Christina Brattström

Rescue therapy with tacrolimus (FK 506) in renal transplant recipients--a Scandinavian multicenter analysis.

Abstract All renal allograft recipients (n= 32) in Sweden and Norway who were converted from cy‐closporin(CyA)‐based immunosuppression to FK 506 (tacrolimus) between October 1992 and June 1995 were analyzed retrospectively. The reasons for conversion were acute refractory rejection (n= 21), chronic rejection (n= 4), and suspected CyA toxicity (n= 6); one patient was converted for psychological reasons. The mean time from transplantation to conversion was 29 (range 1–243) weeks and there was a mean follow‐up of 46 (2–143) weeks. Overall graft survival was 59 %, with graft survival 52 % in patients converted because of acute rejection, 50 % in patients converted because of chronic rejection, and 83 % in patients converted because of CyA toxicity. There was no significant correlation between preconversion serum creatinine and outcome. Seventy‐two percent of the patients had significant side effects during FK 506 treatment, the most frequent ones being neurological and gastrointestinal symptoms. These improved after dose reduction. Two patients became overimmunosup‐pressed and developed lymphoma. One patient died of the primary kidney disease, hemolytic uraemic syndrome. We conclude that FK 506 therapy is able to salvage kidneys with acute refractory rejection and that it is an alternative in patients with CyA toxicity. However, the risk of overimmunosuppression must be considered.

Cytomegalovirus the predominant cause of pneumonia in renal transplant patients. A two-year study of pneumonia in renal transplant recipients with evaluation of fiberoptic bronchoscopy.

The microbiological etiology of pneumonia in 34 renal transplant patients with clinical and X-ray evidence of pulmonary parenchymal disease was studied. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB) and brushing was performed on 18 patients. Laboratory evaluation included histological and cytological methods, cultures for bacteria, fungus and virus and immunofluorescence techniques for the detection of Pneumocystis carinii, cytomegalovirus (CMV) and legionella. Serum samples were obtained concomitantly for antibody studies. CMV, the most common etiology, was considered to be the cause of disease in 18/34 patients. All but one of these patients had positive CMV isolates in culture on leucocytes. Pulmonary edema was found in 7 patients, bacterial pneumonia in 11 patients, P. carinii in 4 patients and Candida albicans in 1 patient. Multifactorial etiology was found in 12/34 cases. The overall mortality was 32%. Bronchoscopy gave correct diagnosis in 13/14 patients with infectious pulmonary diseases (93%). Bronchoscopy procedures were well tolerated and should be considered in transplant patients with evidence of pulmonary parenchymal disease.

Pancreas-Specific Protein New Serum Marker for Graft Rejection in Pancreas-Transplant Recipients

A radioimmunoassay for a novel human pancreatic protein (pancreas-specific protein, PASP) has been developed. We studied the possibility that serum PASP levels reflect pancreas-graft rejections in human pancreas-transplant recipients. Ten patients subjected to combined pancreas-kidney transplantation and 4 patients subjected to pancreas transplantation alone were studied. Twelve kidney recipients served as control subjects. On several occasions, PASP levels were elevated at kidney rejections in patients with combined pancreas-kidney grafts and then decreased after antirejection therapy, although no other indications for concomitant pancreas-graft rejection were at hand. In the recipients of pancreas grafts alone, PASP levels increased before or at the same time as graft rejections were indicated by current methods. In two cases of chronic graft rejection, PASP rose to high levels long before hyperglycemie occurred. In the control group of kidney-graft recipients, PASP levels were stable and were not affected by high serum creatinine levels, kidneyrejection episodes, or antirejection therapy. This study indicates that PASP may be a good serum marker for pancreas-graft rejection.

Penetration of imipenem into human pancreatic juice following single intravenous dose administration.

The penetration of imipenem into the human pancreatic juice following a single intravenous dose of 500 mg was investigated in five patients who had undergone pancreatic transplantation. With a special technique for segmental pancreatic transplantation it was possible to collect pure pancreatic juice at regular intervals. Simultaneous blood and pancreatic juice samples were collected immediately before drug administration and then at 0.5, 1, 1.5, 2.5, 3.5 and 5.5 h thereafter. The antibiotic concentrations were determined by the agar diffusion method. The mean peak level in serum was 24.6 +/- (SE) 2.6 mg/l and occurred 0.5 h after administration. The mean peak concentration in pancreatic juice was not reached until 1.5 h after administration, and the level was then 1.7 +/- (SE) 0.3 mg/l. Thereafter the levels in serum and pancreatic juice declined in parallel, and the concentration in pancreatic juice was then about 13% of that in serum. Although imipenem penetrates into the pancreatic juice at a very low degree, the concentrations exceeded the MIC values for many bacteria associated with pancreatic infections. Imipenem could therefore be an alternative as monotherapy in the treatment of pancreatic infections.

