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PubMed2006

Is brain natriuretic peptide clinically useful after cardiac transplantation?

The clinical use of brain natriuretic peptide (BNP) in patients after cardiac transplantation remains to be defined. Over the last decade, a series of small studies have been performed to determine any potential use of this assay in the assessment of allograft function and prognosis. From the available evidence, it appears that a low BNP level in transplant recipients has a high negative predictive value for death. Why patients with higher BNP levels should be disadvantaged appears to be multifactorial. BNP titer may be influenced by severe rejection episodes and diastolic dysfunction, and possibly intracardiac pressure derangement. Although the concept of using a simple blood test to assess these patients sounds very attractive, further work is needed to define the exact role of this assay. Presently, it cannot be confirmed whether BNP can replace any of the current methods of assessing allograft performance and prognosis after transplantation.

Echocardiography↗

PubMed1997

Cardiac operations in solid-organ transplant recipients.

BACKGROUND: The success of solid organ transplantation has resulted in an increasing pool of patients that subsequently require cardiac surgical procedures, yet the perioperative management of these patients is not well documented. We report a single institutional experience with the management techniques used and the outcomes of the cardiac surgical procedures performed in solid organ transplant recipients with functioning allografts. METHODS: Sixty-four patients underwent 66 cardiac procedures broken down as follows: coronary artery bypass grafting, 30; single or combined valve replacement-repair, 24; combined coronary artery bypass grafting and valve repair, 3; aortic repair, 4; pericardiectomy, 3; transmyocardial laser revascularization, 1; and native cardiectomy, 1. Patients consisted of 40 kidney, 16 liver, 5 heart, 2 lung, and 1 liver and kidney transplant recipients. The mean interval from the time of transplantation to the cardiac operation was 53 months (range, 1 day to 220 months). Forty-six male and 18 female patients in New York Heart Association functional class III or IV had a mean age of 53 years (range, 19 to 77 years); 50% (32/64) were diabetic, and 97% (62/64) were hypertensive. Immunosuppressive therapy, cardiopulmonary bypass, and medical management were similar in all patients. RESULTS: There were two (3%) perioperative deaths, one of which was caused by an arrhythmia-induced cardiac arrest, and there were seven (11%) late deaths from non-cardiac-related causes. Major complications included 12 infections (19%), ten mediastinal reexplorations for the control of bleeding (16%), and nine others (15%). Sixteen of the 64 (25%) transplant recipients had chronic renal failure (serum creatinine levels, > 3 mg/dL), including 13 of 40 (33%) kidney transplant patients. Acute renal failure developed postoperatively in 7 (54%) of these 13 patients; the grafts failed permanently in 3 (23%). Three patients (5%), 2 kidney transplant recipients and 1 lung transplant recipient, experienced transient acute rejection. Fifty of the 55 surviving patients are alive and well (New York Heart Association functional class I or II) without recurrent cardiac disease at a mean follow-up period of 22 months. CONCLUSIONS: Although the short-term morbidity was significant, the low mortality and low incidence of permanent graft dysfunction indicate that solid organ transplant recipients can safely and effectively undergo subsequent cardiac surgical procedures.

Adult↗

PubMed2005

Dissecting aortic aneurysm in a renal transplant recipient.

There have been few reports of surgical repair of acute aortic dissection in renal transplant recipients. The incidence, operative risk, or perioperative management of aortic dissection with functioning allografts remains unknown. Herein we report our experience in successful treatment of type I dissecting aortic aneurysm in a renal transplant patient. A 35-year-old man was admitted to our hospital complaining of severe chest pain. He had undergone a living renal transplant from his mother for chronic renal failure caused by immunoglobulin A nephropathy 11 years prior to admission. An immunosuppressive regimen had been maintained continuously. Preoperative chest computed tomography demonstrated a thoracic dissecting aortic aneurysm (DeBakey classification type I). An emergent graft replacement for the ascending aorta was placed under circulatory arrest. Although continuous hemodiafiltration was required postoperatively because of deteriorated renal function, he recovered uneventfully and his renal function returned to preoperative values. He was discharged on postoperative day 26 without any complications.

