Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monitoring of immunoglobulin-secreting cells in peripheral blood was performed in 88 renal transplant recipients using a reverse hemolytic plaque-forming cell assay. Comparison with other in vitro tests for rejection (plasma neopterin, CD4/CD8 ratio) demonstrated that the number of immunoglobulin-secreting cells in peripheral blood provides a highly sensitive rejection marker. Evidence of rejection was obtained 1.7 +/- 0.4 (mean +/- SEM) days before a rise in creatinine, with a significant PFC rise in 95% (73/77) of rejection episodes. The PFC response was not influenced by HLA matching, number of preoperative blood transfusions, acute tubular necrosis, or uremia. A significant PFC rise in the absence of an ongoing rejection episode occurred in the presence of bacterial or viral infections, in case of posttransplant surgical complications, and regularly during the early posttransplant period (days 4-9). However, even early posttransplant the PFC peak was significantly higher in patients with an ongoing rejection episode than in patients without rejection (P less than 0.001).
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PMID:B lymphocyte response as an indicator of acute renal transplant rejection. I. Immunoglobulin-secreting cells in peripheral blood. 257 82

Vascular endothelial cells express membrane bound adhesion molecules which play a direct role in the localization and subsequent movement of leucocytes from the blood into sites of inflammation. E-Selectin is a cytokine induced adhesion molecule, known to be expressed by endothelial cells in inflammatory conditions, which binds to various leucocyte subpopulations. In a prospective study we have investigated the expression and distribution of E-selectin on renal allograft needle biopsies taken from 16 pretransplant kidneys and 119 post-transplant kidneys. Post-transplant biopsies were taken at times of graft dysfunction and at times of normal graft function. Formal histology was also performed and assessed independently. E-Selectin was found predominantly on the intertubular endothelium and on the endothelium of larger vessels. E-Selectin was present, at low intensity, in some pretransplant biopsies and also some post-transplant biopsies which were reported histologically as normal. In post-transplant biopsies taken for dysfunction E-selectin was present in the majority of cases. Expression was strong in biopsies showing acute cellular rejection and this was associated with a CD4 positive cellular infiltrate. Biopsies showing other causes of dysfunction, in particular acute tubular necrosis, also were E-selectin and CD4 positive with lower intensity than those with acute cellular rejection. These results suggest that E-selectin is a good marker for endothelial activation in renal transplant biopsies. Its presence in histologically apparently normal biopsies suggests that its in vivo kinetics may differ from previously reported in vitro kinetics. E-Selectin may be a potential target for therapeutic intervention.
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PMID:The importance of E-selectin as a marker for renal transplant rejection. 753 43

We have analyzed 245 transplant aspirative cytologies (TACs) from 96 renal allograft patients. TACs were divided in two chronological groups: Early (TACs performed during the first 3-mo posttransplantation) and late (TACs performed after the third month post-transplantation), in order to assess the effect of allograft tolerance on TAC features. Both morphological and immunocytochemical aspects were evaluated, including CD4, CD8, IL2-R, and HLA-DR immunolabeling. A final diagnosis for each case of allograft dysfunction was achieved by other independent diagnostic means. Four diagnostic groups were considered in the present study: acute rejection (AR), chronic rejection (CR), acute tubular necrosis (ATN), and Cyclosporin A toxicity (CsA-T). In addition, a control group (C) was established from patients with stable allograft function. We found that immunocytochemical analysis of TACs is particularly helpful in the diagnosis of late allograft dysfunction, a time period when the simple cytological study of renal infiltrate is not informative enough to help take therapeutic decisions.
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PMID:Transplant aspirative cytology: analysis of morphological and immunocytochemical parameters in renal allograft dysfunction. 851 13

