UMLS:C0033687 - FACTA Search

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Query: UMLS:C0033687 (proteinuria)
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Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7-8%, mainly due to primary glomerulonephritis (70-80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14-50% DR, 40-60% GL; atypical haemolytic uraemic syndrome 20-80% DR, 10-83% GL; membranoproliferative glomerulonephritis 30-100% DR, 17-61% GL; membranous nephropathy approximately 30% DR, approximately 50% GL; lipoprotein glomerulopathy approximately 100% DR and GL; primary hyperoxaluria type 1 80-100% DR and GL) or with a low risk of GL [immunoglobulin (Ig)A nephropathy 36-60% DR, 7-10% GL; systemic lupus erythematosus 0-30% DR, 0-5% GL; anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis]. Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus, sickle cell disease, endemic nephropathy, and sarcoidosis. In other primary diseases, the post-Tx course may be complicated by specific events that are different from overt recurrence: proteinuria or cancer in some genetic forms of nephrotic syndrome, anti-glomerular basement membrane antibodies-associated glomerulonephritis (Alport syndrome, Goodpasture syndrome), and graft involvement as a consequence of lower urinary tract abnormality or human immunodeficiency virus (HIV) nephropathy. Some other post-Tx conditions may mimic recurrence, such as de novo membranous glomerulonephritis, IgA nephropathy, microangiopathy, or isolated specific deposits (cystinosis, Fabry disease). Adequate strategies should therefore be added to kidney Tx, such as donor selection, associated liver Tx, plasmatherapy, specific immunosuppression protocols. In such conditions, very few patients may be excluded from kidney Tx only because of a major risk of DR and repeated GL. In the near future the issue of DR after kidney Tx may benefit from alternatives to organ Tx, such as recombinant proteins, specific monoclonal antibodies, cell/gene therapy, and chaperone molecules.
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PMID:Disease recurrence in paediatric renal transplantation. 1924 94

Childhood human immunodeficiency virus-associated nephropathy (HIVAN) is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal segmental glomerulosclerosis, in combination with the microcystic transformation of renal tubules. This review discusses the pathogenesis of childhood HIVAN and explores how the current pathological paradigm for HIVAN in adults can be applied to children. The Human Immunodeficiency Virus-1 (HIV-1) induces renal epithelial injury in African American children with a genetic susceptibility to develop HIVAN. The mechanism is not well understood, since renal epithelial cells harvested from children with HIVAN do not appear to be productively infected. Children with HIVAN show a renal up-regulation of heparan sulphate proteoglycans and a recruitment of circulating heparin-binding growth factors, chemokines, and mononuclear cells. Macrophages appear to establish a renal HIV-reservoir and transfer viral particles to renal epithelial cells. All of these changes seem to trigger an aberrant and persistent renal epithelial proliferative response. The paradigm that viral products produced by infected renal epithelial cells per se induce the proliferation of these cells is not supported by data available in children with HIVAN. More research is needed to elucidate how HIV-1 induces renal epithelial injury and proliferation in HIV-infected children.
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PMID:Taking a hard look at the pathogenesis of childhood HIV-associated nephropathy. 1928 42

Human immunodeficiency virus (HIV)-infected children are at risk of developing several types of renal diseases, including HIV-associated nephropathy (HIVAN), which is usually seen during late stages of infection in children with a high viral load. This disease is defined by the presence of proteinuria associated with mesangial hyperplasia and/or global-focal segmental glomerulosclerosis combined with microcystic transformation of the renal tubules. Because HIVAN can have an insidious clinical onset, renal biopsy is the only definitive way of establishing a diagnosis. Given the risk of performing this procedure in HIV-infected children with other AIDS-defining illness, we sought to identify informative biomarkers such as growth factors in the urine of 55 HIV-infected children that might be predictive of the extent and activity of the renal lesions characteristic of HIVAN. We found that the levels of epidermal growth factor were lower in the urine of children with renal disease, whereas levels of fibroblast growth factor-2 and metalloproteinase-2 were higher as compared with those levels in infected children without renal disease. Similar changes were observed in HIV-Tg26 mice correlating with the progression of renal disease in this model of HIVAN. Our findings suggest that this urinary growth factor profile may be useful in facilitating the diagnosis of HIV-infected children at risk of developing HIVAN when interpreted in the appropriate clinical setting.
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PMID:A urinary biomarker profile for children with HIV-associated renal diseases. 1956 54

