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)

Apparently healthy Wistar rats of body weight 250-300 g were chosen for the experiments. A group of 6 rats were assigned for each fraction. The dose of Russell's viper venom (RVV) fraction used for in vivo experiments was 0.75 microgram/g body weight. Of each batch of 6 rats 3 were sacrificed on the third day and the remaining 3 on the fifth day after the administration of test venom fractions. Daily urine output with proteinuria and serum creatinine were determined on the day they were sacrificed. Kidneys from the rats were also examined under light microscopy after hematoxylin and eosin staining. In the in vitro experiment, kidney slices (1 mm thickness) from normal rat was incubated with RVV fractions of 5 mg/ml concentration. The predominant renal lesions observed in both sets of animal experiments were tubular degeneration and necrosis. The changes were mostly confined to proximal tubules. Glomerular changes were mild. Similar tubulotoxic effects were produced by whole RVV as well as single fractions. Therefore, it is possible that RVV contains a common nephrotoxic (protein) component which is present in all fractions of the venom. The renal damage caused by RVV seemed to be due to both systemic effects (mainly DIC and renal ischemia) and direct tubulotoxic effects of the venom.
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PMID:Russell's viper venom fractions and nephrotoxicity. 956 25

Rats recovering from acute renal ischemia exhibit tubule loss and interstitial fibrosis followed by development of proteinuria and glomerular sclerosis. The current study assessed the contribution of angiotensin II (AngII) to these processes. The contribution of AngII to early tubule loss and interstitial fibrosis was assessed in rats studied for 35 d after right nephrectomy and transient occlusion of the left renal artery. One group of rats received no treatment, while a second group received losartan beginning at 2 d following ischemia. Studies at 35 d showed that losartan did not improve GFR (2.04 +/- 0.30 ml/min treated, 2.16 +/- 0.21 ml/min untreated), reduce the fraction of glomeruli that were no longer connected to normal tubule segments (42 +/- 9% treated, 42 +/- 13% untreated), or limit expansion of the interstitial volume fraction (25 +/- 3% treated, 25 +/- 4% untreated). The contribution of AngII to progressive glomerular injury following initial recovery from ischemia was assessed in similarly prepared rats studied for 140 d. One group of rats received no treatment, while a second group received enalapril beginning at 35 d following ischemia. Enalapril markedly reduced proteinuria (78 +/- 17 mg/d treated, 229 +/- 52 mg/d untreated) and the prevalence of segmental glomerular sclerosis (14 +/- 9% treated, 45 +/- 10% untreated). Untreated rats developed sclerotic lesions in glomeruli not connected to normal tubules, as well as in glomeruli connected to normal tubules. Enalapril prevented injury in both classes of glomeruli. These results indicate that AngII does not contribute to interstitial fibrosis during recovery from ischemic injury. Reduction of AngII activity, can, however, prevent secondary glomerular injury in kidneys initially damaged by ischemia.
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PMID:Contribution of angiotensin II to late renal injury after acute ischemia. 1086 84

The present study examined the long-term consequences of warm renal ischemia (WRI) with or without renal ablation. Male Sprague-Dawley rats (250-300 g) were subjected to 60 min of complete WRI by pedicle clamping and then followed for 52 wk. Animals were organized into four groups: rats in which both kidneys were subjected to warm ischemia (2WIK); rats with left WRI and right nephrectomy (1WIK); uninephrectomized rats with a left nonischemic kidney (1NK); and sham-operated rats (2NK). Additional animals were studied at 24 h, 7 days, and 16 and 32 wk. In the first week after WRI, rats from the 2WIK and 1WIK groups displayed a similar degree of acute renal damage. After recovering from acute renal failure, 1WIK rats developed progressive and severe proteinuria, whereas it was mild in the 2WIK group, as well as in the 1NK and 2NK groups. Only animals from the 1WIK group developed severe chronic renal failure, glomerulosclerosis, interstitial fibrosis, and upregulation of transforming growth factor-beta(1) (TGF-beta(1)) gene, which was associated with increased TGF-beta(1) protein expression in tubular epithelial cells, arterioles, and in areas of mononuclear interstitial cell infiltrate. On the contrary, long-term renal TGF-beta(1) expression, function, and histology were similar in 2WIK and 2NK rats. The present study shows that prolonged bilateral WRI, when both kidneys are retained in place, induces very mild long-term renal lesions as opposed to the severe renal scarring observed when WRI is combined with contralateral nephrectomy.
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PMID:Influence of nephron mass in development of chronic renal failure after prolonged warm renal ischemia. 1091 44

