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)

Especially in damaged organs, adequate organ preservation is critically important to maintain viability. Institut Georges Lopez-1 (IGL-1) is a new preservation solution, with an extracellular sodium/potassium ratio and polyethylene glycol as a colloid. The influence of warm and cold ischemia was evaluated in a rat Lewis-Lewis transplant model with a follow up of 14 days. Eight groups of donation after cardiac death donor kidneys were studied with warm ischemia of 0 and 15 min followed by 0- or 24-h cold storage (CS) preservation in IGL-1 or UW-CSS. Blood was collected daily during the first week and at day 14. Recipients were placed in metabolic cages at day 4 and 14 after transplantation allowing urine collection and adequate measurement of glomerular filtration rate. Focussing on inflammation, reactive oxygen species production, proximal tubule damage, proteinuria, histology, and renal function after transplantation we could not show any relevant difference between IGL-1 and UW-CSS. Furthermore, the combination of 15-min warm ischemia and by 24-h cold ischemia did not result in life sustaining kidney function after transplantation, irrespective of the used solution. In the present experiment, static CS preservation of ischemically damaged rat kidneys in either IGL-1 or UW-CSS rendered equal results after transplantation.
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PMID:Static cold storage preservation of ischemically damaged kidneys. a comparison between IGL-1 and UW solution. 1822 93

The benefit of prescribing angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor antagonists (ARB) to kidney transplant recipients remains controversial. We investigated determinants and prescribing patterns of ACEi/ARB during the first year following kidney transplantation. All recipients of a first kidney transplant performed at the university hospital of Nancy (France) between January 1997 and June 2004 were included. Determinants of ACEi/ARB prescription were identified by Cox models among various recipient characteristics (at transplantation and during follow-up), donor characteristics and transplant parameters. Of 491 patients, 28.9% started using ACEi/ARB during the year after transplantation, and 26.9% were taking them at one yr. Recipient determinants of ACEi/ARB use were male sex (HR: 1.82, p = 0.003), pre-transplant hypertension (HR: 2.27, p = 0.0002) and ACEi/ARB administration (HR: 1.85, p = 0.002), post-transplant proteinuria (HR: 1.62, p < 0.0001) and anemia (HR: 4.08, p < 0.0001). Glomerular filtration rate level was not associated with ACEi/ARB use. Post-transplant hypercholesterolemia (HR: 0.42, p = 0.013) and higher donor age (HR: 0.98, p = 0.015) were associated with a lower likelihood of ACEi/ARB use. Fewer HLA mismatches (HR: 1.16, p = 0.029) and shorter cold ischemia duration (HR: 1.02, p = 0.045) were also independent predictors of ACEi/ARB use. Regardless of recipient characteristics, nephrologists were more likely to prescribe ACEi/ARB after kidney transplantation when the transplant parameters were favorable.
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PMID:Determinants and patterns of renin-angiotensin system inhibitors' prescription in the first year following kidney transplantation. 1831 41

To assess the relationship between interstitial capillary density and interstitial macrophages we prospectively measured these factors in situ in 110 patients with chronic kidney disease. Macrophage numbers and urinary MCP-1/CCL2 levels significantly correlated inversely with capillary density which itself significantly correlated inversely with chronic damage and predicted disease progression. In 54 patients with less than 20% chronic damage, there was a significant correlation between the urinary albumin to creatinine ratio and MCP-1/CCL2, and MCP-1/CCL2 and macrophages but not between MCP-1/CCL2 and capillary density. Conversely, in 56 patients with over 20% chronic damage there was no correlation between MCP-1/CCL2 and macrophages but there were significant inverse correlations between capillary density and both macrophages and chronic damage. The expression of VEGF mRNA significantly correlated with macrophage infiltration, capillary density and chronic scarring. In an ischemic-hypertensive subgroup there was upregulation of the hypoxia marker carbonic anhydrase IX and with over 20% chronic damage an increased macrophage to CCR2 ratio. Our study shows that proteinuria and MCP-1/CCL2 are important for macrophage recruitment in early disease. As renal scarring evolves, alternative pathways relating to progressive tissue ischemia secondary to obliteration of the interstitial capillary bed predominate.
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PMID:The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease. 1867 Apr 2

