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PubMed1989

Plasma alpha-2 glycomicroglobulin in monitoring allograft function and in predicting rejection episodes in kidney transplantation (preliminary results).

This study reports clinical evaluation of a newly-discovered protein, alpha-2 glycomicroglobulin (A2GM), for monitoring renal function and in the identification and characterization of rejection episodes in kidney transplant recipients. Using a sensitive enzyme-linked immunosorbent assay technique, plasma levels of A2GM were measured prior to, and following, transplantation. There was an initial decrease in plasma A2GM in all patients following transplantation, but the decrease was significantly (P less than 0.023) greater in patients with initial good function than in those with initial poor function associated with initial acute tubular necrosis or rejection. The decrease in A2GM did not correlate with subsequent graft function and viability. Levels of A2GM were found to be sensitive to changes in renal function and correlated well with creatinine. A sustained rise in A2GM was indicative of rejection. A2GM predicted rejection episodes 48-72 h before any significant rise in plasma creatinine in five of seven rejections studied. It is concluded that plasma A2GM levels may be clinically useful in assessing allograft function and in predicting rejection crises in kidney transplant recipients.

Biomarkers↗
PubMed1988

Monitoring of canine pancreas allograft function with measurements of urinary amylase.

A canine model of whole pancreas transplantation with pancreaticocystostomy was studied for predictability of graft rejection using urinary amylase (UA) monitoring. Six pancreatectomized dogs were transplanted without immunosuppression and with acute rejection occurring at a median of 9.5 days (range 7-12 days). A differential loss of allograft exocrine and endocrine function was demonstrated, with a gradual decrease in UA after transplantation but maintenance of fasting blood glucose levels (FBGL) till the day before complete loss of graft structure. Another 13 dogs treated with cyclosporin (25 mg/kg per day) had prolonged graft survival (P less than 0.01) with an actuarial median survival of 91 days (range 8-159 days). Five allografts were lost because of rejection and eight dogs died with functioning grafts. Fasting spot levels of UA less than 5000 iu/l or less than 10,000 iu/l had a positive predictivity of graft failure of 71% or 31%, respectively. Falls of UA levels of greater than 75% in 24 h and 48 h were seen equally in both rejecting and functioning allografts. This study confirmed the role of UA as an earlier marker of rejection than FBGL. The clinical role of UA will be important, but its use as a predictor of pancreas rejection may be dependent on a fall to a predetermined level rather than the rate of fall.

Amylases↗
PubMed1991

Effect of intravenous infusion of atriopeptin 3 on immediate renal allograft function.

Thirty-eight recipients of nineteen pairs of cadaveric kidneys were entered into a double-blind randomized study in which one recipient received a 12-hour intravenous infusion of Atriopeptin III (AP-3), a synthetic analogue of atrial natriuretic factor, commencing at release of the vascular clamps, and the other received a placebo infusion. In an initial dose ranging study, successive groups of six kidneys (3 pairs) were randomized to receive each of 0.0125, 0.025, 0.05 micrograms/kg/min AP-3 or placebo. Thereafter 20 kidneys (10 pairs) received 0.1 micrograms/kg/min or placebo. There was no discernable effect of AP-3 on allograft creatinine clearance or sodium excretion either when the highest dose of AP-3 was considered alone or when all doses were considered together. Averaged creatinine clearance over the period 0 to 24 hours after transplantation was 20.1 +/- 14.7 ml/min in patients receiving active treatment and 18.2 +/- 13.7 ml/min in those receiving placebo. Thus, despite the documentation of a protective effect of atrial natriuretic factor in animal models of renal ischemia, it is unlikely that intravenous infusion of AP-3 in this dose range will be of benefit in improving immediate renal allograft graft function.

Atrial Natriuretic Factor↗
PubMed1992

Sequential metabolic studies of pancreas allograft function in type 1 diabetic recipients.

