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)

To evaluate changes in T-lymphocyte subsets and DR expression on tubular cells, 74 fine-needle allograft aspirates (FNAB) were evaluated in 31 patients with cadaver kidney transplants. Monoclonal antibodies against T helper CD4+, cytotoxic/suppressor CD8+, and HLA-DR were used with an indirect alkaline-phosphatase-staining technique. Cases with acute rejection (n = 11) showed a significant increase of CD8+: CD4+ ratio versus those with stable function (n = 21), acute tubular necrosis (n = 10) or CsA toxicity (n = 7) (ANOVA F = 10; P less than 0.01). Cases with chronic rejection or CMV infection showed no differences in the CD8+: CD4+ ratio with the other groups. DR expression on tubular cells was frequently found in cases of acute rejection, chronic rejection and CMV (73%, 66%, and 43% respectively), occasionally found in CsA toxicity (14%), but never seen in controls or ATN. Both tests, the CD8+: CD4+ ratio and the DR expression on tubular cells, had a high sensitivity and specificity in differentiating acute rejection versus controls, acute tubular necrosis, and CsA toxicity. When both tests are taken together no case without rejection showed a CD8+:CD4+ ratio greater than 1.6 and DR expression on tubular cells. Cases with acute rejection who lost the graft (n = 6) had a CD8+:CD4+ ratio significantly greater than those who responded to antirejection therapy (n = 5) (t = 2.9; P less than 0.05).
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PMID:Monoclonal analysis of fine-needle aspiration biopsy in kidney allografts. 212 91

In an attempt to clarify the participations of cellular immunity in the development of tubulo-interstitial lesions, aberrant expressions of major histocompatibility complex (MHC) class II antigens and Ki-67 nuclear antigen on the renal tubular epithelial cells were studied. Ki-67 antigen was known to appear in all phases of cell cycle except for Go. Nine normal kidney specimens (4 males and 5 females) and 117 kidney specimens obtained from patients with kidney diseases (54 males and 63 females) were examined with the indirect immunofluorescence technique using murine monoclonal antibodies against HLA-DR (lal), HLA-DQ (Leu10) and Ki-67 nuclear antigen. Patients included 100 with glomerular diseases, and 16 with tubulo-interstitial diseases consisting of 4 acute tubular necrosis (ATN), 7 acute tubulo-interstitial nephritis (AIN), one renal allograft rejection and 4 sarcoidosis. In normal kidney, HLA-DR was solely noted in only two specimens (22.2%) at the basal portion of proximal tubular epithelial cells. In tubulo-interstitial diseases 11 (68.8%) out of 16 patients showed diffuse and intense expressions of HLA-DR concomitant with HLA-DQ in 6 of 13 (42.9%), and 11 of 13 (84.6%) were positive for Ki-67 nuclear antigen. Especially, in AIN and allograft rejection, intense expression of HLA-DR, DQ and Ki-67 nuclear antigen were observed in 100%, 86%, 100%, respectively. In ATN 3(75%) were positive for HLA-DR and Ki-67, but not for HLA-DQ. In contrast, only 12(15.6%). 2(2.6%) and 2(4.8%) of primary glomerular disease were weakly positive for HLA-DR, DQ and Ki-67 nuclear antigen, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Aberrant expression of major histocompatibility complex class II. (HLA-DR/DQ) antigens and proliferative nuclear antigen. (Ki-67) in renal tubular epithelial cells]. 262 37

Graft survival was examined in 15 renal allograft recipients from a group of 20 patients with IgM autolymphocytotoxic antibody that could be removed in a crossmatch assay using a reducing agent, dithioerythritol (DTE). The significant differences in this group of 20 patients compared with end-stage renal disease (ESRD) patients lacking autolymphocytotoxic antibodies included an increased frequency of black patients (P = 0.002), a lack of previous transplants (P = 0.003), and an increased frequency of the HLA-DR1 phenotype (P = 0.0001). Sex and the number of transfusions did not appear significant, whereas the cause of ESRD was primarily systemic lupus erythematosus. Fifteen of the 20 patients were transplanted against a positive donor crossmatch. Eleven were recipients of cadaveric kidneys, nine of which are still functioning for periods ranging from 0.5 to 40 months. Two fo the cadaveric recipients died with functional grafts. Four received living-related donor transplants, one of which was lost to acute rejection one month posttransplant, while the remaining three have survived 1.5, 9, and 21 months, respectively. Fourteen patients had immediate allograft function with no hyperacute rejection and only one case of acute tubular necrosis (ATN) was found. In summary, a negative crossmatch using DTE-treated, autologous reactive recipient sera may identify a group of patients who can be transplanted with minimal concern for hyperacute rejection or ATN. In addition to cause of ESRD, race, transplant history, and HLA-DR phenotype may further define this group of transplant candidates having IgM autolymphocytotoxic antibody. Extrapolation of these conclusions to transplant candidates lacking autolymphocytotoxic antibodies is not warranted.
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PMID:Successful renal allografts in recipients with crossmatch-positive, dithioerythritol-treated negative sera. Race, transplant history, and HLA-DR1 phenotype. 264 5

