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

---

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

Conditional transgenic mice that express one of the human immunodeficiency virus (HIV)-1 accessory genes, vpr, selectively in podocytes using a podocin promoter and a tetracycline-inducible system develop renal injuries similar to those of patients with HIV-associated nephropathy (HIVAN). We have shown that a heminephrectomy accelerates podocyte injury, which is alleviated by angiotensin II (ANG II) type 1 receptor blocker (ARB). The current study further explores the role of ANG II in the genesis of HIVAN in this murine model. With ANG II infusion, heavy proteinuria was observed at 1 wk after the initiation of doxycycline administration to induce vpr expression in podocytes. Severe morphological and phenotypical changes in the podocytes were observed at 2 wk, together with extensive glomerulosclerosis. Norepinephrine infusion, instead of ANG II, increased the systemic blood pressure to the same level as that achieved using ANG II. However, albuminuria and glomerular injury were modest in norepinephrine-infused mice. Treatment with an ARB, olmesartan, almost completely inhibited glomerular injury. In contrast, lowering the blood pressure with a vasodilator, hydralazine, partially decreased albuminuria but did not produce any histological changes. ANG II infusion alone without doxycycline resulted in a lower level of albuminuria and minimal histological changes. These data demonstrate that excessive ANG II accelerates vpr-induced podocyte injury in a mouse model of HIVAN.
...
PMID:Angiotensin II provokes podocyte injury in murine model of HIV-associated nephropathy. 1765 72

Human immunodeficiency virus (HIV)-related glomerular disease is a cause of end-stage renal disease, though there is no recent data from Brazil concerning this syndrome. Persistent proteinuria (PPt) is the main marker for glomerular disease, especially levels above 1.5 g. We examined the prevalence of and associated risk factors for PPt, along with the prevalence of HIV-associated nephropathy (HIVAN) among AIDS patients. We interviewed 411 patients who were attended at the HIV/AIDS section of the Clinical Hospital of the Federal University of Pernambuco (Brazil) from January through June 2004. PPt was defined as a positive urine dipstick exam on at least two occasions. The analyzed risk factors were: black race, a low CD4 lymphocyte count (<200 cells/mm(3)), an HIV RNA level of >100,000 copies/mL and patients on highly-active antiretroviral therapy (HAART). The patients were classified according to urinary protein/creatinine ratio (Up/Uc) < 1.0, 1.0-3.0 and > 3.0. Patients with Up/Uc >3.0 were submitted to renal biopsy. Among the 411 HIV/AIDS patients, the mean age was 37 years, 70% were male, 37.5% were black, the mean CD4 count was 363 cells/mm(3) (+/- 95), the mean RNA HIV count was 44,475 copies/mL (+/- 40,369), and 92% were on HAART. The prevalence of PPt was 5.6% (95% CI = 3.6 to 8.3%), and it was significantly associated with a low CD4 lymphocyte count (p<0.048). HIVAN was found in just one patient, and two patients improved after HAART.
...
PMID:Prevalence of persistent proteinuria in stable HIV/AIDS patients and its association with HIV nephropathy. 1796 69

Human immunodeficiency virus-associated nephropathy (HIVAN) has rarely been reported in African children. In this single-center study, we analyzed ten children diagnosed with HIVAN from January 2000 to October 2006. There were eight boys and two girls, with a male:female ratio of 4:1. Their ages were from 5 months to 15 years (mean 6.8+/-6.2 years), with a peak age of 5-9 years. The presenting complaints included generalized edema (60%) and hypertension (50%). All patients had proteinuria on urine dipstick, with four (40%) at nephrotic range (proteinuria >or=500 mg/dl). Nine (90%) patients were in renal failure, with elevated serum creatinine (6.3-24 mg/dl) and serum urea (70-120 mg/dl). Renal disease was the first manifestation of HIV infection in six patients, whereas the diagnosis was made on autopsy in three. The duration from HIV infection to development of HIVAN ranged from 5 months to 10 years. CD4(+) cell count, done in only three patients due to financial constraints, was below 200/mm(3). The kidneys were hyperechoic on abdominal ultrasound in all patients, and three (30%) showed grossly enlarged kidneys. Histology of renal tissues available by autopsy in three patients showed mainly collapsing focal segmental glomerulosclerosis. Treatments given were angiotensin-converting enzyme (ACE) inhibitors and highly active antiretroviral therapy (HAART) in four and two patients, respectively, and one patient underwent peritoneal dialysis. On outcome analysis, seven (70%) patients died, two were lost to follow-up, and one was alive on HAART therapy at the writing of this article. In conclusion, HIVAN occurs in Nigeria children, and the mortality is very high from uremia.
...
PMID:Human immunodeficiency virus-associated nephropathy (HIVAN) in Nigerian children. 1798 61

