Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with human immunodeficiency virus (HIV) infection are prone to the development of focal segmental glomerulosclerosis, a lesion in which increased mesangial cell proliferation and matrix synthesis may play a role. We undertook the present study to determine whether HIV sera may affect mesangial cell proliferation and matrix synthesis either directly or indirectly via effects on macrophage supernatants. Pooled HIV sera was found to significantly enhance (P < 0.01) mesangial cell proliferation in a concentration-related manner. Mesangial cell proliferation was significantly suppressed by two medications commonly utilized in HIV-infected patients, azidothymidine and trimethoprim/sulfamethoxazole, and was not significantly altered by lipopolysaccharide, suggesting that these medications as well as recurrent infection are unlikely to account for the proliferative effect of HIV sera. Supernatants from HIV sera-treated macrophages were found to significantly enhance (P < 0.01) mesangial cell incorporation of [3H]proline, a marker for synthesis of the matrix component collagen, compared to supernatants from control sera-treated macrophages. These results suggest that HIV sera may directly enhance mesangial cell proliferation and may indirectly increase mesangial cell matrix synthesis by altering macrophage secretory products. These effects may play a role in the development of glomerulosclerosis in patients with HIV infection.
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PMID:Effects of human immunodeficiency virus sera and macrophage supernatants on mesangial cell proliferation and matrix synthesis. 836 79

Neither the initiating factors nor the proximate causes of injury that produce proteinuria in nephrotic syndrome have been clearly defined. Immune mechanisms have been postulated in minimal-change nephrotic syndrome (MCNS), focal segmental glomerular sclerosis (FSGS), and glomerular sclerosis associated with human immunodeficiency virus (HIV) infection. Circulating factors have been proposed in MCNS and FSGS, although no specific mediator has been identified. Prompt remission of proteinuria following steroid treatment and the presence of altered immune responsiveness in patients with MCNS have been used to support the participation of an immune mechanism in the pathogenesis of MCNS. Both FSGS and HIV-related nephropathy are usually steroid-resistant. Immune mechanisms are postulated in FSGS because of early recurrence after transplantation, and in HIV-related nephropathy because of the numerous associated immune abnormalities. Experimental models of nephrotic syndrome based on neutralization of glomerular charge, toxic injury to podocytes, injection of antibodies to glomerular components, or abnormalities in transgenic mice have been used to define mechanisms of glomerular injury. This review summarizes physiologic and immunologic abnormalities in MCNS, FSGS, and HIV-associated nephropathy and in several experimental models of nephrotic syndrome, and outlines the immunologic mechanisms and cellular reactions that may be responsible for glomerular dysfunction in these entities.
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PMID:Mechanisms of proteinuria in noninflammatory glomerular diseases. 846 12

The pathogenesis of human immunodeficiency virus-associated nephropathy (HIVAN) is unknown, but it is characterized by aggressive glomerulosclerosis, tubulopathy, and interstitial inflammation. Currently, no therapy has been proven effective for HIVAN. Angiotensin II has been implicated in the pathogenesis of progressive renal disease in the absence of HIV infection, and treatment with captopril enhances renal survival in patients with diabetic glomerulosclerosis. Serum angiotensin-converting enzyme levels are elevated in patients with HIV infection. We therefore compared the course of 18 patients with biopsy-proven HIVAN (nine treated three times per day with captopril and nine not treated [controls]). The controls were matched to the study patients by age, race, gender, and level of serum creatinine concentration. Renal survival was measured from time of biopsy and treatment with captopril until onset of therapy for end-stage renal disease. Differences between the groups' survival were assessed by Kaplan-Meier and Cox regression analyses. Seven African-American men and two women were in the captopril-treated group, and eight African-American men and one woman were in the control group. No control patient died before the initiation of dialysis. There was no difference between initial mean serum creatinine concentration (3.4 +/- 0.7 mg/dL v 3.7 +/- 0.5 mg/dL), CD4 count (66 +/- 27/microL v 92 +/- 15/microL), or age (41.4 +/- 4.1 years v 36.4 +/- 2.6 years) in the study patients and controls, respectively, but the mean urinary protein to creatinine ratio was higher in the study patients. Renal survival was enhanced in the patients compared with the controls (mean renal survival, 156 +/- 71 days v 37 +/- 5 days, respectively; curves different; P < 0.002, Mantel-Cox log-rank test). Captopril and antiretroviral therapy were associated with enhanced renal survival in a Cox regression analysis, while age, level of serum creatinine, urinary protein to creatinine ratio, and CD4 count were not. These data suggest that treatment with captopril and antiretroviral therapy might be useful in delaying the rapidly progressive renal failure characterizing HIVAN. Captopril might exert its effects by reducing angiotensin II levels, or, alternatively, through decreasing renal tissue expression of growth factors and cytokines or by affecting HIV protease activity and therefore extent of productive renal infection. Such findings must be confirmed by randomized, double-blind, placebo-controlled trials.
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PMID:Captopril and renal survival in patients with human immunodeficiency virus nephropathy. 876 14