Indirect immunoperoxidase analysis using monoclonal antibodies (Mo Ab) was performed in 33 renal biopsies with interstitial cellular infiltration obtained from non-transplanted patients. We reviewed four acute interstitial nephritis (IN), three chronic IN, four granulomatous IN, four acute tubular necrosis, four vasculitis, seven primary glomerulonephritis and seven active lupus nephritis (LN). We used Mo Ab recognizing T and B cell markers [OKT3, OKT8, T4, B1, IOT14 (IL2 receptor)], HLA-DR related antigen (I2) and monocytes/macrophages (LeuM3). In all cases the interstitial cellular infiltrates were predominantly T cells, whereas the B cell population accounted for less than 20% of the infiltrate. LeuM3+ cells were present in 28 of 32 cases, usually in a lesser proportion than T cells. IOT14+ cells were exceptional. T4+/T8+ cells were clearly greater than one in three acute IN, three granulomatous IN, two LN and two vasculitis. The T8+ cell population predominated in one case of chronic IN related to a non-steroidal anti-inflammatory drug. In all the remaining cases T4+ and T8+ cells were equally present. Aberrant strong HLA-DR expression within tubular cells was noted in nine cases (4 LN) irrespective of the presence of tubular lesions. On the basis of the phenotypic analysis, our data do not support a specific pattern of the infiltrate in regard to a given etiology and thus cannot be used as a diagnostic tool. However, such analysis may aid in understanding the mechanisms of tissue injury.
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PMID:Characterization of mononuclear cell subsets in renal cellular interstitial infiltrates. 352 2

Fifty-two consecutive patients receiving cadaveric renal transplants were prescribed cyclosporin A and steroid therapy. Three of the recipients underwent re-transplantation and two of the patients were grafted with kidneys shipped from the United States. One year actuarial patient and graft survival rate with no exclusions were 94.2 percent and 81.6 percent, respectively, this rate being significantly better than results in case of the conventional combination of azathioprine, steroid and antilymphocyte globulin. The role of HLA-DR matching on cyclosporin A treatment was studied. One year actuarial graft survival rates of two HLA-DR matched and one HLA-DR matched were 91.7 percent and 78.9 percent, respectively. To assess the effects of cyclosporin A in the management of patients with acute tubular necrosis, the patients were divided into two groups, in terms of whether or not hemodialysis treatment was required for acute tubular necrosis. Although in the present protocol, cyclosporin A administration was begun before the operation, no significant differences in the graft survivals were evident between the two groups. Nephrotoxicity, hepatotoxicity and other side-effects of cyclosporin A could usually be dealt with by dosage adjustments, making feasible the chronic ingestion of this agent. The exceptional effectiveness and safety of cyclosporin A were evident throughout these early trials.
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PMID:Cyclosporin A effective therapy for fifty-two cadaver kidney recipients. 389 12