In the present study, we analyzed human renal allografts using immunohistochemical techniques to determine the site, identity, and frequency of (a) cytotoxic and apoptotic cells, as identified by staining for GMP-17 (TIA-1), a component of cytotoxic granules; and (b) DNA fragmentation in situ, as detected by the TUNEL method. In acute cellular rejection (n = 15), GMP-17+ mononuclear cells accounted for 29% +/- 12% of the infiltrating cells in the interstitium (341 +/- 164/mm2) and were significantly more concentrated in tubulitis lesions, where they amounted to 65% +/- 14% of the mononuclear cells (96 +/- 61/mm2) (p < 0.01 versus interstitium). GMP-17+ mononuclear cells were also found in sites of endothelialitis. An estimated 80% of the GMP-17+ lymphocytes expressed CD8, and 10% to 20% expressed either CD4 or the macrophage marker CD14. The latter finding led us to analyze normal peripheral blood monocytes by flow cytometry, all of which were found to contain GMP-17. NK cells and neutrophils, which are known to express GMP-17, were detected only rarely in allografts. Specimens with cyclosporine A toxicity (n = 7) or acute tubular necrosis (n = 13) showed fewer GMP-17+ cells in the interstitium (22 +/- 46/mm2 and 62 +/- 50/mm2, respectively) and tubules (2 +/- 6/mm2 and 10 +/- 10/mm2, respectively) (all p < 0.01 versus rejection). These differences were due largely to less intense mononuclear cell infiltration. In cyclosporine A toxicity, however, the percentages of GMP-17+ mononuclear cells within tubules and the interstitium were significantly lower than in rejection (p = 0.02), whereas in acute tubular necrosis significantly lower percentages were found in the tubules (p = 0.04) but not in the interstitium. Native kidneys with end-stage diabetic nephropathy (n = 5) had very low proportions of GMP-17+ cells in interstitial infiltrates (7% +/- 6%) and in tubules (11% +/- 15%), although the infiltrates were focally intense (517 +/- 355/mm2). TUNEL+ cells were found in acute cellular rejection, predominantly in areas with intense mononuclear infiltrates and also within lesions of tubulitis and endothelialitis. Although some TUNEL+ cells were intrinsic renal cells, most appeared to be infiltrating mononuclear cells, and we were able to detect CD3 in some. In areas of intense cellular infiltration, the percentages of TUNEL+ cells (range, 0.5% to 4.2%) were comparable to those seen in the rat thymus, indicating a high level of apoptosis. Overall, in the allograft samples, the numbers of GMP-17+ cells and TUNEL+ cells were significantly correlated (r = 0.79; p < 0.01). These data provide new evidence that T cell (and possibly macrophage)-mediated cytotoxicity plays an important role in acute renal allograft rejection, particularly in the case of tubular injury, and furthermore suggest that apoptosis may be a mechanism not only for graft cell destruction, but also for elimination of activated T cells in the infiltrate.
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PMID:Cytotoxicity and apoptosis in human renal allografts: identification, distribution, and quantitation of cells with a cytotoxic granule protein GMP-17 (TIA-1) and cells with fragmented nuclear DNA. 916 83

