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Biomedical subjects

L Fricke

Publications and source records attributed to L Fricke.

At least 37 records · Page 2Linked to original sources

Renal graft rejection or urinary tract infection? The value of myeloperoxidase, C-reactive protein, and alpha2-macroglobulin in the urine.

Previous investigations have shown that the determination of two acute-phase proteins in the urine, C-reactive protein (CRPu) and alpha2-macroglobulin (alpha2-MGu), allows a noninvasive diagnosis of acute renal graft dysfunction. A reliable differentiation between rejection and urinary tract infection can be made only when considering the C-reactive protein in serum and urine at the same time (CRPs:CRPu ratio). Therefore, a diagnostic procedure independent of parameters other than urinary proteins is needed. As granulocytes play only a minor role in graft rejection but are a common feature in urinary tract infection, we determined a marker of granulocytes (myeloperoxidase) in urine (MPOu). Eighty-nine renal transplant recipients were included in the study. In normal courses, CRPu, alpha2-MGu, and MPOu were within the normal range. In 15 cases of acute interstitial rejection, an increased excretion of CRPu and alpha2-MGu could be confirmed, but MPOu could not be detected. On the occasion of acute vascular rejection (n=6), with the exception of one case, MPOu could not be observed. The pattern of the three urinary proteins differed in urinary tract infections (n=40): MPOu could be detected in all cases, CRPu in 50% of cases, and alpha2-MGu in 73% of cases. In patients with cytomegalovirus infection (n=7), no MPOu, CRPu, or alpha2-MGu was found. In conclusion, the simultaneous measurement of the three proteins allows a complete, noninvasive, differential diagnostic procedure of renal graft dysfunction.

Biomarkers↗

[The significance of risk-adapted antiviral prophylaxis and modern virus diagnosis for organ survival after kidney transplantation].

BASIC PROBLEM AND OBJECTIVE: Viral, especially cytomegalovirus (CMV), infections are after rejection reaction the most serious problem following organ transplantation. The risk of disease correlates with the CMV donor/recipient constellation and the degree of immunosuppression. The importance of antiviral prophylaxis remains unresolved. Whether drug prophylaxis adapted to the individual risk is of clinical value was investigated in a prospective study. PATIENTS AND METHODS: A risk-adapted stepwise antiviral prophylactic regimen was given to 62 patients with renal transplants. All patients at risk of CMV infection were given acyclovir, 200 mg four times daily for 3 months. Patients with rejection reaction for which they were receiving i.v. immunosuppressive treatment additionally received CMV hyperimmunoglobulin (2 ml/kg body weight on days 1 and 14). High-risk patients (donor CMV positive and recipient CMV negative) were given as basic prophylaxis CMV hyperimmunoglobulin i.v. on days 1 and 14 after transplantation, and additionally i.v. ganciclovir during any rejection treatment. The results were compared with those of a retrospectively selected patient cohort (n = 52) who had received only acyclovir as basic prophylaxis. The diagnosis of CMV infection was made by demonstrating CMVpp65 antigen in blood. In the prospectively studied patients measurement of beta 2 microglobulin concentration was used to determine viruria in 24-hour urine. RESULTS: Among the high-risk group (donor CMV positive/recipient CMV negative) the additional prophylactic regimen significantly reduced the proportion of CMV-associated cases of rejection (14% compared with 42%, P < 0.05) in the basic prophylaxis only group. Similar results were obtained for CMV-caused transplant loss within the first 3 years (19% vs 50%, P < 0.05). The additional prophylaxis had no influence on the incidence of CMV infection. In case of active infection an isolated rise of beta 2-microglobulin in urine occurred in active infection at a mean of 6 days before CMVpp65 antigenaemia (sensitivity of 89%). CONCLUSIONS: These results indicate that risk-adapted antiviral prophylaxis can decisively influence the long-term prognosis for a renal transplant, but not the incidence of CMV infection. The early and reliable diagnosis of active CMV infection is made possible by the combined use of beta 2-microglobulinuria and pp65 antigenaemia.

Acyclovir↗

Laparoscopic bilateral nephrectomy: results in 11 renal transplant patients.

