To improve our understanding of posttransplant infections, we analyzed bacterial, viral, fungal, parasitic, and other infections in 604 consecutive recipients of kidney (n = 518), kidney-pancreas (n = 82), kidney-liver (n = 3), or kidney-islet (n = 1) allografts (355 cadaveric, 14 living-unrelated, 235 living-related donors) who also received cyclosporine, azathioprine, and prednisone immunosuppression. Recipients of cadaveric grafts received additional induction immunosuppression (antilymphocyte globulin or murine monoclonal antibody OKT3). Rejection episodes were treated with high-dose steroids, and either antilymphocyte globulin or OKT3 was administered when clinically indicated. Perioperative antibiotics and posttransplant prophylactic acyclovir sodium or ganciclovir sodium, trimethoprim-sulfamethoxazole, and clotrimazole or nystatin (Mycostatin) were administered to all recipients. Two hundred thirteen patients (35.3%) were found to have had no identifiable infections, while 391 (64.7%) had either isolated bacterial (97 [16.1%]), viral (53 [8.8%]), or fungal (34 [5.6%]) infections or combination (concurrent or sequential) infections with bacterial plus viral (46 [7.6%]), bacterial plus fungal (66 [10.9%]), viral plus fungal (20 [3.3%]), bacterial plus viral plus fungal (64 [10.6%]), or bacterial plus viral plus fungal plus parasitic (11 [1.8%]) pathogens in the posttransplantation period. Renal allograft survival (percentage, actuarial method) was diminished in patients with infections at both 1 year (91% vs 83%) and 3 years (81% vs 76%) after transplantation, as was actuarial patient survival (1 year, 97% vs 92%; 3 years, 93% vs 88%). We conclude that infection remains a major cause of both patient demise and allograft loss following successful solid-organ transplantation.
Between September 1984 and August 1991, 265 whole pancreaticoduodenal transplants were done at our institution, with bladder drainage of exocrine secretions through a duodenocystostomy. Seventeen patients subsequently underwent conversion from bladder to enteric drainage at 2 to 64 months after transplant. Eight conversion procedures were done to correct chronic intractable metabolic acidosis due to bicarbonate loss from the allograft: seven to alleviate severe dysuria, presumed secondary to the action of graft enzymes on uroepithelium; one to prevent recurrent allograft pancreatitis, presumed secondary to back pressure from the bladder; and one because of graft duodenectomy for severe cytomegalovirus duodenitis with perforation. None were done to correct technical complications from the initial transplant operation. The conversions were done by dividing the graft duodenocystostomy, then re-establishing drainage through a graft duodenal-recipient jejunal anastomosis. A simple loop of recipient jejunum was used for the duodenojejunostomy in 15 cases, and a Roux limb in two. One of those two cases had a previously created Roux limb that was available for use. The other was in the patient who underwent graft duodenectomy and subsequent mucosa-to-mucosa anastomosis of the pancreatic duct to a newly created Roux limb of jejunum. All patients experienced relief of their symptoms after operation. Two patients had surgical complications (12%), an enterotomy in one case, which was closed operatively, and an enterocutaneous fistula in the other case, which healed spontaneously with bowel rest and parenteral nutrition. The drawback to conversion is loss of urine amylase as a marker for rejection, particularly in recipients of solitary pancreas grafts (n = 5). In recipients of simultaneous pancreas-kidney (SPK) allografts (n = 12), the kidney can still be used to monitor for rejection (two with follow-up < 1 year, 10 with follow-up > 1 year). None of our solitary pancreas recipients, however, have lost graft function (follow-up, 10 to 36 months). The only pancreas allograft loss was in an SPK recipient who also rejected the kidney 6 months after conversion. She received a second SPK transplant with enteric drainage, and is insulin independent and normoglycemic 10 months after retransplantation. Patients converted for metabolic acidosis tended to have impaired renal function (mean creatinine, 2.14 +/- 0.98 mg/dL at time of conversion) due to chronic rejection, progression of native kidney diabetic nephropathy, or cyclosporine toxicity, and possibly could not compensate for bicarbonate loss from the pancreas allograft.(ABSTRACT TRUNCATED AT 400 WORDS)
15-Deoxyspergualin (DSG), a macrophage immunomodulatory agent, was used as a probe in a murine model of islet transplantation to examine 1) the significance of the nonspecific, macrophage-mediated effector arm of beta-cell injury in recipients of a marginal mass of isologous islets by analyzing the duration of temporary posttransplant hyperglycemia, a parameter of immediate beta-cell function; and 2) whether long-term (> 100 days) functional survival could be achieved in recipients of a marginal mass of allogeneic islets. A dose-response study of the number of islets required to ameliorate diabetes showed that 150 isologous islets per recipient resulted in a 75% incidence of cure at a mean of 39.2 +/- 5.8 days posttransplant. DSG-treated (0.625 mg.kg-1.day-1 intraperitoneally) recipients of isologous islets demonstrated a significant (P < 0.01) reduction in the duration of temporary posttransplant hyperglycemia (16.8 +/- 3.2 vs. 39.2 +/- 5.8 days), and DSG-treated recipients of allogeneic islets demonstrated a significant (P < 0.03) improvement in the rate of achieving long-term functional survival (75 vs. 22% in untreated control animals). Finally, identical rates of islet engraftment were found among control animals and DSG-treated animals by measurement of tissue insulin content in transplanted specimens. The results are consistent with the hypothesis that DSG alters the duration of temporary posttransplant hyperglycemia and extends long-term functional survival in murine recipients of a marginal mass of islets, not by affecting the efficiency of islet engraftment, but by suppression of the inhibitory effects on beta-cell function by nonspecific, macrophage mediators.
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