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Biomedical subjects

W Amend

Publications and source records attributed to W Amend.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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 outcome following renal transplantation with reduction in the immunosuppression therapy for rejection episodes.

Renal transplantation is superior to hemodialysis in terms of rehabilitation and cost, but it is offered to only a minority of patients with end-stage renal failure because of complications related to immunosuppression therapy. To reduce morbidity, we modified out therapy of patients with transplant rejection from high dose intravenous methylprednisolone (group A: January 1968--September 1972) to lower dose oral prednisone (group B: September 1972--December 1977). Patient survival in group B was significantly improved over that in group A, both in recipients of cadaver transplants (91 per cent versus 81 per cent, respectively, at one year, p less than 0.0009) and in recipients of transplants from living related donors (99 per cent versus 86 per cent, respectively, at one year p less than 0.001). The improvement in patient survival was the result of a significant decrease in the incidence of infections. Patients with multiple rejection episodes, a very high risk group, experienced an 18 per cent increase in patient survival in group B. With reduction and rapid tapering of corticosteroids for the treatment of patients with acute rejection and curtailment of the therapy of patients with multiple rejection episodes, survival after renal transplantation becomes comparable to that following hemodialysis; in addition, graft function is not compromised.

Adult↗

Deliberate donor-specific blood transfusions prior to living related renal transplantation. A new approach.

In order to select MLC incompatible one-haplotype related donor-recipient pairs that would achieve better graft survival and in an effort to alter the recipient immune response, 45 patients received three fresh blood transfuions from their prospective kidney donors. Recipient sensitization was evaluated by cross-match testing weekly sera obtained during and after the blood transfusions against donor T- and B-lymphocytes at 5 C (cold) and 37 C (warm). Thirteen (29%) of the 45 potential related recipients developed a positive warm T-cell cross-match or a persistent warm B-cell cross-match to their blood donor and related transplantation was not performed. Thirty-two (71%) patients had an appropriate negative cross-match to their blood donor. Thirty of these patients subsequently received kidneys from their blood donor. Ninety-seven per cent of the kidneys are functioning from one to 25 months with a single graft failure due to a patient discontinuing immunosuppressive medication. In addition to the excellent graft survival there was an unusually low incidence of rejection episodes in the recipients of kidneys from their blood donor so that the posttransplant course paralleled that of HLA-identical siblings. This approach may have future application with two-haplotype mismatched donor-recipient pairs, both related and unrelated.

Adult↗

Diabetic management by insulin infusion during major surgery.

In five insulin-requiring, uremic diabetic patients undergoing renal transplantation, we infused insulin intravenously at a low rate to maintain plasma glucose levels between 100 and 200 mg/100 ml. In those patients receiving 100 mg or more of prednisone per day and 5 per cent dextrose solution, the hourly infusion rate was determined from tthe following equation: insulin (U) = plasma glucose value divided by 100. When prednisone was not given or when the patient was thin, the ratio became: plasma glucose value divided by 150. Results were compared with those of nineteen similar transplant patients treated with conventional subcutaneous insulin therapy during surgery, and significantly better glucose control was achieved with the low dosage, intravenous infusion.

Adult↗

The influence of donor age on graft survival.

Recent papers report differing conclusions concerning use of kidneys from different donor age groups. We analyzed graft survival of 652 consecutive cadaver kidney donor-recipient pairs. Overall cumulative graft survival was 45 per cent at two years post transplantation. Kidneys from donors aged less that fifteen, sixteen to thirty. thirty-one to forty-five, and forty-six to sixty years had a cumulative graft survival of 51, 44, 39, and 40 percent, respectively. The difference is not statistically significant. When both donor and recipient ages are controlled, the pediatric aged kidney may be superior in the pediatric recipient or the older normotensive adult recipient. Use of properly selected cadaver kidneys in patients of all age ranges is encouraged.

Adolescent↗

Pretransplant cytotoxic antibodies do not segregate kidney transplant recipients into responder and non-responder groups.

In a study of 687 primary cadaver transplants, we found no correlation between the degree of presensitisation and graft survival. Graft survival was adversely affected in non-transfused recipients and was significantly improved in trnasfused recipients, independent of the level of presensitisation (63%, 61%, 67% at one year for patients with 0-10%, 11-50%, and 51-100% preformed cytotoxic antibodies, respectively). Humoral presensitisation to HLA antigens does not reflect the immunoresponsiveness of the host to the renal allograft, but it may prolong the wait for a compatible donor kidney.

Antilymphocyte Serum↗

Immunologic factors determining survival of cadaver-kidney transplants. The effect of HLA serotyping, cytotoxic antibodies and blood transfusions on graft survival.

We assessed immunologic factors determining graft survival in 510 recipients of primary cadaver allografts at one center. The degree of HLA match grade did not directly affect graft survival (54 per cent in no-antigen match, and 42 per cent in three-antigen match, at two years). There was no correlation between the HLA match grade and the degree of stimulation of the mixed lymphocyte culture. Patients receiving more than five blood transfusions had a significantly better graft survival than nontransfused recipients (52 versus 23 per cent, respectively, at two years, P less than 0.001). The beneficial effect of transfusions was noted whether or not lymphocytotoxic antibodies were produced, provided adequate screening was performed before transplantation. Transfusions did not alter the degree of stimulation in the mixed lymphocyte culture. More liberal use of transfusions and frequent screening for cytotoxic antibodies would probably result in more effective cadaver-kidney transplantation.

Blood Transfusion↗