SEARCH · PubMed Health

Results for “Allograft function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 811 records · Page 45Linked to original sources

PubMed1981

Imbalances in peripheral blood T-cell subpopulations in renal transplant patients.

The distribution of T-lymphocyte subpopulations bearing receptors for the Fc portion of IgG (TG) or IgM (TM) was monitored in 22 renal allograft recipients treated with immunosuppressive therapy and in 10 uraemic patients on haemodialysis. No significant difference in the distribution of T cells and T-cell subsets was found between normal controls and haemodialysed patients. In transplanted patients, however, a significant reduction of the total T-cell percentage (P less than 0.005), of TM subset percentage (P less than 0.025) and absolute number (P less than 0.005) and of TG absolute number (P less than 0.05) was observed. Considering patients with allografts functioning for more than 1 year only, the reduction in TM cells in terms of percentage (P less than 0.0005) and absolute number (P less than 0.025) was significant, while TG subset levels did not change significantly. In patients transplanted less than 1 year previous to our study, total T cells and T-cell subsets were reduced significantly only as absolute numbers. During the 1st year we observed several increments of TM values towards normal levels, especially in the first 2 months after transplantation. During this period, TM subset levels sharply increased at acute rejection crisis and returned to previous values with rejection reversal. Our results suggest that the TM subset plays a prominent role in the mechanisms involved in the immunological response to allografts, and therefore repeated TM cell monitoring could be useful in the follow-up of renal transplant patients.

Graft Rejection↗

PubMed2000

Pregnancy outcome in renal transplant recipients.

OBJECTIVE: To correlate pregnancy outcome with complications in pregnancy and transplantation-to-pregnancy interval in renal transplant recipients in Croatia. METHOD: Data on 23 pregnancies after prepregnancy stabilization of blood pressure and normalization of graft function were retrospectively analyzed. RESULT: The mean interval between transplantation and conception was 3.1 years. Primary renal disease was chronic glomerulonephritis in 7, chronic pyelonephritis in 7 and agenesis of right kidney and stenosis of left renal artery in 1 patient. There were 10 term and 5 preterm deliveries, 6 induced and 2 spontaneous abortions. The mean gestational age was 38.1 weeks and the mean newborn birthweight was 3015 g. The prematurity rate was 21.7%. Patients with arterial hypertension in pregnancy, elevated serum creatinine level and bacteriuria, as well as those with conception occurring less than 2 years after transplantation, had a higher rate of therapeutic and spontaneous abortions, preterm deliveries and low birth weight infants. CONCLUSION: The interval between transplantation and conception, as well as allograft function during pregnancy, seem to be of great importance for successful obstetric outcome in renal transplant patients.

Adult↗

PubMed1992

HLA in human serum--quantitation of class I by enzyme immunoassay.

A solid-phase, enzyme-linked immunoassay was used to quantitate the soluble fraction of HLA-class I. The sera of 318 individuals were studied, as well as the urine of six individuals with normal renal function. The stability of blood concentrations of the soluble HLA was also evaluated. The data justify the following six conclusions. (1) All normal people have circulating HLA (mean = 357 ng/ml). (2) The population can be divided into one group of low secretors (mean = 162.4 +/- 65.2 ng/ml) and another group of high secretors (mean = 540.7 +/- 185.9 ng/ml) (P less than 0.01). (3) Blood levels in each individual are reasonably consistent over short (days) and long (years) periods of time. (4) The mean concentration of soluble HLA-class I in all renal failure patients was 590 ng/ml, significantly higher than normal (P = less than 0.05); it was highest in patients on peritoneal dialysis (mean = 683 ng/ml) in spite of substantial chronic loss in peritoneal dialysate. (5) Renal allograft recipients with stable allograft function also had mean values greater than normal at 554 ng/ml (P less than 0.05). (6) Soluble HLA-class I was not detected in the urine of individuals with normal renal function.

Enzymes, Immobilized↗

PubMed1994

COL4A5 gene deletion and production of post-transplant anti-alpha 3(IV) collagen alloantibodies in Alport syndrome.

