Assessment of Arterial Stiffness and Body Composition in Stable Liver Transplant Recipients.

INTRODUCTION: Arterial stiffness and central arterial pressure are important factors in the diagnosis of cardiovascular diseases. The tendency of patients after liver transplantation to reach above-normal BMI values promotes the development of arterial stiffness and lipid disorders. METHODS: The study was conducted on a group of 42 patients after liver transplantation at the Nephrology and Transplantology Outpatient Clinic, Medical University of Warsaw, the Infant Jesus Teaching Hospital, Warsaw 0.5-17 years after surgery. The body composition test was carried out with the Tanita Mc780 device, and the central pressure and pulse wave velocity (PWV) with the Schiller BR-102 PLUS PWA device, using the oscillometric method on the brachial artery. Medical documentation was analyzed and the laboratory parameters values routinely determined during follow-up visits were assessed. RESULTS: There was a statistically significant correlation between central diastolic pressure and BMI (r = 0.46, P < .05), and a lack of correlation between patients' age and PWV value (r = 0.06, P < .05), which indicated the age of patients in this study was not associated the stiffness of their arteries. PWV level in patients after liver transplantation whose BMI value is within the normal range was 7.62 m/s, while overweight and obese patients had PVW values of 8.58 m/s (P < .05). CONCLUSIONS: In conclusion, our data indicate that 1. the level of central arterial pressure increases with the development of stiffness in the arteries; 2. patients after liver transplantation tend to grow in terms of body weight and body fat content over time after surgery; and 3. the level of bilirubin in the blood is significantly increased among patients with fat content above the upper limit of the normal range.

Evaluation of Quality of Life and Severity of Depression, Anxiety, and Stress in Patients After Kidney Transplantation.

INTRODUCTION: End-stage renal disease (ESRD) has a significant impact on a patient's quality of life (QoL). The optimal treatment for ESRD is kidney transplantation (KTx), which aims to extend and improve QoL. The aim of the study was to assess a QoL in KTx recipients. METHODS: Our study included 118 post-KTx patients. The research tool employed for assessment was a questionnaire consisting of standardized instruments: the 36-item Short Form (SF-36); the Kidney Disease Quality of Life (KDQOL) instrument; and the Depression, Anxiety, and Stress (DASS) scale. In addition, patients were provided with information on their own weight and height, followed by calculation of body mass index. RESULTS: Correlation analysis showed a statistically significant influence of age on general health (R = 0.191, P = .039), physical functioning (R = -0.295, P = .001), and general physical health (R = -0.275, P = .003) assessment. The mean severity of depression, anxiety, and stress among subjects changed over time since KTx. For the post-KTx periods studied (ie, <1 year, 1-10 years, and >10 years), the following changes were observed: for depression, 14.0 vs 11.2 vs 13.1, respectively; for anxiety, 15.6 vs 9.8 vs 14.0, respectively; and for stress, 22.0 vs 13.5 vs 16.8, respectively. CONCLUSION: In this study we found that: 1. QoL in patients after KTx showed a good level for everyday life functioning, and 2. general health assessment, physical functioning, pain, sleep quality, occupational status, vitality, social activity, staff support, and quality of care were major factors associated with QoL after KTx.

24-hour Arterial Stiffness Monitoring in Kidney Transplant Recipients in the Early Postoperative Period.

INTRODUCTION: Laboratory tests and anthropometric assessments are essential in determining the risk for cardiovascular disease in patients after kidney transplantation (KTx). Patients with hypertension and elevated pulse wave velocity (PWV) are at a higher risk of cardiovascular mortality. The purpose of this study was to determine the role of blood pressure, arterial stiffness, and selected laboratory and anthropometric parameters in estimating the risk of cardiovascular disease in KTx patients. METHODS: A total of 17 KTx patients of the Clinical Department of Gastroenterological Surgery and Transplantation at Central Clinical Hospital of Ministry of the Interior and Administration (MSWiA Hospital) in Warsaw, Poland, were enrolled in this study between 3 to 7 days after undergoing kidney transplantation. Medical records of these patients were reviewed for the selected laboratory parameters. The patients' blood pressure and PWV values were monitored for 24 hours and their body mass index (BMI) values were calculated (BMI ≥ 25.0 is considered overweight). RESULTS: Hemoglobin concentration showed a negative correlation with PWV (r = -0.6), whereas red blood cell distribution width (RDW) showed a positive correlation with the PWV value (r = 0.29). There was a significant correlation (r = 0.21) between overweight measured via BMI and the PWV values. For results of kidney function blood tests, the estimated glomerular filtration rate (GFR) and creatinine levels showed no significant correlation with 24-hour PWV values (GFR r = -0.03; creatinine r = 0.03). CONCLUSIONS: The following were shown to be important indices of cardiovascular risk in the evaluated population of KTx patients: age, BMI, blood pressure, PWV, hemoglobin levels, red blood cells, and RDW%.