Adult↗

PubMed2003

Kidney and liver transplantation in human immunodeficiency virus-infected patients: a pilot safety and efficacy study.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have historically been excluded from consideration for transplantation out of concern for the effects of immunosuppression on the progression of HIV disease. Improvements in HIV-related morbidity and mortality with the use of highly active antiretroviral therapy (HAART) have prompted a reevaluation of transplantation as a treatment option for HIV-infected patients with end-stage kidney and liver disease. METHODS: Eligible patients met standard transplant criteria. They had undetectable plasma HIV-1 RNA levels (viral load) for 3 months (kidney) or were predicted to achieve viral load suppression posttransplantation if unable to tolerate HAART (liver); a CD4+ T-cell count of more than 200 cells/microL (kidney) or more than 100 cells/microL (liver) for 6 months; and no history of opportunistic infections and neoplasm. Standard immunosuppression included prednisone, mycophenolate mofetil (CellCept, Roche Pharmaceuticals, Basel, Switzerland), and cyclosporine (Neoral, Novartis, East Hanover, NJ). RESULTS: Fourteen patients received transplants (10 kidney transplants, mean follow-up 480 days; four liver transplants, mean follow-up 380 days). All of the kidney transplant recipients (100%) are alive and with functioning grafts, and three of four liver transplant patients (75%) are alive and well with functioning grafts (all liver transplant patients with normal liver function tests). The one death occurred 445 days posttransplantation in a liver recipient coinfected with hepatitis C virus, who died as the result of its rapid reoccurrence. Rejection occurred in 5 of 10 kidney transplant recipients but did not occur in any of the four liver transplant recipients. HIV viral loads have remained undetectable in all patients maintained with HAART. CD4 counts have remained stable in patients not treated for rejection. Patients receiving protease inhibitors require 25% of the dose of cyclosporine compared with patients receiving nonnucleoside reverse transcriptase inhibitors. CONCLUSIONS: There has been no evidence of significant HIV progression and no adverse effect of HIV on allograft function. Rejection is a concern in kidney transplant recipients, as is the possible poor outcome in hepatitis C virus-coinfected liver transplant recipients. Preliminary data are encouraging and indicate that transplantation should be a treatment option for individuals with well-controlled HIV disease.

Adult↗

PubMed2006

Renal allograft injury is associated with urinary tract infection caused by Escherichia coli bearing adherence factors.

Urinary tract infections are the most common infection in renal transplant patients and Escherichia coli (E. coli) is the most common clinical isolate. Although acute allograft injury (AAI) secondary to urinary tract infection (UTI) has been reported, the incidence of AAI associated with UTI, the virulence factors express by uropathic E. coli and whether virulence factors are associated with renal allograft outcome have not been described. We collected E. coli from our renal transplant patients with UTI, determined O:H serotypes, P and Dr fimbriae expression and the clinical presentation and allograft function during the UTI and post-UTI period. Pyelonephritis occurred in 40% of our patients, 82% of which had AAI (>20% increase in SCr). Sixty-two percent of E. coli isolates that expressed P fimbriae were associated with AAI, whereas only 29% that did not express P fimbriae had AAI (p = 0.03). The pattern of P fimbriae and O serotypes differed from reported isolates, as the P fimbriae PapG class II and the O25 serotype were the most common. Dr adhesin was expressed on 7 isolates, including 2 of 3 with urosepsis. We propose a unique pattern of uropathogenic serotypes and adherence factors contribute to acute allograft injury in renal transplant patients with UTI.

Adult↗

PubMed1982

Role of blood transfusions on the induction of antibodies against recognition sites on T lymphocytes in renal transplant patients.

We have tested sera from 23 renal allograft recipients to study the effects of blood transfusions on the induction of antibodies directed against recognition sites on T lymphocytes. The results demonstrate that antibodies capable of inhibiting responses in MLC could be induced by blood transfusion. This inhibition in MLC is observed by treatment of responder lymphocytes with serum plus rabbit complement and is mediated by IgG antibodies. Also, the inhibitory effect is specific for certain responder cells and is not mediated by antibodies against common surface antigens of either the responder or the stimulator lymphocytes. The antibodies inhibiting proliferative responses in MLC against antigens present on the kidney donor were demonstrable in renal transplant recipients with functional allografts, but not in patients who had rejected the graft. The data suggest that antibodies directed against recognition sites on T lymphocytes could be induced by blood transfusions and these antibodies may be associated with prolonged graft survival.

Autoantibodies↗

PubMed1986

Prolongation of renal allograft survival in antilymphocyte-serum-treated dogs by postoperative injection of density-gradient-fractionated donor bone marrow.