A rhesus macaque (Macaca mulatta) infected with simian-human immunodeficiency virus (SHIV) while undergoing AIDS research, required a comprehensive physical examination when it presented with slight peripheral edema, hypoalbuminemia, and proteinuria. Many of the clinical findings were consistent with nephrotic syndrome, which is an indication of glomerular disease, but the possibility of concurrent disease needed to be considered because lentiviral induced immune deficiency disease manifests multiple clinical syndromes. The animal was euthanized when its condition deteriorated despite supportive care that included colloidal fluid therapy. Histopathology confirmed membranoproliferative glomerulonephritis, the result of immune complex deposition most likely due to chronic SHIV infection. Clinical symptoms associated with this histopathology in SHIV-infected macaques have not previously been described. Here we offer suggestions for the medical management of this condition, which entails inhibition of the renin-angiotensin-aldosterone system and diet modifications.
...
PMID:Peripheral edema with hypoalbuminemia in a nonhuman primate infected with simian-human immunodeficiency virus: a case report. 1821 Sep 98

The ability of the human immunodeficiency virus, type 1 (HIV-1) protein Nef to induce cytoskeleton changes in infected host cells is a key event in viral replication. In renal podocytes, we found that Nef induced loss of stress fibers and increased lamellipodia, pathological changes leading to proteinuria in HIV-associated nephropathy. These morphological changes were mediated by Nef-induced Rac1 activation and RhoA inhibition. We identified a new interaction between Nef and diaphanous interacting protein (DIP), a recently described regulator of Rho and Rac signaling. We found that the Src homology 3 binding domain of DIP and the Nef PXXP motif were required for this interaction. Nef also interacts with Vav2 in podocytes. DIP and Vav2 both interact directly with Nef in a competitive manner. DIP interacts with p190RhoGAP, and intact DIP was required for Nef-induced phosphorylation of p190RhoGAP. DIP also interacts with Vav2, and although DIP enhanced baseline phosphorylation of Vav2, it was not required for Nef-induced Vav2 activation. In Nef-infected podocytes, Src kinase induces phosphorylation of DIP, p190RhoGAP, and Vav2, leading to RhoA inhibition and Rac1 activation. Inhibition of the Nef-induced signaling pathway by using a dominant negative of either Src or DIP or siRNA for DIP or p190RhoAGAP restored RhoA activity and stress fiber formation in Nef-infected podocytes, whereas siRNA for Vav2 reduced Rac1 activity and formation of lamellipodia. We conclude that in HIV-infected podocytes, Nef, through the recruitment of DIP and p190RhoAGAP to Nef-Src complex, activates p190RhoAGAP and down-regulates RhoA activity.
...
PMID:HIV-1 Nef disrupts the podocyte actin cytoskeleton by interacting with diaphanous interacting protein. 1823 68

To correlate CD 4 counts with albuminuria and glomerular lesions in patients infected with human immunodeficiency virus (HIV), we studied 104 HIV positive patients (68 males, 36 females) of whom 100 patients were infected by heterosexual contact, 3 by transfusion, and 1 by i.v. drug abuse. We screened over nine months for albuminuria by urine dip stick method, and performed renal biopsy on patients with albuminuria 2+ or more. Histological examination was accomplished by light microscopy in all and by electron microscopy when it was feasible. Albuminuria was observed in 29 (27%) patients, and it revealed a significant negative correlation with CD4 count (p<0.01). Patients with CD4 cells <350 cells/mm(3) disclosed a 3.5 fold increased risk of albuminuria as compared with patients with CD4 >350 cells/mm(3). There was no significant correlation between proteinuria and the duration of infection from the time of diagnosis. Albuminuria also demonstrated a significant negative correlation with the levels of hemoglobin (p<0.05). In addition, low numbers of CD4 cells were associated with lower levels of hemoglobin (p<0.001). Only 10 patients received renal biopsies, and the results revealed HIV-associated nephropathy (HIVAN) in 7 (70%) patients, chronic tubulointerstitial nephritis in 1, membranous glomerulopathy in 1, and diffuse proliferative glomerulonephritis in 1. Acute renal failure was present in 5 patients, of whom four had a pre renal component and one had multiorgan dysfunction syndrome. We conclude that our study demonstrates that both proteinuria and HIVAN are common in HIV infected patients. Proteinuria has a negative correlation with the CD4 counts and hemoglobin levels.
...
PMID:Correlation of CD4 counts with renal disease in HIV positive patients. 1858 20