PURPOSE: We report our experience with bilateral laparoscopic nephrectomy after renal transplantation. MATERIALS AND METHODS: Between August 1994 and October 1995, 11 patients who had previously undergone renal transplantation underwent bilateral laparoscopic nephrectomy at our hospital due to poorly controlled hypertension. The records of 10 patients undergoing bilateral open nephrectomy were reviewed for comparison. RESULTS: Mean operative time in the laparoscopy group was 195 minutes (range 125 to 270). Mean blood loss was 345 ml. and 1 patient required conversion to an open operation. Oral intake and mobilization were begun 1 day postoperatively. Mean postoperative morphine equivalent consumption was 14 mg., mean hospital stay was 4.2 days (range 3 to 6) and mean return to normal activities was 14 days. At a mean followup of 10.4 months blood pressure had improved significantly in 8 patients (73%). Mean operative time in the open surgery group was 145 minutes (range 115 to 170) and mean postoperative morphine equivalent required was 44 mg. Compared to the laparoscopy group the interval to resumption of oral intake (3.5 days), duration of hospital stay (10.7 days) and return to normal activities (36 days) were prolonged in the open surgery group. CONCLUSIONS: According to our results, bilateral laparoscopic nephrectomy could be an effective alternative for the treatment of severe hypertension after renal transplantation. Compared to open nephrectomy most patients benefit from the laparoscopic approach.

Adult↗

Laparoscopy in renal transplant patients.

OBJECTIVES: To evaluate the use of laparoscopic techniques in patients with a renal transplant. METHODS: Since 1992, 358 patients have undergone urologic laparoscopy at our hospital. Among these, 37 procedures (10.4%) were performed in patients with a renal transplant: 14 bilateral nephrectomies for severe drug-resistant hypertension, 9 marsupializations of symptomatic lymphoceles, 6 renal allograft biopsies in patients with clotting abnormalities, 6 unilateral nephrectomies, and 2 nephroureterectomies for recurrent episodes of pyelonephritis and symptomatic vesicoureteral reflux, respectively. RESULTS: Five complications (14%) and three conversions (8%) occurred. Patients who underwent successful laparoscopic operations began mobilization and oral intake on the day after the operation. The hospital stay ranged from 1 to 6 days. In the nephrectomy groups, perioperative urine outputs remained stable and post-operative urine outputs were increased as compared with those in the perioperative period (P < 0.05). Post-operatively, serum creatinine remained stable or improved in patients who underwent nephrectomy or marsupialization of lymphocele. CONCLUSIONS: Our results indicate that laparoscopic techniques are safe and effective in the treatment of patients with a renal transplant. Renal allograft function apparently is not affected by laparoscopic procedures.

Adult↗

ICAM-1, soluble-CD23, and interleukin-10 concentrations in serum in renal-transplant recipients with Epstein-Barr virus reactivation.

Primary and reactivated Epstein-Barr virus (EBV) infections after organ transplantation are associated with the development of posttransplant lymphoproliferative malignancies. Since viral reactivation frequently stays asymptomatic, early diagnosis and treatment are challenges during posttransplant patient monitoring. Both soluble-CD23 (sCD23) and intercellular adhesion molecule 1 (ICAM-1) cell surface expression as well as interleukin-10 (IL-10) production are closely associated with viral gene expression. Therefore, immunoglobulin M (IgM), IgG, IgA, sCD23, ICAM-1, and IL-10 concentrations were measured in serum samples from patients during EBV reactivation (n = 14) and were compared with those in samples from patients without EBV reactivation (n = 10) following renal transplantation. In addition, serum sCD23, ICAM-1, and IL-10 concentrations were measured longitudinally in weekly to biweekly samples from 10 patients with EBV reactivation for at least 20 weeks following transplantation. A significant elevation of sCD23 was found during viral reactivation (P < 0.05), whereas ICAM-1 levels showed a nonsignificant increase. The finding of a highly significant elevation of the serum IL-10 concentration during EBV reactivation (P < 0.001) may support speculations about its role in EBV-induced lymphoproliferation and in the development of opportunistic infections and secondary malignancies. Maximum serum IL-10 levels at the time of EBV reactivation were found in 7 of 10 patients. Well-defined ICAM-1 and sCD23 concentration peaks were found in 9 of 10 and 8 of 10 patients, respectively. Although both markers are not specific for EBV reactivation and therefore may not be useful for primary diagnosis, sCD23 and ICAM-1 might be potent tools for the clinical monitoring of EBV activity and virus-induced lymphoproliferation.

