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Biomedical subjects

W Amend

Publications and source records attributed to W Amend.

At least 19 recordsLinked to original sources

Acute renal allograft dysfunction secondary to suprarenal arterial stenosis: a case series and review of the literature.

Stenosis of vessels proximal to the renal artery is an unusual cause of allograft ischemia. We report four patients who had such 'suprarenal' arterial stenoses leading to graft dysfunction that was reversed with revascularization. We additionally review the existing literature on this entity, outline the etiologies of such stenoses, as well as discuss the surgical and non-surgical therapeutic options in patients with this uncommon cause of allograft dysfunction.

Acute Disease↗

Immunologic and patient selection strategies for successful utilization of less than 15 kg pediatric donor kidneys--long term experiences with 40 transplants.

Renal transplantation using infant donors is associated with significantly less graft survival (GS) and increased morbidity, especially from very young and small donors. We report our results using specific strategies to determine which age and size donor require en bloc renal transplant reconstruction and associated immunologic protocols for optimization of subsequent GS. Forty cadaveric pediatric en bloc renal transplants were performed. Mean donor age was 23.6+/-18.4 months with subgroups: 2-12 months, n=14; 13-24 months, n=19; and 25-60 months, n=7. Mean donor weight was 14.4+/-4.5 kg. All kidneys were placed in primary, nonsensitized (peak PRA = 7.9+/-5.6%) adult (41.6+/-16 years) recipients. Low weight was preferred (62.4+/-12.8 kg). Mean cold ischemia time was 26.9+/-8.6 hr. Immunosuppression consisted of quadruple immunosuppression (QI) with OKT3 induction. All patients had ureteral stents placed intraoperatively. Mean follow-up was 16.9 months. Actuarial GS at 12, 24, and 33 months were 100% (n=13), 85% (n=20), and 71% (n=7), respectively. Total GS was 35/40=88%. All grafts functioned immediately and there were no technical losses. Biopsy proven rejections occurred in 12 (30%) patients, developing at 16-167 days postoperatively (mean = 50.3 days). Mean serum creatinine at one week and 1, 6, 12, and 18 months were 2.1+/-2.0, 1.5+/-0.8, 1.3+/-0.5, 1.1+/-0.4, and 0.9+/-0.4 mg/dl, respectively. Functional isotopic renography, as well as sonographic monitoring reflected rapid initial and continued growth in these kidneys. Mean BP at 12 and 24 months postoperatively were 145/83+/-18/13 and 122/76+/-20/10 mmHg, respectively, with no significant proteinuria noted. Excellent results with minimal complications utilizing very small and young infant donors can be achieved with QI immunosuppression, and selection of low immune reactive and noncomplicated adult recipients. Additionally, maximal renal dosing by minimizing recipient weight may prevent future hyperfiltration damage.

Actuarial Analysis↗

Recurrent focal glomerulosclerosis: natural history and response to therapy.

PURPOSE: Recurrent focal glomerulosclerosis (FGS) has been well documented since it was first reported in 1972. However, the course of the disease after transplantation and the optimal treatment regimen have not been well defined since the introduction of newer treatment modalities. PATIENTS AND METHODS: We reviewed all the charts of patients with biospy-proven FGS who received renal transplants at our institution from January 1980 through December 1990. Case histories consistent with diagnoses other than primary FGS (such as reflux nephropathy or intravenous drug use) were eliminated from the study. During this time period, 78 allografts were received by 71 patients with FGS. Independent variables that were analyzed included sex, race, time in months between the diagnosis of FGS and end-stage disease (dialysis or transplantation), age at time of transplantation, type of dialysis, source of allograft (cadaveric or living related), haplotype matching, donor-specific transfusions, age and sex of the donor, post-transplantation acute tubular necrosis, rejection episodes, immunosuppression regimen, use of plasmapheresis and angiotensin converting enzyme (ACE) inhibitors, and outcome. RESULTS: FGS recurred in 25 allografts (32%) of 21 patients. Biopsy-proven diagnosis of recurrence was made a mean of 7.5 months (range: 0.5 to 44 months) after transplantation. Patients who had rapid progression to end-stage disease tended to experience more frequent recurrences. Of seven patients who received a second transplant, five patients lost the first graft to recurrent FGS, and four of those patients (80%) had a recurrence in the second allograft. Recurrent disease developed in 34% of patients concurrently treated with cyclosporine and in 28% of those treated with prednisone and azathioprine alone (NS). Patients with recurrent FGS who were treated with ACE inhibitors benefited from a significant reduction of proteinuria. Six patients underwent plasmapheresis after diagnosis of the recurrence. Three of five patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had reversal of epithelial foot process effacement and remission of proteinuria. End-stage disease eventually developed in 14 allografts (56%) an average of 23.7 months (range: 1 to 65 months) after diagnosis of recurrent disease. The cause of failure was chronic rejection in four allografts and recurrent disease in the remaining 10 allografts. CONCLUSIONS: FGS recurs in approximately 30% of allografts and causes graft loss in half of these. Patients who have lost a first allograft to recurrent FGS are at high risk for developing recurrent disease in a second allograft. Prolonged allograft survival is possible in patients with recurrent FGS and may best be obtained with a combination of treatment modalities including cyclosporine (perhaps in higher dosages than are routinely used in clinical renal transplantation), ACE inhibitors, and early use of plasmapheresis. The efficacy of these modalities supports the notion that recurrent FGS is caused by a circulating humoral mediator.

