Diagnostic and prognostic value of antibody-dependent cellular cytotoxicity and lectin-induced cellular cytotoxicity tests for renal graft rejection.

Peripheral blood lymphocytes from both normal subjects and kidney allograft recipients, before and on the 4th to 5th days after transplantation, were examined for antibody-dependent cellular cytotoxicity (ADCC) and lectin-induced cellular cytotoxicity (LICC). The graft recipients were treated with standard immunosuppression, which included azathioprine and prednisolone. 51Cr-labeled L1210 cells were used as targets for these two tests. ADCC and LICC activity were evaluated in the presence of rabbit anti-L1210 anti-serum and phytohemagglutinin (PHA), respectively. Comparison of the results obtained from healthy subjects with those of patients before grafting showed a significantly higher LICC activity in the latter group. The ADCC activity did not differ between the groups of healthy females and those awaiting transplantation but it was significantly decreased in the group of males awaiting transplantation as compared to healthy males. Four to 5 days after transplantation, the activity of ADCC and LICC remained unchanged in spite of the immunosuppressive treatment in 37 and 61% of the patients studied, respectively. In most of the patients, high ADCC and/or LIcC activity was followed by an accelerated acute rejection episode. A correlation between the ADCC and LICC activities, measured 4 to 5 days after transplantation, and the time of the first rejection episode was found. We conclude that double screening with ADCC and LICC tests in the 1st week after transplantation is valuable.

Study of antibody dependent cellular cytotoxicity (ADCC). II. ADCC activity in renal graft recipients and acute accelerated graft rejection.

ADCC activity in 27 cadaver renal allograft recipients was studied. All the patients were given standard immunosuppressive treatment. Significant positive correlation between high ADCC activity during first 5 days after grafting and accelerated rjection crisis was found. The high positive ADCC test may signalize the possibility of acute accelerated rejection of renal allograft.

Low dose heparin: efficacious treatment for chronic renal allograft rejection.

Recent data indicate that aside from its anti-coagulant action heparin has potent immunobiological activities inhibiting cell trafficking to a site of antigen. In addition, heparin inhibits smooth muscle cell proliferation and decreases the synthesis of the extracellular matrix proteins. As those phenomena are thought to play a major role in the pathogenesis of chronic allograft rejection, we performed a trial evaluating the efficacy of low dose heparin (5 U/kg/day) in 23 recipients of renal allografts with biopsy-proven rejection. In 16 patients (70%) a tendency for improvement was seen which in 57% was statistically significant. Our data suggest that low dose non-anticoagulant heparin may be an efficacious means for treatment of chronic rejection.

The comparison of antibody-dependent (ADCC) and lectin-induced (LICC) cytotoxic activities of human blood lymphocytes in healthy and diseased subjects.

Antibody-dependent and PHA-induced cytotoxicity of peripheral blood lymphocytes in healthy human subjects and in patients with primary glomerulopathies (non-treated and on immunosuppressive treatment) as well as hemodialyzed and transplanted patients were investigated. Heavy disorders of ADCC and LICC activity in the groups of uremic patients and in patients on immunosuppressive therapy were found. Higher sensitivity to immunosuppressive treatment demonstrated that the lymphocytes exerted an antibody-dependent rather than a PHA-induced cytotoxicity. Results presented suggested the participation of two different lymphocyte subpopulations with ADCC and LICC activity in the regulatory and pathological processes.

36-month follow-up of 75 renal allograft recipients treated with steroids, tacrolimus, and azathioprine or mycophenolate mofetil.

OBJECTIVES: The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS: Seventy-five renal allograft recipients enrolled in the COSTAMP study were followed for a period of 3 years. Patients were randomized to receive either Tac and MMF (n = 41) or Tac and Aza (n = 34) concomitantly with steroids. Follow-up assessments were performed at 3, 6, 12, 24, and 36 months. RESULTS: Patient survival at month 36 was 91.18% in the Tac/Aza/S group and 97.56% in the Tac/MMF/S group. Graft survival at month 36 was 82.35% and 85.37%, respectively. During the study period, 22 cases of biopsy-proven AR were diagnosed in 17 patients (22.6%). After 36 months the total number of AR was 11 in the Aza-treated group (32.4%) and 11 in the MMF-treated group (26.8%). DM was diagnosed de novo in 17 individuals (22.6%). During 36 months, 10 patients from Aza-treated group (29.4%) and seven from MMF-treated group developed DM (17.1%). Serum creatinine values were not significantly different in both arms of the study. Comparison of arterial blood pressure and total cholesterol revealed no significant changes in any of the studied groups. CONCLUSIONS: We conclude that combinations of steroids, tacrolimus, and azathioprine or MMF provide good results with regard to renal function.