Mutations in the COL4A5 gene encoding the alpha 5(IV) chain of type IV collagen have been implicated as the primary defect in X-linked Alport syndrome. Several kinds of mutations have been reported so far, spanning point mutations to complete gene deletions. About 5% of Alport patients, who undergo renal transplantation, develop anti-glomerular basement membrane (GBM) nephritis, causing loss of allograft function. In one such patient, COL4A5 gene deletion was recently identified. In the present study, the GBM constituent, targeted by the anti-GBM alloantibodies from the patient who had complete COL4A5 gene deletion was identified. Its identity was determined on the basis of circulating antibody binding to various GBM constituents, domains of bovine type IV collagen and recombinant NC1 domain of human type IV collagen. These results establish, for the first time, the absence of the alpha 5(IV) chain in Alport GBM and, in the same patient, the production of an alloantibody that is targeted to a different chain of type IV collagen, the alpha 3(IV) chain. These findings provide further support for the hypothesis that: (1) anti-alpha 3(IV) collagen alloantibodies mediate the allograft glomerulonephritis; and (2) COL4A5 gene mutations cause defective assembly of the alpha 3(IV) collagen alloantibodies mediate the allograft glomerulonephritis; and (2) COL4A5 gene mutations cause defective assembly of the alpha 3(IV) chain in Alport GBM, as reflected by the production of anti-alpha 3(IV) alloantibodies.

Basement Membrane↗

PubMed1998

Morbidity, functional status, and immunosuppressive therapy after heart transplantation: an analysis of the joint International Society for Heart and Lung Transplantation/United Network for Organ Sharing Thoracic Registry.

BACKGROUND: The morbidity and mortality studies on heart transplantation to date have come from single-center or multicenter studies that often have required collection of data over periods of time greater than a year. Data are now available from the International Society for Heart and Lung Transplantation/United Network for Organ Sharing (ISHLT/UNOS) Thoracic Registry from all centers in the United States performing heart transplantation, which allows analysis of morbidity and mortality rates on an annual basis. METHODS: All transplantation centers in the United States are now required to submit registration (at the time of transplantation) and 1-year follow-up clinical data on all heart transplant recipients to the ISHLT/UNOS Thoracic Registry. Data forms were submitted to the Registry regarding pretransplantation diagnoses, causes of death, rehospitalization, functional and work status at 1 year, immunosuppressive therapy, and the development of complications such as hypertension, hyperlipidemia, renal insufficiency, diabetes, and malignancy. This study is an analysis of this database for the period of April 1, 1994, through March 31, 1995, examining specifically morbidity, functional status, and other clinical events occurring during the period after the initial hospitalization and up to the first-year follow-up. The study cohort consisted of the 1853 patients who survived the initial hospitalization and for whom matching registration and 1-year follow-up forms were available. RESULTS: Rehospitalization during the first year after the initial admission was required by more than 40% of survivors, and at least one third of these required admission to the intensive care unit. Infection and rejection were the most common reasons for rehospitalization, each accounting for about 20%. Complications during the first year occurring in 10% or more of survivors included hypertension, diabetes, renal dysfunction, and hyperlipidemia. Less common complications included symptomatic bone disease, chronic liver disease, cataracts, stroke, and malignancy. Allograft function was excellent among survivors at 1 year, with a mean ejection fraction of 57.4% and less than 7% of patients requiring pacemaker therapy or having development of coronary artery disease. Eighty-three percent of survivors reported no functional limitations, but only 27% were working full-time. Eighty-nine percent of survivors were receiving prednisone at their 1-year follow-up. CONCLUSION: Clinical data are now available from the ISHLT/UNOS Thoracic Registry on the basis of the initial registration and 1-year follow-up of all patients undergoing heart transplantation in the United States. Analysis of these data from April 1, 1994, through March 31, 1995, demonstrates that the first year after the initial hospitalization for heart transplantation is a period of significant morbidity and frequent rehospitalization but excellent survival. In spite of a high level of functional capacity at 1-year follow-up, only a minority of patients return to work. The ISHLT/UNOS Thoracic Registry can now serve as a valid source of data for future analysis of trends in heart transplantation in the United States.

Activities of Daily Living↗

PubMed1983

Zinc metabolism and taste acuity in renal transplant recipients.