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by a prolonged subclinical course of gradual renal cyst expansion, resulting in massively enlarged kidneys and renal failure by the fifth to sixth decade. Renal cyst expansion results in intrarenal ischemia and activation of the renin-angiotensin-aldosterone system (RAAS) and relates to the development and maintenance of hypertension in ADPKD. Hypertension relates to disease progression in ADPKD with regard to renal volume, proteinuria, cardiovascular complications, and progression to end-stage renal disease. Novel magnetic resonance imaging methods developed in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) provide accurate estimates of change in renal volume over a short period of time in ADPKD patients with intact renal function. In CRISP an increase in renal volume of 63.4 ml/yr was found. PKD1 status, male gender, hypertension, reduced renal blood flow, and proteinuria are associated with increased renal volume and change in renal volume over time. HALT-Polycystic Kidney Disease (HALT-PKD) is designed to test whether blockade of RAAS and/or rigorous blood pressure control play a role in slowing renal progression during early (using magnetic resonance imaging methods developed in CRISP) and during late (using measures, including composite of time to doubling of serum creatinine, onset of end-stage renal disease, or death) phases in ADPKD. Findings from CRISP and the rationale for interventions in ADPKD are described, and the design of the HALT-PKD clinical trial is outlined.
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PMID:Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies. 1857 74

Eclampsia is characterized by generalized convulsions in pregnant women with hypertension and proteinuria. Little is known about what triggers the convulsions in this syndrome. The prevailing view is that convulsions are caused by cerebral vasospasm and cerebral edema. However, many important clinical findings argue against cerebral edema or hypertensive encephalopathy as the sole causes of convulsions in eclampsia. The utero-placental ischemia causes the release of certain molecules such as neurokinin B, inflammatory cytokines, endothelins, and tissue plasminogen activator. These molecules stimulate excitatory neuronal receptors and alter neuronal excitability, synaptic transmission, and neuronal survival independent of any vascular effects. Highlighting the neuromodulatory and the convulsive effects of each of these molecules which are elevated in pre-eclampsia, offers a new perspective on the mechanisms of convulsions in eclampsia.
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PMID:Mechanisms of convulsions in eclampsia. 1884 Mar 93

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

Pre-eclampsia is a pregnancy-associated disease of the second part of the pregnancy, occurring mainly after 20th weeks gestation. The prevalence of hypertension in pregnancy is between 5 to 11% and affects mainly women under 20 years of age. An inadequate invasion of trophoblasts with consequential placental ischemia as a result of insufficiently dilated uterine spiral arteries is thought to be an initial cause in the pathogenesis of pre-eclampsia. The clinical symptoms of pre-eclampsia, such as loss of intravascular volume and edema, are caused by generalized endothelial dysfunction. These symptoms are potentiated by hypertension and reduced colloid osmotic pressure in the plama. The organs being affected by pre-eclampsia are those of the vascular-, hepatic-, renal-, cerebral- and coagulatory systems. The prognosis is much more severe when pre-eclampsia develops very early in the pregnancy. The symptoms include elevated blood pressure (over 140 mmHg systolic, 90 mmHg diastolic) combined with proteinuria. Frequent symptoms are hyperreflexia and edema. The etiology of pre-eclampsia has not been clearly defined. Risk factors/triggers for the development of pre-eclampsia can include chronic hypertension, advanced maternal age at first pregnancy (over 35 y), nephropathy, thrombophilia (heterozygous factor V Leiden mutation, antiphospholipid syndrome, heterozygous prothrombin mutation and homozygous MTHFR), multiple gestation and prior pregnancy with preeclampsia. The incidence of preeclampsia is higher in nulliparous than multiparous women. In many countries pre-eclampsia is still most frequent cause of maternal perinatal mortality. HELLP-Syndrome (haemolysis-elevated liver enzyme- low platelets) is a severe progressive course of this disease. Eclampsia, characterized by generalized tonic-clonic convulsion, is the most dangerous complication of pre-eclampsia, and may develop before or after delivery. This form of pre-eclampsia is associated with higher maternal and fetal mortality. Constant maternal hypertension potentially alter vascular integrity of the placenta with further consequences in fetal blood supply leading to growth restriction or zero growth and subsequently resulting in low birth weight or fetal death. The sooner the disease is detected and confirmed, the better the maternal and fetal prognoses are. This is the reason why it is major importance, together with the employment of preventive measures, to identify patients with risk factors with pre-eclampsia though an adequate screening method, thereby detecting the disease earlier and ensuring better pregnancy outcomes for both mother and child.
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PMID:[Pre-eclampsia screening in first and second trimester]. 1897 29

