration (Cmax) in patients was lower than in volunteers (30.7 vs 40.7 ng.ml-1, while the mean area under the concentration-time curve (AUC0-24 h) was higher (525 vs 473 ng.h-1.ml-1). ACE activity on day 15 was almost completely inhibited in both groups. Plasma renin activity, angiotensin I and angiotensin II levels documented marked inhibition of converting enzyme in volunteers and patients. Furthermore, average mean arterial blood pressure in patients decreased by 5 mmHg and proteinuria from 3.9-2.7 g per 24 h after 15 days of treatment with the reduced dose of lisinopril. Adjustment of the dose of lisinopril prevents significant accumulation of the drug in patients with advanced renal failure during chronic therapy. Mean serum levels did not exceed this in subjects with normal renal function receiving a standard dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacokinetics and pharmacodynamics of lisinopril in advanced renal failure. Consequence of dose adjustment. 799 22

Rats with puromycin aminonucleoside (PAN) nephrosis were given either angiotensin I converting enzyme inhibitor (ACEI), angiotensin II type 1 receptor antagonist (Ang IIRA), or no treatment for four weeks and were then monitored for an additional 12 weeks. In untreated PAN rats, proteinuria reached a maximum at two weeks (271 +/- 38 mg/day). Proteinuria in this early phase was markedly attenuated by ACEI (96 +/- 35 mg/day, P < 0.01), but unaffected by Ang IIRA (306 +/- 34 mg/day). Acute administration of a bradykinin antagonist substantially dampened the antiproteinuric effect of ACEI in PAN rats, resulting in an average increase in proteinuria of 41 +/- 14% in ACEI-treated rats (P < 0.05, ACEI vs. ACEI+bradykinin antagonist). Acute phase therapy for four weeks with ACEI or Ang IIRA did not attenuate subsequent glomerulosclerosis. Separate groups of PAN rats with similar degree of glomerulosclerosis, assessed at 16 weeks after PAN by renal biopsy, were then treated as follows: ACEI [50 mg/liter drinking water (DW), or 200 mg/liter DW], Ang IIRA (20 mg/liter DW, or 80 mg/liter DW) or no treatment, starting after renal biopsy. Whereas glomerulosclerosis increased from biopsy to autopsy at 28 weeks with emergence of low grade proteinuria in untreated PAN rats, proteinuria was absent and glomerulosclerosis was ameliorated or reversed in ACEI and Ang IIRA groups. The results indicate that the early phase proteinuria of PAN nephropathy is independent of Ang II, and that the antiproteinuric effect of ACEI is, at least in part, channeled through activation of bradykinin, whereas the subsequent progression of glomerulosclerosis is caused by a mechanism involving endogenous Ang II actions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin converting enzyme inhibitor modulates glomerular function and structure by distinct mechanisms. 816 42

Angiotensin converting enzyme (ACE) inhibition causes specific renal effects, such as a rise in effective renal plasma flow, a fall in filtration fraction and a lowering of proteinuria. The mechanism of these renal effects is still debated. Recent animal studies suggest that non-angiotensin (Ang) II related actions of ACE inhibition, such as bradykinin accumulation, may have a role. We therefore investigated the effects of specific intervention in the renin-angiotensin system with the Ang II receptor antagonist losartan, and compared these effects to those obtained with ACE inhibition, as this comparison might resolve the question whether or not the effects of ACE inhibition are Ang II related. The effects of losartan and enalapril were studied in eleven patients with non-diabetic proteinuria and hypertension. The protocol consisted of seven periods, each lasting one month, in which patients received once daily placebo, 50 mg losartan, 100 mg losartan, placebo, 10 mg enalapril, 20 mg enalapril, and placebo, respectively. At the end of each study period proteinuria, blood pressure, and renal function were determined. On both doses of losartan and enalapril proteinuria and blood pressure fell, whereas ERPF increased and GFR remained stable. The fall in urinary protein excretion was similar for both drugs: 46.3% (28.3% to 63.1%) on 100 mg losartan versus 51.6% (37.0% to 69.2%) on 20 mg enalapril (expressed as Wilcoxon-based estimated median with 95% CI).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system? 819 89