To determine the effect of renal transplantation on taste acuity and zinc metabolism, we tested 43 patients with functioning allografts for 2.5 to 96 months. They were tested for taste by the 3-drop stimulus technique. In 30 of them, we determined zinc levels in plasma, hair, and urine. Subnormal plasma and hair zinc, as well as hyperzincuria, was present in all of the 15 patients less than 12 months posttransplant. In contrast, 10 patients who were more than 12 months posttransplant had plasma zinc levels, hair zinc, and urinary zinc excretions in the normal range. Zinc concentrations in plasma and hair of 5 patients who were more than 12 months posttransplant with renal failure, were subnormal and were similar to those in hemodialysis patients. Similarly, taste detection and recognition thresholds for sodium chloride, sucrose, urea, and hydrochloric acid were normal only in patients more than 12 months posttransplant with normal renal function. Plasma zinc, hair zinc, and urinary zinc were not related to prednisone or azathioprine dosage. These results suggest that abnormalities of zinc and taste persist up to 12 months posttransplant and may be related to increased urinary zinc losses.

Adult↗

PubMed1990

Thyroid function in brain-dead donors.

Twenty brain-dead potential organ donors were studied prospectively to establish thyroid function. Two or three consecutive blood samples were obtained during brain death. Seven times a sample was available before brain death occurred. Free triiodothyronine (FT3) fell in most patients (80%). Very low (less than 1.6 pmol/l) and subnormal levels (between 2 and 3 pmol/l) were found in 65% and 15% of the patients, respectively. Serum reverse total triiodothyronine (rT3) was inversely correlated with FT3. Free thyroxine (FT4) was less often decreased (mean 14.68 +/- 1.42 pmol/l) and 35% of the patients had normal levels. Mean thyroid stimulating hormone (TSH) remained normal (0.71 +/- 0.15 microU/ml). The study of consecutive samples during brain death did not show a constant, progressive decrease in hormonal levels. There is no statistical difference between values observed before and after brain death. No correlation was found between FT3 levels and hemodynamic data or immediate allograft function. The pattern of thyroid function in these patients was typical of the sick euthyroid syndrome with a low T3 or low T3 and low T4 serum levels. This syndrome usually does not need to be treated. However, many experiment findings and some clinical data argue in favor of T3 therapy in donors and possibly in recipients. The dosage regimen must be adjusted to be effective without causing harm to multiorgan donors before it can be widely used. It remains to be proved that low FT3 serum indicates low intracellular FT3 and worse metabolic function in clinical conditions.

Adolescent↗

PubMed1996

Delayed development of obliterative bronchiolitis syndrome with OKT3 after unilateral lung transplantation. A plea for multicenter immunosuppressive trials.

There is no consensus regarding the optimal induction immunosuppression regimen after lung transplantation (LT). In addition to the potential benefit of a reduced incidence of early acute allograft rejection, cytolytic induction immunosuppression may impact on long-term allograft function. We retrospectively assessed our incidence of obliterative bronchiolitis syndrome (OBS) stages Ia and IIa in LT survivors given two different cytolytic induction immunosuppression regimens: (between March 1989 and October 1990) OKT3 (5 mg/d)x10 to 14 days (n=11) vs (between November 1990 and April 1993) Minnesota antilymphocyte globulin (MALG) (10 to 15 mg/kgdx5 to 7 days. Cyclosporine (CSA) (whole blood polyclonal assay=600 to 800 ng/mL), azathioprine (1 to 2 mg/kg/d), and maintenance prednisone (0.2 mg/kg/d) were similar. Surveillance spirometry was performed monthly, in accordance with accepted American Thoracic Society criteria. Fiberoptic bronchoscopy with transbronchial biopsies (TBBs) were performed for clinical indications. Surveillance TBBs were not performed during the era of this study. As defined by the ISHLT "Working Formulation for the Standardization of Nomenclature and for Clinical Staging of Chronic Dysfunction in Lung Allografts," latencies to development of OBS stages Ia and IIa were determined by Kaplan-Meir analysis. Stepwise regression (Cox proportional hazards model) was performed for the variables: cytolytic induction regimen, episodes cytomegalovirus (CMV) pneumonitis, episodes CMV infection, serologic CMV donor (+): recipient (-) mismatch, prior pregnancy, HLA (A,B,DR +/- DQ) mismatches, episodes greater than grade A1 acute cellular rejection (ACR). We found that the OKT3 cohort experienced longer latencies for OBS stages Ia and IIa. Latencies to OBS stages Ia for OKT3 ve MALG were 962 +/- 65 vs 354 +/- 85 days (X +/- SEM) respectively. Brookmeyer-Crowley 95% confidence intervals for median latencies were 744 to 1,180 vs 266 to 510 days for OKT3 vs MALG, respectively. The Cox model was significant only for the variable of the induction cytolytic immunosuppression regimen (p=0.0015). By physiologic criteria, a longer course of OKT3 appeared superior to the short-course MALG protocol in delaying chronic lung allograft dysfunction. These effects may be related either to inherent differences in the antilymphocyte preparations or, alternatively, the difference in duration of treatment between groups. Surveillance TBB and treatment of detected occult ACR may serve to negate the observed differences in latencies for OBS.