Antibodies, Viral↗

[Does preoperative corticoid administration reduce the incidence of acute rejections after kidney transplantation?].

Primary immunosuppressive therapy in renal transplantation is mediated by glucocorticosteroids with a delay of several hours. Consequence of the common practice of using first dose of steroids intraoperatively is a first contact of antigens with an unaltered immune system. In a prospective study on 111 renal transplant patients, we could show by the parameters of in vitro cytokine generation and acute rejection episodes that immunological responsiveness can be altered by early (5 h) preoperative use of glucocorticosteroids.

Adult↗

Preoperative application of glucocorticosteroids efficaciously reduces the primary immunological response in kidney transplantation.

Early acute rejection episodes have a considerable influence on long-term prognosis of renal transplants. Therefore the aim of primary immunosuppressive therapy must be effective suppression of the immunological response following antigen recognition. Owing to their pharmacological properties, intravenously given glucocorticosteroids are suitable for the alteration of the primary immunological response. However, even after intravenous administration, glucocorticosteroids have a latency of hours prior to reaching maximum activity. In a prospective clinical study, 111 patients undergoing renal transplantation were preoperatively treated with 500 mg methylprednisolone for immunosuppressive induction. A historical group of 40 patients who had received the same dose as intraoperative bolus, was used for comparison. Postoperative immunosuppression did not substantially differ between the two groups. The incidence of acute rejections within 30 d after transplantation was a clinical parameter of the study. The mitogenic cytokine induction was measured in blood samples which were collected intraoperatively and on days 1, 2, and 5 after transplantation. Cytokine release served as an in vitro parameter for the immunological responsiveness of the transplant recipient. In the group under study, the incidence of acute rejections was 21% (23/111) and, in contrast, 43% (17/30) in the historical group (p < 0.05). 89% of the patients in the group being studied showed normal renal function after 1 yr, compared to 78% in the reference group (n.s.). Following preoperative (mean 5.09 h) administration of glucocorticosteroids, mitogenic cytokine induction (IL-1 beta, IL-2, sIL-2R and IFN-gamma) was almost completely blocked at the time of transplantation. A prospective, randomized study has just been started to evaluate the effect of preoperative administered glucocorticosteroids on the incidence of acute rejections and long-term allograft survival.

Adult↗

Coincidence of Epstein-Barr virus reactivation, cytomegalovirus infection, and rejection episodes in renal transplant recipients.

Reactivation of the Epstein-Barr virus was reported to occur frequently under immunosuppressive therapy following organ transplantation. However, little is known about the clinical significance of these EBV reactivations. Therefore, we searched for correlations among the treatment with various immunosuppressive drugs, the incidence of CMV infections, rejection crises, and serological signs of EBV reactivation. EBV-specific antibodies were measured with novel ELISAs, utilizing the recombinant antigens p72 (for anti-EBV nuclear antigen [EBNA]1-IgG), p54, and p138 (anti-early antigen [EA]-IgM, -IgG, -IgA) in a follow-up study of 79 renal transplant recipients. Patients receiving antithymocyte globulin or antilymphocyte globulin therapy showed increasing anti-EA-IgG and -IgA more often than did patients not receiving antithymocyte globulin or antilymphocyte globulin therapy (P < 0.05). In patients receiving OKT3 antirejection therapy, anti-EA-IgM seroconversion was found more frequently (P < 0.01). A significant correlation was also found between groups of patients who had had at least one rejection episode versus patients without any sign of organ rejection, and the incidence of increasing anti-EA-IgG (P < 0.05). Since in most of these patients signs of EBV reactivation followed the appearance of the rejection episode, this may not be due to viral-induced rejection but may be caused by the reinforced immunosuppression during antirejection therapy. As opposed to patients with no signs of CMV infection and with nonsymptomatic CMV infection, patients undergoing symptomatic CMV infection showed anti-EA-IgM seroconversion (P < 0.01), increasing anti-EA-IgA (P < 0.01), and decreasing anti-EBNA-IgG (P < 0.01) more frequently. Our results confirm the role of immunosuppressive therapy in the pathogenesis of EBV reactivation. We further demonstrate a striking coincidence of EBV reactivation and symptomatic CMV infection.