Urinary samples from 20 kidney transplant recipients were studied to determine the cellular composition of the sediments using an immunocytological (IC) technique. The expression of HLA class I (A, B, C) and class II (DR, DQ, DP), CD2, CD3, CD4, CD8, and interleukin (IL)-2 receptor (IL-2R) on lymphocytes was assessed using a panel of monoclonal antibodies. The results were correlated with graft function and with the number of episodes of acute renal graft rejection (AR) during a period of 6 months posttransplantation. The cellular infiltration of lymphocytes (LC) and polymorphonuclear cells (PMNC) also was studied using a standard cytology (SC) technique. During this period, 17 of 30 episodes of graft dysfunction due to AR occurred in 12 patients: 8 to acute tubular necrosis (ATN) (n = 8); 4 to cyclosporine (CsA) toxicity (n = 4) and 1 to amphotericin toxicity (n = 1). The diagnosis of AR was made clinically by 3 independent observers, using biopsy in some cases. The immunocytology showed a significantly increased expression of HLA-DR, DO, and DP namely, greater than 20% positivity in 10% of samples on the tubular epithelial cells (TEC) of patients presenting with versus without AR (P < or =.001). In addition, a high correlation was observed between the expression of IL-2R and the presence of AR (p < or =.002). The standard cytology results showed a significantly increased percentage of LC and decreased percentage of PMNCs in samples obtained 2 days prior to the clinical manifestations of patients who developed AR (P =.001). A greater level of expression of antigen determinants was observed prior to AR. These results suggest that immunocytology of urinary sediments, which is a noninvasive technique, has enormous clinical potential for the differential diagnosis of AR, ATN, and CsA toxicity. In our study, the use of HLA class IL-specific monoclonal antibodies (Abs) gave a 100% specificity, 95% sensitivity, and 95% predictability. Although our results also indicate a potential value in the increased IL-2R expression, these findings must be confirmed by further studies. Furthermore, the combination of both immunologic and SC techniques in urinary sediments allows early detection of AR and is cost effective and simple features that could be used routinely for follow-up of renal transplant recipients.
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PMID:Clinical graft evolution of lymphocytes, polymorphonuclear cells, and antigen expression in tubular renal cells in the urine sediment of 20 renal allograft recipients. 1461 96

There are still lacking data supporting a role for natural killer T (NKT) cells in the maintenance of human tissue-specific tolerance. We are interested to study NKT cell frequency in kidney transplant recipients and its correlation with graft function. Peripheral blood T cell receptors (TCR) Valpha24(+)Vbeta11(+) NKT cells were phenotyped according to CD4 and CD8 expression in normal controls (NC), in 10 years rejection-free cadaver kidney allografts maintained with minimal immunosuppression (long-term rejection free [LTRF]), in patients with acute rejection (AR) and in patients with acute tubular necrosis (ATN). Results were expressed as percentages of CD4(+)CD8(-) (CD4(+) NKT) or CD4(-)CD8(-) (double negative--DN NKT) Valpha24(+)Vbeta11(+) cells. The percentages of Valpha24(+)Vbeta11(+) cells were 0.09%, 0.14%, 0.02% and 0.09% on gated lymphocytes respectively in AR, ATN, LTRF and NC groups (p=0.263). DN NKT cells were more frequent in NC patients (52.11%) and less present in ATN patients (11.04%). In contrast, CD4(+) NKT (IL-4-producing NKT cells subset) was more frequent in AR (42.86%), and corresponded to almost 3 to 7 folds more what we obtained in the other groups. Although total Valpha24(+)Vbeta11(+) cells did not significantly differ among the groups, the lowest frequency was observed in the LTRF group. In conclusion, we observed that total number of NKT cells did not differ significantly among transplant patients when compared to normal controls, although specific-subsets seem to be more frequent in determined events.
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PMID:Frequency of Valpha24+Vbeta11+ NKT cells in peripheral blood of human kidney transplantation recipients. 1558 59

HIV-infected patients may undergo renal damage related to the HIV infection itself, to the presence of co-infections, arterial hypertension, diabetes or to the exposure to nephrotoxic drugs. Tenofovir has been associated with the development of acute renal failure with Fanconi syndrome and acute tubular necrosis and, albeit rarely, with chronic liver disease. Patients with low CD4 cell count, low body weight and with concomitant diseases such as arterial hypertension and diabetes or co-infections with HCV, HBV or Treponema pallidum seem at higher risk of tenofovir-related nephrotoxicity. Other risk factors include previous exposure to nephrotoxic drugs and the association of tenofovir with boosted protease inhibitors or with didanosine. However, from the analysis of published papers the incidence of tenofovir-related renal toxicity seems low, as confirmed also by our personal casuistry (SCOLTA Project). Thus, a careful selection of patients including the evaluation of existent renal disease before starting an antiretroviral regimen including tenofovir is necessary to prevent renal damage. Furthermore, frequent monitoring of renal function in patients at higher risk of renal damage is strongly recommended, as well as a tenofovir dose adjustment if an alteration of renal function is detected.
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PMID:[Renal toxicity in HIV-infected patients receiving HAART including tenofovir]. 1712 26