Pharmacological inhibition of the renin-angiotensin-aldosteron system (RAAS) constitutes a cornerstone strategy in the management of patients with chronic nephropathies with proteinuria and with chronic renal failure. Angiotensin converting enzyme inhibitors (ACEI) as well as angiotensin II subtype 1 receptor antagonists have been shown to decrease proteinuria, reduce the local renal inflammatory processes and slow the progression of renal insufficiency. Despite recent progress, there is still no optimal therapy that would stop progression of renal disease. May be pentoxifilline (PTF)--the old medication which is still used to treat peripheral vascular disease and brain ischemia will be the new adjunct to RAAS blockade. In addition, PTF has been shown to decrease the production of pro-inflammatory cytokines and reactive oxygen species. PTF therapy may improve the hemoglobin response in patients with previously rh-EPO resistant anemia in renal failure. This may occur due to inhibition of proinflammatory cytokine production. Probably in the next few years we will get answer to the question of PTF role in nephrology.
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PMID:[Pentoxifylline old drug or new hope for nephrology?]. 1900 36

The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3-4 chronic kidney disease who had no history of smoking, cardiovascular events or use of erythropoietin-based agents. Patients with hemoglobin concentrations above the cohort median of 11.6 g/dl were found to have significant reductions in flow-mediated dilatation compared to those below the median. This inverse relationship remained significant after adjustment for potential confounders, including insulin sensitivity, glomerular filtration rate, proteinuria, body mass index, serum urate, etiology of underlying renal disease, treatment with anti-hypertensive drugs, and traditional Framingham risk factors. Given that hemoglobin can act as an important nitric oxide carrier and buffer, our studies suggest that the mechanism by which hemoglobin influences the endothelium-dependent microcirculation requires its nitrosylation; however, more direct studies need to be performed.
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PMID:Hemoglobin is inversely related to flow-mediated dilatation in chronic kidney disease. 1926 60

The long-term problems after kidney transplantation have changed considerably in recent years. While formerly immunosuppression and prevention of acute rejection were of prime concern, now attention focuses on chronic alterations of the transplanted organ and long-term survival of the patients. The transplantation procedure itself has evolved into a standardized technique with a high level of surgical quality. Problems involving organ preservation and ischemia/reperfusion damage also play a role, especially in view of chronic aspects. Monitoring of long-term complications should follow a program for the transplanted organ as well as a program for the patient. Monitoring kidney function should address the organ more precisely than has previously been the case. Serum creatinine level and proteinuria alone provide insufficient information and only change long after cellular deterioration has begun. Hence it is imperative that new testing methods be developed. One possibility is offered by protocol biopsies that allow histological and molecular analysis of the kidney at regular intervals. The patient programs concentrate on diagnostics and treatment of the cardiovascular diseases. Furthermore, the patients must be screened for occurrence of neoplasia. There are no prospective studies covering all cardiovascular risk factors after kidney transplantation. This pertains particularly to the subject of hypertension.
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PMID:[Current problems of kidney transplantation]. 1939 13


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