We have previously shown that the loss of acute first phase insulin secretion precedes pancreas allograft rejection and development of glucose intolerance in Type 1 diabetic patients. In order to examine whether there is a progressive loss of phases of insulin secretion and beta-cell function in technically successful pancreas transplants during the first year, we measured glucose, insulin, and C-peptide responses to physiological (mixed meal) and pharmacological (IV glucose and IV glucagon) stimulation in 27 glucose-tolerant, insulin-independent allograft recipients at 3, 6, and 12 months. Mean +/- SE fasting serum glucose levels were normalized throughout the study period. Postprandial serum glucose profiles tended to increase by 12 months compared to 3 and 6 months, although peak glucose levels were not statistically different. Following pancreas transplantation, basal serum insulin levels were high at 3 months (163 +/- 17 pM), 6 months (165 +/- 22 pM), and 12 months (248 +/- 54 pM, p = NS) in the Type 1 diabetic pancreas allograft recipients when compared to normal (25 +/- 3 pM). We observed slight elevations in postprandial insulin and C-peptide profiles at 12 months compared to 3 and 6 months. Following IV glucose and glucagon stimulation, serum insulin and C-peptide levels as well as phases of insulin release did not differ over the 12-month study period. Similarly, the glucose decay constant (KG) was nearly identical at 3, 6, and 12 months. In summary, 1 year following successful whole cadaveric, heterotopic pancreas transplantation in Type 1 diabetic recipients, fasting serum glucose remains normalized, while postprandial glucose tends to rise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Urinary protein/creatinine ratio as an indicator of allograft function following live related donor renal transplantation.

In a study of 656 urine specimens from 53 consecutive recipients of live related donor renal allografts we found an excellent correlation between the protein content of 24-h urines and protein/creatinine ratio (Up/Ucr) in overnight urine samples. Using this ratio, we evaluated proteinuria up to 180 days after renal transplantation (overnight urine samples analysed, n = 2745). Heavy proteinuria in the immediate post-operative period had no prognostic significance. Eighty-nine percent of all clinically observed acute rejection episodes were accompanied by an increase over baseline of Up/Ucr; in 56.5% of these episodes elevation of Up/Ucr preceded that of serum creatinine. However, as a marker of rejection the usefulness of this parameter was limited owing to large number of false positive elevations. In 50 recipients whose grafts survived for more than 3 mth, proteinuria was graded into minimal, moderate and heavy. Renal function at the end of six months was good in all patients who exhibited proteinuria with Up/Ucr less than 100 mg/mmol creatinine. Persistent proteinuria with Up/Ucr above 100 mg/mmol preceded significant deterioration of graft function. Therefore, a protein-creatinine ratio of 100 mg/mmol can be considered as an apparent cut-off to differentiate stable from deteriorating graft function in long term evaluation of transplant recipients.

Adolescent↗
PubMed1986

Improved renal allograft function and survival following nonspecific blood transfusions. I. Induction of soluble suppressor factors inhibiting the mitogenic response.

A small number of blood transfusions (1-3) seems sufficient to improve the cadaveric renal allograft outcome, probably via induction of some nonspecific suppressive activity. This activity was assessed by the concanavalin A (Con A) enhancement method; when present, the response of freshly isolated patients' cells to a submitogenic dose of Con A was lowered, leading to a Con A ratio greater than 5, significantly (P less than 0.0001) higher than the one observed in normal controls or untransfused uremic patients. The correlation between this suppressive activity and graft outcome was determined. Thirty-five patients were studied over a 12-month period for graft function (creatinine level) and survival. Both parameters were significantly improved in the group of patients whose Con A ratio was greater than 5 after transfusions. A soluble suppressor factor, or factors, released into the supernatant of patients' lymphocytes cultured for 48 hr, seems responsible for this suppressive activity. Moreover this process is nonspecific, since it suppresses mitogenic response of cells isolated from normal untransfused volunteers, and could be observed when peripheral blood mononuclear cells were used, but not with purified adherent or nonadherent cells. Addition of indomethacin to the cells during the elaboration of the supernatant abolished this activity. However, amounts of PGE2 secreted into the supernatant during the 48 hr of culture could not be correlated with this suppressive activity. These findings suggest that induction of nonspecific immunosuppression by a few blood transfusions could predict a better kidney graft outcome.