Posttransplantation diabetus mellitus under calcineurin inhibitor.

BACKGROUND: The development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state. METHODS: This analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration. RESULTS: During the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels. CONCLUSIONS: The conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM.

Intraglomerular fibronectin and laminin turn-over in chronically rejected kidney allografts in humans.

Chronic rejection is primarily responsible for the late loss of allografted organs and remains an important clinical problem. Chronic rejection in the kidney is characterised by arteriolosclerosis and nephrosclerosis, glomerulonephritis and interstitial fibrosis. Recently, a large number of studies have indicated that proteolytic enzymes play important roles as mediators of glomerular injury. The aim of the study was to assess intraglomerular fibronectin and laminin contents as well as cysteine proteinases in activity chronically rejected human kidneys. We investigated kidney tissue from graftectomy specimens obtained from 11 patients with end-stage renal disease following chronic rejection. A group of 9 patients undergoing nephrectomy because of cancer served as a control group, but only not involved parts of the kidneys were used. When intraglomerular laminin contents were related to DNA content, significant accumulation in chronically rejected allografts was found in comparison to controls (382 +/- 171 micrograms per microgram DNA and 190 +/- 82 micrograms per microgram DNA, respectively, p < 0.01. The accumulation of fibronectin was higher than in controls, however the difference was not significant. When proteinase activity was related to intraglomerular DNA content, significantly enhanced cathepsin B and L activity was found in rejected kidney allografts (57 +/- 16 nmol AMC/min per mg DNA) in comparison to controls (15 +/- 2 nmol AMC/min per mg DNA). Summarizing, we observed accumulation of fibronectin and laminin in glomeruli and simultaneously an excess of proteolytic activity in human chronically rejected kidneys. The above phenomenon indicates that a very active metabolic process takes place in glomeruli during rejection.

Liver transplantation in the experience of the centre commencing the program.

From 1989 to 1999, 43 orthotopic liver transplantations (OLT) in 40 patients (3 retransplantations) were performed in our Department. The most common indications for OLT were noninflammatory, primary cholestatic liver diseases and postinflammatory liver cirrhosis. Fourty OLT's were done for elective indications, three--on emergency basis, because of fulminant liver failure. The majority of transplantations was performed with classical technique with the excision of retrohepatic vena cava and routine use of the extracorporeal veno-venous bypass. Only in 4 patients the piggyback technique was used and performed without temporary portocaval anastomosis. All 3 patients transplanted for fulminant liver failure died in the perioperative period. Twenty four patients are still alive and well, the longest period of observation exceeding 5 years.

[Ovarian function in women after kidney transplantation]. / Czynnosc jajnika u kobiet po przeszczepieniu nerek.

The full recovery of reproductive age patients suffering from chronic renal failure due to a successful transplant should include the restoration of normal reproductive functions. In the study data are presented concerning the resumption of menstruation and the evaluation of the ovarian function of renal transplant recipients. After a successful renal transplant the ovarian function improves considerably but isn't always fully restored which can be attributed to the renal efficiency grade or result from the administered immunosuppressive treatment. Approximately 40% of the patients have ovulatory cycles with a normal length of the luteal phase. 40% have also ovulatory cycles but the luteal phase is shorter and the progesterone values are lower. The remaining patients have anovulatory cycles with low estrogen values and a high FSH and LH concentration.

[Levels of myoglobin (Myo) in blood of patients during an early phase after kidney transplantation]. / Stezenie mioglobiny (Myo) we krwi u chorych we wczesnej fazie po transplantacji nerki.

UNLABELLED: In uremic subjects Myo levels were significantly higher than in normals. In the present study we aimed to assess the Myo levels immediately after KT. Myo levels were assessed in 25 uremic patients at the early phase after KT and in 12 controls (patients immediately after cholecystectomy). All uremic patients were divided on two groups: group I--patients with immediately good graft function after KT (12 patients) and group II--patients with acute failure of the transplanted kidney (13 patients). In all examined subjects immediately before and during following 30 days after KT or cholecystectomy the Myo levels were assessed using RIA methods. There were found the significant correlations between plasma creatinine and Myo levels in uremic patients. CONCLUSIONS: 1. In all examined KTP the tendency to normalisation Myo levels after transplantation was observed. 2. Acute failure of transplanted kidney delayed normalization Myo levels. 3. Normalization of Myo levels was preferently dependent on the graft function.