The objective of this study was to define the demographic, immunologic, and clinical characteristics of children with acquired immunodeficiency syndrome (AIDS) and AIDS nephropathy, and contrast this with the existing adult data. Data from 62 pediatric patients with AIDS who were treated at SUNY Health Science Center, Brooklyn, New York, between 1983 and 1993 were analyzed. Human immunodeficiency virus (HIV) infection was acquired during the neonatal period by vertical transmission (n = 60) or blood transfusion (n = 2). All children with AIDS who exhibited clinical nephropathy died (n = 16), with mean survival of 55.3 months. In contrast, 32 of 56 AIDS patients (70%) who did not manifest nephropathy were alive at the end of the study period. Patients with nephropathy were noted to have significantly lower CD4+ lymphocyte counts than those without nephropathy. These observations suggest that the predominant renal lesion in pediatric patients who acquired HIV infection during the perinatal period is focal segmental glomerulosclerosis, although a variety of other histological lesions were present. As in adults, the survival in children is dismal following the onset of clinical renal disease. In contrast to the adult population in whom multiple risk factors can potentially contribute to AIDS-associated nephropathy, occurrence of nephropathy in children with vertical HIV transmission provides convincing evidence for the pathogenetic role of HIV infection.
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PMID:Childhood AIDS nephropathy: a 10-year experience. 880 30

Electron microscopy is routinely utilized in most centers in the evaluation of native renal biopsies. Several studies, primarily from the 1960s and early 1970s, provide justification for its use. Conducted by Siegel et al. (1), the largest study evaluated 213 consecutive renal biopsies and found that electron microscopy was needed for a correct diagnosis in 11%, as well as for confirmation or additional information in another 36%. However, nearly all of these studies were conducted before the use of immunofluorescence in renal biopsy diagnosis became widespread and before several new glomerular diseases and variants were described. In light of this situation and the expense of the procedure, the routine use of electron microscopy in native renal biopsies also examined by immunofluorescence and routine light microscopy was reevaluated. From January 1996 to June 1996, 288 native renal biopsies were received, and all were evaluated by the same pathologist. Of those, 233 met criteria for inclusion in this study, which were > or = 5 glomeruli for light microscopy, > or = 2 for immunofluorescence, and > or = 1 for electron microscopy, not including globally scarred glomeruli. Light microscopy (hematoxylin and eosin, periodic acid-Schiff stains) and immunofluorescence--for immunoglobulin (Ig) G, IgA, IgM, C3, C1q, fibrinogen; kappa/lambda when needed--were evaluated on each biopsy within 48 h of receipt, and a preliminary diagnosis was recorded if possible. Electron microscopy was then performed, and a final diagnosis was made. In 50 cases (21%), electron microscopy was needed to make the final diagnosis; in two of these cases, the preliminary diagnosis was incorrect, and in 48, a firm preliminary diagnosis could not be made. In the other cases, the preliminary diagnosis was correct, but in 48 (21%), ultrastructural study was felt to provide important confirmatory data, and in eight cases (3%), an additional, unrelated diagnosis was supported by the ultrastructural findings. Diagnoses most frequently requiring electron microscopy included minimal change nephropathy, early diabetic nephropathy, membranous lupus nephritis, membranoproliferative glomerulonephritis, postinfectious glomerulonephritis, thin basement membrane nephropathy (or exclusion of this in cases of otherwise unexplained hematuria), and human immunodeficiency virus-associated nephropathy (or exclusion of it in cases of collapsing glomerulopathy). Common diagnoses usually not requiring electron microscopy included IgA nephropathy, diffuse proliferative lupus nephritis, focal segmental glomerulosclerosis (not collapsing glomerulopathy variant), pauci-immune crescentic glomerulonephritis, acute interstitial nephritis, and amyloid nephropathy. This study confirms that, as was the case 20 to 30 yr ago, electron microscopy provides useful diagnostic information in nearly half of native renal biopsies. If electron microscopy cannot be performed routinely on all such biopsies, it is recommended that tissue for ultrastructural studies be set aside in each case.
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PMID:A reevaluation of routine electron microscopy in the examination of native renal biopsies. 901 50