Acute Disease↗

PubMed2000

Acute renal allograft rejection with severe tubulitis (Banff 1997 grade IB).

Recent studies have correlated renal allograft function with individual histologic lesions defined in the Banff schema of kidney transplantation pathology. The clinical significance of severe tubulitis (Banff 97 grade t3) has not been specifically examined. We compared the clinical course and response to antirejection therapy in 36 patients with t3 tubulitis, and 137 patients with milder grades of tubulitis and varying grades of intimal arteritis. Rejection associated with severe tubulitis (grade t3) was associated with graft outcome that was worse than mild to moderate tubulitis (grades t1 or t2) and approached that seen in grade v1 intimal arteritis. Rejection characterized by grade v2 or v3 intimal arteritis had worse prognosis than v1 intimal arteritis and all grades of tubulitis without coexisting intimal arteritis. These observations validate the Banff 97 recommendation that the severity of both tubulitis and intimal arteritis needs to be graded in renal allograft biopsies. In addition, grade t3 tubulitis is identified as a lesion which should be a cause for clinical concern.

Acute Disease↗

PubMed2004

Sirolimus increases transforming growth factor-beta1 expression and potentiates chronic cyclosporine nephrotoxicity.

BACKGROUND: Sirolimus (SRL) is increasingly being used to decrease cyclosporine (CsA) exposure. SRL is not known to be nephrotoxic and has a mechanism of action distinct from CsA. We investigated the effect of combining CsA and SRL on renal structure and function and on transforming growth factor-beta1 (TGF-beta1) and extracellular matrix (ECM) proteins in a model of chronic CsA nephrotoxicity. METHODS: Rats treated with vehicle, SRL 0.3 mg/kg/day, CsA 5 or 10 mg/kg/day, or CsA5+SRL were sacrificed at 7 or 28 days. Physiologic and histologic changes were studied in addition to TGF-beta1 mRNA and protein expressions, and mRNA expression of plasminogen activator inhibitor-1 (PAI-1) and ECM proteins biglycan and types I and IV collagen. RESULTS: While SRL alone did not alter renal function and structure, it potentiated the nephrotoxic actions of CsA when used in combination with low-dose CsA5 and resulted in significant changes similar to high-dose CsA10. In addition, SRL alone increased TGF-beta1 by 44% to 49% (P < 0.05 vs. VH). When used in combination with low-dose CsA5, SRL potentiated TGF-beta1 mRNA and protein by 121% and 176%, respectively (P < 0.05 vs. VH and CsA5), to levels achieved with high-dose CsA10. The expression of the ECM proteins followed that of TGF-beta1; a similar effect was observed with PAI-1, suggesting a decrease in ECM degradation. CONCLUSION: Because SRL augments nephrotoxicity, caution should be exercised when it is used in combination with CsA. More studies are needed to determine the long-term clinical impact of SRL on nephrotoxicity and allograft function.

Animals↗

PubMed1999

Partial liquid ventilation for acute allograft dysfunction after canine lung transplantation.

BACKGROUND: This study was designed to investigate the efficacy of partial liquid ventilation (PLV) on acute allograft dysfunction after lung transplantation. METHODS: The canine left lung allotransplantation model was used, with the graft preserved in 4 degrees C low-potassium dextran glucose solution for 18 hours. The control group (n = 6) had conventional mechanical ventilation, and the PLV group (n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated. After the evaluation, myeloperoxidase activity of the graft tissue was assayed. RESULTS: All dogs survived for 360 minutes. In the PLV group, PaO2, shunt fraction, and alveolar to arterial gradient for O2 were significantly better than those in the control group after 120, 180, and 120 minutes, respectively (p < 0.05). After 240 minutes, peak airway pressure became significantly lower than that in the control group (p < 0.05). The PaO2 at 360 minutes was 102 +/- 55 mm Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/- 5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group was lower than that in the control group. CONCLUSIONS: The study shows that PLV alleviated acute allograft dysfunction after lung transplantation.