Posttransplant injection of fractionated donor bone marrow cells results in the prolonged survival of mouse skin allografts. In this investigation, we extended the study to the use of donor bone marrow fractionated by density-gradient centrifugation in a larger animal model, canine renal transplantation. Renal allografts were placed in outbred, histoincompatible dogs treated daily with rabbit or horse antilymphocyte serum (ALS) from days -6 to +7 relative to kidney transplantation on day 0. Fresh, unfractionated donor bone marrow (BM) or a bone marrow fraction (BM Fr3) produced by centrifugation in a discontinuous Percoll density gradient was intravenously infused into recipients on days +13 or +14. Alternatively, frozen/thawed (F/Th) BM or BM Fr3 was infused after storage at -80 degrees C for two weeks. BM Fr3 and unfractionated BM significantly (P less than 0.005) prolonged for median allograft function time (MFT) beyond the controls treated only with ALS (46 and 35 days vs. 18 days). The longer MFT with BM Fr3 was achieved with 20-40% of the unfractionated BM cell dose. In addition, BM Fr3-treated dogs exhibited a slower rate of loss of kidney function. F/Th BM was as effective as fresh BM in prolonging graft survival. A reduced mixed lymphocyte response to donor and third-party cells and markedly reduced responsiveness to Con A, PHA, and pokeweed mitogens at 30-45 days posttransplant suggested that animals were nonspecifically immunosuppressed during this period. By 60 days posttransplant, in two dogs treated with BM Fr3, the MLR to third-party cells, but not to donor cells, and the responsiveness to mitogens had returned to pre-ALS treatment values. Thus, treatment with ALS combined with fresh or F/Th BM that has been fractionated is an effective method for the prolongation of kidney allografts in dogs. The development of specific, long-term immunosuppression induced by fractionated bone marrow and success with F/Th BM in this canine renal allograft model suggests that application to human transplantation may be effective with fresh or F/Th BM fractions obtained from living-related or cadaveric donors.

Animals↗

PubMed1994

Nephrotoxic effects of primary immunosuppression with FK-506 and cyclosporine regimens after liver transplantation.

OBJECTIVE: We conducted a treatment trial to determine the relative toxicity of FK-506 and cyclosporine A (CSA) in liver transplant recipients. DESIGN: Between October 1990 and October 1991, 37 patients were enrolled in an open-labeled, randomized study of two immunosuppressive regimens after liver transplantation. MATERIAL AND METHODS: Of the 23 men and 14 women, 20 received FK-506 plus prednisone, and 17 received CSA plus prednisone and azathioprine. Renal function was assessed before and after transplantation (day 1, month 1, month 4, and month 12) by measurements of serum creatinine (SCr) and glomerular filtration rate (GFR) as determined by urinary iothalamate or creatinine clearance (or both). FK-506 trough plasma levels (enzyme immunoassay) were to be maintained between 0.2 and 5.0 ng/mL, and CSA trough blood levels (whole blood high-performance liquid chromatography) were to be maintained between 250 and 400 ng/mL. Severe nephrotoxicity was defined as sudden decreases in urine output to less than 10 mL/h or rapid increases in SCr (more than 0.5 mg/dL daily) that necessitated withdrawal of study medication for more than 48 hours. Mean patient age and values for SCr and GFR were comparable between the two groups at entry. RESULTS: Both study groups demonstrated a similar deterioration in renal function during a 12-month follow-up, although patients who received FK-506 had a significantly (P < 0.05) lower GFR when measured at 12 months than did patients treated with CSA (45 +/- 4 versus 64 +/- 6 mL/min per body surface area). Mild nephrotoxicity that responded to decreased drug doses was noted in 9 CSA-treated patients (53%) and 10 FK-506-treated patients (50%). Severe nephrotoxicity that necessitated drug withdrawal occurred in only four patients, all of whom were in the FK-506 group. These severe nephrotoxic reactions to FK-506 occurred early after transplantation, often during intravenous administration of the drug, and were not associated with poor liver allograft function or drug levels outside the therapeutic range. CONCLUSION: Both FK-506 and CSA are significantly nephrotoxic in liver transplant recipients. In this trial, however, we observed an early development of severe nephrotoxic reactions only in some patients who received FK-506.

Acute Kidney Injury↗

PubMed1996

Need for reduction of cyclosporin dosage in renal transplant patients with hypertriglyceridemia but not hypercholesterolemia.