A 67-year-old woman with systemic lupus erythematosus (SLE) was admitted to our hospital because of lupus nephritis. Methylprednisolone minipulse therapy dramatically reduced her proteinuria; however; she then complained of general fatigue with low-grade fever. Radiological and culture studies revealed no infectious focus, but she was treated with meropenem and micafungin, considering her immunosuppressive state. Cytomegalovirus antigenemia was later determined and ganciclovir was added. She became afebrile, but complained of nausea and headache, and disorientation, without meningeal signs. Because a brain computed tomography (CT) scan showed no abnormality, we initially suspected some kind of drug interaction. Despite the discontinuation of all drugs, however, she still suffered from disturbance of consciousness. A lumbar puncture revealed yeast cells stained by India ink. A diagnosis of cryptococcal meningitis was confirmed. Though fluconazole and meropenem were administered, the patient died. Autopsy findings revealed disseminated cryptococcosis concomitant with pulmonary aspergillosis. Micafungin is a recently approved echinocandin-class antifungal agent that is now widely used in Japan because of its minimal toxicity and broadspectrum activity. However, such echinocandins have limited activity against a number of fungi. Indeed, breakthrough trichosporonosis is becoming a significant problem in patients with hematological malignancies who are receiving echinocandins. To the best of our knowledge, breakthrough cryptococcosis, as seen in our patient, has not been reported previously in patients who were receiving micafungin as an empiric antifungal therapy. This case highlights that cryptococcosis should be kept in mind as a possible breakthrough infection during the administration of echinocandins, especially in patients with cellular immunodeficiency.
...
PMID:Breakthrough cryptococcosis in a patient with systemic lupus erythematosus (SLE) receiving micafungin. 1870 36

Collapsing glomerulopathy (CG) is a distinct clinicopathological entity characterized by high levels of nephrotic range proteinuria, rapidly progressive renal failure, marked parenchymal injury, and poor response to present therapeutic regimens. Growing awareness has led to the identification of associated conditions other than human immunodeficiency virus (HIV) and idiopathic. We report a case of CG from India in a HIV-negative young female, presenting with heavy proteinuria and rapidly progressing renal failure preceded by a febrile illness.
...
PMID:A case of collapsing glomerulopathy associated with febrile illness. 1900 78

The classic kidney disease of human immunodeficiency virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which shows collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression.
...
PMID:HIV-associated nephropathy: clinical presentation, pathology, and epidemiology in the era of antiretroviral therapy. 1901 22

Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in the HIV-1-seropositive population. HIVAN, which is characterized by heavy proteinuria and a rapid decline in renal function, is caused by infection and subsequent expression of viral genes in renal epithelial cells, although the exact mechanism of viral entry into these cells is unknown. The infected renal epithelium is a distinct compartment that supports the evolution of viral strains that may diverge from those found in the patient's blood. Research using animal models and in vitro studies has shown that vpr and nef are the HIV-1 genes most responsible for inducing the characteristic clinical and histopathologic syndrome of HIVAN. Dysregulation of several host factors, including mediators of inflammation, apoptosis, proliferation, transcription, and cell-cell interactions, are also critical factors in determining whether infection of the renal epithelium will lead to HIVAN. Additional research is required to delineate the mechanisms of HIVAN pathogenesis further so that more effective interventions can be implemented to prevent and treat this disease.
...
PMID:Pathogenesis of HIV-associated nephropathy. 1901 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---