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)

Two young human immunodeficiency virus (HIV)-infected patients, a 25-year-old woman and a 26-year-old man, consumed large amounts of germanium lactate citrate 18% as an "immunostimulant" for 9 months. The woman, who had stage II HIV infection, developed severe renal dysfunction (creatinine clearance, 7 mL/min/1.73 m2) and slight proteinuria (0.28 g/d) after ingesting 260 g germanium lactate citrate 18%. Hepatomegaly with liver dysfunction (SGOT, 102 U/L; gamma-glutamyl transferase (GT), 159 U/L) and lactic acidosis (plasma lactate, 7.3 mmol/L) developed simultaneously. Renal biopsy revealed tubulointerstitial nephropathy with vacuolar cell degeneration and periodic acid-Schiff-positive intracellular deposits mainly in distal tubules. Liver biopsy disclosed severe hepatic steatosis; liver function tests returned to normal within 5 weeks. Since renal failure persisted for 2 years after ingestion of germanium (creatinine clearance, 14 mL/min/1.73 m2; proteinuria, 0.84 g/d), a second renal biopsy was performed, which showed marked but focal distal tubular atrophy and slight interstitial fibrosis. The male patient, who had stage III HIV infection, had ingested the same compound; he presented with a creatinine clearance of 43 mL/min/m2 and proteinuria of 0.36 g/d. Renal biopsy disclosed tubulointerstitial changes similar to those found in the female patient. After 9 months off germanium, creatinine clearance remained unchanged. Neutron activation analysis of all biopsy specimens in both cases documented germanium concentrations 10 to 70 times normal in renal tissue and 140 times normal in liver tissue.
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PMID:Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate. 848 24

Mycoplasma fermentans (incognitus strain) has been linked with acquired immunodeficiency syndrome-associated nephropathy. Ten (23%) of 43 urine sediment specimens from 40 human immunodeficiency virus (HIV)-positive patients at different stages of acquired immunodeficiency syndrome disease tested positive in the polymerase chain reaction using a primer pair found in the insertion sequences specific to M fermentans. Mycoplasma fermentans was isolated from two HIV-positive patients' urine sediment specimens and on a repeated basis from one. All three culture-positive urine sediment specimens tested positive in the polymerase chain reaction. Fifty urine sediment specimens from age-matched HIV-negative healthy controls tested negative for M fermentans by polymerase chain reaction. Mycoplasma fermentans was not isolated from any of the control urine sediment specimens. Our results show a high prevalence of M fermentans in urine sediment specimens from HIV-positive patients but not from urine sediment specimens of HIV-negative healthy controls.
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PMID:Detection and isolation of Mycoplasma fermentans from urine of human immunodeficiency virus type 1-infected patients. 848 41

Renal transplantation continues to be the goal of therapy for children with end-stage renal disease. Patient age, primary renal disease, psychosocial status, living versus cadaver donor allograft, optimal immunosuppressive therapy, urologic status, and maximization of growth and development must be considered in determining the optimal time for transplantation. Immunizations should be up to date, and the immune status of both the donor and the recipient with regard to Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, and hepatitis A, B, and C must be known. Prednisone, imuran, cyclosporine, and T cell antibodies remain the mainstay of immunosuppression. However, new therapies, such as FK-506, rapamycin, mofetil, brequinar, leflunomide, and human leukocyte antigen-derived peptides, are under investigation for use in transplantation. Complications, including infection, rejection, and malignancy, continue to be problematic in pediatric renal transplantation. Although patient and graft survival has improved over time, outcomes in pediatric renal transplantation continue to lag behind those in young adults.
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PMID:Progress in renal transplantation for children. 862 Mar 69