Animals↗

PubMed1995

Detection of circulating adhesion molecules ICAM-1, VCAM-1 and E-selectin in Wegener's granulomatosis, systemic lupus erythematosus and chronic renal failure.

The adhesion molecules ICAM-1, VCAM-1 and E-Selectin are regulated by proinflammatory cytokines and play an important role in the binding and activation of leukocytes in inflammatory diseases. This study measured the serum concentrations of circulating adhesion molecules (cICAM-1, cVCAM-1, cE-Selectin) by sandwich ELISA in systemic vasculitis with renal involvement (Wegener's granulomatosis WG, n = 25; systemic lupus erythematosus SLE, n = 50) in comparison to chronic glomerulonephritis (n = 10), stable renal allograft function and end-stage renal disease (CAPD/hemodialysis, each n = 10). Both cICAM-1 and cVCAM-1 levels, but not cE-Selectin, were significantly increased (p < 0.001) in active WG compared to healthy controls. cICAM-1, not cVCAM-1 differed significantly between active and inactive WG. Only cVCAM-1 was significantly elevated in active/inactive SLE (p < 0.01). WG with rapidly progressive glomerulonephritis had significantly raised levels of cICAM-1 and cVCAM-1, but not cE-Selectin, compared to controls (p < 0.005). In lupus nephritis only cVCAM-1 was significantly elevated (p < 0.01). cICAM-1 and cVCAM-1 levels were significantly raised in WG patients, that were hemodialysed and in patients with hemodialysis because of different reasons when compared to controls. However, cVCAM-1 but not cICAM-1 was significantly higher in WG with HD than without HD. Patients with chronic glomerulonephritis, renal allografts or CAPD also had significantly raised cVCAM-1 concentrations. These data suggest, that levels of circulating adhesion molecules might reflect different pathophysiologic processes in systemic vasculitides and endothelial/immune activation in non-inflammatory renal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

[Coronary ischemia after kidney transplantation in patients over 60 years of age].

Many elderly patients (aged over 60) are waiting for renal allograft but are considered a risk population for myocardial infarction or sudden cardiac death. Between 1987 and January 1st, 1990, 22 elderly patients (16 men and 6 women; mean age 63.4 +/- 0.7 years; range 60-69 years) underwent cadaveric kidney transplantation. Twenty patients had been on haemodialysis for 4.8 +/- 1 years (range: 1-16.3), one had been on peritoneal dialysis for 5 years and one had developed chronic rejection of a previous cadaveric allograft. Among these 22 patients, 6 (27 percent) developed antibodies directed against the random lymphocyte panel and one had a second transplant. Cardiovascular risk factors were systematically estimated, including medical history, cervical arterial Doppler, echocardiography and stress thallium testing (STT). Coronary angiography was performed if there was evidence of myocardial ischaemia. STT did not show any coronary disease in 16 patients and was not maximal (less than 60 percent of maximal theoretical stress) in 4 patients. In 2 patients, STT showed myocardial ischaemia: one, with a history of angina, underwent coronary angiography and angioplasty; the other had silent ischaemia and refused coronary angiography. Two patients died of myocardial infarction. One of them was the patient with silent ischaemia and positive STT test. The patient with angioplasty had a successful transplantation 20 months later, without any cardiovascular complication. After 9 to 32 months of follow-up, 19 patients have functioning allografts (mean serum creatinine level 151 +/- 6 mumol/l). One patient lost his kidney from urinary fistula. Eight patients (36 percent) developed acute rejection and all responded to intravenous corticosteroids. No immunological transplant loss was observed. After 18 months, the graft actuarial survival rate was 85 percent. We conclude that elderly patients free of clinical or silent myocardial ischaemia are good transplant recipients. The cardiovascular risk could be prevented by using STT during the pretransplant screening. If the STT is not maximal or shows coronary ischaemia, coronary angiography is mandatory.

Actuarial Analysis↗

PubMedDate not supplied

Donor stem cell infusion after non-myeloablative conditioning for tolerance induction to HLA mismatched adult living-donor liver graft.

