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)

In Wistar rats just after weaning, 5/6 of renal parenchyma were removed surgically. Thereafter, the rats were fed either a "high-protein" (21%) or two types of a "low-protein" (6%) diet; in one of the latter the lack of protein was substituted by saccharide, in the other by fat, making the substitution "isocaloric" in either case. In all three diet groups, subgroups were formed drinking either tap water or water containing either the ACE inhibitor enalapril (Ena) or the calcium antagonist diltiazem (Dil), or both (Ena + Dil). In the high-protein diet group, increases in the weight of kidney remnants, in proteinuria and in systolic blood pressure (SBP) were seen. This was prevented by feeding either type of the low-protein diet but also by Ena and Ena + Dil. Ena and Ena + Dil not only prevented the increase in SBP but actually lowered it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and proteinuria. No additive protective action of Ena + Dil or Ena + low protein or Ena + Dil + low protein was seen, suggesting that a bottom limit of these protective action was reached by the low-protein diet alone. There was no substantial difference between either type of the low-protein diet except a small and transient decrease in body weight in the first week of fat-rich diet administration.
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PMID:A comparison of the effect of feeding a low-protein diet and of pharmacological intervention on the course of ablation nephropathy in the rat. 777 Jun 41

The effect of inhibiting the renin-angiotensin system was evaluated in male Sprague-Dawley rats with reduced renal mass produced by right nephrectomy and infarction of two-thirds of the left kidney. Separate groups of rats were then administered the angiotensin receptor antagonists, A-81988 or losartan (DuP 753), the angiotensin converting enzyme inhibitor, enalapril, or vehicle (tap water) in their drinking water for 4 weeks. Tail cuff blood pressures and blood samples were obtained weekly. Excretory function during week 4 was evaluated using metabolic cages. Rats with reduced renal mass were characterized by a significant elevation in systolic blood pressure and urinary protein excretion along with a reduced urine osmolality. At 1 mg/kg/day, A-81988 prevented the hypertension and the development of proteinuria. A-81988 administration also improved urinary concentrating ability because urine osmolality was significantly higher in this group compared to untreated controls. The same dose of losartan or enalapril was ineffective at controlling the development of the hypertension, indicating that A-81988 is more potent in vivo. Despite the maintenance of systemic hypertension, losartan significantly blunted the proteinuria compared to vehicle-treated controls. At a dose of 10 mg/kg/day, losartan and enalapril also prevented the increase in systolic blood pressure and proteinuria and produced an increase in urine osmolality. These data support the hypothesis that angiotensin receptor antagonists have beneficial effects in forms of renal failure associated with proteinuria and diminished concentrating ability.
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PMID:Angiotensin II receptor blockade improves renal function in rats with reduced renal mass. 824 38

Calcium entry blockers, particularly diltiazem, have been shown to lower not only systemic blood pressure but also improve proteinuria in non-insulin-dependent diabetic patients. The presence of proteinuria is attributed to the loss of glomerular heparan sulfate, which confers a negative charge on the basement membrane. In the present study, we evaluated the efficacy of diltiazem in lowering blood pressure and proteinuria in diabetic rats and also examined the possibility that diltiazem prevents proteinuria through glomerular preservation of heparan sulfate. Diabetes was induced in male Wistar rats by streptozotocin (60 mg/kg). One group of diabetic rats was treated with diltiazem (25 mg/L) in drinking water for 20 weeks. Another group of diabetic rats and a group of nondiabetic rats were given tap water only. Systolic blood pressure was measured at 4, 8, 12, and 20 weeks. Urinary excretion of albumin was done at 4, 8, 12, 16, and 20 weeks. At the end of 20 weeks, all rats were killed, kidneys were removed, and glomeruli were isolated. Total glycosaminoglycan and heparan sulfate synthesis were determined by incubating glomeruli in the presence of [35S]sulfate. Diltiazem lowered blood pressure significantly in diabetic rats at 8, 12, and 20 weeks. Diabetic glomeruli synthesized less total glycosaminoglycan and heparan sulfate than glomeruli from normal rats. Characterization of heparan sulfate by ion-exchange chromatography showed that the fraction eluted with 1 M NaCl was significantly lower and the fraction eluted with 1.25 M NaCl significantly higher in diabetic than in normal rats. Diltiazem therapy returned not only glomerular synthesis but also various fractions of heparan sulfate to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of diltiazem on glomerular heparan sulfate and albuminuria in diabetic rats. 850 Aug 60

