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.

[Risk of CMV infection and illness after kidney transplantation]. / Das CMV-Infektions- und Erkrankungsrisiko nach Nierentransplantation.

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.

[Spontaneous kidney transplant rupture--effect of immunosuppressive therapy on incidence of rupture]. / Die spontane Nierentransplantatruptur--Einfluss des immunsuppressiven Therapieregimes auf die Rupturfrequenz.

In an analysis of 302 cadaveric kidney transplantations performed from 1986 to 1988 the frequency of spontaneous kidney allograft ruptures could significantly reduced by introduction of cyclosporine therapy. Therefore, the importance of rejection in the etiology of allograft rupture is emphasized. In comparison with an earlier analysis the prognosis of rupture with respect to organ repair has been impaired (41 vs. 68%). The importance of intense and effective immunosuppressive therapy in the early period after kidney transplantation is emphasized.

[Use of OKT-3 in treatment of rejection following kidney transplantation]. / Einsatz von OKT-3 bei der Rejektionsbehandlung nach Nierentransplantation.

Application of OKT-3 as rescue therapy in steroid-resistant rejection was effective in 7 out of 9 patients early after cadaveric kidney transplantation. Under attention of instructions for use of OKT-3 the adverse first-dose reactions are rare. The problem of OKT-3 therapy is early use and its reuse.

[Follow-up of the transplantation of contaminated kidneys]. / Verlauf der Transplantation von kontaminierten Nieren.

102 kidney transplantation were performed in 1987 in the Kidney Transplant Center at Berlin. The course of 22 contaminated grafts (22%) was analyzed. The main bacteria were staphylococcus aureus and pseudomonas aeruginosa. In 6 out of 22 contaminated transplants (27%) a delayed wound healing did occur. In 2 cases the infection was the cause of graft removal and 2 patients died due to septical complications of the contaminated graft. Therefore, the contaminated kidney is a potential risk for graft and patient survival and strong asepsis and effective perioperative antibiotic prophylaxis is necessary.

[4-way immunosuppression in pre-sensitized recipients of allogenic cadaver kidney transplants]. / Vierfach-Immunsuppression bei präsensibilisierten Rezipienten allogener Leichennierentransplantate.

As a result of introduction of quadruple immunosuppression using cyclosporine, antithymocyte globulin, azathioprine and prednisone in immunological high-risk patients with a presensitization greater than or equal to 80% and/or multiple grafts the rate of immediate graft function could significantly increased, the frequency of rejection and graft rupture was reduced and the patient survival rate could improved to 100%. The problem of vascular rejection should resolved by a more aggressive biopsy approach.

Effect of increased donor age on kidney transplant outcome.

Donors over the age of 50 years provided kidneys for 28 of our 226 recipients (12.4%) transplanted from January 1, 1987 to December 31, 1988. Immediate function following transplantation occurred in 36% of the kidneys from donors both over and under the age of 50. The overall 3-month graft survival rate for transplants from donors over 50 years was 89%, compared with 78% for transplants from donors under 50 years (p greater than 0.05). Thus kidneys from well-selected older donors make an important contribution to the total pool of organs available for transplantation.

[Physiologic performance of clinically non-functioning kidney transplants]. / Physiologische Leistungen klinisch funktionsloser Nierentransplantate.

The excretion capacity of 24 kidney allografts which had been dialyzed because of non-function was examined. It has been shown that only 4 out of 24 allografts (16.7%) were truly without function. All other transplants did show a slight or more improvement of the excretion capacity prior to irreversible loss of graft function. As a cause the non-identified graft rejection is discussed.

[Personal experiences with kidney transplantation in the elderly]. / Unsere Erfahrungen mit der Nierentransplantation bei älteren Patienten.

From January 1987 to December 1988 226 cadaveric renal allotransplants were performed in the Kidney Transplant Center of the Friedrichshain Hospital. 38 of the recipients (17%) were older than 50 years. The results of transplantation are comparable with younger recipients, except a higher frequency of age-related urological complications of benign prostatic hyperplasia.