Comparative Analysis of Arterial Stiffness and Body Composition in Early and Late Periods After Kidney Transplantation.

INTRODUCTION: Diseases of the cardiovascular system are the most common cause of death in patients after kidney transplantation (KTx). Pulse wave velocity (PWV) measurement is a simple, noninvasive, and increasingly popular method to assess arterial stiffness, and thus to assess cardiovascular risk. The aim of the study was to compare arterial stiffness and body composition in patients after KTx in the early and late postoperative periods. METHODS: This research was carried out from January to November 2017 at two locations: (1) Department and Clinic of General and Transplant Surgery and (2) Nephrology and Transplantology Clinic Medical University of Warsaw, the Infant Jesus Teaching Hospital, Warsaw, Poland. The study group consisted of 30 patients in the early postoperative period (2-7 postoperative days) and 151 patients in the late period (6 months to 27 years) after KTx. A single blood pressure measurement, PWV, was performed using a Schiller BR-102 plus PWV. Body composition analysis was performed using a Tanita MC-780 device. RESULTS: The average PWV for patients in the early period after KTx was 8.02 ± 2.21 m/s and in the late period 8.09 ± 1.68 m/s. Positive correlations were found between adipose tissue in the abdominal cavity (R = 0.444, P = .033) and PWV value. There was no correlation between the values of PWV and time after transplantation (R = 0.034, P = .777). Upon analyzing patients after transplantation and taking into account the type of dialysis therapy, lower systolic blood pressure (142 ± 21 mm Hg vs 156 ± 24 mm Hg) and diastolic blood pressure (84 ± 13 mm Hg vs 98 ± 11 mm Hg) values were observed in patients treated with hemodialysis compared with those treated with peritoneal dialysis. CONCLUSION: Using PWV measurement, we found that arterial stiffness levels were similar for early and late periods after transplantation.

Long-term Outcomes in Simultaneous Pancreas-Kidney Transplant Recipients: Single-center Experience From Poland.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with end-stage renal disease (ESRD) due to type 1 diabetes mellitus (DM1). Since the 1980s, pancreas transplantation has become the most effective strategy to restore normoglycemia in patients with DM1. The aim of this study was to present long-term outcomes data for SPKT. METHODS: We performed a retrospective analysis of 73 SPKT recipients followed in our outpatient center who underwent transplantation between 1988 and 2015. RESULTS: A total of 50.7% of the patients were male. At the time of surgery, patients' mean age was 37.38 ± 7.44 years. Patients were diagnosed with DM1 at an average of 25 ± 6.08 years before SPKT. For 21.9% of patients, the transplant was done preemptively. Most (91.8%) had enteric drainage. All patients received induction of immunosuppression (either polyclonal immunoglobulins anti-thymocyte globulin or thymoglobulin [64.4%] or monoclonal globulins daclizumab or basiliximab [35.6%]). Patient survival at 1, 5, 10, 15 years was 99%, 97%, 89%, and 75%; kidney survival was 99%, 96%, 84%, and 67%; and pancreas survival was 95%, 92%, 84%, and 64%, respectively. There was a notable tendency toward increased creatinine level (from 1.18 at 1 year to 1.78 at 15 years) and decreased hemoglobin level (from 13.84 at 1 year to 12.65 at 15 years). CONCLUSION: Diabetic patients with ESRD have a poor prognosis without transplantation. SPKT provides marked prolongation of the patient's life and freedom from insulin injections. Enteric drainage is currently the surgical technique of choice. SPKT should remain as the treatment of choice in this patient population.

Analysis of Hospitalizations in Simultaneous Pancreas-Kidney Transplant Recipients: A Single-center Experience in Poland.

