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J Kaden

Publications and source records attributed to J Kaden.

At least 19 recordsLinked to original sources
PubMed2002

Lipopolysaccharide-binding protein as a new and reliable infection marker after kidney transplantation.

The early and reliable differentiation of rejections, viral infections and bacterial infections is one of the main problems after organ transplantation. One promising solution to this problem is the lipopolysaccharide-binding protein (LBP), which is regulated upwards in gram-negative sepsis and related conditions. Therefore, the aim of our study was to explore the diagnostic potential of LBP serum levels in well-defined, non-infectious and infectious events after kidney transplantation (KTx). In a retrospective study the LBP serum levels were measured in a total of 686 serum samples from 52 kidney graft recipients. In all pre-KTx sera tested, the mean LBP level was 8.8+/-3.5 microg/ml (reference range: 2.0-15.2 microg/ml). In 7 of 52 recipients without intraoperative T-cell depletion, the mean LBP level was significantly ( P<0.01) increased (13.0+/-1.5 microg/ml) at post-KTx day 1, but was within the reference range. In contrast, the intraoperative T-cell depletion by antilymphocyte antibodies resulted in a significant ( P<0.01) increase to 25.8+/-11.4 microg/ml (range: 13.3-47.2 microg/ml). In recipients with immediate ( n=14) or delayed ( n=9) graft function without any other complications, all post-KTx values (except the post-KTx peak) were within the reference range. In 10 recipients with steroid-sensitive rejections and in 11 recipients with steroid-resistant rejections, no rejection-associated changes of the LBP levels could be shown. In six recipients with cytomegalovirus infection, the detection of an antigenemia (pp65) also was not associated with alterations of the LBP levels. In addition, there was no correlation between LBP levels and the number of pp65-positive leukocytes in peripheral blood. In contrast, a strong elevation of LBP levels was seen in five recipients with gram-positive bacteremia as well as in other severe bacterial infections (e.g., purulent extravasate, heavily infected grafts, bacterial pneumonia and contaminated hematoma). In two recipients with superinfected (bacterial and mycotic or viral) Pneumocystis carinii pneumonias requiring assisted ventilation, LBP levels were elevated, too. Thus, in our study only systemic non-viral infections and massive lymphocytolysis were associated with elevated LBP serum levels.

Acute-Phase Proteins↗
PubMed2001

Massive elevation of procalcitonin plasma levels in the absence of infection in kidney transplant patients treated with pan-T-cell antibodies.

OBJECTIVE: To determine the value of procalcitonin (PCT) monitoring in transplant patients receiving pan-T-cell antibody therapy. DESIGN: Retrospective clinical study. SETTING: A collaborative study between the Institute of Medical Immunology, the Department of Nephrology and Internal Intensive Care, both Charite, Humboldt University Berlin, and the Department of Laboratory Medicine, Friedrichshain Hospital, Berlin, Germany. PATIENTS AND INTERVENTIONS: Thirty-one patients were included in the study: 8 kidney transplant patients with acute rejection episodes, 5 receiving OKT3 monoclonal antibody therapy, 3 receiving steroid bolus therapy; 21 patients undergoing renal transplantation, 11 receiving ATG perioperatively, 10 without ATG administration; 2 patients undergoing renal transplantation and receiving anti-IL-2R mAb. MEASUREMENTS AND RESULTS: Procalcitonin (PCT) and tumor necrosis factor (TNF) alpha plasma levels were measured in infection-free transplant patients treated with the pan-T-cell antibodies ATG or OKT3. We found PCT plasma concentrations up to 600 ng/ml (reference < 0.5 ng/ ml), which are comparable to those seen in severe sepsis. Increases in TNF-alpha plasma levels preceded the rises in PCT. After peaking on day 1 of therapy the PCT plasma concentrations returned to normal values independently of further antibody administration. In contrast, steroid bolus therapy or anti-interleukin 2 receptor mAb administration did not increase plasma PCT or TNF-alpha levels. CONCLUSIONS: PCT monitoring for evaluating infectious complications in kidney transplant patients must be very careful during pan-T-cell antibody therapy.

Antilymphocyte Serum↗
PubMed2000

Increasing urinary IL-6 levels announce kidney graft rejection.