Antibodies, Viral↗

A longitudinal prospective study of cytomegalovirus pp65 antigenemia in renal transplant recipients.

Cytomegalovirus (CMV)-encoded pp65 antigen in peripheral blood leukocytes (CMV antigenemia) was investigated in 1017 serial samples from 64 patients for 16 weeks after renal transplantation in a prospective study. In 110 samples from 24 patients, at least one antigen-positive leukocyte was identified. The median number of stained cells was 4 (range 1-1000) per 4 x 10(5) leukocytes. Twenty-one of 24 patients with serological signs of an active CMV infection were antigen-positive (sensitivity 87.5%), whereas 3 patients with antigenemia did not show serological signs of infection during the observation period (specificity 92.5%). Positive results were obtained 19 days (median) before serological response and 9 days (median) before the onset of CMV syndrome. The sensitivity in defining a CMV syndrome was 100% (n = 8). In all patients who presented with CMV syndrome, antigenemia was present prior to the onset of symptoms or on the same day. In contrast, serological monitoring rendered the diagnosis of CMV infection possible at the onset of clinical symptoms in only two of eight patients. We conclude that (1) insufficient results obtained with the CMV antigenemia assay by other investigators are mainly due to technical problems that can easily be overcome by the protocol presented and (2) the detection of CMV pp65 antigen in peripheral blood leukocytes is an excellent tool for rapid and early diagnosis of CMV infection.

Antibodies, Viral↗

The long persistence of CMV DNA in the blood of renal transplant patients after recovery from CMV infection.

A total of 30-50% of all renal transplant recipients undergo infections caused by human cytomegalovirus. With the introduction of ganciclovir and foscarnet for specific antiviral therapy there is an increasing demand for diagnostic tools that allow the early and rapid identification of CMV as the causative agent of the observed disease. We and others previously showed the direct detection of pp65 antigen in peripheral blood leukocytes to be an excellent marker for active cytomegalovirus infection. In order to establish whether the detection of CMV DNA by the polymerase chain reaction (PCR) supplies further information in this regard, we compared both methods. In 41 renal transplant patients the PCR assay yielded a sensitivity of 100% compared with 87.5% of the antigenemia assay. Specificities reached 67% and 92.5%, respectively. In 5 patients without both serological signs of infection and antigenemia, CMV DNA was also found. The duration of CMV DNA detection in PBL during active infection was significantly longer than antigenemia. Even after successful treatment of symptomatic CMV disease, DNA was present for a period of weeks without any relapse of disease. In contrast, antigenemia disappeared after antiviral therapy and reappeared only in one patient with relapse of CMV disease. We conclude that PCR offers no advantages over antigen detection in monitoring for CMV infections after renal transplantation.

Base Sequence↗

HLA DNA preorgan retrieval donor typing in renal transplantation.

For the first time, a DNA technique was used in clinical practice for pre-organ donor retrieval typing in renal transplantation. The method is based on the polymerase chain reaction with nested sequence-specific pairs (nested PCR-SSP) for all serological HLA-DR specificities of DR1-DR18. A panel of reference-typed individuals (n = 101) was investigated in a blind quality control study and the results revealed a sensitivity of 99.5% and a specificity of 100%. Semi-automation of PCR-SSP provided rapid, accurate and reliable typing results demonstrating that this DNA test is most suitable for replacing the error-prone HLA-DR serological technique. Twenty-seven consecutive cadaveric organ donors have been successfully typed so far. The results were available within less than 3 h after blood sampling and in all cases prior to the retrieval of organs. In conclusion, the introduction of this accurate DNA typing in HLA matching programs may significantly improve the graft survival rate in renal transplantation.

Blood Grouping and Crossmatching↗

[C-reactive protein in the urine. The differential diagnosis of renal functional disorders following kidney transplantation].

A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications.

Adult↗