The role of blood transfusions in renal transplantation.
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Adolescent↗
Biomedical subjects
F Vincenti
Publications and source records attributed to F Vincenti.
Furosemide assays and disposition in healthy volunteers and renal transplant patients.
A variety of furosemide assays and their application to biological samples have been described over the past 2 decades. We describe development of a specific, sensitive assay appropriate for efficient measurement of large numbers of biological samples. With development of this methodology we have demonstrated that the putative 2-amino-4-chloro-5-sulfamoylanthranilic acid metabolite is an artifact of sample preparation. In addition, some preparative techniques overestimate furosemide because they hydrolyze the glucuronide conjugate back to the parent compound. Applications of this assay to studies of normal subjects and patients who have received kidney transplants demonstrate a relatively constant amount of glucuronide formation and evidence that this conjugation occurs in the kidney. We also show that patients with renal transplants who are resistant to the effects of furosemide appear to have decreased secretion of the drug into the urinary site of action, the mechanism of which is unknown.
Furosemide↗
Urinary kallikrein excretion after renal transplantation: relationship to hypertension, graft source, and renal function.
The role of the renal kallikrein-kinin system in the pathogenesis of hypertension and various forms of renal dysfunction after human renal transplantation has been assessed by measurement of urinary kallikrein activity in 41 renal transplant recipients. The urinary tosyl arginine methyl esterase assay was used. The urinary kallikrein in these patients appeared to originate from the transplanted kidney and not their own diseased kidneys. Twenty-three recipients had hypertension (mean blood pressure 156 +/- 3/98 +/- 2 mm Hg) and excreted less kallikrein (4.0 +/- 1.2 versus 12.5 +/- 4.0 esterase units [EU] per 24 hours, p less than 0.05) than their 18 normotensive counterparts (mean blood pressure 132 +/- 2/77 +/- 1 mm Hg, both p less than 0.01). Subjects with renal complications of transplantation (acute tubular necrosis [ATN], nine patients, or acute rejection [AR], eight patients) also excreted less kallikrein than the 28 subjects without such complications (3.4 +/- 0.9 versus 10.3 +/- 2.7 EU/24 hours, p less than 0.02). Among those with acute renal complications, subjects with ATN excreted less kallikrein than those with AR (1.3 +/- 0.3 versus 5.7 +/- 1.7 EU/24 hours, p less than 0.02). Cadaver graft recipients excreted less kallikrein than living related donor graft recipients (2.1 +/- 0.4 versus 13.0 +/- 3.5 EU/24 hours, p less than 0.01), perhaps reflecting their higher blood pressures (mean systolic pressure 151 +/- 3 versus 140 +/- 3 mm Hg, p less than 0.04), relatively impaired renal function (creatinine clearance values 42 +/- 8 versus 62 +/- 5 ml/min, p less than 0.04), and higher incidence of ATN (nine cases versus none). The kallikrein-kinin system may be involved in the pathogenesis of hypertension and some forms of renal dysfunction after renal transplantation.
Creatinine↗
Prognostic features of early renal transplant rejections.
In an analysis of 632 cadaver transplants, the early renal transplant course gave important prognostic information depending on temporal and/or renofunctional characteristics of rejection episodes. Two transplant rejections occurring within the first 2 mo posttransplant were associated with either 37%, 27%, or 6% 1-yr graft survivals depending on whether these episodes were separate, temporally back-to-back, or were without interrejection renofunctional recovery, respectively. This compares to 1-yr graft survivals of 89% or 73% in those patients who had no rejection or one with recovery early posttransplant. Patient survival in groups with multiple early rejections was also associated with a poor prognosis. Ninety to 93% 1-yr patient survival was noted when there was no or one rejection. There was only a 74%-83% 1-yr patient survival with two early treated rejections. Transplant rejection therapy must be individualized or even withheld in order to ensure optimum graft and patient survival.
Blood Transfusion↗
Prednisone and prednisolone bioavailability in renal transplant patients.
Prednisone and prednisolone are drugs with the potential for therapeutic inequivalence due to bioavailability problems. The objective of our study was to compare the systemic bioavailability of prednisolone from oral prednisone and prednisolone. Nine kidney transplant patients receiving prednisone (12.5 to 22.5 mg per day) were administered, in a randomized fashion, the same dose of oral prednisone (Deltasone), oral prednisolone (Delta-cortef) and intravenous prednisolone (Hydeltrasol). Prednisolone and prednisone levels were measured using a specific high-pressure liquid chromatographic assay. Since prednisolone exhibits dose-dependent pharmacokinetics because of nonlinear plasma protein binding, bioavailability from oral prednisone and oral prednisolone, compared to the intravenous dose, was 84.5 +/- 17.8% and 95.5 +/- 17.6% using unbound drug concentrations. These differences were not statistically significant. Furthermore, no significant differences were observed between the two oral formulations in peak prednisolone levels, time of peak levels or half-life using either total or unbound drug concentrations. The results from our study indicate that both of the oral preparations tested provide similar bioavailability of active prednisolone and the conversion of prednisone to prednisolone occurs rapidly.