The effects of nifedipine and enalapril on age-associated renal interstitial fibrosis were investigated in 60 CF1 female mice. Mice received 20 mg enalapril (ENAL) per L (N = 20), or 40 mg nifedipine (NIF) per L (N = 20) in their drinking water. Control (CONT) mice received tap water ad libitum. The percentages of both interstitial peritubular sclerosis (IPS) in cortex and interstitial medullary sclerosis (IMS) were determined. Kidney tissue was studied using immunological techniques and optical (OM) and electron microscopy (EM) to analyze the expression of renin. alpha-SM-actin and vimentine expression were also evaluated. The results showed that blood pressure levels in ENAL or NIF animals were not different from those of CONT. Renin expression was observed in arcuate vessels (AV) in ENAL animals, whereas no renin staining in AV was found in either NIF or CONT animals. Renin immunoreactivity in the juxtaglomerular apparatus was more intense in ENAL mice, as compared with NIF or CONT animals. Laboratory testing showed the following values: proteinuria (mg/mL): CONT 6.1 +/- 0.6, NIF 11.2 +/- 2.3, and ENAL 1.0 +/- 0.6 (P < 0.05); creatinine: CONT 1.37 +/- 0.24, NIF 0.87 +/- 0.16, and ENAL 0.63 +/- 0.1 (P < 0.01). The percentages of interstitial sclerosis were: %IPS: CONT 18.12 +/- 1.1, NIF 17.40 +/- 0.9, and ENAL 3.42 +/- 1.3 (P < 0.01); %IMS: CONT 23.41 +/- 1.5, NIF 21.80 +/- 1.9, and ENAL 6.12 +/- 1.2 (P < 0.01). Percentages of alpha-SM-actin expression were: CONT 13.10 +/- 1.9, NIF 13.80 +/- 0.2, and ENAL 1.00 +/- 0.1 (P < 0.01). Vimentine staining showed no differences among the groups. It was concluded that enalapril reduces the peritubular and medullar interstitial fibrosis, whereas nifedipine has no effect.
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PMID:Renal interstitial sclerosis in aging: effects of enalapril and nifedipine. 873 1

It has been demonstrated that intraperitoneal administration of proteolytic enzymes ameliorates the progression of renal diseases in various animal models. In the present study, we employed the rat remnant kidney model to study the effectiveness of oral administration of proteases. Twenty male Wistar rats underwent sham operation (CTRL), while 25 were subjected to 5/6 nephrectomy (5/6 NX). Rats were randomised into placebo (PL) (2 ml tap water/day by gavage), or Phlogenzym (E; fixed mixture of trypsin 2.42 mg, bromelain 4.54 mg, and rutozid 5.04 mg added as antioxidant, in 2 ml tap water daily by gavage) treated group. Duration of the study was 45 days. Rats were pair-fed. Enzyme treatment exerted salutary effects on various functional and morphological parameters. Proteinuria was higher in both 5/6 NX group rats throughout the study. Administration of proteases ameliorated its rise effectively (data at sacrifice: CTRL-PL 6.27 +/- 1.25, CTRL-E 9.27 +/- 0.99, 5/6 NX-PL 74.04 +/- 21.33, 5/6 NX-E 39.09 +/- 7.93 mg/24 h; P < 0.01). Increased urinary excretion of the fibrogenic cytokine transforming growth factor (TGF-beta 1) was improved, too (CTRL-PL 0.349 +/- 0.051, CTRL-E 0.693 +/- 0.230, 5/6 NX-PL 3.044 +/- 0.540, 5/6 NX-E 1.390 +/- 0.238 ng/mumol creatinine; P < 0.05). At sacrifice, tubulointerstitial fibrosis was less pronounced in E-treated rats. Correspondingly, the volume fraction of tubulointerstitial tissue in the renal cortex was improved in 5/6 NX-E rats (CTRL-PL 9.9 +/- 0.2, CTRL-E 10.0 +/- 0.2, 5/6 NX-PL 17.9 +/- 1.8, 5/6 NX-E 13.8 +/- 0.9%; P < 0.05). The protein/DNA ratio in isolated glomeruli and tubules, as an estimate of glomerular matrix accumulation and hypertrophy of tubules, was enhanced in 5/6 NX groups and a tendency towards lower values was observed after E treatment. Renal function as evaluated by serum creatinine and urea levels was not influenced by the enzyme therapy. No between-group differences in blood pressure were observed. In summary, oral administration of proteolytic enzymes improved proteinuria and urinary TGF-beta 1 excretion, as well as the severity of tubulointerstitial fibrosis without signs of toxicity.
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PMID:The effect of oral protease administration in the rat remnant kidney model. 1063 1