Because both renal disease and immune activation predict progression to acquired immunodeficiency syndrome (AIDS), we evaluated the associations between proteinuria>or=1+, as determined by dipstick analysis (7 [7%] of 1012 subjects); creatinine clearance of <90 mL/min (195 [18%] of 1071 subjects); and percentages of peripheral activated CD8 cells (CD8+CD38+HLA-DR+ cells) in antiretroviral-naive, human immunodeficiency virus (HIV)-infected subjects who were enrolled in AIDS Clinical Trials Group studies 384 and A5095. Proteinuria, but not creatinine clearance, was associated with higher percentages of CD8+CD38+HLA-DR+ cells (55% vs. 50%; P=.01), with even more pronounced differences noted among men and among blacks and Hispanics. Proteinuria may be a surrogate measurement of greater immune activation in HIV-infected patients initiating antiretroviral therapy.
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PMID:Proteinuria, creatinine clearance, and immune activation in antiretroviral-naive HIV-infected subjects. 1959 72

Chronic kidney disease (CKD) is a worldwide public health problem. Little is known about its burden in Africa. This paper reviews the knowledge of CKD in Kinshasa, summarizing four studies undertaken in the general population and traditional health system of Kinshasa. CKD was defined by either kidney damage (proteinuria> or =300 mg/day) or reduced kidney function (eGFR<60 ml/min/1.73 m(2)). In the general population, the prevalence of CKD all stage is 12.4 %. Our work shows also the high prevalence of proteinuria among subjects who do not have diabetes or hypertension, the lack of early detection and management of CKD risk factors in the traditional health care system leading to late referral or premature deaths, and the limits of renal replacement treatment. CKD affects young people in the DRC, in contrast to the United States, where CKD is more prevalent in older people. Major determinants of CKD in our studies were hypertension, diabetes, overweight, age, lower socioeconomic status, and Human immunodeficiency virus (HIV) infection. Glomerular nephropathy (mainly focal segmental glomerulosclerosis) remains the leading cause of end stage renal disease. An annual screening of the population for proteinuria and CKD risk factors is feasible and will, it is hoped, provide the basis for building a nationwide prevention strategy.
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PMID:[Epidemiology of chronic kidney disease in the Democratic Republic of Congo: review of cross-sectional studies from Kinshasa, the capital]. 2040 70

Many children in Cape Town are co-infected with human immunodeficiency virus (HIV) and tuberculosis (TB). Granulomatous TB interstitial nephritis is a recognized entity. Our objective was to establish if TB plays a role in renal disease in HIV-infected children. We identified children co-infected with TB and HIV from our database and reviewed their biopsies and clinical notes. Since 2002, 12 renal biopsies or postmortem examinations were performed on HIV-infected children at our institution. The clinical scenario and renal biopsies in four cases (median age 73 months, range 24-108 months) were consistent with TB involvement. The mean CD4 count and percentage of these four patients were 508 cells/microl and 23%, respectively. All four patients presented with culture-proven disseminated TB (not yet on treatment) and had nephrotic range proteinuria and hypoalbuminemia. Three of these patients had renal impairment. The prominent features of the renal biopsies were a severe interstitial inflammatory infiltrate and mild to moderate mesangial proliferation. An interstitial granuloma was seen in one patient. With treatment for the TB, the proteinuria resolved and renal function improved in all four patients. Based on these results, we conclude that TB contributes to proteinuric renal disease in HIV-infected children and that the renal disease improves following TB treatment.
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PMID:Renal manifestations in children co-infected with HIV and disseminated tuberculosis. 2042 26