Acute rejection (AR) is the recipient's inflammatory response to the grafted organ. Within the graft-infiltrating cells, a high ratio of IL-6 producing cells can be found, indicating local IL-6 production. Therefore, in cases of kidney transplantation, urinary (u) IL-6 should be detectable. In order to establish the dynamics and diagnostic relevance, uIL-6 levels were determined daily by Quantikine IL-6 immunoassay (R & D Systems, Minneapolis, Minn.) in 101 kidney graft recipients (n = 1915 urine samples) during their post-transplant hospital stay. Immunosuppression consisted of azathioprine, steroids, cyclosporine and an intraoperative high-dose single antithymocyte globulin (ATG)-Fresenius bolus (9 mg/kg). In all the uncomplicated courses (n = 31) mean uIL-6 level was determined, after a post-transplant peak of 174 pg/ml, to be between 4 and 8 pg/ml. In contrast, delayed graft function (n = 16) was always associated with very high uIL-6 levels (> 200 pg/ml), dropping down only with commencement of graft function. Steroid-sensitive AR (n = 14) was consistently associated with significantly increasing uIL-6 levels prior to antirejection therapy (from 23 to 82 pg/ml). In cases of steroid-resistant AR, following antirejection therapy with methylprednisolone (5 days 5 mg/kg), there was no obvious trend towards normalization, indicating the persistence of inflammation (mean uIL-6 peak prior to OKT3 or ATG therapy: 99 pg/ml). In addition, AR-associated uIL-6 levels were found to be of much greater diagnostic relevance than AR-associated serum IL-6 levels. In bacterial urinary tract infections (n = 20), increased uIL-6 levels (peak 53 pg/ml) coincided with the commencement of antibiotic therapy. In mild cytomegalovirus diseases (n = 8), the development of leukocytopenia was associated with a slight increase of uIL-6 (peak 26 pg/ml), showing graft involvement. All increased uIL-6 values returned towards baseline after successful treatment. Thus, uIL-6 provides information about the intragraft inflammatory situation. Its determination is simple, expressive, non-invasive and can be recommended.

Analysis of Variance↗
PubMed1998

Epstein-Barr virus infection after kidney transplantation.

Besides the well-known association of Epstein-Barr virus (EBV) and lymphomas developing posttransplantation, there are only a few data concerning the prevalence of EBV antibodies (abs) in organ donors and recipients, the posttransplant development of antibody titer in the recipient population, the extent of EBV-IgM seroconversion, and the clinical and laboratory signs associated with infection. Therefore, in a retrospective analysis, we evaluated the data of 119 organ donors and 215 kidney graft recipients who received their kidney allografts between 1993 and 1995. A total of 665 sera were quantitatively tested by means of immunofluorescence assay for EBV abs against capsid (CA; IgM, IgG), early (IgG), and nuclear (IgG) antigens. Recipient sera were obtained for testing before kidney transplantation (KTx) and at post-KTx days 32, 67, and 649 (mean values). Pre-KTx all organ donors and 98.65% of the recipients wre EBV-CA-IgG positive, only in two cases was there a D+/R- (donor/recipient) combination leading to primary EBV infection. In comparison with the organ donors, in kidney graft recipients the pre-KTx IgG antibody titers (geometric mean) against EBV-CA were significantly elevated (1:428 vs 1:574; U-test). Post-KTx, EBV-CA-IgM seroconversion was observed in 29.5% (52 out of 176) of first graft recipients and in 47.8% (11 out of 23) of regrafted patients up to the last follow-up day 649. In 219 out of these 52 recipients, IgM abs again cytomegalovirus (CMV) could also be detected; the other 23 did not develop CMV-IgM abs. The most frequently associated clinical signs were fever (74%), elevated aminotransferases (57%), and deterioration of graft function (26%). In the EBV-IgM+/CMV-IgM+ group there were significantly more rejection therapies than in the EBV-IgM+/CMV-IgM- group. With respect to the severity of EBV infections, 68% were asymptomatic or mild, 27% moderate, and 4% (only 1) severe. Thus, besides the post-KTx CMV monitoring, EBV monitoring should also belong to the follow-up checks.

Adult↗
PubMed1996

A critical analysis of soluble interleukin-2 receptor levels in kidney allograft recipients.

Soluble interleukin-2 receptor (sIL-2R) was measured by the Cellfree Kit (T Cell sciences) in 103 pretransplant and 1590 posttransplant samples from 103 patients with cadaveric kidney allografts. The mean values (+/- SD) detected in pretransplant sera were significantly higher (1932 +/- 1389 U/ml) than in 72 healthy adults (267 +/- 139 U/ml), but after transplantation they continuously fell towards normal levels within the first 3 postoperative weeks. Recipients with acute rejection episodes showed higher sIL-2R levels (1762 +/- 904 U/ml) than those with stable transplants at discharge (937 +/- 398 U/ml). Highest values were detected during antirejection therapy with antithymocyte globulin (4996 +/- 2166 U/ml) or OKT3 (5905 +/- 3910). Increases were also observed during bacterial and viral infections and even, in some cases, without any apparent cause. Because of this lack of specificity, elevated sIL-2R levels should be interpreted cautiously. Nevertheless, sIL-2R level can be useful for monitoring kidney allograft recipients. Increases point to a cellular immune activation process and can predict rejections or infections.