Acute kidney injury (AKI) is a challenging problem in Africa because of the burden of disease (especially human immunodeficiency virus [HIV]-related AKI in sub-Saharan Africa, diarrheal disease, malaria, and nephrotoxins), late presentation of patients to health care facilities, and the lack of resources to support patients with established AKI in many countries. The pattern of AKI is vastly different from that in more developed countries. There are no reliable statistics about the incidence of AKI in Africa. Infections (malaria, HIV, diarrheal diseases, and others), nephrotoxins, and obstetric and surgical complications are the major etiologies in Africa. AKI in hospitalized antiretroviral therapy (ART)-naive HIV-1-infected patients is associated with a 6-fold higher risk of in-hospital mortality. The most common risk factors are severe immunosuppression (CD4 count, <200 cells/mm(3)) and opportunistic infection. The most common causes are acute tubular necrosis and thrombotic microangiopathy. In the post-ART era, HIV-1-infected patients with AKI still have an increased risk of in-hospital mortality and these episodes of AKI seem more frequent in the first year of ART. Subsequently, survival is comparable in those with and without HIV infection. More resources are required to prevent AKI and to provide renal support for those patients requiring dialytic therapy.
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PMID:Epidemiology of acute kidney injury in Africa. 1862 Sep 57

A 58-year-old man admitted for fever, nausea, vomiting, and anuria after the start of HAART, including tenofovir, had a viral load of 1.1 x 10(5) copies/mL, a CD4-positive lymphocyte count of 81/microL, and serum creatinine of 0.8 mg/dL before HAART. He underwent renal biopsy and temporary dialysis. We concluded that the patient had acute tubular necrosis because of potentially impaired renal function and the high amount of medication, and judging from the renal biopsy specimen and clinical course. When implementing HAART, physicians should be aware of and monitor potential patient misunderstanding of instructions on dosage and administration and for possible complications in medicinal combinations and potential side effects. TDF taken together with lopinavir may increase the plasma concentration of TDF or other medications that could worsen renal function. It should also be noted that renal dysfunction is a potential complication in the elderly.
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PMID:[A case of acute renal failure involving high amounts of tenofovir after HAART start]. 1908 22

The incidence of acute rejection of the kidney allograft in the world has been around 15% during the period between 2001 and 2003. It is clinically defined as an elevation in the level of serum creatinine by more than 0.3 mg/dL and is diagnosed by kidney biopsy. On pathologic examination, the interstitium of the allograft is diffusely edematous and infiltrated by CD4 and CD8 lymphocytes. Tubulitis occurs when the lymphocytes and monocytes extend into the walls and lumina of the tubules. Presence of leukocytes determines infection or antibody-mediated rejection. Typically C4d staining is negative. Other causes of acute allograft dysfunction included prerenal factors, interstitial nephritis, infection, acute tubular necrosis, toxicity by drugs, and obstruction in the urinary tract. The primary diagnostic assessments include history, especially adherence to immunosuppressive therapy, physical examination, blood and urine laboratory tests, measurement of the serum levels of the drugs, and ultrasonography. Diagnosis of acute cellular rejection depends on biopsy, CD20 staining for refractory cases, negative C4d staining, presence of markers of activating lymphocyte, and proteomic study. Treatment of acute cellular rejection in kidney transplant recipients include pulse steroid for the first rejection episode. It can be repeated for recurrent or resistant rejection. Thymoglobulin and OKT3 are used as the second line of treatment if graft function is deteriorating. Changing the protocol from cyclosporine to tacrolimus or adding mycophenolate mofetil or sirolimus might be effective. Prognosis depends on number of rejection episodes, the use of potent drugs, time of rejection from transplantation, and response to treatment.
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PMID:Acute cellular rejection. 1936 77


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