BACKGROUND: End-stage renal disease due to type 1 diabetes mellitus appears to be a regular indication for simultaneous pancreas and kidney transplantation (SPKT). Although transplantation improves a patient's health condition, it does not mean that all complications will be eliminated. METHODS: We performed a retrospective analysis of 73 patients who underwent SPKT and follow-up between 1988 and 2015 at our institute. The number, duration, and reasons for hospitalization at 1, 5, 10, and 15 years after SPKT were analyzed. RESULTS: The average number of hospitalizations at 1, 5, 10, 15 years after SPKT were 1.66, 0.39, 0.36, and 0.33, respectively. The main reason for hospitalization over the 15-year period was infections, at 32.4% (SD, 6.8%). Within the first year after SPKT, 6.8% of hospital admissions were caused by cytomegalovirus (CMV) infection. Over time, the percentage of hospitalizations for cardiovascular complications increased from 0.6% at 1 year to 29% at 12-15 years. Incidence of hospitalization due to cardiovascular complications correlated with a longer period of dialysis and a diagnosis of ischemic heart disease before transplant (r = 0.56, P = .004; r = 0.54, P < .0001, respectively). At 12-15 years after transplantation, 18.2% of hospitalizations were caused by secondary complications of diabetes. CONCLUSION: The most common reason for hospitalization after SPKT is infectious complications. In the first year posttransplant, there is a high percentage of CMV infections. Hospitalization associated with cardiovascular complications was found to be most common in the latter follow-up period and showed a correlation with longer dialysis period.

Results of a 6-month, multicenter, open-label, prospective study concerning efficacy and safety of mycophenolate sodium in de novo kidney transplant recipients.

BACKGROUND: Mycophenolate sodium (MPS) was designed to reduce the gastrointestinal side effects of mycophenolic acid. The aim of our study was to determine the safety and efficacy of MPS in de novo renal transplant recipients. PATIENTS AND METHODS: This 6-month, multicenter, open-label, single-arm, prospective study was carried out in three centers in Poland. Thirty patients were recruited. Immunosuppressive regimen contained of MPS and cyclosporine (CsA) with or without steroids. RESULTS: The 6-month graft and patient survival was 100%. The incidence of suspected acute rejection episodes (ARE) was 5/30 (16.7%), including biopsy-proven ARE in 2 (6.7%) cases. ARE reversed after therapy. At month 6, the mean serum creatinine level was 1.4 mg/dL, and the mean creatinine clearance (according to the Cockroft-Gault formula) was >70 mL/min. The most frequent adverse effects included diarrhea, delayed graft function, anemia, and lymphocele. Among infections, most common were infections of urinary tract, cytomegalovirus infections, and infections of respiratory tract. Only three patients (10.0%) terminated the study prematurely, including two who discontinuated because of an adverse event, and one because of noncompliance. CONCLUSIONS: An immunosuppressive regimen, including MPS and CsA, with or without steroids, provided effective antirejecton prophylaxis and was well tolerated.

The influence of immuosuppressive therapy on the development of CD4+CD25+ T cells after renal transplantation.

A growing number of studies suggest that CD4(+)CD25(+) T regulatory (Treg) cells play a significant role to downregulate the immune response to alloantigens. In this study, we investigated the possible influence of immunosuppressive therapy, including cyclosporine (CsA) or rapamycin (sirolimus), on the level of CD4(+)CD25(+), CD4(+)CD25(+)FOXP3(+), and CD4(+)CD25(+)CTLA-4(+) T cells in the peripheral blood of renal allograft recipients. The study was performed on renal allograft recipients who displayed uneventful stable courses (RAR-S; n = 15) versus biopsy-proven chronic rejection (RAR-CH; n = 12). The patients were divided based on the immunosuppressive protocol: group 1 (prednisone+CsA+Aza) and group II (prednisone+sirolimus). The control group consisted of 10 healthy blood donors. We examined the expression of CD4, CD25, CTLA-4, and Foxp3 in peripheral blood T cells. Flow cytometry was performed with a FACSCalibur (BD Biosciences) instrument with data analyzed using Cell Quest software. The percentage of CD4(+)CD25(+)Foxp3(+) T cells in rapamycin (sirolimus) treated patients did not differ from that observed in healthy individuals, but was significantly higher compared with CsA-treated patients. CsA therapy resulted in a reduction in the percentage of CD4(+)CD25(+)CTLA-4(+) and CD4(+)CD25(+)Foxp3(+) regulatory T cells after renal transplantation in both groups (RAR-S and RAR-CH) compared with patients treated with rapamycin or to healthy donors. The type of immunosuppressive therapy (with or without calcineurin inhibitors) may have an important role in tolerance induction and graft function.

Early hyperglycemia after allogenic kidney transplantation.