Currently there is a paucity of data regarding the influence of high serum triglyceride levels on cyclosporin A (CyA) levels and dosing. We therefore undertook a retrospective study to determine the relationship of serum lipid levels to CyA levels and CyA dosages. Renal transplant patients at a 0.5-to-3-year post-transplant stage, with a stable CyA dosage, who were not on medications that affect CyA metabolism or renal function, were entered into the study. The CyA dosage was adjusted by clinicians to maintain whole blood. 12-h CyA trough levels between 200 and 250 ng/ml (monoclonal TDX method, which measures the parent compound). Forty-four patients qualified for the study. The data clearly indicated that high cholesterol levels (> 300 mg/dl and with normal triglyceride levels) did not influence the CyA levels or the dosages. Conversely, high triglyceride levels ( > 500 mg/dl) significantly reduced the amount of CyA required. A decreased clearance of CyA in the presence of hypertriglyceridemia led to high CyA levels in some patients. Reducing the CyA dosage to achieve levels between 200 and 250 ng/ml improved renal allograft function and decreased other side effects attributed to CyA toxicity. These studies indicate that high triglyceride levels, but not high cholesterol levels, increase CyA levels, which can lead to CyA toxicity.

Adolescent↗

PubMed2006

Age-dependent chronic rejection after experimental heart transplantation.

BACKGROUND: The progressive decline of allograft function is predominantly a consequence of chronic rejection, but the etiology of this process is not fully understood. To evaluate the influence of age we performed heart transplantation in an experimental model of chronic rejection using inbred rats of different age. METHODS: Lewis rats served as donors and F344 rats were used as recipients. Young rats were 4 weeks of age, whereas adult rats were 4 months of age. Transplanted animals were grouped as follows: Group I, old to old; Group II, old to young; Group III, young to old; and Group IV, young to young. Intra-abdominal heterotopic heart transplantation was performed. Thereafter, functional evaluation was performed by daily palpation and surface electrocardiogram (ECG) to calculate the functional heart rejection index (fHRI). One month after transplantation the hearts were explanted and examined pathohistologically. RESULTS: Functional deterioration was noted in all groups, but all hearts were still beating when explanted. Young recipients and young donors showed significantly better results. Transplantation of young recipients led to a better fHRI (p < 0.001) and to a less critical chronic graft vasculopathy, especially when there was a young heart transplanted (p = 0.03). Furthermore, whenever a young donor heart was used, there was a better graft performance and less severe chronic rejection (p = 0.02). CONCLUSIONS: Experimental cardiac transplantation of young hearts leads to a better graft performance as well as to a lower incidence of a severe chronic graft disease. Thus, older donor age may adversely influence long-term performance of cardiac allografts.

Age Factors↗

PubMed2006

The impact of daily sodium intake on posttransplant hypertension in kidney allograft recipients.

INTRODUCTION: Posttransplant hypertension is a well-known risk factor for long-term allograft failure and mortality in kidney recipients. Although dietary sodium restriction is a widely recommended nonpharmacological measure for control of blood pressure (BP), no detailed investigation has been conducted regarding the impact of dietary sodium restriction on this condition. METHODS: Thirty-two patients on antihypertensive treatment completed the study. They were randomly divided into two groups: controls (group 1) versus strict sodium diet (group 2; 80 to 100 mmol sodium daily). After randomization, 24-hour urine for sodium measurement, BP, and allograft functions were recorded at baseline and after 3 months. BP treatment was reevaluated at each visit throughout the study. RESULTS: At baseline, there was no significant difference in age, sex, serum creatinine, systolic and diastolic BP, antihypertensive drugs, or 24-hour urinary sodium levels between the groups. After 3 months, daily urinary sodium excretion (from 190+/-75 to 106+/-48 mEq/d, P<.0001), systolic BP (from 146+/-21 to 116+/-11 mm Hg), and diastolic BP (from 89+/-8 to 72+/-10 mm Hg) had significantly decreased in group 2, while no significant changes were observed in group 1. CONCLUSION: Low sodium intake in combination with antihypertensive treatment appears to efficiently control BP in kidney allograft recipients with hypertension. Twenty-four-hour urinary sodium excretion should be checked regularly in these patients as a useful marker to indicate whether the patient complies with low sodium intake.

Adult↗

PubMed2005

Molecular evaluation of BK polyomavirus nephropathy.