Administration, Oral↗
Septic arthritis following renal transplantation.
Monoarticular septic arthritis without disseminating sepsis occurred in 4 patients following renal transplantation. The septic arthritis was preceded by an infection with the same organism in an extraarticular location (3 urinary tract, 1 upper respiratory). All patients were on prednisone-azathioprine immunosuppressive regimen but none had granulocytopenia. Prompt antibiotic therapy resulted in quick resolution of the joint infection in 3 patients. Impaired host defenses, possible inadequate prior antibiotic therapy, and intrinsic joint alterations are potential contributing factors to the development of septic arthritis following renal transplantation.
Adult↗
Blood transfusions and kidney transplantation.
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Blood Transfusion↗
Blood transfusions before and on the day of transplantation: effects on cadaver graft survival.
Pre-BTs significantly improve the survival rate for first cadaver transplants, by a mechanism that remains obscure. The maximal influence is seen with smaller numbers of pre-BTs (1-5 units), but is also observed with larger numbers of pre-BTs. The possible beneficial influence of Tx-BTs on graft survival is not proven, and if it exists at all is not nearly as striking as the effect seen with pre-BTs. Tx-BTs neither potentiate nor nullify the benefit of pre-BTs on graft survival. It is therefore recommended that pre-BTs in smaller numbers, such as 1-5 units, be administered to candidates for first cadaver transplants to increase the probability of a successful outcome. Tx-BTs should be utilized when clinically indicated but not with the expectation that they will necessarily improve graft survival.
Antilymphocyte Serum↗
Update of the University of California at San Francisco experience with donor-specific blood transfusions.
Prospective pretreatment with deliberate DST has afforded MLC reactive related donor-recipient pairs enhanced opportunity for successful transplantation. The sensitization rate in patients receiving DST prior to primary transplantation was 30%, but this sensitization has been generally specific and narrow-those patients developing a positive DSXM do not appear to be jeopardized regarding later cadaver transplantation. Graft survival rates in 86 recipients of kidneys from their blood donors are 95% (1-year) and 93% (2-year). This graft survival rate appears to outweigh the minimal risk of possible unfavorable sensitization. Potentially unsuccessful transplants in immunologically disparate related donor-recipient pairs can be avoided, and the transplants actually performed have enhanced prospects of success.
Adolescent↗
Decreased secondary hyperparathyroidism in diabetic patients receiving hemodialysis.
Biochemical and bone scintigraphic studies were performed in nondiabetic and diabetic patients receiving hemodialysis at the time of kidney transplantation to assess the degree of secondary hyperparathyroidism. Despite lower serum calcium concentrations, diabetic patients had significantly lower parathyroid hormone (PTH) levels than nondiabetic patients. In addition, diabetic patients had lower graded total-skeletal scintigraphic scores than nondiabetic patients. The PTH levels showed positive correlations with bone scan scores and with alkaline phosphatase in nondiabetic patients but not in diabetic patients. Avascular necrosis occurred in 17% of nondiabetic patients and in only 2% of diabetic patients. Patients with avascular necrosis had significantly higher PTH levels than patients without avascular necrosis. Diabetes mellitus seems to confer a protective effect from the skeletal manifestations of secondary hyperparathyroidism, including avascular necrosis.
Bone and Bones↗
1,500 renal transplants at one center: evolution of a strategy for optimal success.
From analysis of results of more than 1,500 renal transplants has evolved a plan for donor selection and immunosuppressive management whereby patients with end-stage renal disease can obtain maximum graft and patient survival. With superior results in both patient and graft survival with living-related transplantation, this modality should be considered initially. Pretreatment with third party blood transfusions appears effective in all donor categories. Donor-specific blood transfusions have afforded 1-haplotype mixed lymphocyte culture-incompatible recipients enhanced opportunity for successful transplantation. Current results with living-related transplantation suggest realistic expectations of 1 and 2 year graft survival rates of greater than 90 percent. Curtailment of steroid therapy has resulted in improved patient survival at 1 and 2 years: 98 and 97 percent for recipients of living-related grafts, and 91 and 88 percent for recipients of cadaver grafts. These results, in combination with proper donor selection and appropriate recipient pretreatment with blood transfusions, have made renal transplantation a very effective therapeutic method in patients with end-stage renal disease.
Adolescent↗
Furosemide kinetics and dynamics after kidney transplant.
We examined differences between responder (R) (40 to 80 mg/day) and nonresponder (NR) (greater than or equal to 120 mg/day) patients after kidney transplant with respect to furosemide kinetics and dynamics. Nonresponders had reduced plasma clearance (NR 64 +/- 21.4 and R 105 +/- 23 ml/min, two-sample t test; p less than 0.05), renal clearance (NR 18.4 +/- 8.1 and R 47.1 +/- 11.0 ml/min; p less than 0.005), and renal clearance to creatinine clearance ratio (NR 0.43 +/- 0.15 and R 0.80 +/- 0.07; p less than 0.005). Half-life rose in the nonresponders (NR 130 +/- 13 and R 87.6 +/- 16.3 min; p less than 0.005). There was no difference between groups with respect to nonrenal clearance, extent of availability, volume of distribution steady state, and the fraction of the dose excreted unchanged in the urine after intravenous administration. These results suggest that nonresponders have less ability to secrete furosemide into tubular fluid as well as less ability to respond to drug.