[Analysis of T-cell subpopulations and expression patterns of lymphocytic activation markers in patients in the early phase following kidney transplantation using laser flow cytometry]. / Analyse von T-Zellsubpopulationen und Expressionsmustern lymphozytärer Aktivierungsmarker bei Patienten in der Frühphase nach Nierentransplantation mittels Laser-Durchflusszytometrie.

In 10 patients after kidney transplantation the T cell subpopulations (CD4, CD8) and the number of activated lymphocytes (IL-2R and transferrin receptor+, 4F2+, HLA-DR+, CD3+) in the peripheral blood were determined. In 9 out of 9 cases with rejection a clear immune activation could observed. In patients with CMV-associated rejection crisis the CD4/CD8 ratio was significantly higher compared with patients with rejection crisis but without CMV infection. In all patients with CMV infection (n = 5) an increase of activated lymphocytes was observed. In a clinical-immunological monitoring the dynamics of the CD4/CD8 ratio, the expression of activation marker (especially CD3+, HLA-DR+ and 4F2+) and the absolute number of lymphocyte subpopulations should included.

[Detection of cytomegaloviruses using monoclonal antibodies in aspiration biopsy material of kidney transplants]. / Cytomegalievirusnachweis mittels monoklonaler Antikörper an Aspirationsbiopsiematerial von Nierentransplantaten.

In 56 kidney transplant recipients 93 specimens from transplant aspiration biopsy and peripheral blood were examined on the presence of cytomegalovirus (CMV) using the monoclonal antibody (mab) H 11. The used mab H 11 did react safe and exclusive in the acute infection period with the virus antigen. This antigen detection makes possible the laboratory diagnosis of a CMV infection 11 days (median value) prior to detection of specific IgM antibodies. In comparison with the cytological evaluation of fine needle aspiration biopsy the rejection process could be differentiated from infection.

Individually disparate anti-inflammatory in-vivo susceptibility to corticosteroids in renal transplant recipients.

We used the strength of suppression of the interleukin-1-induced peak CRP response (CRPmax) post-transplant as a measure for the individual steroid susceptibility in vivo. This suppressive effect proved to be fully reversible after abrogation of steroid therapy following graft removal. The standardized suppressive therapy immediately post-transplant led to extremely different results in individual patients ranging from no suppression (26.1% of the patients) to a strong or practically absolute suppression of CRP synthesis in 20.7% of the patients studied. This behaviour is also reflected in anti-rejection bolus therapy whereby the percentage of prednisolone resistant patients strongly correlated with increasing (unsuppressed) CRPmax values. From our data we conclude that the disparate anti-inflammatory susceptibility for corticosteroids seems to be an individual feature of patients under high-dose steroid treatment.

Diagnostic significance of some urinary enzymes for detecting acute rejection crises in renal-transplant recipients: alanine aminopeptidase, alkaline phosphatase, gamma-glutamyltransferase, N-acetyl-beta-D-glucosaminidase, and lysozyme.

We compared the diagnostic validity of five urinary enzymes--alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), and lysozyme (EC 3.2.1.17)--as indicators of acute rejection crises in renal-transplant recipients. In 82 patients (group A), the excretion of each of these five enzymes was measured daily from transplantation until discharge from hospital. In another 69 patients (group B), enzyme determinations were made when the patient came for regular checkups (about every four to eight weeks). We used an "activity ratio" (the activity measured at a particular time compared with the activity on the preceding determination) value of 1.5 as the decision point. In group A, use of this discrimination point for alanine aminopeptidase, gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase yielded a specificity and sensitivity of about 90%. In group B, only alanine aminopeptidase had a greater diagnostic sensitivity than creatinine alone. Evidently, measurement of alanine aminopeptidase can be a helpful indicator of acute rejection crises, when interpreted in combination with other available relevant clinical, biochemical, and immunological data.

[Serologic studies in patients with early transplant failure]. / Serologische Untersuchungen an Patienten mit frühem Transplantatversagen.

The appearance, specificity and dynamics of donor reactive antibodies have been studied in 9 patients who experienced early irreversible graft failure. In 5 out of 9 patients we were able to detect donor reactive antibodies. Their reaction patterns may be ascribed to a common responder type ("high responder"). Diagnostic and preventive possibilities for preventing early irreversible graft failures have been discussed.