To determine the nephron segment distribution of tubular epithelial damage and regeneration and the proliferative activity of various nephron segments in human acute tubular necrosis (ATN) with an antibody to proliferating cell nuclear antigen (PCNA) and to compare the findings in native kidneys with ATN with those in transplant kidneys with ATN, archival tissues from 12 native and 21 transplant kidney biopsy specimens and nine transplant nephrectomy specimens were collected that all showed obvious morphological signs of ATN. Nineteen patients with transplant kidneys with ATN were immunosuppressed with cyclosporine and 11 were immunosuppressed with prednisone and azathioprine. There was a predominance of "regenerating" tubules (tubules with thin epithelium) in the distal nephron in native kidneys with ATN; in the transplant kidneys this was less conspicuous. The number of Tamm-Horsfall protein (THP)-positive tubules was decreased in all kidneys with ATN compared with normal human kidneys. In contrast, the number of THP-positive casts was much higher in all kidneys with ATN than in the normal kidneys. In transplant kidneys with ATN the number of THP-positive casts was substantially lower than in native kidneys with ATN. The macula densa appears to maintain its morphological integrity in kidneys with ATN. Both regenerating and normal appearing tubules expressed vimentin and HLA-DR. The proliferation index (PI; ie, percentage of PCNA-positive nuclei) of the renal tubular epithelium in normal control kidneys varied between 0.22 and 0.33, depending on the tubule segment. The highest PI was noted in the transplant kidneys with ATN not treated with cyclosporine (8.0), followed by the native kidneys with ATN (4.4) and the transplant kidneys with ATN treated with cyclosporine (4.3). We did not find any significant difference in the PI between the regenerating (5.0) and normal appearing (5.6) tubules. Proximal tubules (8.7) showed significantly higher PI values than distal tubules (3.5) in transplant kidneys with ATN. Our results show substantial differences between native kidneys and transplant kidneys with ATN. Tubular epithelial cell proliferation in human ATN is prominent and appears to correlate with the severity of ATN. Light microscopically normal appearing tubules and regenerating tubules participate equally in the regeneration of injured tubules. Cyclosporine may have an inhibitory effect on cell regeneration (proliferation) in human transplant kidneys with ATN.
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PMID:Human acute tubular necrosis: a lectin and immunohistochemical study. 786 54

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

ICAM-1 and HLA-DR expressions were studied on parenchymal cells obtained by aspirative biopsies of renal allografts. Patients were evaluated during 3 months after transplantation. Conventional cytology and immunoperoxidase stainings using anti-ICAM-1 and anti-HLA-DR antibodies were employed. The value of the total corrected increment was significantly higher (p < 0.05) during acute rejection episodes than during acute tubular necrosis or stable renal function. The percentage of HLA-DR positive cells were higher in rejection than in stable function periods (p < 0.05). The percentage of ICAM-1 positive cells was higher in rejection than in acute tubular necrosis periods (p < 0.05). The sensitivities to the diagnosis of rejection were 71.8% (TCI), 68.4% (ICAM-1) and 55.0% (HLA-DR). The specificities were 87.3%, 81.3% and 68.4% respectively. Combinations of the tests resulted in increased sensitivity. We concluded that the use of these monoclonal antibodies improves the sensitivity of conventional aspiration cytology to the diagnosis of acute renal rejection.
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PMID:Analysis of ICAM-1 and HLA-DR expression on renal allograft aspirates. 888 12

The shortage of cadaver kidneys available for organ donation compared to growing demand has led to an increase in the use of living-unrelated donors (LURD) for renal transplantation (Tx). Results from trials in adults show that 1-year graft survival rates in LURD are similar to living-related donor (LRD) rates and superior to those of cadaver renal donor (CAD) transplants. We report our experience with 38 LURD transplants for children enrolled in NAPRTCS that were performed between 1987 and 1997. Ages of recipients at Tx were 0-5 years (n=8), 6-12 (n=10), and >12 years (n=20). Twenty nine were primary Tx, seven were second Tx, and two were third Tx. HLA antigen data showed that the number of 2-antigen mismatches for each locus was 44.7% for HLA-A, 71.1% for HLA-B, and 55.3% for HLA-DR. There were 7 donor/recipient pairs with a 6-antigen mismatch, 12 pairs with a 5-antigen mismatch, while there were 6 pairs with a 3-antigen match of which 3 pairs had at least one match at each of the A, B, and DR loci. A total of 38 acute rejection episodes occurred in 25 LURD recipients. Among primary grafts the incidence of first acute rejection at 30 d post-Tx was 46% in LURD vs. 29% in LRD and 37% in CAD recipients; at 1 year post-Tx it was 76% in LURD vs. 48% in LRD and 62% in CAD recipients. Acute tubular necrosis (ATN) was reported in four or 10.5% of LURD transplants compared with 5.4% in LRD and 19.0% in CAD recipients. There were 12 LURD graft failures, due to vascular thrombosis (3), acute rejection (2), recurrence of original disease (1), infection (3), and patient death (3). Estimated primary graft survival probabilities (+/- SE) at 12 months post-Tx are 0.825 +/- 0.071 for LURD, compared to 0.911 +/- 0.006 for LRD, and 0.815 +/- 0.009 for CAD. We conclude that data from this study show that LURD Tx in children have a low rate of ATN that is similar to that of LRD Tx. However, LURD Tx have a high incidence of acute rejection, and the graft survival at 12 and 24 months post-Tx is inferior to LRD Tx. There is a high frequency of graft loss due to causes other than rejection, and these may be related to adverse recipient selection criteria.
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PMID:Living-unrelated renal transplantation in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 1008 40

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


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