To determine whether human immunodeficiency virus (HIV) infection is associated with incipient tubular or glomerular defects, we determined the urinary excretion of four low molecular weight proteins (LMWP); beta2-microglobulin (U-beta2-m), cystatin C (U-cyst C), Clara cell protein (U-CC16), and retinol-binding protein (U-RBP), the markers of tubular dysfunction, the excretion of albumin (U-Alb), a marker of glomerular defect, and the excretion of N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of structural damage of the proximal tubular epithelium. Their determinants have been assessed by stepwise regression analysis using as possible predictors age, sex, serum-beta2-m (S-beta2-m), CD4 lymphocyte count, or HIV infection stage and therapy. The study involved 76 HIV-infected patients without renal disease, 56 with S-beta2-m < 5 mg/L (Group B1), 20 with S-beta2-m > or = 5 mg/L (Group B2), and 30 HIV-negative controls. Fourteen patients (18.4%) had no abnormal urinary protein loss, and 62 (81.6%) had elevated urinary excretion of at least one protein (Alb, LMWP, or NAG). A single urinary protein was abnormal in 21 patients (U-beta2-m, n = 9; U-RBP, n = 2; U-CC16, n = 4; and U-Alb, n = 6). At least two LMWP were abnormal without increased U-Alb in 23 patients (12 with increased and 11 with normal U-NAG). Ten patients had an increased urinary excretion of at least one LMWP together with U-Alb (5 with increased and 5 with normal U-NAG). An increased urinary excretion of all proteins was observed in the last 8 patients. The average urinary excretion of all proteins (except cyst C) was significantly higher in HIV than in the control group. As expected, U-beta2-m and the prevalence of abnormal U-beta2-m values were higher in the B2 than in the B1 group (P = 0.0001), whereas the average urinary excretion and the prevalence of elevated values of Alb, LMWP (except beta2-m) or NAG were the same in both HIV groups. By stepwise regression analysis, age emerged as a significant determinant of urinary excretion of beta2-m and CC16, whereas male sex was associated with increased U-CC16. S-beta2-m, CD4-lymphocyte count, or HIV infection stage emerged as significant determinants only for U-beta2-m as a consequence of a close correlation between S-beta2-m and either HIV infection stage (r = -0.52, P = 0.0001), or CD4 count (r = -0.45, P = 0.0002). Over 80% of HIV-infected patients without overt renal disease have evidence of glomerular permeability defects or tubular dysfunction, whatever the stage of the disease. U-Alb, RBP, and CC16 appear as the most sensitive and reliable early markers of these abnormalities. Their cause and prognostic value remain to be determined.
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PMID:Low molecular weight proteinuria in human immunodeficiency virus-infected patients. 865 Dec 44

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

The introduction of molecular therapy through the delivery of nucleic acids either as oligonucleotides or genetic constructs holds enormous promise for the treatment of renal disease. Significant barriers remain, however, before successful organ-specific molecular therapy can be applied to the kidney. These include the development of methods to target the kidney selectively, the definition of vectors that transduce renal tissue, the identification of appropriate molecular targets, the development of constructs that are regulated and expressed for long periods of time, the demonstration of efficacy in vivo, and the demonstration of safety in humans. As the genetic and pathophysiologic basis of renal disease is clarified, obvious targets for therapy will be defined, for example, polycystin in polycystic kidney disease, human immunodeficiency virus (HIV) type 1 in HIV-associated nephropathy, alpha-galactosidase A in Fabry's disease, insulin in diabetic nephropathy, and the "minor" collagen IV chains in Alport's syndrome. In addition, several potential mediators of progressive renal disease may be amenable to molecular therapeutic strategies, such as interleukin-6, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta(TGF-beta). To test the in vivo efficacy of molecular therapy, appropriate animal models for these disease states must be developed, an area that has received too little attention. For the successful delivery of genetic constructs to the kidney, both viral and nonviral vector systems will be required. The kidney has a major advantage over other solid organs since it is accessible by many routes, including intrarenal artery infusion, retrograde delivery through the uroexcretory pathways, and ex vivo during transplantation. To further restrict expression to the kidney, tropic vectors and tissue-specific promoters also must be developed. For the purpose of inhibition of endogenous or exogenous genes, current therapeutic modalities include the delivery of antisense oligodeoxynucleotides or ribozymes. For these approaches to succeed, we must gain a much better understanding of the nature of their transport into the kidney, requirements for specificity, and in vivo mechanisms of action. The danger of a rush to clinical application is that superficial approaches to these issues will likely fail and enthusiasm will be lost for an area that should be one of the most exciting developments in therapeutics in the next decade.
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PMID:Molecular therapy for renal diseases. 884 Sep 36