Adolescent↗

Improved results with combined donor-specific transfusion (DST) and sequential therapy protocol.

A combined DST-sequential CyA therapy protocol has been described that results in optimum graft survival for 1- and 2-haplotype mismatched living related donor-recipient combinations. In addition to the excellent graft survival obtained through 4 years, lower prednisone and CyA dosage levels are achieved with significantly decreased infection rates during the posttransplant period.

Blood Transfusion↗

The association of cyclosporine with the 1-year costs of cadaver-donor kidney transplants.

Cyclosporine is associated with lower hospitalization costs for transplantation of cadaver kidneys. Whether this cost-lowering effect persists after discharge was assessed for 203 patients who received cadaver kidneys at the University of California, San Francisco, between July 1982 and June 1986. During the transplantation hospitalization period, cyclosporine was associated with significantly better graft survival (88.7% vs 71.0%) and lower (standardized) costs ($37,174 vs $52,983). Following discharge, however, there were no significant differences in graft survival, total charges ($29,716 vs $34,434), the number of readmissions, the total number of days hospitalized, or physician charges, although cyclosporine was associated with higher drug costs ($3885 vs $373). The results suggest that the initial association of cyclosporine with lower costs diminished substantially over time. For grafts that survive beyond several months, there may be little additional cost-reducing benefits of cyclosporine.

Adolescent↗

The effect of cyclosporine on the use of hospital resources for kidney transplantation.

Over the past decade the clinical results of kidney transplantation have improved substantially, with much of the benefit being attributed to the introduction in late 1983 of the immunosuppressive drug cyclosporine. To assess the effect of cyclosporine on the use of hospital services, we studied 702 patients who received kidney transplants at the University of California, San Francisco, between July 1982 and June 1986. All services were priced in constant 1985 dollars, and multiple regression analysis was used to adjust for changing patient and hospital characteristics. The introduction of cyclosporine for patients receiving kidneys from cadavers was associated with a significantly shorter adjusted mean postoperative stay (26.4 days as compared with 37.0 for patients not taking the drug; P less than 0.0001) and lower adjusted mean hospital charges ($28,649 as compared with $37,895; P less than 0.0001), although cyclosporine was not associated with changes in the use of services by patients who received transplants from living related donors. Cyclosporine was also associated with a reduction in the use of certain ancillary services, such as laboratory tests and radiographic procedures. In patients without diabetes who received cadaver kidneys, a sequential cyclosporine regimen (in which a combination of antilymphoblast globulin, prednisone, and azathioprine was given before cyclosporine) reduced the use of hospital services even more than did a cyclosporine regimen in which the combination was not given. The results suggest that new medications, such as cyclosporine, that reduce the frequency of complications and improve outcomes may also reduce the use of hospital resources.

Adult↗

Cardiac consequences of renal transplantation: changes in left ventricular morphology and function.

To characterize changes in left ventricular morphology and function associated with renal transplantation, noninvasive cardiac evaluations were performed in 41 adults at the time of surgery and at follow-up. At the time of transplantation, 36 patients had undergone hemodialysis through a fistula for 2.3 +/- 2.5 years (mean +/- SD); their hematocrit level was 26 +/- 6% and systolic blood pressure was 151 +/- 19 mm Hg. Perioperatively, left ventricular hypertrophy was present in 93% of patients by echocardiography, but in only 37% by electrocardiography. Abnormal left ventricular diastolic function was present in 67% of patients and indicated a high risk for perioperative pulmonary edema. At follow-up (1.5 +/- 1.4 years), mean hematocrit level increased to 39 +/- 7%, systolic blood pressure decreased to 132 +/- 14 mm Hg and spontaneous closure of the fistula occurred in 13 patients. Left ventricular mass by echocardiography decreased from 237 +/- 66 to 182 +/- 47 g (p less than 0.001), a decrease of 23%. Left ventricular volumes and cardiac index also decreased significantly, reflecting the rapid resolution of a pretransplant high output state. Despite proportionate regression of left ventricular hypertrophy within months of transplantation, diastolic function did not improve. The significant regression of left ventricular hypertrophy that occurs after renal transplantation may help explain the improved cardiovascular survival of patients with a renal transplant over that of patients on long-term dialysis.

