Stored-blood donor-specific transfusions with cyclosporine in distantly related and unrelated donor-recipient pairs.
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Biomedical subjects
Publications and source records attributed to J M Barry.
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A parallel incision, unstented extravesical ureteroneocystostomy was used in 203 human kidney transplants. The reoperation rate was 1 per cent. Extravasation of urine occurred in 3 patients, 1 of whom required surgical repair. One patient required transurethral fulguration of a ureteral bleeder. Two patients had grade 1 reflux and none required repair. No patient had ureteral obstruction at the anastomosis. This simple technique is useful because ureteral length and bladder dissection are minimal, and no separate cystotomy is required. The adequacy of the submucosal tunnel is judged when the ureter is passed through it.
During a 5-year period 77 adults received single kidney cadaver transplants from donors 16 months to 16 years old. Cyclosporin immunosuppression was not used. Three recipients had ischemic ureteral complications, 1 of which resulted in allograft loss. Of the kidney grafts 34 were from donors 8 years old or younger, and comparison of renal function was made with the 43 adult recipients of cadaver kidneys from older children. The mean 1-month serum creatinine nadir was significantly higher in the recipients of kidneys from the younger children (2.6 plus or minus 1.6 versus 1.9 plus or minus 0.8 mg./per dl.). There were no statistically significant differences in 1-week dialysis requirement, 1-month kidney graft function or actuarial kidney graft survivals and serum creatinine levels at 3, 6, 12 and 24 months after grafting. Cadaver kidneys from young donors can be transplanted successfully into adults.
High doses of furosemide have been reported to reduce the requirement for dialysis following cadaveric kidney transplantation. Depending on recipient age, alternate cadaver kidney transplant recipients received infusions of 200 to 400 mg. furosemide just before restoration of renal circulation. All recipients received infusions of mannitol during the hour before renal revascularization. All 50 kidneys were preserved with intracellular electrolyte solutions. Mean cold storage times (33.4 plus or minus 11.4 hours for recipients given furosemide versus 35.7 plus or minus 12.3 hours for controls) were not significantly different between the 2 groups. There were no significant differences in first week dialysis requirement between recipients given furosemide and controls (75 versus 73 per cent, respectively), first day urine output (2.2 plus or minus 4.2 versus 1.0 plus or minus 0.81., respectively), 1-month serum creatinine nadirs (2.1 plus or minus 1.1 versus 1.9 plus or minus 1.1 mg . per dl., respectively) and 1-month function rate (92 versus 92 per cent, respectively). High doses of furosemide did not prevent significant acute tubular necrosis following human cadaveric kidney transplantation when the recipients also received infusions of mannitol.
Donor-specific blood transfusions have improved significantly 1-haplotype living related donor kidney transplant results. We have applied this concept successfully in 2 spousal kidney transplants. This technique may provide an additional source of kidney grafts, especially in developing countries without cadaver kidney transplant programs.
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Infections involving cysts of patients with autosomal-dominant polycystic kidney disease (PCKD) are often refractory to therapy possibly because of poor penetration of antibiotics into cyst fluid. Ten patients with PCKD had blood urine and cyst fluid sampled at surgery or autopsy for antibiotic concentrations. Cysts were categorized as to their nephron site of origin by cyst fluid sodium concentrations. Drugs active against anaerobes such as metronidazole and clindamycin were present in therapeutic concentrations in both proximal and distal cysts. Ampicillin and trimethoprim-sulfamethoxazole had the best profiles considering likely infecting organisms and the antibiotic concentrations achieved in both type of cysts. It is likely that prolonged therapy with both of these drugs is necessary to insure therapeutic success. Other drugs that can be detected in cysts are lipid soluble, undergo tubular secretion, or have high pKa values. These include erythromycin, vancomycin, and cefotaxime. Aminoglycosides because of their predominant glomerular filtration and thus low filtration rate per single cystic nephron are undetectable in both proximal and distal cysts. Clinically, alternatives to aminoglycosides should be chosen for infected cysts in PCKD.
Six patients who underwent a prospective blood transfusion protocol developed antibodies reactive with 41-95% of a lymphocyte panel. These antibodies disappeared 9-18 months later, and all six patients were successfully transplanted with cadaver kidneys in spite of positive crossmatches with donor T and B cells using their most reactive noncurrent sera. Crossmatches with their current sera were negative. No patient underwent plasmapheresis, blood transfusions, or immunosuppression between the time of maximum panel reactivity and transplantation. Graft survival was 100% after a mean of 22.3 months, and the mean serum creatinine level was 2.1 mg/dl one year after grafting. A positive anti-donor T or warm B cell crossmatch with the most reactive serum may be disregarded if the most recent serum is crossmatch-negative with a cadaver kidney transplant donor.