Adult↗
PubMed1996

Dynamics of donor-reactive IgG, IgA and IgM antibodies against T and B lymphocytes early after clinical kidney transplantation using flow cytometry.

Using flow cytometry, 32 kidney graft recipients were monitored retrospectively for at least 1 month to study the dynamics of serum IgG, IgA and IgM antibodies against donor T and B lymphocytes before and after transplantation. Donor spleen lymphocytes were used as targets. In the B cell cross-match, the surface immunoglobulins were blocked with an anti-human immunoglobulin antibody. A high frequency of donor-reactive antibodies was detected early after transplantation, especially when the sera were tested against B lymphocytes. Surprisingly, donor-reactive antibodies of the IgA isotype made up a substantial proportion of all antibodies detected. Within the first month after transplantation, six out of 32 patients (19%) developed IgG antibodies against donor T lymphocytes and nine out of 35 patients (28%) formed IgG antibodies against B lymphocytes. A similar situation was found for IgA antibodies: 22% of the recipients were positive for IgA antibodies against donor T lymphocytes and 34% against B lymphocytes after transplantation. Lower antibody frequencies were found for IgM antibodies (16% and 19%, respectively). From our data we conclude that for at least some of the parameters studied their individual dynamics reflect the complex immunological mechanisms occurring early after transplantation.

Antibodies, Anti-Idiotypic↗
PubMed1994

Failure of in vitro T-cell assays to predict clinical outcome after human kidney transplantation.

Allotransplant rejection is a T-cell-dependent reaction. Functional in vitro T-cell assays are being used widely for donor-recipient matching in bone marrow transplantation and have recently been used in some centres for transplant monitoring. In order to assess tolerance induction after clinical transplantation, we measured the T-cell response of the host against donor spleen cells of 33 kidney transplant patients before and every 3 months after transplantation over a period of 18 months. The T-cell reactivity before transplantation was not significantly different in any of the assays in rejecting and non-rejecting patients. In the classical mixed lymphocyte culture (MLC), a donor-specific loss of reactivity was seen only in a patient with a CMV-associated irreversible transplant rejection. One patient with chronic rejection acquired a very high MLC response against donor spleen cells and a high response against third-party cells. Little or nonspecific changes were seen in the MLCs of all other patients. Using the method of limiting dilution analysis (LDA), we found a significant reduction of donor-specific cytotoxic T-cell precursors (CTL-p) within the first 3 months after transplantation in most patients with high antidonor CTL-p frequencies before transplantation. The reduction of donor-specific CTL-p was seen in patients with rejection episodes as well as in patients without. Thus we conclude, in contrast to others, that MLC and CTL-p LDA have no predictive value on the outcome of clinical transplantation.

Clonal Deletion↗
PubMed1994

Urinary Tamm-Horsfall protein as a marker of renal transplant function.

In a total of 428 urine samples collected from 15 patients aged between 23 and 60 years after cadaveric kidney transplantation during a postoperative hospital stay, Tamm-Horsfall protein (THP) was quantitatively determined using the ELIAS SYNELISA-THP immunoassay. All patients were treated with azathioprine, cyclosporine, prednisolone, given an intraoperative high-dose single antilymphocyte globulin bolus and discharged with functioning grafts. In clinically uncomplicated courses, even after immediate transplant function, the recovery of graft function took on average 7 days. Thereafter the urinary THP excretion was relatively stable and amounted, on average, to 14.5 +/- 4.9 mg/24 h (i.e. was at the lower limit of normal urinary THP excretion). In cases of delayed onset of graft function of undetermined origin accompanied by extremely reduced urinary THP excretion, the functional recovery, whether spontaneous or brought about by treatment, was characterized by a continuous increase in urinary THP excretion. In connection with interstitial rejections urinary THP excretion seems not to be a recommendable diagnostic parameter. Daily measurement of urinary THP is, however, suitable for monitoring the functional state of transplanted kidneys.

Adult↗
PubMed1994

Effects of PUVA therapy on kidney allografts: results of a randomized prospective double-blind study.