BACKGROUND: The aim of the study was to establish the impact of early hyperglycemia on development of diabetes mellitus (DM) in patients after kidney transplantation and to evaluate possible risk factors for post-transplantation DM. We also sought to assess the impact of early hyperglycemia and DM on the renal graft function in the long term (3 year follow-up). MATERIAL/METHODS: 1200 transplant patients from one center, were followed up for 3 years. The rate of chronic rejection, CMV infection, hypertension and dyslipidemia were analyzed. The renal allograft function was examined and pancreatic function peptide C concentration was determined. RESULTS: Early hyperglycemia (within first week after transplantation) was detected in 76 out of 1131 patients (6.7%). In this group within three years observation posttransplantation diabetes mellitus (PTDM) was observed in 57 patients (relative risk 75%). In comparison, transplanted patients with good early glucose control had 8% risk of developing DM within the same period after transplantation. In addition early hyperglycemia predisposed to worse renal graft function and higher proteinuria. The incidence of hypertension as well as the rate of CMV infection was comparable in the DM group and in non-DM patients. PTDM patients had higher values of serum peptide C concentration (p < 0.05), additionally hyperinsulinemia was observed. The kidney allograft function assessed as serum creatinine level was significantly impaired after 3 years in PTDM group compared to non-DM patients. CONCLUSIONS: Our date show the importance of normal glucose concentration in early period after transplantation as predictive factor for diabetes mellitus development and worsening of transplanted organs.

Insulin resistance in kidney allograft recipients treated with calcineurin inhibitors.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is one of the main complications observed in patients after organ transplantation. The incidence of PTDM in transplant recipients is about 9 times higher than in general population. The reported incidence of PTDM varied throughout the years due to different diagnostic criteria of diabetes mellitus. Nowadays the rate of PTDM amounts to 3-19%. MATERIALS/METHODS: 1270 patients after kidney transplantation, who remained under medical care in the outpatient service at the Transplantation Institute in Warsaw, were taken into consideration. The investigated group comprised 207 patients. 133 of them developed DM that constitutes the incidence of PTDM at 10.5%. RESULTS: In the present study several risk factors that are important for PTDM development were observed: male gender, HLA A3, family history of DM, increased body weight (rather than BMI only), tacrolimus--based immunosuppressive regimen, early hyperglycemia. Patients with PTDM developed hypertension more frequently, had higher serum triglycerides levels in the period before the onset of diabetes. The rate of acute rejection episodes in this group was higher compared with the nondiabetic transplant controls. The PTDM group presented with worse graft function and higher levels of proteinuria in 1-year observation. Tacrolimus--based therapy led to higher peripheral insulin resistance and hyperinsulinemia in comparison to cyclosporine--based regimen. CONCLUSIONS: The proper management of the above described risk factors and the right treatment of PTDM may considerably influence life expectancy rate and quality of life in transplanted patients.

Economic evaluation of sirolimus-based immunosuppressive regimens in kidney graft recipients.

INTRODUCTION: The aim of this study was an economic evaluation of three sirolimus (SRL)-based regimens in the first 2 years after renal transplantation. MATERIALS AND METHODS: The three SRL-based immunosuppressive regimens in renal transplant patients between June 2000 and September 2002 were: (1) SRL + steroids + cyclosporine (CsA) permanently; (2) SRL + steroids + tacrolimus (Tac); and (3) SRL + steroids + CsA, with CsA discontinuation at 3 months posttransplant. Ten patients were included in each group in an intent-to-treat analysis. Cost was calculated according to the hospital price list and recast into euros (EUR) with a 5% discount rate. RESULTS: The number of patients free of an acute rejection episode during 2 years posttransplant were 6, 8, and 5, with 2-year graft and patient survivals of 9, 10, and 9 for regimens 1, 2, and 3, respectively. As differences in clinical effects were not statistically significant, cost analysis was appropriate instead of cost-effectiveness analysis. The mean cost of the 2-year treatment was 15,759 EUR; 25,593 EUR; and 21,197 EUR per patient for regimens 1, 2, and 3, respectively. Sensitivity analysis for the main variables confirmed that the results were not dependent on changes in costs. CONCLUSIONS: Regimen 1 was the most economical immunosuppressive therapy during the 2 years after kidney transplantation. Studies on a larger group of longer observation would be more useful for clinical analysis.

Use of drotrecogin alpha (recombinant human activated protein C, rhAPC) in the treatment of severe sepsis induced by graft pancreatitis after simultaneous pancreas and kidney transplantation: a case report.