BACKGROUND AND AIM OF THE STUDY: The induction of transplantation tolerance, defined as the survival of a functioning allograft in the absence of continuing immunosuppressive therapy, would be a major advance. Clinical and experimental data have shown that transplantation tolerance could be induced by pre-transplant myeloconditioning and infusion of donor hematopoietic cells. We investigated the feasibility and safety of a protocol to induce tolerance to HLA mismatched living-donor liver graft by pre-transplant non-myeloablative conditioning followed by donor stem cells (SC) infusion, in patients with advanced liver cancers. PATIENTS AND METHODS: Two patients with intrahepatic cancers who did not fulfill criteria for cadaver liver transplantation were included in the study. Preparative regimen consisted in cyclophosphamide and anti-thymocyte globulin, followed by infusion of purified donor CD34(+) stem cells. Living-donor liver transplantation (LDLT) using the liver right lobe was performed after hematological reconstitution, respectively 40 and 55 days after donor stem cell infusion. Immunosuppressive therapies were discontinued when liver graft function returned to normal. RESULTS: The procedure could be completed in the two patients. No severe toxicity of the preparative regimen was observed. Neither patient presented graft versus host reaction after donor stem cell infusion. A transient macrochimerism was observed in the first case, while no chimerism could be detected in the second. Immunosuppression was discontinued, respectively 90 and 28 days, after liver transplantation, without subsequent rejection episode. In the two cases, liver function remained normal for the study period. In both patients, the period of immune reconstitution was prolonged, as illustrated by persisting low CD4(+) cell counts. Mixed lymphocyte cultures, performed after immunosuppression withdrawal, demonstrated donor specific hyporesponsiveness in the first case, but in a context of global hyporeactivity in the two patients. The first patient died from tumor recurrence 370 days after liver transplantation. The second patient is alive, 270 days after liver transplantation, but with a suspicion of tumor relapse as indicated by the reappearance of tumor marker in blood. CONCLUSION: In the two cases, acceptance of HLA mismatched living-donor liver graft was obtained after non-myeloablative conditioning and donor stem cell infusion. Improving the rate of immune reconstitution appears as a priority to reduce the risk of tumor recurrence in such patients.

Antilymphocyte Serum↗

PubMedDate not supplied

Breath pentane is a marker of acute cardiac allograft rejection.

Breath pentane, a product of lipid peroxidation that serves as a noninvasive marker of tissue inflammation and injury, was measured as a potential marker of acute cardiac allograft rejection. We prospectively studied 37 consecutive outpatients with stable cardiac allograft function. Breath pentane levels were measured with gas chromatography, and the results were compared the findings from routine surveillance endomyocardial biopsy. Data analysis was performed with the receiver operating characteristic curve and negative and positive predictive values. Statistical methods include analysis of variance and two-sample t-tests. Histopathologic findings consistent with rejection were present on endomyocardial biopsy in 52% of the subjects. Pentane levels in healthy control subjects did not differ from those of patients undergoing transplantation without rejection. Average pentane excretion for subjects with mild rejection (4.2 +/- 2.8 nmol/L) or moderate rejection (5.4 +/- 2.6 nmol/L) exceeded that seen in subjects who did not have rejection (1.7 +/- 0.9 nmol/L) (p < 0.02). A pentane cutoff value of 2.43 nmol/L, chosen to give the highest negative predictive value, had a sensitivity of 0.80. We concluded that breath pentane excretion is a sensitive noninvasive screening test for the detection of cardiac allograft rejection.

Adult↗

PubMed2001

Improving tolerability of immunosuppressive regimens.

CNIs and corticosteroids are associated with adverse effects that can diminish quality of life and detrimentally affect long-term allograft and patient survival. Nephrotoxicity is the major side effect of CNI therapy. A search has been ongoing for improved immunosuppressive regimens that will provide adequate protection against acute allograft rejection, while decreasing the nephrotoxic and other effects associated with CNIs. This paper reviewed the immunosuppressive agent sirolimus as a potential new option in transplantation, focusing on its mechanism of action and clinical efficacy as well as potential antiproliferative and antineoplastic properties. The findings and lessons learned from key clinical studies in which sirolimus was used to augment or replace CNIs and/or corticosteroids were highlighted, and the importance of clinical pharmacokinetics and therapeutic drug monitoring in these regimens were discussed. Preliminary studies of combination therapy with sirolimus and tacrolimus in solid organ transplantation indicate that sirolimus/tacrolimus combination therapy may provide strong protection against acute rejection and diminish the nephrotoxicity associated with CNI-based therapy. Other studies suggest that sirolimus can be used as base immunosuppressive therapy, thereby completely avoiding the nephrotoxicity associated with CNI-based therapies, while continuing to provide powerful protection against rejection. With patients surviving longer with functional allografts, quality of life is becoming an increasing important clinical endpoint in transplantation. The studies reviewed here suggest that sirolimus might be used to improve quality of life significantly without increasing the risk of allograft rejection or shortening patient survival.