The authors recently observed an age-dependent reduction in the diuretic and natriuretic responses to plasma volume expansion in uninephrectomized control and glucose-intolerant rats. To determine the involvement of angiotensin II AT receptors in this phenomenon, the authors tested the hypothesis that chronic candesartan treatment preserves renal excretory function in the uninephrectomized rat. Control and glucose-intolerant rats underwent right nephrectomy at 4 weeks of age. Two weeks later, the animals in each group were further subdivided and maintained on tap water containing either candesartan cilexetil (10 mg. kg(-1). day(-1) ) or vehicle. Renal excretory responses to acute extracellular fluid volume expansion (5% of body weight over 30 min) were determined in the 9-month-old conscious animal. Candesartan treatment markedly reduced the mean arterial pressure of controls and glucose-intolerant rats. Nonetheless, the baseline rates of fluid and electrolyte excretion, as well as the saline volume-induced diuretic, natriuretic, and kaliuretic responses, were greater in the candesartan-treated rats than in their vehicle-treated counterparts. The augmented baseline rates of fluid and sodium excretion in candesartan-treated rats were caused by a reduction in tubular reabsorption activity and an increase in glomerular filtration rate. However, the candesartan-mediated enhancement in saline volume-induced diuresis and natriuresis was caused by a reduction in tubular reabsorption activity. In addition to improving renal function, candesartan treatment reduced proteinuria in both groups. In conclusion, chronic blockade of the angiotensin II receptors exerts hypotensive and renoprotective effects in the aging uninephrectomized rat.
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PMID:Renoprotective effects of chronic candesartan treatment in uninephrectomized rat. 1250 25

Cadmium is a pervasive environmental contaminant. The primary route of exposure to the general population occurs via contaminated drinking water or food supplies. Our hypothesis was that cadmium could be a trigger for inducing autoimmune disease (AD) in genetically predisposed populations. Therefore, New Zealand Black/White F1 (NZBW) mice were exposed to cadmium via drinking water. Mice were exposed to: 0, 3, 30, 3000 or 10000 parts per billion (ppb) of cadmium in tap water for 2, 4, 28, or 31 weeks. After 4 weeks of exposure, in the group of mice exposed to 10000 ppb cadmium, there was an increased incidence of antinuclear antibodies (ANA). There was also deposition of immune complexes in all groups after 4 weeks of exposure. After 31 weeks, there were increases in IgG2a in mice exposed to low doses of cadmium. In an attempt to establish the progression from an autoimmune reaction to the development of AD, the biological marker for AD, proteinuria, was assessed. Onset of proteinuria was exacerbated by 11 weeks in mice exposed to cadmium. This data suggests that short-term exposure may result in a type of autoimmune reaction since the mice are beginning to produce ANA after only 4 weeks of exposure and there is immune-complex deposition in the kidney. Long-term exposure to cadmium appears to result in the exacerbation of AD as indicated by the development of proteinuria and continued presence of immune complexes in the kidney. The mechanism may involve the increased production of IgG2a, which is capable of forming immune complexes and causing autoimmune glomerulonephritis.
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PMID:Drinking water exposure to cadmium, an environmental contaminant, results in the exacerbation of autoimmune disease in the murine model. 1276 94