Administration, Oral↗
An alternative to cadaver kidney transplants for patients with insulin-dependent diabetes mellitus.
The benefits of successful kidney transplants for patients with end stage renal disease associated with insulin-dependent diabetes mellitus are well known, and the potential advantages of earlier transplantation have been emphasized in other reports. Cadaver transplants, which are not always available for these patients, have not provided a high degree of success in many centers. This has discouraged the use of transplants unless well matched related donors are available. Most patients do not have well matched family members who are able to donate. We have attempted to increase the availability of related transplants for diabetic patients by using a new protocol in which related donors who are poorly matched by mixed lymphocyte culture (MLC) testing (stimulation index (SI) greater than or equal to 7) can often serve as the source of the transplant. This protocol of pretransplant donor-specific transfusions (DSTs) has been applied to 20 diabetic patients. Sixteen transplants have been performed after serial immunological studies following the DSTs detected no specific evidence of recipient sensitization to the respective transfusion donors. Only one of the transplants has been rejected, and this occurred in a patient who intentionally terminated immunosuppressive therapy. Graft survival for the group of 16 patients is 93 and 84% at 1 and 3 years, respectively. The quality of renal function for most of the patients is very good, with a mean serum creatinine of 1.9 and 1.5 ml/dl for those transplants at risk for 12 and 24 months. This new method has given encouraging results for poorly matched related transplants in diabetic patients and makes earlier transplantation possible by providing an alternative to cadaver transplants.
Adult↗
Incidence, characteristics, and outcome of recipients sensitized after donor-specific blood transfusions.
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Antibody Formation↗
Recurrent systemic lupus erythematosus involving renal allografts.
Two cases of recurrent lupus erythematosus involving renal transplants are described. Neither case showed changes of transplant rejection. The clinical course, serologic tests, and renal histopathologic findings remarkably paralleled those seen during each patient's primary disease presentation. Typical and severe extrarenal manifestations of dermatitis, pleuritis, and polyarthritis were noted before renal allograft lupus involvement. Rapid renofunctional deterioration was halted in one patient by plasmapharesis. In the second patient a more protracted course involving the allograft is anticipated. Although previous experiences suggest that lupus disease activity "burns out" after the development of chronic renal failure, findings from these two cases argue against this presumption. Longer periods of transplant follow-up may show more recurrence of lupus erythematosus.
Adult↗
Prevention of prednisone-induced negative nitrogen balance. Effect of dietary modification on urea generation rate in patients on hemodialysis receiving high-dose glucocorticoids.
To assess whether increasing dietary protein and calorie intake can ameliorate the negative nitrogen balance induced by 70 to 120 mg/d prednisone, we studied nitrogen intake and net urea generation rate in patients undergoing hemodialysis for 10 to 14 days after renal transplantation. Seven patients receiving prednisone with moderately restricted protein (0.73 +/- 0.03 g/kg of body weight per day) and calorie (20 +/- 4 kcal/kg of body weight per day) intake had high urea nitrogen generation rates (199 +/- 18 mg/kg.d) and protein catabolic rates (1.45 +/- 0.12 g/kg.d) and were in marked negative protein balance (-0.72 +/- 0.12 g/kg.d). An increase in protein (1.30 +/- 0.06 g/kg.d) and calorie (33 +/- 3 kcal/kg.d) consumption in another eight prednisone-treated patients resulted in protein balance (-0.02 +/- 0.12 g/kg.d) without further increasing urea generation (174 +/- 9 mg/kg.d). Six control patients undergoing hemodialysis after surgery who were not receiving prednisone had lower urea generation rates (109 +/- 15 mg/kg.d) and were in nitrogen balance. Nitrogen wasting is therefore not an inevitable consequence of high-dose glucocorticoid therapy and can be effectively prevented by simple nutritional modification without increasing hemodialytic requirements.
Adult↗
Pretreatment with donor-specific blood transfusions in related recipients with high MLC.
Pretreatment with deliberate DST has not resulted in hyperacute or irreversible rejection in patients receiving kidneys after negative donor-specific crossmatches, but has afforded immunologically disparate related recipients enhanced opportunity at successful transplantation. Additionally, with a post-transplant course paralleling that of HLA-identical siblings, high-dose immunosuppressive therapy for rejection has been spared in many recipients. Transplantation, however, proved unsuccessful in a patient receiving a kidney from his positive B-warm crossmatch blood donor in a protocol departure. This case experience and subsequent antibody studies have reconfirmed our initially established criterion of not proceeding with transplantation against a persistently positive B-warm donor-specific crossmatch. By pursuing the initially established DST protocol, it appears that a potentially unsuccessful living related transplant can be avoided, while the transplants actually performed have enhanced prospects of success. The nature of the various immunologic responses in this patient population remain to be more clearly defined.
Antibody Formation↗
Improved graft survival with donor-specific transfusion pretreatment.
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B-Lymphocytes↗