Adrenal Cortex Hormones↗

PubMed1993

Avascular necrosis of bone following renal transplantation.

This study was undertaken to determine the incidence and clinical features of avascular necrosis of bone in 69 transplant recipients all of whom had a functioning allograft for at least 12 months. An attempt was also made to identify any potential predisposing factors. The patients were assessed by an orthopaedic surgeon. The diagnosis of avascular necrosis was made on the basis of radiographs and isotope bone scans. Fourteen patients (20.2%) developed avascular necrosis with a mean onset of 19 months post-transplantation. The hip joint was most commonly affected. The isotope bone scan was the most sensitive diagnostic tool; abnormalities were detected before the onset of symptoms in 4 patients. Avascular necrosis was more common in Indian transplant recipients and was also associated with: (i) cadaver transplants; (ii) more frequent bouts of acute rejection (P < 0.05); and (iii) a greater incidence of other steroid-associated side-effects (P < 0.05). Alcohol consumption and radiological evidence of osteoporosis were more prevalent in the avascular necrosis group (42.8% v. 29.0% and 28.5% v. 7.2% respectively). Avascular necrosis did not correlate with age, sex, renal function at 1 year or severe secondary hyperparathyroidism. This study suggests that corticosteroid therapy plays an important role in the pathogenesis of avascular necrosis. Excessive alcohol consumption and osteoporosis also appear to be risk factors.

Adult↗

PubMed1984

Serial monitoring of T-cell subset ratios with monoclonal antibodies in steroid- and antithymocyte globulin-treated patients with renal allotransplants.

Sequential changes in T-cell subsets or their ratios were employed to predict severity of rejection crises and to identify those patients who might require future antirejection therapy. Forty-two percent of the transplant recipients had a pretransplant OKT4:8 ratio in the range of 1.3 +/- 0.5. By contrast, only 11% had a OKT4:8 ratio of 2.9 or greater. Examination of the entire study group demonstrated that the mean OKT4:8 ratios fell (P less than 0.01) in the first week following the transplant procedure. All patients had at least one episode of acute rejection. There was a marked increase (P less than 0.05) in the OKT4:8 ratio between the first week value and the value immediately preceding (within 3 days) the start of the rejection episode which was 2.64 +/- 0.27. The mean OKT4:8 ratio in the 15 patients leaving the hospital with a functioning transplant was 1.18 +/- 0.35. Three months post-transplant, the OKT4:8 ratio was 1.98 +/- 0.39 in the 12 patients with functioning allografts. This value was not different from those patients' initial pretransplant values. Clinically, the rejection episodes could be divided into two groups based on their response to intravenous methylprednisolone therapy. The first group (n = 9) had milder rejection crises which responded rapidly to administration of one course of methylprednisolone. The second group of patients (n = 9) were also treated initially with methylprednisolone, to which they did not respond, and subsequently received antithymocyte globulin in an attempt to control their ongoing rejection crises. Following the transplant procedure, the OKT4:8 ratio decreased in patients who were destined to have steroid-responsive rejection episodes (P less than 0.01). The OKT4:8 ratio however, failed to fall in those who required ATG for control of their transplant rejection episodes. The onset of rejection episodes was associated with an increase in OKT4:8 ratio in both groups. Following steroid administration, two patterns of OKT4:8 cell responses were observed. Those in whom renal function improved demonstrated a decline in OKT4:8 ratio from 2.4 +/- 0.4 to 1.4 +/- 0.4 (P less than 0.05). However, no change occurred in the OKT4:8 ratios with steroid therapy (2.6 to 2.4 +/- 0.33, P greater than 0.05) in individuals in whom the serum creatinine concentration failed to decline. The patients who failed to respond to steroid therapy were treated with antithymocyte globulin (ATG).(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