Acute episodes of severe renal ischemia result in acute renal failure (ARF). These episodes are followed by a characteristic recovery and repair response, whereby tubular morphology and renal function appear completely restored within approximately 1 mo. However, the chronic effects of such an injury have not been well studied. Male rats were subjected to 60-min bilateral ischemia followed by reperfusion, yielding a characteristic injury. Postischemic animals manifested severe diuresis, peaking at 1 wk postinjury (volume: >45 ml/day, ARF vs. 18 ml/day, sham; P < 0.05). Urine flow subsequently declined but remained significantly elevated vs. sham animals for a 40-wk period. The prolonged alteration in urinary concentrating ability was attributable, in part, to a diminished capacity to generate a hypertonic medullary interstitium. By week 16, proteinuria developed in the post-ARF group and progressed for the duration of the study. Histological examination revealed essentially normal tubular morphology at 4 and 8 wk postinjury but the development of tubulointerstitial fibrosis at 40 wk. Transforming growth factor (TGF)-beta1 expression was elevated at 40 wk, but not at 4 and 8 wk postinjury. Microfil analysis revealed an approximately 30-50% reduction in peritubular capillary density in the inner stripe of the outer medulla at 4, 8, and 40 wk in post-ARF groups vs. sham animals. In addition, post-ARF rats manifested a significant pressor response to a low dose of ANG II (15 ng x kg(-1) x min(-1)). We hypothesize that severe ischemic injury results in a permanent alteration of renal capillary density, contributing to a urinary concentrating defect and the predisposition toward the development of renal fibrosis.
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PMID:Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. 1159 47

Clusterin is a secreted glycoprotein that is synthesized after several types of tubular injury. We therefore wondered whether the urinary excretion of clusterin could serve as a parameter to determine the severity of tubular damage. Using an affinity-purified rabbit antiserum raised against recombinant clusterin, we established an enzyme-linked immunosorbent assay to measure the urinary excretion of clusterin after bilateral renal ischemia, in the (cy/ +) rat model of autosomal-dominant polycystic kidney disease and in the FHH rat model of focal segmental glomerulosclerosis. After bilateral renal ischemia, the urinary excretion of clusterin paralleled the excretion of total protein and albumin and correlated with the extent of tubular damage. Male (cy/ +) rats, but not female (cy/ +) rats, excreted more clusterin than age-matched (+/ +) rats, a finding consistent with the more rapid course of the disease in males. FHH rats presented with pronounced proteinuria and albuminuria but did not excrete increased levels of clusterin. Urinary clusterin levels could therefore serve as a valuable marker for the severity of tubular damage. Furthermore, clusterin may also help to differentiate between tubular and glomerular forms of proteinuria.
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PMID:Urinary clusterin levels in the rat correlate with the severity of tubular damage and may help to differentiate between glomerular and tubular injuries. 1245 27

Renal ischemia not only causes injury but also induces repair mechanisms, such as the cellular induction of the 72-kilodalton heat shock protein HSP-72. The aim of this study was to determine whether HSP-72 is excreted in urine after ischemic renal injury. The first urine of six pediatric allograft recipients was examined for proteinuria and urinary HSP-72 excretion. Sprague-Dawley rats were treated with renal ischemia or hyperthermia and renal cortex and urinary HSP-72 levels were determined. HSP-72 was excreted in the first urine of renal allografts. In rats, renal HSP-72 was induced both by renal ischemia or hyperthermia. However, only renal ischemia resulted in urinary excretion of HSP-72. Urinary excretion of HSP-72 indicates an increased renal stress response and loss of tubular cell integrity after clinical and experimental renal ischemia.
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PMID:Urinary heat shock protein-72 excretion in clinical and experimental renal ischemia. 1257 95

A case report in the journal Pediatric Nephrology describes a 15-month-old girl with the syndrome of hypertension and hyponatremia (HH syndrome) due to underlying unilateral renal artery stenosis. This syndrome is typically associated with hypokalemia and severe volume depletion and sometimes proteinuria, all of which, along with hypertension and hyponatremia, are usually corrected by resolution of the underlying renal ischemia. Gross and probably sudden activation of the renin-angiotensin system in response to renal ischemia is central to the pathophysiology although the cardiac atrial and B-type natriuretic peptides probably contribute also. Initial control of the severe hypertension may, in some cases, require careful volume repletion prior to introduction of blockade of the renin-angiotensin system in order to avoid first-dose hypotension, after which correction of the underlying renal ischemia is required. Whereas the syndrome has rarely been reported in children, it is possible that, as in adults, this reflects its lack of recognition by clinicians. The HH syndrome due to unilateral renal ischemia in children may be much more common than we think.
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PMID:Unilateral renal ischemia causing the hyponatremic hypertensive syndrome in children--more common than we think? 1677 97