In order to determine the activity of the renin-angiotensin system in the nephrotic syndrome, the plasma concentration of angiotensinogen was measured in rats with puromycin aminonucleoside (PA)-induced nephrosis using two different methods: a direct radioimmunoassay, which measures both angiotensinogen and des-angiotensin I-angiotensinogen, and an indirect assay, which measures angiotensin I liberated from angiotensinogen by excess renin. The plasma concentration of angiotensinogen as measured by the direct assay increased before the appearance of PA-induced hypoproteinemia or proteinuria and subsequently decreased to normal levels simultaneously with the appearance of proteinuria. The indirect assay of angiotensinogen also demonstrated an increased concentration of plasma angiotensinogen before the development of nephrosis, but the level decreased to below normal after the appearance of proteinuria. Both plasma renin concentration and renin activity also increased simultaneously with the increase in plasma angiotensinogen. The difference between the concentrations of plasma angiotensinogen determined by these methods increased before and during the early phase of PA-induced nephrosis, suggesting the increased consumption of angiotensinogen by renin during this period. Measurement of plasma corticosterone and serum interleukin-6 revealed that these circulating factors were not involved in the elevation of plasma angiotensinogen in rats with PA-induced nephrosis. These results indicate that the renin-angiotensin system is activated before the appearance of PA-induced nephrotic syndrome.
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PMID:Elevation of plasma angiotensinogen in rats with experimentally induced nephrosis. 844 57

The 'discovery' of losartan represents three separate discoveries: (1) losartan as the unique biphenyltetrazole molecule and the first of a new chemical class; (2) losartan as a tool to identify AT1-subtype receptors; and (3) losartan as a specific probe for exploring the multiple roles of angiotensin II (Ang II) in normal physiology and pathologic states. Losartan is the first nonpeptide orally active Ang II receptor antagonist to reach clinical trials. Losartan was selected for its affinity for Ang II receptors, functional antagonism of Ang II, lack of agonist properties, and oral anti-hypertensive effects. Losartan has been widely used to define the distribution and function of AT receptor subtypes. Although possible roles of the AT2 subtype have been reported, virtually all of the known effects of Ang II are blocked by losartan. Specific AT1 receptor blockade has been broadly compared with ACE inhibition. Possible differences on the basis of AT1 selectivity, bradykinin potentiating effects and Ang II formed by non-ACE pathways are discussed. Losartan blocks the vascular constrictor effect of Ang II, the Ang II-induced aldosterone synthesis and/or release, and the Ang II-induced cardiovascular 'growth' in vitro and in vivo. In various models of experimental hypertension, losartan prevents or reverses the elevated blood pressure and the associated cardiovascular hypertrophy similar to ACE inhibitors. Likewise, in models of renal failure (for example reduced renal mass, puromycin, ochratoxin), losartan, like ACE inhibition, markedly reduced the elevation in blood pressure, proteinuria or sclerosis. In aortocaval shunt, coronary ligation and ventricular pacing models of heart failure, losartan demonstrated a pathological role for Ang II by reversing the associated haemodynamic findings. In SHR-stroke prone, losartan dramatically increased survival while having a limited effect on blood pressure, suggesting a non-pressure dependent effect of Ang II. These collective data show that Ang II exerts complex pathological effects in experimental models of vascular, cardiac, renal and cerebral disease. The effectiveness of losartan in experimental models of heart failure supports its evaluation in clinical trials with patients with heart failure.
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PMID:Discovery of losartan, the first angiotensin II receptor antagonist. 858 79

The kidney vasculature is under tonic control by nitric oxide (NO) and in cortex, NO controls RA and Kf. Systemic NO inhibition leads to systemic hypertension, increases in RE, mediated by Ang II and ET, and direct effects on RA and Kf. The relationship between NO and other vasoconstrictor systems is variable. In the conscious relaxed animal, vasoconstrictor activity is low, yet acute NO inhibition leads to pressor and renal vasoconstrictor responses. At physiologic levels, ET unexpectedly is a renal vasodilator, possibly via NO generation at RA. When vasoconstrictor activity is high, NO is very important in maintenance of renal perfusion. Chronic L-NAME produces dose dependent systemic and glomerular capillary hypertension and eventual proteinuria and glomerular damage. NO deficiency is key in this process, although the hypertension becomes refractory to L-arginine administration and dependent on Ang II and the SNS, by mechanisms not yet defined. In contrast, the renal vasculature remains fully responsive to L-arginine, suggesting that pressor and renal vascular responses to chronic NO inhibition are separately regulated. NO generated from iNOS does not normally control BP or renal hemodynamics. The relative contributions of NO from bNOS and eNOS, and importance of NOS in different locations in the kidney, remain to be determined.
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PMID:Importance of nitric oxide in the control of renal hemodynamics. 874 86

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