Adult↗
PubMed1986

Circadian stage-dependent prolongation by cyclosporine of segmental pancreatic allograft function in the rat.

While the toxicity of many drugs has been reduced by their administration at certain circadian rhythm stages (if not at certain times of day), as shown herein, direct therapeutic benefit from the improvement of the desired effect can be obtained by the circadian timing of intraperitoneal cyclosporine (Cs) for Lewis rats bearing an ACI segmental pancreas allograft. Under conditions of light (L) and darkness (D) alternating at 12-hour intervals, staggered by 8 h in 3 rooms kept at 24 degrees C, the effect of Cs in delaying graft rejection was improved by timing. When the mean time to rejection during the L span is equated to 100%, graft function is prolonged by 40% at the right time (injection daily during the D span) as compared to the wrong time (injection daily during the L span).

Animals↗
PubMed1992

Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats.

Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1976

Antibody response to influenza vaccination in renal transplant patients: correlation with allograft function.

Thirty renal transplant recipients received 0.5 ml of Influenza Virus Vaccine, Bivalent, USP, intramuscularly. Serum hemagglutination-inhibiting and nasal secretory neutralizing antibodies were measured before and 3 to 4 weeks after vaccination. Creatinine clearance and urinary protein excretion were measured before and weekly for 4 to 8 weeks after vaccination. Ten of 13 patients (77%) with creatinine clearance of greater than or equal to 70 ml/min-1.73m2 (group I) had greater than or equal to a fourfold increase in hemagglutination-inhibiting antibody titers to influenza A or B virus after vaccination, while only six of 17 patients (35%) with creatinine clearance of greater than 70 ml/min-1.73m2 (group II) had a similar increase (chi-square = 5.129; P less than 0.05). Six of 13 patients (46%) in group I had greater than or equal to a fourfold increase in neutralizing antibody titers to influenza A or B virus after vaccination, whereas none in group II had a similar increase (chi-square = 7.135; P less than 0.01). There were no adverse effects on the allografts. Only minor side effects were noted in a few patients. Because of its safety and antigenicity, influenza vaccination should be offered to renal transplant recipients particularly during threats of epidemic outbreaks.

Adolescent↗
PubMed1992

Thrombocytopenia post liver transplantation. Correlations with pre-operative platelet count, blood transfusion requirements, allograft function and outcome.

This study reports that thrombocytopenia is a universal phenomenon post hepatic transplantation. In 53 consecutive adult patients undergoing liver transplantation the platelet count fell by a mean of 63% (157 x 10(9)/l to 50 x 10(9)/l). The platelet count reached a nadir at Day 5 post-transplant but returned to pre-operative levels by Day 14. Non-parametric regression analysis found that pre-operative platelet count, blood transfusion requirements and maximum post-operative ALT values were independent predictors of the percentage fall in platelet count. No correlation was seen with length of graft cold ischaemic time or the use of University of Wisconsin (UW) solution. The nadir day correlated with maximum post-operative bilirubin and ALT, graft ischaemic time and use of UW solution. Maximum post-operative ALT was also an independent predictor of nadir platelet count. It was observed that patients who did not survive the hospital admission had lower post-operative platelet counts and these did not return to pre-operative levels by Day 14. The percentage fall in platelet count was an independent predictor of survival. Severe thrombocytopenia was associated with cerebral haemorrhage in 3 patients. This report provides evidence that allograft dysfunction (maximum post-operative bilirubin and/or AST/ALT) was the most consistent independent predictor of the nadir platelet count, nadir day and percentage fall in platelet count post liver transplantation although the exact mechanism(s) of the platelet changes remain uncertain.

Blood Transfusion↗
PubMed1991

Long-term renal allograft function under maintenance immunosuppression with cyclosporin A or azathioprine. A single center, five-year follow-up study.