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Fourteen adult recipients of living-donor kidneys preserved with ice-cold intracellular electrolyte solution were randomly assigned to receive either high fluid replacement (total volume of urine output + 30 ml/hr) or low fluid replacement (constant 125 ml/hr) during the first 48 hr after grafting. High replacement recipients had significantly higher fluid intake and urine output than did low replacement recipients. However, net fluid balance at the end of the 48-hr study period was positive for both groups and not significantly different. Fractional excretion of sodium was directly related to urine output in all patients. Serum osmolality, serum sodium concentration, and urine sodium concentration were not significantly different in the treatment groups. Urine osmolality was significantly higher in the low-replacement group at 24 and 36 hr after transplantation. The i.v. replacement of total urinary output is unnecessary in adult recipients of living-donor kidneys preserved with ice-cold intracellular electrolyte solution because such grafts can conserve sodium and water immediately after transplantation.
Being called to the operating room to repair a surgically damaged ureter is an opportunity and challenge that requires on-the-spot decisions based on our training and experience and can result in restoring urinary tract continuity and avoiding secondary operations. A variety of functional reparative techniques are available; however, after consideration of each case in the context in which it arises, the best solution can usually be selected.
Prolonged cold storage following intracellular electrolyte flushing increases the probability of significant acute tubular necrosis after cadaver kidney transplantation. The renal function of primary cadaver kidney grafts was compared in 68 recipients who required dialysis and 92 who did not require dialysis during the first week after transplantation. All kidneys were retrieved from beating-heart cadaver donors by our center, flushed with ice-cold intracellular electrolyte solution and cold-stored until transplantation at our hospital. Recipients requiring dialysis during the first week after transplantation received kidneys with a significantly longer cold storage time (27.4 plus or minus 10.2 versus 23.2 plus or minus 7.6 hours) and had significantly higher 1-month serum creatinine nadirs (2.1 plus or minus 1.3 versus 1.5 plus or minus 0.6 mg./dl.). Actuarial kidney graft survivals and serum creatinine levels 1 to 5 years after grafting were not significantly different. Acute tubular necrosis following primary cadaver kidney transplantation does not adversely affect long-term function of kidney grafts flushed with intracellular electrolyte solution and cold-stored until transplantation.
A cooperative clinical trial was conducted among 5 transplant centers in the western United States to determine the value of magnesium sulfate in intracellular electrolyte flush solutions for hypothermic, human kidney storage. Kidneys from alternate donors were flushed with either magnesium-free Euro-Collins' solution or magnesium-containing Collins' 2 solution. Donor and recipient ages, and mean preservation times were not significantly different between the 2 groups. There was a significantly lower dialysis requirement during the first week in the magnesium-containing Collins 2 group (33 per cent) versus the Euro-Collins group (54 per cent). Function rates and serum creatinine nadirs at 1 month were not significantly different. The beneficial effect of magnesium sulfate was more evident when preservation times exceeded 24 hours.
A total of 14 impotent men without Peyronie's disease underwent implantation of paired, semirigid penile prostheses after determination of the subcoronal dorsal diameters of the saline erections. The subcoronal saline erection diameter was divided by the diameter of the semirigid penile prosthesis, and the best lateral and distal fitting occurred when the quotient was 3 or greater. Dividing the subcoronal saline erection dorsal diameter by 3 allows selection of the appropriate semirigid penile prosthesis diameter.
A horseshoe kidney was retrieved en bloc with the aorta and inferior vena cava, divided at the isthmus and transplanted into 2 recipients. This anomaly is not a contraindication to cadaver kidney donation.
No kidney transplant center responding to a kidney preservation questionnaire would accept a kidney flushed with an intracellular electrolyte solution and cold-stored for over 40 hours. This study from one center is a comparison of 50 primary cadaver kidney grafts preserved with an intracellular electrolyte flush followed by cold storage for 40 to 61 hours to 82 primary cadaver kidney grafts preserved by the same method for 9 to 24 hours. Kidneys cold-stored for over 40 hours had a significantly increased requirement for dialysis in the 1st week following transplantation (82% versus 34%) and a significantly increased 1-month serum creatinine nadir (2.3 mg/dL versus 1.7 mg/dL). Actuarial graft survivals and serum creatinine levels at 1, 2, and 3 years after grafting were not significantly different. Cadaver donor methylprednisolone (30 to 60 mg/kg) two to nine hours prior to kidney removal significantly reduced the requirement for 1st-week hemodialysis in the kidneys cold-stored for over 40 hours (60% versus 91%). Kidneys preserved by flushing with cold intracellular electrolyte solution can be successfully transplanted after over 40 hours of simple cold storage when the warm ischemia time is very short.
A fibroblast growth regulator, which inhibits the growth and division of proliferating fibroblasts, has been isolated from medium conditioned by exposure to density-inhibited mouse 3T3 cells. This partially purified preparation of the growth-inhibitory activity, termed FGR-s, contained two major polypeptides (Mrs, 10,000 and 13,000). Using FGR-s as the immunogen, we have carried out in vitro immunization of rat splenocytes and have generated hybridoma lines, each secreting an antibody directed against components of the FGR-s preparation. One such monoclonal antibody, designated 2A4, specifically bound the Mr 13,000 polypeptide of FGR-s. Antibody 2A4 also neutralized the growth-inhibitory effect of FGR-s in a concentration-dependent fashion. These results strongly suggest that the Mr 13,000 polypeptide carries growth-inhibitory activity.
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