Understanding at a molecular level, the immunologic response of polyomavirus nephropathy (PVN), a critical cause of kidney graft loss, could lead to new targets for treatment and diagnosis. We undertook a transcriptional evaluation of kidney allograft biopsies from recipients with PVN or acute rejection (AR), as well as from recipients with stable allograft function (SF). In both the PVN and AR groups, Banff histologic scores and immunohistochemical analysis of inflammatory infiltrates were similar. Despite their different etiologies, the transcriptional profiles of PVN and AR were remarkably similar. However, transcription of genes previously linked to AR including CD8 (65.9 +/- 18.8) and related molecules IFN-gamma(55.1 +/- 17.0), CXCR3 (49.9 +/- 12.8) and perforin (153.8 +/- 50.4) were significantly higher in PVN compared to AR (30.9 +/- 2.0, 14.0 +/- 7.3, 12.1 +/- 7.3 and 15.6 +/- 3.8-fold, respectively; p < 0.01). Importantly, transcription of molecules associated with graft fibrosis including matrix collagens, TGFbeta, MMP2 and 9, as well as markers of epithelial-mesenchymal transformation (EMT) were significantly higher in PVN than AR. Thus, renal allografts with PVN transcribe proinflammatory genes equal in character and larger in magnitude to that seen during acute cellular rejection. BK infection creates a transcriptional microenvironment that promotes graft fibrosis. These findings provide new insights into the intrarenal inflammation of BK infection that promotes graft loss.

Adult↗

PubMed1995

Effect of 1-28 alpha-h atrial natriuretic peptide on acute renal failure in cadaveric renal transplantation.

The efficacy and safety of (1-28) alpha-human ANP in preventing acute tubular necrosis (ATN) in cadaveric renal transplantation was tested by comparing ANP infusion with a maximal hydration (MH) regimen which we previously reported as effective in lowering the incidence of ATN (1, 2). Since the production of endogenous ANP increases with volume overloading (3), we hypothesized that increased endogenous ANP production may contribute to the beneficial effects of MH in renal transplant recipients. We thus conducted an open randomized study comparing the effect on early renal allograft function of MH (control group) versus moderate hydration plus ANP infusion (ANP group). Forty patients were blindly paired in two groups of 20 according to the duration of cold ischemia time (mean +/- 2 h). The demographic characteristics of donors and recipients were similar. Using a Swan-Ganz catheter, hemodynamic parameters were monitored for 4 h after transplantation. The group receiving ANP and moderate hydration was perfused to a mean pulmonary arterial pressure (PAP) of < or = 20 mmHg. The PAP in patients receiving MH was driven to > or = 25 mmHg. In the ANP group, a bolus of 100 micrograms of ANP was infused into the graft's renal artery at the time of unclamping, followed by 24 h of continuous intravenous infusion at 0.03 microgram/kg/min. Thereafter, the patients received ANP at a rate of 0.01 microgram/kg/min until the serum creatinine reached < 2 mg/dl. As a consequence of the hydration regimen, the PAP at unclamping was lower in the ANP group than in the control group; 20 +/- 3 and 26 +/- 4 mmHg, respectively (p < 0.05). The ANP plasma levels were significantly higher during the first 3 d in the ANP group (p < 0.001). The median recovery rate of renal function was similar in both groups. No patients in the ANP group experienced ATN while 4 patients (20%) in the control group did (p = 0.125). The need for hemodialysis was markedly reduced in the ANP group compared to the control group (1 ANP-treated patient required dialysis once whereas 5 patients from the control group underwent dialysis a total of 26 times; p = 0.068). ANP administration was well-tolerated and no hypotensive episodes were reported. This preliminary study suggests that ANP infusion is at least as effective as maximal hydration in preventing ATN and represents an efficient alternative for transplantation centers which do not use maximal hydration as a standard regimen in managing kidney allograft recipients.

Acute Kidney Injury↗

PubMed1989

Combined cold storage-perfusion preservation with a new synthetic perfusate.