A 43-year-old man with rapidly evolving renal failure from biopsy-proven human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) and superimposed thrombotic microangiopathic changes was treated with prednisone. His serum creatinine decreased from 7.5 to 3.9 mg/dL, and the 24-hour protein excretion decreased from 15.7 to 6.1 g over 6 to 8 weeks. As the prednisone was tapered, however, the creatinine began to increase, and a repeat biopsy was done to assist with therapeutic decisions. The major differences from the pretreatment biopsy were marked reductions in interstitial lymphocytes and macrophages and absence of thrombotic microangiopathic lesions. This is the first report comparing pretreatment and posttreatment renal biopsy specimens and the findings provide some insight into the means by which prednisone exerts its beneficial clinical effects acutely on this disease.
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PMID:Clinicopathologic correlates of prednisone treatment of human immunodeficiency virus-associated nephropathy. 884 Sep 56

We describe a 39-year-old bisexual man with clinical category B2 human immunodeficiency virus (HIV) infection who subsequently developed systemic lupus erythematosus (SLE). SLE was diagnosed on the basis of a clinical presentation of malar rash, polyarthritis, membranous glomerulonephritis, and characteristic serology. To our knowledge, this is the fourth reported case of a patient with HIV infection to develop SLE and the second adult patient with HIV and coexistent SLE nephropathy.
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PMID:SLE nephropathy in a patient with HIV infection: case report and review of the literature. 941 70

Viable and potentially infectious HIV-1 has been recovered from the peritoneal dialysis effluent (PDE) of patients with end-stage renal disease (ESRD) who are infected with the human immunodeficiency virus (HIV). No information had previously been available as to how long HIV-1 could survive in this environment, and no data were available as to how long HIV-1 could survive on peritoneal dialysis exchange tubing (PDET). Therefore, this study was designed to answer these questions. HIV-1 Mn was added to PDE and allowed to incubate at room temperature for 0 to 14 days. Following centrifugation, the cellular component of the PDE mixture was placed in co-culture with peripheral blood mononuclear cells (PBMC) from HIV negative donors. Aliquots from the co-cultures were removed after 14 days and assayed for the HIV-1-P24 antigen. High levels of HIV P24 antigen were recovered up to and including seven days of room temperature incubation. HIV could not be recovered from PDE that had been incubated at room temperature for 10 to 14 days. Ten milliters of HIV-PDE mixture was placed within PDET and incubated at room temperature for 10 minutes. The solution was then removed by gravity drainage. After drying times of 0 to 168 hours, the tubing was flushed with HIV culture medium and placed in co-culture with PBMCs from HIV negative donors. The culture supernatant was assayed for the HIV-1 P24 antigen as a marker of viral replication. High levels of HIV-1 P24 antigen were recovered from the PDET wash for up to and including 48 hours of drying time. No viable virus could be detected for drying times of between 72 and 168 hours. To determine if common disinfectants found in the dialysis unit could inactivate HIV, dilutions of Amukin 50% and household bleach were prepared at final concentrations ranging from 1:32 to 1:2048. These disinfectant solutions were incubated with PDE containing HIV for 10 minutes. The cellular fraction of the PDE was isolated by centrifugation, washed, and placed in co-cultures with peripheral blood mononuclear cells. HIV P24 antigen levels were assayed every three days for 28 days. Amukin 50% and a 10% household bleach solution were effective in killing HIV in PDE at dilutions up to and including 1:512. These results indicate that HIV can survive in PDE at room temperature for up to seven days. HIV can survive on peritoneal dialysis exchange tubing for up to 48 hours. Final dilutions of 1:512 Amukin 50% and 10% household bleach, after 10 minutes of exposure, are effective viricidal agents in disinfecting PDE.
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PMID:HIV-1 survival kinetics in peritoneal dialysis effluent. 891 33


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