The renal pathologic features of 120 consecutively autopsied patients affected by acquired immunodeficiency syndrome was investigated by light microscopic analysis. Variously associated renal changes were found in 82 patients (68.3%). Glomerular changes were present in 25. The following diagnoses were made: mesangial glomerulonephritis (16 patients), defined by the presence of deposits in the mesangium and/or mesangial cell proliferation; membranous glomerulonephritis (4 patients), cirrhotic glomerulosclerosis (2 patients); and lupuslike glomerulonephritis (3 patients). Glomerular diseases seemed to be significantly associated with chronic hepatitis or liver cirrhosis. Interstitial inflammation was present in 19 cases: chronic pyelonephritis (2 patients), focal nephritis (5 patients), multiple cortical abscesses (7 patients), granulomatous nephritis (5 patients). Cryptococci were found in one and undetermined microorganisms in two cases of multiple cortical abscesses. Atypical mycobacteria were found in two cases of granulomatous nephritis. Mycotic infections were identified in another 6 patients, in whom they did not elicit any inflammatory response. It is worth stressing that, although various generalized infections are common in patients with acquired immunodeficiency syndrome, only cryptococci and atypical mycobacteria also frequently involve the kidney. Focal tubular necrosis was observed in 15 patients. Benign nephrosclerosis was the most common vascular change (27 patients). Changes recalling hemolyticuremic and localized intravascular coagulation were found in three and six patients, respectively. Our data, dealing with a European Caucasian population, considerably differ from those reported in North American literature, in as much as we found no cases of human immunodeficiency virus nephropathy. Conversely, immune-mediated glomerular diseases were frequent, in agreement with recent studies on renal biopsy specimens from AIDS patients with acquired immunodeficiency syndrome. This type of infections, supplies multiple sources of antigens that may stimulate immune complex formation and, therefore, glomerular diseases.
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PMID:Renal changes in patients with acquired immunodeficiency syndrome: a post-mortem study on an unselected population in northwestern Italy. 907 21

Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, "collapsing" glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and "collapsing" glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group.
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PMID:Immune complex glomerulonephritis in patients coinfected with human immunodeficiency virus and hepatitis C virus. 910 39

Human immunodeficiency virus-associated nephropathy (HIVAN) is characterized by massive proteinuria with rapidly progressive renal failure. We report an adult with HIV infection who developed nephrotic-range proteinuria and acute renal failure requiring hemodialysis. Renal biopsy findings were consistent with HIVAN, exhibiting focal and segmental glomerulosclerosis with dilated microcystic tubules filled with pale eosinophilic material. Institution of corticosteroid therapy was followed by significant improvement in renal function and proteinuria. Corticosteroids were tapered, and the patient experienced worsening of his renal failure and proteinuria. A second course of corticosteroids was again associated with improved renal function. This and other reports suggest that corticosteroids may improve the clinical course of HIVAN.
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PMID:Clinical response to prolonged corticosteroids in a patient with human immunodeficiency virus-associated nephropathy. 910 55

Human immunodeficiency virus (HIV)-1 infection may be complicated by progressive renal glomerular disease, including focal segmental glomerulosclerosis (FSGS) and proliferative glomerulonephritis. We examined renal tissue from 71 patients, including biopsies and autopsies from patients in the presence and absence of HIV-1 infection. We assessed the extent of TGF-beta, interstitial fibrosis, and interstitial CD45-positive cellular infiltrate using immunohistochemistry. Extracellular TGF-beta 1/beta 3 was largely confined to the renal interstitium, with the highest scores in HIV-seropositive renal disease and crescentic nephritis. Among all biopsies, the TGF-beta 1/beta 3 score correlated with the fibrosis score (r = 0.79, P < 0.0001) and with the CD45 score (r = 0.60, P < 0.0001). Biopsies from HIV-infected patients, taken together, showed marginally more TGF-beta 1/beta 3 compared to biopsies from HIV-uninfected patients (P = 0.05); similarly, HIV-associated FSGS showed marginally more TGF-beta 1/beta 3 compared to FSGS biopsies obtained from HIV-uninfected patients (P = 0.05). Intracellular TGF-beta 1 and TGF-beta 3 were both expressed by renal tubular epithelial cells and in extraglomerular crescents, whereas TGF-beta 3 was also present within interstitial mononuclear cells and eosinophils, and, exclusively in HIV-infected patients, within glomerular cells. In conclusion, TGF-beta expression was increased in several progressive glomerular diseases, and was particularly but not uniquely elevated in HIV-associated renal diseases.
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PMID:Renal TGF-beta in HIV-associated kidney diseases. 915 Apr 74

We report the case of a patient with acquired immunodeficiency syndrome (AIDS) who developed nephrotic syndrome and progressive renal failure mimicking human immunodeficiency virus (HIV)-associated focal segmental glomerulosclerosis (FSGS) who required initiation of hemodialysis and was found on renal biopsy to have membranous nephropathy. Hepatitis B and C serologies were negative. Although she required hemodialysis, she was treated with prednisone and experienced a progressive decline in her serum creatinine from 10.1 mg/dL to 1.9 mg/dL, which permitted the discontinuation of hemodialysis. After she abruptly discontinued prednisone, her creatinine level increased to 4.8 mg/dL, and she experienced marked worsening of her nephrotic syndrome. Resumption of prednisone resulted in normalization of serum creatinine and reduction in urine protein excretion. No adverse effects of prednisone occurred during this time. She remains off of hemodialysis for 1 year with a serum creatinine level of 1.0 mg/dL and urine protein excretion of 0.4 g/d. Although most patients with HIV infection, nephrotic-range proteinuria, and renal failure have FSGS, a minority may have membranous nephropathy. Although typically not a steroid-responsive lesion in the setting of advanced renal failure, membranous nephropathy may be a highly steroid-responsive lesion in the HIV-infected patient, and treatment may help avert the need for dialysis in a patient population that generally has a poor outcome on dialysis.
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PMID:AIDS-associated membranous nephropathy with advanced renal failure: response to prednisone. 921 10


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