The mechanism responsible for proteinuria in non-genetic idiopathic nephrotic syndrome (iNS) is unknown. Animal models suggest an effect of free radicals on podocytes, and indirect evidence in humans confirm this implication. We determined the oxidative burst by blood CD15+ polymorphonucleates (PMN) utilizing the 5-(and-6)-carboxy-2',7'-dichlorofluorescin diacetate (DCF-DA) fluorescence assay in 38 children with iNS. Results were compared with PMN from normal subjects and patients with renal pathologies considered traditionally to be models of oxidative stress [six anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis, seven post-infectious glomerulonephritis]. Radicals of oxygen (ROS) production was finally determined in a patient with immunodeficiency, polyendocrinopathy, enteropathy X-linked (IPEX) and in seven iNS children after treatment with Rituximab. Results demonstrated a 10-fold increase of ROS production by resting PMN in iNS compared to normal PMN. When PMN were separated from other cells, ROS increased significantly in all conditions while a near-normal production was restored by adding autologous cells and/or supernatants in controls, vasculitis and post-infectious glomerulonephritis but not in iNS. Results indicated that the oxidative burst was regulated by soluble factors and that this regulatory circuit was altered in iNS. PMN obtained from a child with IPEX produced 100 times more ROS during exacerbation of clinical symptoms and restored to a near normal-level in remission. Rituximab decreased ROS production by 60%. In conclusion, our study shows that oxidant production is increased in iNS for an imbalance between PMN and other blood cells. Regulatory T cells (Tregs) and CD20 are probably involved in this regulation. Overall, our observations reinforce the concept that oxidants deriving from PMN are implicated in iNS.
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PMID:Failure of regulation results in an amplified oxidation burst by neutrophils in children with primary nephrotic syndrome. 2049 93

Human immunodeficiency virus (HIV) involves glomerular, tubulointerstitial, and vascular compartments of the kidney. The most common glomerular lesion is HIV-associated focal segmental glomerulosclerosis (FSGS) and related mesangiopathies collectively termed HIV-associated nephropathy (HIVAN). A variety of immune-complex mediated glomerular diseases such as membranoproliferative glomerulonephritis (MPGN), IgA nephropathy, and lupus-like glomerulonephritis also occur. HIVAN is restricted to patients presenting with proteinuria and progressive reduction of renal function and with distinctive but not pathognomonic pathology (FSGS often coexisting with glomerular collapse and tubular microcystic dilatations). The worldwide incidence of collapsing glomerulopathy (CG) in HIV-positive patients is high in Americans. But in India and other Asian countries, other forms of kidney diseases are more commonly seen. We report the first case of CG in the state of Jammu and Kashmir which also happens to be a very low incidence belt for HIV.
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PMID:Collapsing glomerulopathy in an HIV-positive patient in a low-incidence belt. 2120 85