In order to evaluate long-term renal graft function, 149 cyclosporin A and prednisolone (CyA/P)-treated renal transplant recipients were compared with 119 azathioprine and prednisolone (Aza/P)-treated patients. Only patients who had a functioning graft for at least 1 year and who were maintained on their initial immunosuppressive protocol were included. The minimum follow-up period was 4 years. Renal graft function was estimated by yearly determinations of serum creatinine and creatinine clearance. The CyA/P-treated patients had a significantly higher serum creatinine and a significantly lower creatinine clearance at every point in time post-transplantation than Aza/P-treated patients (P less than 0.001). The evolution of renal graft function, as reflected in the line of regression for serum creatinine and creatinine clearance versus time, was estimated for each individual patient. There was an almost stable renal function, as assessed by the median of the slopes of the regression line for serum creatinine versus time in both groups. The median increase in serum creatinine was only 1.4 mumol/l per year for Aza/P-treated patients and 2.4 mumol/l per year for CyA/P-treated patients (difference NS). The median decline in creatinine clearance was 2.18 ml/min per 1.73 m2/year in the Aza/P group and 1.07 ml/min per 1.73 m2/year in the CyA/P group (P = 0.05). In patients with a functioning graft for at least 5 years, creatinine clearance remained unchanged in both groups during the study period. In conclusion, renal graft function, as assessed by measurements of serum creatinine and creatinine clearance, remained essentially unchanged for at least 5 years after transplantation, regardless of the immunosuppressive protocol used.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Evaluation of initial hepatic allograft function with changes of free plasma amino acids in canine orthotopic liver transplantation.

We investigated the correlation between amino acid level and hepatic graft function. Plasma amino acid levels were measured at three time periods during canine orthotopic liver transplantation. During the anhepatic phase, plasma amino acid levels rose except for tryptophan. Cystine and alanine (Ala) increased significantly to 210 +/- 28% (n = 20, mean +/- SEM) and 203 +/- 11% from preoperative values (100%), respectively. In animals successfully surviving without hepatic insufficiency after transplantation of fresh livers (n = 7), plasma amino acid levels were restored to preoperative values within 3 hr following reperfusion. On the other hand, in animals that died from hepatic insufficiency within 5 days after grafting of warm ischemically damaged livers (n = 8), plasma amino acids, especially Ala, phenylalanine, total free plasma amino acids, and aromatic amino acids progressively increased to 216 +/- 25, 274 +/- 36, 152 +/- 15, and 152 +/- 15% at 3 hr after reperfusion. These were significantly higher compared to those of the group of animals transplanted with fresh livers (P less than 0.01-0.05). Furthermore, higher values were found in those dogs transplanted with warm ischemically damaged livers surviving for shorter periods. Also in dogs that died from hepatic insufficiency within 8 hr after grafting of livers preserved for 24 hr (n = 5), amino acid levels were at high values at 3 hr. These results suggest that in animals having good graft function, plasma amino acid levels are restored to preoperative values by 3 hr after reperfusion. In other cases, primary nonfunction should be strongly suspected after liver transplantation.

Amino Acids↗
PubMed1990

Improved cardiac allograft function following triiodothyronine therapy to both donor and recipient.

Brain death is associated with neuroendocrine changes, in particular with a significant reduction of plasma-free triiodothyronine (T3) that results in impaired aerobic metabolism. Myocardial energy stores are reduced and tissue lactate increased. Cardiac function deteriorates. Similar metabolic changes are seen in patients undergoing open-heart surgery on cardiopulmonary bypass, including those undergoing heart transplantation. Therapy with T3 leads to a reversal of these metabolic changes, resulting in improved cardiac function. One hundred and sixteen consecutive potential donors have been so treated, as have 70 of the recipients. Immediate posttransplant cardiac function was good in all but 3, and these hearts recovered to normal within a maximum of 24 hr of mechanical support. In 2 small randomized trials in patients undergoing myocardial revascularization on cardiopulmonary bypass, postoperative T3 therapy was associated with a reduced need for inotropic support and diuretic therapy in the first study and improved cardiac output in the second study.

Adenosine Triphosphate↗