Our previous studies indicate that prolonged caffeine consumption exacerbates renal failure in nephropathy associated with the metabolic syndrome. Reduced activity of the antioxidant defense system and beneficial effects of antioxidant therapy have been reported in diabetic rats and humans. The purpose of this study was to examine the early renal effects of caffeine consumption and the effects of concomitant antioxidant therapy in young obese, diabetic ZSF1 rats. Eleven-week-old male ZSF1 rats were randomized to drink tap water, caffeine (0.1%), tempol (1 mmol/L), or a solution containing caffeine and tempol for nine weeks. Caffeine significantly reduced body weight and glycosuria (weeks 2-9), improved glucose tolerance (week 9), had no effect on elevated plasma triglycerides, plasma cholesterol (week 9) and blood pressure (week 9), and significantly increased plasma cholesterol level (weeks 5 and 9). Yet, as early as after two weeks, caffeine greatly augmented proteinuria and increased renal vascular resistance (RVR) and heart rate (HR: week 9). Tempol had no effects on metabolic status and development of proteinuria, did not alter caffeine-induced metabolic changes and early proteinuria, and attenuated caffeine-induced increase in HR and RVR. Immunohistochemical analysis revealed significant glomerular and interstitial inflammation, proliferation, and fibrosis in control animals. Caffeine augmented the influx of glomerular and interstitial macrophages (ED1+ cells) influx, glomerular and tubular proliferative response, and glomerular collagen IV content. Tempol abolished the exacerbation of renal inflammation, proliferation, and fibrosis induced by caffeine. In conclusion, in nephropathy associated with the metabolic syndrome, caffeine--most likely through the interaction with adenosine receptors and interference with anti-inflammatory and/or glomerular hemodynamic effects of adenosine--augments proteinuria and stimulates some of the key proliferative mechanisms involved in glomerular remodeling and sclerosis. Tempol does not prevent early renal injury (i.e., proteinuria) induced by caffeine, yet abolishes late renal inflammatory, proliferative, and fibrotic change induced by chronic caffeine consumption in obese ZSF1 rats.
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PMID:Early renal injury induced by caffeine consumption in obese, diabetic ZSF1 rats. 1799 59

We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic L-NAME administration in rats. The animals were administered tap water containing L-NAME (1 g/l) or L-NAME + nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (iron-nitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of L-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 +/- 8.9 vs. L-NAME 6.0 +/- 3.1 arbitrary units). Coadministration of a low dose of nitrite with L-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the L-NAME-induced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of L-NAME alone. Chronic administration of a medium dose of nitrite attenuated L-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated L-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/L-arginine-dependent NO generation system is compromised.
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PMID:Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury in L-NAME-induced hypertensive rats. 1875 2

SGK1 is critically important for mineralocorticoid/salt-induced glomerular injury. SGK1 inactivates GSK3, which downregulates Snail, a DNA-binding molecule repressing the transcription of nephrin, a protein critically important for the integrity of the glomerular slit membrane. PKB/SGK-dependent GSK regulation is disrupted in mice carrying a mutation, in which the serine in the SGK/PKB-phosphorylation consensus sequence is replaced by alanine. The present study explored whether PKB/SGK-dependent GSK3 regulation influences glomerular proteinuria. Gene-targeted knockin mice with mutated and thus PKB/SGK-resistant GSK3alpha,beta (gsk3(KI)) were compared with their wild-type littermates (gsk3(WT)). gsk3(KI) and gsk3(WT) mice were implanted with DOCA release pellets and offered 1% saline as drinking water for 21 days. Under standard diet, tap water intake and absence of DOCA, urinary flow rate, glomerular filtration rate, and urinary albumin excretion were significantly larger and blood pressure was significantly higher in gsk3(KI) than in gsk3(WT) mice. Within 18 days, DOCA/salt treatment significantly increased fluid intake and urinary flow rate, urinary protein and albumin excretion, and blood pressure in both genotypes but the respective values were significantly higher in gsk3(KI) than in gsk3(WT) mice. Plasma albumin concentration was significantly lower in gsk3(KI) than in gsk3(WT) mice. Proteinuria was abrogated by lowering of blood pressure with alpha(1)-blocker prazosin (1 microg/g body wt) in 8-mo-old mice. According to immunofluorescence, nephrin at 3 and 8 mo and podocin expression at 3 mo were significantly lower in gsk3(KI) than in gsk3(WT) mice. After 18 days, DOCA/salt treatment renal glomerular sclerosis and tubulointerstitial damage were significantly more pronounced in gsk3(KI) than in gsk3(WT) mice. The observations reveal that disruption of PKB/SGK-dependent regulation of GSK3 leads to glomerular injury with proteinuria, which may at least partially be secondary to enhanced blood pressure.
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PMID:Proteinuria in mice expressing PKB/SGK-resistant GSK3. 1898 14


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