Based upon encouraging experimental results, we began employing a synthetic perfusate for cadaver kidney preservation. The new perfusate contains hydroxyethyl starch (HES) as the sole colloid for oncotic support; 107 cadaver kidneys were preserved and transplanted (93 primary, 14 nonprimary) using the HES solution and were compared with our previous experience of 180 cadaver kidneys (161 primary, 19 nonprimary) preserved and transplanted utilizing an albumin-based perfusate. All cadaver kidneys were locally harvested and preserved by machine perfusion. Donor and preservation characteristics in the HES (n = 61) and the albumin (n = 101) groups were comparable, with a mean preservation time of 30.9 hr. Cold storage in combination with hypothermic pulsatile perfusion (HPP) preservation was performed more often in the HES group (68.2% vs. 31.1%, P less than 0.001). Recipient characteristics were also comparable, and all received quadruple immunosuppressive therapy with sequential/Minnesota antilymphoblast globulin/(MALG)/cyclosporine. After primary transplantation, the incidence of immediate function (82.6% vs. 89.2%), preservation-related dialysis (14.9% vs. 8.6%), and primary nonfunction (2.5% vs. 0) were similar between the 2 groups, with trends favoring the latter HES data. One-month serum creatinine (1.8 vs. 1.7 mg/dl) and graft survival (95% vs. 97.8%) also were comparable. Similar trends were present in the retransplant group, including a significantly lower 1-month serum creatinine in the HES group (2.2 vs. 1.5 mg/dl; P less than 0.05). The preservation-related dialysis rate did not differ between primary and nonprimary transplants. Primary nonfunction has not occurred with our new perfusate. Combined cold-storage-HPP preservation with HES perfusate offers advantages over standard retrieval technology and provides excellent immediate allograft function.

Albumins↗

PubMed1994

Surgical treatment of diabetes mellitus with pancreas transplantation.

OBJECTIVE: The authors compared results and morbidity in insulin-dependent diabetes mellitus (IDDM) patients undergoing preemptive pancreas transplantation (PTx) either before dialysis or before the need for a kidney transplant with IDDM patients undergoing conventional combined pancreas-kidney transplantation (PKT) after the initiation of dialysis therapy. SUMMARY BACKGROUND DATA: Combined PKT has become accepted generally as the best treatment option in carefully selected IDDM patients who either are dependent on dialysis or for whom dialysis is imminent. With improving results, the timing of PKT relative to the degree of nephropathy is evolving. However, it is not well established that the advantages of preemptive PTx can be achieved without incurring a detrimental effect on graft function or survival. METHODS: Over a 4-year study period, data on the following 3 recipient groups were collected prospectively and analyzed retrospectively: 1) 38 IDDM patients undergoing combined PKT while on dialysis (PKT:D); 2) 44 IDDM patients undergoing preemptive PKT before dialysis (PKT:ND); and 3) 20 IDDM patients undergoing solitary PTx. All patients underwent whole organ PTx with bladder drainage and were treated with quadruple immunosuppression. RESULTS: Actuarial 1-year patient survival is 100%, 98%, and 93%, respectively. One-year actuarial PTx survival (insulin-independence) is 92%, 95%, and 78%, respectively. The incidence of rejection, infection, operative complications, readmissions, and total hospital days was similar in the three groups. Long-term renal and pancreas allograft function and quality of life were similarly comparable. Rehabilitation potential favored the solitary PTx and PKT:ND groups. CONCLUSIONS: Preemptive PKT or solitary PTx performed earlier in the course of diabetes is associated with good results, facilitated rehabilitation, and may prevent further diabetic complications.

Actuarial Analysis↗

PubMed2000

A 12-day course of FK506 allows long-term acceptance of semi-identical liver allograft in inbred miniature swine.