Adult↗

The clinical course of IgA-nephropathy and Henoch-Schönlein purpura following renal transplantation.

Recurrence of IgA-nephropathy and Henoch-Schönlein purpura is a common finding after renal transplantation. From 1970 to 1984, 1788 transplants were performed at our center. 13 patients had IgA-nephropathy and 3 patients had Henoch-Schönlein purpura. No patient with Henoch-Schönlein purpura had a proved recurrence. Six patients with IgA-nephropathy had a recurrence of IgA disease in the allograft within 3 to 8 months of transplantation. Three patients with a recurrence have retained their kidneys with stable renal function (follow-up of 1.7-2.7 years). Two of these patients lost their graft from severe rejection. One patient, who received an HLA-identical transplant, lost the graft from recurrent IgA disease associated with crescenteric glomerulonephritis. We found no difference in the prevalence of HLA-B 35 among the IgA patients compared with our total transplant population. IgA patients who received living related transplants had a higher recurrence rate of IgA in their allograft when compared with recipients of cadaveric kidneys (83% vs. 14%). Some caution is recommended in using related donors, especially HLA-identical siblings in patients with renal failure secondary to IgA-nephropathy.

Adolescent↗

Renal allograft rejection: US evaluation.

Real-time ultrasonography (US) was performed on the allografts of 100 consecutive renal transplant recipients at the time of allograft biopsy. Evaluation of the sonograms included the grading of parameters previously demonstrated to be indicative of allograft rejection. The appearance of the renal sinus fat, allograft size, corticomedullary ratio, sharpness of the corticomedullary junction, medullary conspicuity, presence of focal parenchymal abnormalities, and thickening of the pelvic or infundibular wall were individually evaluated. The authors correlated the US and the histopathologic findings. While the accuracy of a positive prediction of rejection was relatively high (83%-90%), this result is influenced by the relatively high prevalence of rejection in the biopsy group (83%). Accuracy of a negative prediction was uniformly low (17%-30%). Mild rejection was difficult to differentiate ultrasonographically from no rejection, although severe rejection could usually be differentiated from mild or no rejection, particularly in patients with the interstitial type of rejection.

Graft Rejection↗

Pharmacokinetics of sulfisoxazole in renal transplant patients.

We studied the elimination of sulfisoxazole in eight renal transplant patients. The patients received sulfisoxazole prophylactically for urinary tract infection commencing 7 days postoperatively. The renal elimination of sulfisoxazole (unbound renal clearance) was decreased in this patient population and was highly correlated with creatinine clearance. The unbound metabolic clearance and apparent unbound formation clearance of N4-acetyl sulfisoxazole did not differ from values found in healthy volunteers. The protein binding was marginally lower in this patient population than in healthy subjects after a single dose. The reduced binding was compatible with a reduced albumin concentration. In contrast to the situation for healthy subjects, the binding of sulfisoxazole decreased upon multiple dosing. This is probably due to a relatively higher sulfisoxazole and N4-acetyl sulfisoxazole-to-albumin ratio in this patient population than in healthy subjects. No complications of sulfisoxazole therapy were seen, although in three subjects concentration of the N4-acetyl sulfisoxazole in urine exceeded its theoretical solubility on a few occasions.

Acetylation↗

Dramatic improvement in the success rate for renal transplants in diabetic recipients with donor-specific transfusions.

The chance of achieving successful kidney transplants in diabetic patients was previously limited because few of them had optimally-matched (2-haplotype) related donors. Hence, transplants were usually not carried out until renal failure had already occurred. The application of donor-specific transfusions (DSTs) prior to transplantation to poorly matched donor-recipient pairs (1-haplotype) has been associated with a high success rate for type-I diabetic recipients in our center. The rate of graft survival for 35 consecutive transplants in this category was 88%, 80%, and 73% at 1, 2, and 5 years, respectively. Furthermore, the rate of patient survival was 94%, 90%, and 90% at 1, 2, and 5 years. These patient and graft survival data were without significant difference when compared with the corresponding data for 142 optimally-matched (2-haplotype) related transplants performed without DSTs for nondiabetic recipients, and also when compared with the corresponding data for 130 poorly matched (1 or 0-haplotype) related transplants involving nondiabetic recipients who were prepared for transplantation with DSTs. These good results with DSTs in diabetic recipients emphasize that earlier transplantation utilizing poorly matched related donors should be seriously considered for diabetic patients even before the onset of renal failure, as long as the transplants are carried out in association with DSTs.

Adult↗