We present our experience with recombinant human activated protein C (rhAPC) to treat a 40-year-old preemptive simultaneous pancreas-kidney transplant (spktx) recipient who developed septic shock due to graft pancreatitis. We diagnosed intra-abdominal septic complications with septicemia induced by multiple pathogens and cardiopulmonary insufficiency. Until the 59th posttransplant day, 21 peritoneal lavages were performed to treat peritonitis and intra-abdominal abscesses. On the 53rd day when septic shock was diagnosed, rhAPC was administered, after which the patient improved, vasoconstrictive agents were reduced, and respiratory insufficiency resolved. The Physiologic and Operative Severity Score for enumeration of Mortality and Morbidity (POSSUM) scale showed a decrease in predicted mortality from 93% to 17% on day 7 after rhAPC initiation. The patient was discharged at 128 days after spktx with good function of both grafts. Administration of rhAPC limited systemic inflammatory response syndrome (SIRS) and may be considered when faced with the dilemma of stopping immunosuppression to save a recipient's life but at the cost of rejection of a functioning graft.

Beta 3 integrin expression on T cells from renal allograft recipients.

Recent studies emphasize the paramount significance of beta 3 integrin in cell adhesion and homing, which may be particularly relevant in cancer progression and metastasis. In contrast, the presence and potential role of beta 3 on human T cells is practically unknown. We show that T cells can express significant amounts of alpha-beta 3 integrin (CD41/CD61), and the expression of alpha(v)-beta 3 (CD51/CD61) remains very low. T-cell beta 3 integrin is probably transferred by platelet-derived microparticles.

Biliary liver cirrhosis secondary to cystic fibrosis: a rare indication for liver transplantation.

As more effective therapies prolong the lives of patients with cystic fibrosis, there are now more patients in this population diagnosed with liver diseases. Secondary biliary cirrhosis is not a rare complication of mucoviscidosis. It is diagnosed in 20% of patients with mucoviscidosis; in 2% it is accompanied by portal hypertension. On average patients with portal hypertension and its complications are 12 years old. Liver transplantation is an accepted method of treatment for children with cystic fibrosis and portal hypertension. It eliminates the cause of the portal hypertension, decreases life-threatening medical conditions, and improves their nutritional status and quality of life. Despite immunosuppressive treatment they do not seem to beat increased risk of upper respiratory tract infections. On the contrary improved respiratory function and status are generally observed. We present our first case of orthotopic liver transplantation performed in a 29-year-old man with cystic fibrosis. The donor was a 42-year-old woman who died of a ruptured cerebral aneurysm. The surgery was performed in September 2004. The patient received immunosuppression based on steroids, basiliximab, tacrolimus, and mycophenolic acid due to renal insufficiency. Antibiotic (meropenem) and antiviral prophylaxis (gancyclovir) were used. A 6-month period of observation confirmed the clinical data from the pediatric population-a good prognosis with improved nutritional status, respiratory function, and quality of life.

Comparison of 1-year patient and graft survival rates between preemptive and dialysed simultaneous pancreas and kidney transplant recipients.

It is well known that the main decrease in graft and recipient survival rates is observed during the first 12 months after transplantation. Improving results during this period seems to be crucial for the late outcome. The aim of this study was to compare 1-year survival rates of dialyzed and preemptive pancreas and renal graft recipients and their graft function. From November 1999 to January 2005, 42 whole simultaneous pancreas and kidney transplantations (spktx) were stratified into group I (n = 13): recipients who received a preemptive pancreas and kidney transplant versus group II (n = 29): previously dialyzed spktx recipients. The mean time of dialysis for group II was 39 +/- 16.5 months. We assessed 1-year cumulative survival rates for recipients and grafts for each group. The 1-year cumulative survival rate for preemptive graft recipients was significantly higher than that for dialyzed patients before spktx (100% vs 69%; P = .05). For groups I and II 1-year cumulative graft survival rates for kidney grafts were 100% and 89%, respectively, and for pancreatic grafts 84% and 65.5%, respectively. There was a significant improvement in the 1-year survival rate of preemptive spktx recipients compared with patients dialyzed before spktx. However, 1-year pancreas and kidney graft function did not differ significantly between the groups.

Performance of the MDRD, CKD-EPI, and Cockcroft-Gault Formulas in Relation to Nutritional Status in Stable Renal Transplant Recipients.