BACKGROUND: Spontaneous tolerance to liver allograft has been reported previously in outbred pig models, but the lack of genetic background did not allow to analyze the impact of the major histocompatibility complex (MHC) on tolerance induction. A model of semi-identical liver allograft was therefore developed in inbred miniature swine in order to mimic the clinical situation of living related liver transplant (parent into infant) and to study a protocol for inducing tolerance to liver allograft. METHODS: SLAdd (class Id/d, class IId/d) pigs received orthotopic liver allograft from heterozygous SLAcd (class Ic/d, class IIc/d) miniature swine. Eight animals did not receive immunosuppression. Fourteen SLAdd animals had a 12-day course of FK506 and were divided in two subgroups. In subgroup FK-1, six pigs received a daily intramuscular injection of FK506 at 0.1-0.4 mg/kg, in order to reach daily trough levels between 7 and 20 ng/ml; in subgroup FK-2, eight additional animals received two daily injections of FK506 at 0.05 mg/kg regardless of the daily trough levels. Graft survival, liver biological tests, histology, cellular and humoral immune responses, as well as detection of microchimerism were assessed in all groups. RESULTS: All untreated animals rejected their allograft and died within 28.1 +/- 9.5 days. These rejector animals developed a significant anti-donor cellular and humoral immune response. No peripheral or lymphoid tissue microchimerism was detected in this group. In contrast, long-term survival was obtained in five FK-treated animals (112, 154, 406, 413, and 440 days), whereas several pigs died with a normal allograft function from either overimmunosuppression or intercurrent causes. All FK-treated pigs developed a specific anti-donor unresponsiveness in both cell mediated lymphocytotoxicity and mixed lymphocyte reaction and did not develop anti-donor alloantibodies. The study of the anti-donor immune response by mixed lymphocyte reaction, during the first postoperative week, demonstrated a specific anti-donor unresponsiveness in the peripheral blood from the first posttransplant day. Although microchimerism was detectable in the peripheral blood for several postoperative weeks (maximum 10 weeks) in FK-treated animals, donor cells or DNA were not detected during the long-term follow-up in peripheral blood or lymphoid tissues. CONCLUSIONS: Spontaneous tolerance to semi-identical orthotopic liver allograft did not occur, whereas a 12-day course of FK506 allowed long-term graft acceptance. All FK-treated animals developed in vitro signs of specific immune unresponsiveness and transient peripheral microchimerism. The specific anti-donor cellular unresponsiveness occurred on the first postoperative day after surgery and was of long-term duration. The study of the early immunological events in this model could be of major importance regarding clinical living related liver transplantation.

Animals↗

PubMed1999

Changes in plasma cystatin C after renal transplantation and acute rejection in adults.

BACKGROUND: Cystatin C has recently been proposed as an alternative marker of glomerular filtration rate. The diagnostic value of plasma cystatin C for the longitudinal assessment of kidney function after renal transplantation, however, has not been addressed. METHODS: Renal function was evaluated in 30 adults receiving renal transplants (46 +/- 9 years, mean +/- SD) and in 56 healthy controls (38 +/- 10 years) using cystatin C. Plasma cystatin C was determined daily starting the day of surgery and for 3 weeks after surgery by an immunonephelometric assay. RESULTS: Plasma concentration significantly decreased during the first week (-44% vs -29% for creatinine). Plasma cystatin C correlated with plasma creatinine (r = 0.741; P <0.0001) and the reciprocal of the creatinine clearance estimated by the Cockcroft-Gault formula (r = 0.882; P <0.001). In all three cases of acute renal impairment, the increase in plasma cystatin C values was more prominent than that of creatinine. CONCLUSIONS: Plasma cystatin C is an alternative and accurate marker of allograft function in adult transplant patients. Increased sensitivity compared with creatinine for the detection of acute reduction in glomerular filtration rate allows in some cases a more rapid diagnosis of acute rejection or treatment nephrotoxicity.

Adult↗

PubMed2004

Hypothalamic-pituitary-gonadal axis function after successful kidney transplantation in men and women.

BACKGROUND: Renal transplantation (RT) is the most common solid organ transplant procedure. Several studies have reported on gonadal function in male and female RT recipients with controversial results. METHODS: Forty consecutive patients (20 male, 20 female) with a fully functioning allograft (serum creatinine 0.8-1.3 mg/dl) for at least 15 months after RT were included in the study. Their ages ranged from 23 to 44 years (median 38) and their post-RT follow-up lasted 15-86 months (median 23). FSH, LH, prolactin, 17-beta-estradiol, testosterone, androstenedione and dehydroepiandrostrone were determined in all patients and compared with a group of 80 healthy subjects. Pelvic ultrasonography was performed in all participants. RESULTS: Testosterone was below the normal range in 70% of male patients and within the lowest third in the remainder; a lack of LH increase indicated an inhibition of the reproductive axis. Male testosterone values were negatively influenced by calcineurine inhibitors treatment (P < 0.005), but positively influenced by a better graft function (P < 0.0001). Testicular and prostate volumes were reduced with respect to controls, with the latter related to circulating testosterone levels. Ten of the women (50%) had menstrual cycle disorders after RT, three being affected by transient, and three by persistent, amenorrhea. Another two patients had had transient polymenorrhea. In four women (20%), a premature ovarian failure was diagnosed. No relationship was found between female reproductive function and age, graft function or duration of the post-transplant period. Prolactin was lower in patients on calcineurin inhibitors (P < 0.01). CONCLUSIONS: Abnormalities of the reproductive system were frequent after successful RT in both genders.

Adult↗