[Tuberculosis in patients after kidney transplantation]. / Gruzlica u chorych po przeszczepieniu nerki.

Infection caused by Mycobacterium tuberculosis is common among population in Poland. We analyzed the effect of tuberculosis (TB) on patients and graft survival in the group of renal allograft recipients (RAR), treated in our center. Among 1669 renal allograft recipients transplanted from 1981 to 1992, tuberculosis developed in 33 (2%) patients (16 M/17F, age: 22-57 years). The patients were on following immunosuppressive regiments" Pred+Aza+CsA (12 pts), Pred+Aza (12), Pred+CsA (6) and Pred+Aza+CsA+ATG (3). Acute rejection was diagnosed in 27 of them and was treated with methyloprednisone pulses, and in a few cases additionally with ATG (2 pts) or OKT3 (1 pt). In two pts TB had been diagnosed and successfully treated in the past. In 6 pts, on chest X-ray done immediately before transplantation, healed primary lesion (Ghon complex) had been seen. In 16 pts TB developed in the early posttransplant period (median: 3.8 +/- 1.8, range: 1-6 months) and in 17--late after transplantation (median: 31.2 +/- 1.8, range: 13-156 months). In 19 pts symptoms developed soon after treatment of acute rejection. Clinical manifestations include pulmonary TB (30 pts) and extrapulmonary lesions (15 pts): pleural TB (3 pts), miliary TB (5 pts), tuberculous lymphadenitis (1 pt), uveitis (1 pt), renal allograft (2 pts), skeletal (2 pts) and GI tract (1 pt). Diagnosis of TB was made based on clinical presentation and radiologic findings and it was confirmed by positive cultures in 18 pts, by tissue biopsy in 4 pts and by autopsy examination in 9 pts. Treatment regimen included one of the following drug combinations: INH+EMB+RMP (20 pts), INH+RMB+RMP+PZA (10 pts) or INH+EMB+SM (3 pts). Three pts died before TB was recognized and 4 deaths occurred after treatment was started. All these pts developed renal failure. 26 pts were treated for 3-12 months (median, range: 7.8 +/- 2.9) and in 24 of them complete remission was achieved. In this group renal function remained stable in 16 pts and 6 pts developed terminal failure due to chronic rejection. Authors conclude: 1. TB remains a frequent complication in RAR but can be successfully treated when diagnosed early. 2. Extrapulmonary TB is common in RAR. 3. TB deteriorates one year patients (75%) and graft (49%) survivals.

[Level of erythropoietin and parathormone in blood plasma during acute rejection of kidney transplant]. / Stezenie erytropoetyny i parathormonu w osoczu krwi w okresie ostrego odrzucania przeszczepionej nerki.

The acute rejection of kidney transplant is accompanied by kidney ischaemia which in turn is a triggering factor for erythropoietin (EPO) synthesis. It was shown, on the other hand, that during the rejection an increase in blood serum parathormone (PTH) concentration takes place. The present study was aimed at answering the question what is the effect of acute rejection of kidney transplant on blood serum concentrations of EPO i PTH. Seventeen patients with kidney transplant participated in the study. In all the patients the investigations were carried out four times: 1--few days before rejection, 2--after ascertaining that kidney transplant is being rejected, 3--immediately after rejection, and 4--few days after completing the anti-rejection therapy. High doses of methylprednisolone were used as anti-rejection therapy. Control group consisted of 16 healthy persons. Acute rejection of kidney transplant was accompanied by a significant increase in blood serum concentrations of EPO and PTH. After methylprednisolone therapy, normalization of EPO and decrease in PTH concentration were observed in kidney transplant patients. Significant positive correlations were found between EPO and PTH concentrations in blood serum. It was concluded that acute rejection of kidney transplant is characterized by a significant increase in blood serum concentrations of EPO and PTH. Despite the existence of a significant positive correlation between blood serum concentrations of EPO and PTH in patients with kidney transplant, any pathogenic relation between the observed disturbances of secretion of the two hormones seems to be of little probability.