Since 1984 reports of renal involvement in AIDS patients have been presented in the literature. Different forms of renal disease were noted in the AIDS population including those related to systemic and local renal infections, tubulointerstitial disease, renal involvement by neoplasm and glomerular disease including collapsing glomerulopathy (CG). HIV-associated nephropathy (HIVAN) has been demonstrated to be more severe in the black population. HIVAN is the most common cause of renal failure in HIV-1-seropositive patients. The term HIVAN is reserved for the typical histopathological form of focal and segmental glomerulosclerosis (FSGS) characterized by the findings of coexistent glomerular and severe tubulointerstitial disease. In both humans and the murine model, glomerular lesions include FSGS, glomerular collapse and podocyte hyperplasia. The tubulointerstitial damage as well as the glomerular collapse can also be seen in non-HIV primary collapsing GN, raising the question of common mechanisms to HIV and other non-identified viral agents related to the development of the disease. Although controversial, increasing evidence supports a direct effect of the virus on renal cells either as a result of exposure to viral proteins or direct renal parenchyma infection. The use of a HIV-1 transgenic mouse model has demonstrated a direct etiologic link between HIV-1 expression in kidney and the development of HIVAN with unique viral-host interactions, which depend at the same time on stimulating features of the virus and the individual nature of the host response. The infection of renal cells by HIV-1 could be detected by reverse transcription-polymerase chain reaction (RT-PCR) of gag RNA at a low level. Some studies using an HIV-1 transgenic mouse model have demonstrated that expression of HIV- 1 in the kidney is required for the development of HIVAN. The final common pathway in the development of HIV-associated nephropathy is likely to involve alterations in the patterns of gene expression of renal parenchyma cells by cytokines and growth factors, leading to interstitial fibrosis and enhanced glomerular matrix synthesis. The nature of the host response to viral infection is critical to the development of nephropathy.HLA-linked responses particular to a subset of blacks may explain some of the epidemiologic features of HIVAN. There may also be biological heterogeneity in the strains of HIV-1 that could account for a particular renotropic strain. HIV strains from different parts of the world may vary by as much as 15% at the level of nucleotide sequence. The infectivity of human immunodeficiency virus (HIV-1) in human glomerular cells has been evaluated by exposing homogeneous cultures of human glomerular capillary endothelial, mesangial and epithelial cells to HIV in vitro. The mechanism of access of HIV into glomerular endothelial and mesangial cells is unknown up to now; HIV is generally infectious for cells expressing the CD4 antigen in their cell membrane. Other modes of HIV entry into cells independent of the CD4 receptor are possible through mechanisms involving Fc-receptors or coinfection with other enveloped viruses such as HTLV-l. Our understanding of the pathogenesis of HIVAN has been aided by the development of a transgenic model. The curious fact that only 3 of 8 founded transgenic lines developed nephropathy emphasizes that the expression of viral gene products per se is not sufficient to produce nephropathy. Human renal epithelium does not express CD4 receptors and in vitro attempts to infect glomerular epithelial cells using laboratory strains of HIV-1 have proven fruitless. The striking morphologic and phenotypic similarities between HIVAN and collapsing idiopathic FSGS raise the question whether the altered podocyte gene expression in collapsing idiopathic FSGS may also be due to a viral infection. This hypothesis is further supported by de novo occurrence of collapsing idiopathic FSGS in immunosuppressed renal transplantation patients and by epidemiologic data. In conclusion, there are likely to be common mechanisms in the pathogenesis for collapsing idiopathic glomerulosclerosis and HIVAN. A primary injury of the podocyte leading to dysregulation of the cellular phenotype appears to mediate the glomerular tuft collapse in both conditions. Primary collapsing glomerulopathy recurs post-transplantation, raising the possibility of circulating factors implicated in the pathogenesis of visceral epithelial cell damage in steroid-resistant minimal change disease or recurrent FSGS. Recurrence of CG can occur hours after transplantation, suggesting that the plasma of CG patients contains one or more factors capable of inducing proteinuria due to the damage of the podocyte that results in the increase in glomerular permeability. In a rat model of CG developed by our group, the injection of serum from CG patients resulted in proteinuria, glomerular tuft retraction and podocyte damage at the ultrastructural level (visceral epithelial cell foot-process effacement). No ultrastructural or light microscopy abnormalities were seen in rats injected with serum from non-collapsing FSGS or healthy subjects. Based on the experience of our group, circulating factors play a dominant role in the pathogenesis of idiopathic CG.
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PMID:HIV-associated nephropathy: experimental models. 2125 26

Diffuse infiltrative lymphocytosis syndrome (DILS) is believed to be an immunologic syndrome, most likely in response to human immunodeficiency virus (HIV) antigens, and can be accompanied by decreased kidney function. The spectrum of kidney involvement includes acute or chronic kidney disease, primarily tubular proteinuria; enlarged kidneys on imaging studies; and dense lymphocytic tubulointerstitial infiltrates predominantly composed of CD8(+) T cells on kidney biopsy. We describe 3 newly diagnosed HIV-positive patients of African descent with the histologic and clinical diagnosis of DILS who presented with acute kidney injury associated with Gram-negative bacterial infections. Solely with specific antibiotic therapy without antiviral and/or corticosteroid therapy, all patients recovered from acute kidney injury and had partial to complete resolution of proteinuria and enlarged kidney size. These observations led us to hypothesize that an altered immunologic and/or inflammatory response to the endotoxin derived from Gram-negative bacteria, rather than an immunologic response directed to HIV-related antigens, may be a pathogenetic mechanism for the kidney disease associated with DILS in a subset of HIV-positive patients, especially those of immunogenetically susceptible African descent.
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PMID:Diffuse infiltrative lymphocytosis syndrome presenting as reversible acute kidney injury associated with Gram-negative bacterial infection in patients with newly diagnosed HIV infection. 2129 98

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