Isoamylase levels in bone marrow transplant patients are affected by total body irradiation and not by graft-versus-host disease

The mean total serum amylase levels in patients was 3.2±0.5 μkat/l (±SE) before total body irradiation (TBI) prior to bone marrow transplantation of which 50% was due to pancreatic isoamylase and 50% salivary isoamylase. Total serum amylase increased to a maximum of 100.3±12.3 μkat/l on the first day after TBI and most of this increase was due to an increase in salivary isoamylase (90.0±12.1 μkat/l). In association with this, all patients had clinical symptoms of parotitis. An increase in pancreatic isoamylase was found in 27% of the patients; however; none of them had clinical symptoms of pancreatitis. Serum amylase levels returned to normal within 5 days after TBI but then decreased to subnormal values, remaining below the normal range for 3 weeks. Pancreatic isoamylase returned to pre-irradiation levels 1.5 months after TBI, while salivary isoamylase remained low for the rest of the observation time. TBI of 7.5 Gy at 26 cGy/min gave significantly lower salivary amylase at 2 days after TBI compared with 10 Gy at 4 cGy/min: 32±4 versus 76±13 μkat/l (P<0.05). At 2.5 and 6 months after TBI significantly higher total amylase levels were recorded for patients treated with 7.5 Gy of TBI compared with 10 Gy: 2.5±0.4 and 2.7±0.3 versus 2.0±0.5 and 0.8±0.3 μkat/l, respectively (P<0.01, P<0.05, respectively). Acute or chronic GVHD did not affect acinar cells in this investigation.

Evaluation by Immune Scanning Electron Microscopy of Foscarnet Treatment of Cytomegalovirus Infection in Patients with Renal Transplants

Eight patients, 7 renal and 1 combined renal and pancreas allograft recipients with generalized cytomegalovirus (CMV) infection were treated with continuous intravenous foscarnet infusion (0.15 mg/kg/min) for 10-14 days. Antiviral effect was studied by immune scanning electron microscopy for detection of CMV antigen in serum and urine, by virus isolation in tissue culture in samples from buffy coat, broncholavage and urine and by serology. CMV antigen was detected in serum samples in 8 patients and 5 had positive virus isolation from buffy coat, before institution of therapy. The 3 patients with negative virus isolation in tissue culture had serological evidence of a reactivated CMV infection. Virus replication was inhibited by foscarnet treatment in 7 patients within a week (p less than 0.01) (Wilcoxon log rank test). 7/8 patients had no detectable CMV antigen in serum or urine after 7-10 days of treatment (p less than 0.01) (Wilcoxon log rank test).

Segmental Pancreatic Transplantation in Stockholm

Fifty-nine pancreatic transplantations have been performed at Huddinge Hospital between May 1974 and October 1985 with a substantial improvement in results over the years. In the most recent series, consisting of 19 combined renal and pancreatic transplantations performed May 1984 to September 1985; the 1-year actuarial patient survival and pancreatic graft survival were 86% and 66% respectively. Thirteen of these grafts are functional presently, at 18 to 2 months, and all such patients are insulin free and exhibit normal metabolic control. Our practice includes drainage of the pancreatic juice to the exterior by means of a pancreatic duct catheter during the first 2-3 postoperative weeks, thereby promoting healing of the pancreatico-enteric anastomosis. Although cold ischemia time was kept low in this series, a moderate graft pancreatitis developed, with a peak serum amylase level of 16.8 + 2.2 ukat/l and a peak amylase activity in the peripancreatic fluid of 280 + 110 ukat/l. The volume of pancreatic juice from the ductal catheter was very low in the first postoperative days but then rose to reach a plateau level of about 500 ml/day. The amylase activity in this juice was very high (9100 + 2500 ukat/l) during the first postoperative day, but then gradually decreased to reach a steady level around 3000 ukat/l after 4-7 days.