After successful experimental organ transplant studies on the efficacy of PUVA therapy combining donor pretreatment with the photosensitizer 8-methoxypsoralen (P) and the ex vivo irradiation of organs with long-wave ultraviolet light (UVA) prior to transplantation, we started in 1989 the first randomized, prospective, double-blind study to clarify the efficacy of PUVA therapy in human kidney transplantation. This study included 50 kidney donors, 25 of whom were PUVA-treated. A total of 75 kidneys were transplanted in Berlin, Halle and Rostock. The complete data of these 75 recipients were available for the final evaluation. The PUVA group (n = 36) and the non-PUVA group (n = 39) were not statistically significantly different as to donor and recipient data. Regarding the results, no differences were seen in initial hospitalization time, early graft function, rejection rate, number and time of rejection episodes. After a follow-up of 24 months, both graft survival (PUVA vs. non-PUVA: 75% vs. 71.8%) and patient survival (97.2% vs. 97.4%, respectively) were comparably high. PUVA therapy did not influence the development of vascular rejection. Interestingly, the rate of late graft loss after the 6th posttransplant month was lower, but not statistically significantly so, in the PUVA than in the non-PUVA-group (2 vs. 6 graft losses). Thus, PUVA-pretreated kidneys may be associated with a reduced development of chronic rejection.

Adolescent↗
PubMed1992

Effect of ATG prophylaxis in sensitized and non-sensitized kidney graft recipients.

In our effort to find an optimum immunosuppressive protocol for kidney transplantation we introduced two forms of ATG prophylaxis: 1. high-dose single-bolus prophylaxis (9 mg/kg) in non-sensitized patients (PRA < 5%); and 2. low-dose 8-day prophylaxis (1.5-3.0 mg/kg) in sensitized patients (PRA > 5%). A total of 204 kidney graft recipients were included in this study and treated with a triple-drug therapy (TDT). In comparison with TDT-treated controls, in sensitized patients the 8-day ATG prophylaxis resulted in a reduced rate of rejection episodes (25.5% vs 47%), an improved 1-year graft survival (82% vs 71%) and patient survival (94% vs 90%). In non-sensitized patients the high-dose single-bolus ATG prophylaxis induced a T-cell lymphopenia lasting 4 to 5 days and, in comparison with the corresponding controls, resulted in a shortened hospital stay (31.2 days vs 36.7 days), a reduced rate of rejection episodes (25.5% vs 53%), an improved 1-year graft survival (92% vs 86%) and patient survival (100% vs 94%).

Antilymphocyte Serum↗
PubMed1992

Temporal patterns of immunoblot-reactive antibodies to cytomegalovirus in transplant recipients.

A total of 234 sera from 44 allograft recipients were compared with 12 sera from 9 immunocompetent patients with symptomatic cytomegalovirus (CMV) infection and with 20 sera of 20 healthy individuals with latent CMV infection. The presence of immunoreactive proteins was not associated with a specific transplant group or with different immunosuppressive regimens but rather with the kinetics of the immune response. Acute phase sera demonstrated early antibodies to proteins p38 and p48, followed by high or still rising antibodies to high molecular weight proteins, particularly p150, and their later decline to persistent lower levels. Convalescent phase sera were identified serologically by the transient appearance of IgG antibodies directed to 22-26 kDa polypeptides. Immunoreactive p44 was present in 85% of all patients with mild disease and in 40% of all patients with severe CMV disease. When tested in parallel, the immunoblot analysis was shown to be a more sensitive indicator of early CMV antibodies in allograft recipients than the ELISA technique.

Antibodies, Viral↗
PubMed1991

[Risk of CMV infection and illness after kidney transplantation].

Between 1980 and 1986 465 cadaveric kidney transplants were performed at the Kidney Transplant Centre Berlin-Friedrichshain. The post-transplant risk to acquire a cytomegalovirus (CMV) infection depended on the preoperative CMV antibody status of donor and recipient, on the nettoimmunosuppression and on the recipient's age. The highest infection rate and the most serious courses showed seronegative recipients from seropositive donors. The typical time interval of clinical manifestation included the postoperative months 1-3. A significant dependence of the frequency of infection on different immunosuppressive protocols could not be proven. But there was a significant coincidence between CMV infection and rejection crises. In spite of the raised frequency of rejection crises an influence of the CMV infection on the 1-year-graft and patient survival rates could not be demonstrated. Both an early diagnosis and an adequate therapy are of particular importance.

Age Factors↗