BACKGROUND: Monitoring of the function of the implanted kidney in renal transplant recipients (RTRs) is one of the superior elements of adequate therapeutic actions. The aim of this study was to assess the conventional and unconventional factors affecting the estimated glomerular filtration rate (eGFR) with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault (C-G) formulas among the RTRs. METHODS: The study included 144 RTRs (mean age 52 years). Clinical and laboratory data were analyzed; eGFR was calculated with MDRD, CKD-EPI, and C-G formulas. We compared the results with MDRD as a reference calculating the percentage of reclassifications of chronic kidney disease (CKD) stages. Nutritional status was assessed with a body composition analyzer, Tanita BC 418. RESULTS: Multivariable linear regression analysis with MDRD and CKD-EPI formula as a dependent variable retained the following independent predictors: hemoglobin (Hb) (B = .365; P = .000), and red blood cell distribution width (RDW) (B = -.191; P = .024). Analysis of variance showed the existence of statistically significant differences (all P for trend <.05) between the CKD-EPI, MDRD, and C-G equations within the total scope of eGFR results (51.2 ± 21.2 vs 47.5 ± 18.7 vs 55.6 ± 20.6, respectively) as well as in quartiles of eGFR. CONCLUSIONS: Our data indicate that (1) with a value of eGFR >60 mL/min/1.73 m(2), the MDRD formula shows values that are on average 11% lower than in the CKD-EPI and C-G formulas; (2) with a value of eGFR <60 mL/min/1.73 m(2), the MDRD and CKD-EPI formulas do not show statistically significant differences.

Diminished integrin expression on granulocytes from renal allograft recipients.

Integrin (beta 2 subunit of the LEU-CAM family, CD18) expression on peripheral blood and urinary granulocytes was studied in renal allograft recipients. Circulating granulocyte CD18 expression was normal except for patients with CMV infection. In contrast, the majority of patients with urinary tract infection had low numbers of CD18+ cells collected from urine, and the same abnormality could also be observed in approx. 50% of non-infected recipients. These disturbances were associated with transplantation, as no such deficits were seen in the infected non-transplant patients or patients with glomerular diseases on immunosuppression. Short culture of granulocytes with immunosuppressants did not diminish integrin expression. Deficient granulocyte integrin expression, especially in urinary tract, may be associated with increased susceptibility to infection in renal transplant recipients, although immunosuppression alone could not be incriminated as a sole factor responsible for this deficit.

Value of urine sediment phenotyping in renal allograft recipients.

Leukocytes excreted in urine of renal transplant recipients were phenotyped and the results were correlated with their post-transplant course. The majority of excreted cells were monocytes, a phenomenon that bore no relationship to clinical status of the patients. T-lymphocyturia was associated with both acute rejection and urinary tract infection. In contrast, B cells were excreted in low numbers.

Role of adhesion molecules in chronic allograft rejection.

Endothelial adhesion molecules play an important role in T cell recruitment to an allograft site. Therefore, it could be expected that their blocking may be beneficial for allograft survival. In this report, we show that T cells from patients with chronic rejection have an up-regulated ability to adhere to inflamed endothelium in vitro. Furthermore, this enhanced T cell: endothelial interaction could be blocked by anti-VCAM and anti-E-selectin monoclonal antibodies.

Lymphocyte interactions with extracellular matrix proteins and endothelium in renal allograft recipients.

Recent data indicate that extracellular matrix (ECM) proteins can provide costimulatory signals during the process of T cell activation. Those proteins accumulate in situ during allograft rejection; therefore, it may be expected that local ECM: T cell interactions may be relevant in the immunopathology of rejection. T cell adhesion from allograft of recipients with stable renal function (RAR-S) and patients with biopsy-proven chronic rejection (RAR-CH) to ECM proteins (collagen type IV, fibronectin, elastin) was measured. Furthermore, T cell: endothelial interactions in vitro were studied. Adhesion of PHA-activated T cells from both groups of allograft recipients to fibronectin, collagen type IV and elastin was significantly lower than in healthy blood donors. Moreover, similar pattern of activity was observed when T cell attachment to resting and activated endothelium was studied. There were no significant differences in the number of circulating CD45RO and CD4 positive T cells. We observed a higher (although not significantly) adhesion of the T cells to resting human dermal microvascular endothelial cells (HMEC) in the chronic stages of rejection, which can suggest that the immunosuppressive protocol used in the treatment of chronic rejection is insufficient to control immunopathologic phenomena occurring in that process. Therefore, it may be argued that too low immunosuppression can be one of the factors responsible for the development of this complication.