Despite recent discoveries of molecules in podocytes, the mechanisms behind most conditions of proteinuria are still poorly understood. To understand more about this delicate barrier, we studied the functional and morphological effects of mild (15 min) renal ischemia-reperfusion injury (IRI). Renal function was studied in rats in vivo, followed by a more detailed analysis of the glomerular barrier in cooled (8 degrees C) isolated perfused kidneys (cIPK). Renal blood flow was quickly restored, whereas the glomerular filtration rate remained halved 30 min after IRI. Tubular cell activity was intact as judged from the unaffected Cr-EDTA U/P concentration ratio. In vivo, the fractional clearance (theta) for albumin increased 16 times. In rats subjected to cIPK starting 30 min after in vivo IRI, theta(albumin) was 15 times and theta(Ficoll_36angstroms) 1.8 times higher than in control cIPKs. According to the heterogeneous charged fiber model, IRI reduced the fiber charge density to 38% of control (P < 0.01, n = 7). Morphometric analysis with electron microscopy did not reveal any changes in the podocytes or the glomerular basement membrane (GBM) after IRI, suggesting more subtle changes of the GBM and/or the endothelial glycocalyx. We conclude that mild renal IRI induces formation of reactive oxygen species, massive proteinuria, and loss of charged fibers with no apparent change in morphology. These novel findings stress the importance of other components of the barrier, such as proteoglycans produced by the glomerular cells, and provide a tentative explanation for the mechanisms behind proteinuria in glomerulonephritis, for example.
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PMID:Mild renal ischemia-reperfusion reduces charge and size selectivity of the glomerular barrier. 1737 66

Snakebites have the highest incidence in Asia and represent an important health problem. Clinical renal manifestations include proteinuria, hematuria, pigmenturia, and renal failure. Nephropathy usually is caused by bites by snakes with hemotoxic or myotoxic venoms. These snakes are Russell's viper, saw-scaled viper, hump-nosed pit viper, green pit viper, and sea-snake. Renal pathologic changes include tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Hemodynamic alterations caused by vasoactive mediators and cytokines and direct nephrotoxicity account significantly for the development of nephropathy. Hemorrhage, hypotension, disseminated intravascular coagulation, intravascular hemolysis, and rhabdomyolysis enhance renal ischemia leading to renal failure. Enzymatic activities of snake venoms account for direct nephrotoxicity. Immunologic mechanism plays a minor role.
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PMID:Snakebite nephrotoxicity in Asia. 1862 Sep 59

Glomerular injury is often characterized by the effacement of podocytes, loss of slit diaphragms, and proteinuria. Renal ischemia or the loss of blood flow to the kidneys has been widely associated with tubular and endothelial injury but rarely has been shown to induce podocyte damage and disruption of the slit diaphragm. In this study, we have used an in vivo rat ischemic model to demonstrate that renal ischemia induces podocyte effacement with loss of slit diaphragm and proteinuria. Biochemical analysis of the ischemic glomerulus shows that ischemia induces rapid loss of interaction between slit diaphragm junctional proteins Neph1 and ZO-1. To further understand the effect of ischemia on molecular interactions between slit diaphragm proteins, a cell culture model was employed to study the binding between Neph1 and ZO-1. Under physiologic conditions, Neph1 co-localized with ZO-1 at cell-cell contacts in cultured human podocytes. Induction of injury by ATP depletion resulted in rapid loss of Neph1 and ZO-1 binding and redistribution of Neph1 and ZO-1 proteins from cell membrane to the cytoplasm. Recovery resulted in increased Neph1 tyrosine phosphorylation, restoring Neph1 and ZO-1 binding and their localization at the cell membrane. We further demonstrate that tyrosine phosphorylation of Neph1 mediated by Fyn results in significantly increased Neph1 and ZO-1 binding, suggesting a critical role for Neph1 tyrosine phosphorylation in reorganizing the Neph1-ZO-1 complex. This study documents that renal ischemia induces dynamic changes in the molecular interactions between slit diaphragm proteins, leading to podocyte damage and proteinuria.
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PMID:Ischemic injury to kidney induces glomerular podocyte effacement and dissociation of slit diaphragm proteins Neph1 and ZO-1. 1892 1


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