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Background: We reviewed the incidence of and risk factors for venous thromboembolic complications in our population of kidney (KTx) and simultaneous kidney-pancreas transplant (SPK) recipients., Methods: Information was collected retrospectively from a database on 1833 KTx and 276 SPK recipients who underwent transplant surgery between January 1985 and August 1995., Results: The incidence of deep venous thrombosis (DVT) was 6.2% (n= 132), with significantly higher rates after SPK (18.1%) vs. KTx (4.5%) (P < 0.001). The number of DVT episodes was highest in the first month; 17.5% occurred during this time. For KTx recipients, early thrombotic events were more common on the side of the graft (P=0.03); however, after 1 month, no correlation existed between the side of the graft and the side of DVT. For SPK recipients, DVT tended to be more common on the side of the pancreas (57%) vs. the kidney (43%) (P=0.10). By multivariate analysis, risk factors for DVT were: age > 40 years (odds ratio [OR]=2.2, P < 0.001), diabetes mellitus (DM) (OR=2.0, P=0.002), previous DVT (OR=4.4, P=0.001), and SPK transplant (OR=2.8, P < 0.001). Pulmonary embolus (PE) was identified in 44 recipients (incidence, 2.1%) and was fatal in 13 (30%). The incidence was significantly higher in SPK (4.71%) vs. KTx recipients (1.69%) (P < 0.01). The risk of death from PE was 0.5% in KTx recipients and 1.37% in SPK recipients (P=0.08). Risk factors for PE included DM (OR=2.6, P=0.005) and recent DVT (OR=8.9, P=0.0001)., Conclusions: Based on risk and extrapolating from the general surgical literature, our recommendations for prophylaxis against DVT are use of graduated compression stockings for all recipients and, in addition, low-dose heparin for moderate and high-risk recipients (previous DVT, SPK, age > 40 years, DM).

Background: Simultaneous pancreas-kidney transplantation has become a widely accepted treatment option for selected uremic patients with insulin-dependent diabetes mellitus (IDDM). Patient survival rates at 1 year exceed 90%, and rates of pancreas graft survival, 70%. However, solitary pancreas transplantation for nonuremic patients with IDDM has been controversial because of the less favorable outcome and the need for long-term immunosuppression with its associated morbidity and mortality., Methods: We studied the outcome of 225 solitary pancreas transplants during three immunosuppressive eras: the precyclosporine (CsA) era (n=83), the CsA era (n=118), and the tacrolimus era (n=24). Only patients with labile IDDM (e.g., hypoglycemic unawareness, insulin reactions, > or = 2 failed attempts at intensified insulin therapy for metabolic control) underwent solitary pancreas transplantation. Using univariate and multivariate analyses, we looked at patient and graft survival, the risk of surgical complications, and native kidney function during these three eras., Results: Pancreas graft survival improved significantly over time: 34% at 1 year after transplantation in the pre-CsA era, 52% in the CsA era, and 80% in the tacrolimus era (P=0.002). Pancreas graft loss due to rejection decreased from 50% at 1 year in the pre-CsA era, to 34% in the CsA era, to 9% in the tacrolimus era (P=0.008). The rate of technical failures (i.e., the risk of surgical complications) decreased from 30% in the pre-CsA era, to 14% in the CsA era, to 0% in the tacrolimus era (P=0.001). Patient survival rates at 1 year have ranged between 88% and 95% in the three eras (P=NS). Matching for at least one antigen on each HLA locus and avoiding HLA-B mismatches significantly decreased the incidence of rejection. The incidence of native kidney failure due to drug-induced toxicity decreased significantly over time, in part because only recipients with pretransplant creatinine clearance > or = 80 ml/min received transplants., Conclusions: Solitary pancreas transplantation has become a viable alternative for nonuremic patients with labile IDDM. The risks of surgical complications and drug-induced nephrotoxicity have significantly decreased over time. Using tacrolimus as the mainstay immunosuppressant, patient and graft survival rates now no longer trail those of simultaneous pancreas-kidney transplantation.

Cadaver renal allografts with immediate excellent function have good long-term outcomes, while grafts with delayed function have been associated with an increased incidence of acute rejection (AR) and subsequent poor long-term graft survival. There is, however, an intermediate group with initial slow function whose outcome is not well defined. This group was examined by reviewing 510 patients that received primary cadaver transplants between 1/85 and 8/95. Recipients were grouped by initial function into: 1) those with immediate graft function (IGF), defined by serum creatinine (Cr) level < 3 mg/dl on post-operative day (POD) 5 (n = 237); 2) those with slow graft function (SGF), defined by serum Cr > 3 mg/dl on POD 5 but no need for dialysis (n = 160); and 3) those with delayed graft function (DGF), defined by the need for dialysis in the first week post-transplant (n = 113). Five-year graft survivals were determined for each group by Kaplan-Meier methods and compared by a generalized Wilcoxon test. The incidence of AR in the first 6 months was significantly higher in those with SGF (40%) vs. those with IGF (30%) (p < 0.05); both groups had a lower incidence than those with DGF (47%) (p < 0.05). In the absence of AR, 5-yr graft survival was similar between the 3 groups, 94%, 97% and 92% for IGF, SGF and DGF respectively. In the presence of AR, 5-yr graft survival was significantly reduced in all groups, but most notably in those with SGF (51%) or DGF (53%), as compared to those with IGF (80%), (p < 0.001). We conclude that recipients with SGF, but no AR, have excellent outcomes, comparable to those with IGF. However, there is an increased incidence of early AR associated with SGF. In recipients with SGF or DGF, AR has a more profound detrimental effect on long-term graft survival than in the IGF group. Thus, recipients with SGF are at increased risk for AR with resultant poor long-term graft survival, and may need modified immunosuppressive protocols.

Acute rejection is the greatest risk factor for development of biopsy-proven chronic rejection and late kidney allograft loss. We previously noted that low cyclosporine (CsA) levels were a risk factor for early acute rejection in pediatric recipients (1). In our current study, we used logistic regression to identify risk factors for acute rejection in 726 adult kidney transplant recipients on triple therapy (prednisone, azathioprine, CsA). Variables considered for logistic regression analysis were donor organ source (cadaver vs. living), degree of HLA mismatch (1 to 6 vs. 0 antigen mismatch), transplant number (primary vs. retransplant), CsA levels (< 125 vs. > or = 125 ng/ml, < 150 ng/ml vs. > or = 150 ng/ml, and < 175 vs. > or = 175 ng/ml), and acute rejection episodes (0 vs. > or = 1). Of 726 recipients, 401 (55%) received cadaver kidneys; 325 (45%), living related. Overall, 572 (79%) had a primary transplant; 154 (21%), a retransplant. The vast majority of acute rejection episodes occurred within the first 2 months posttransplant; 68% of recipients had no acute rejection episodes by 2 months and 58% had none by 60 months posttransplant. Logistic regression analysis revealed that a cadaver donor kidney (vs. living) (p = 0.004), a 1 to 6 antigen mismatch (vs. 0 mismatch) (p = 0.001), and CsA levels < 150 ng/ml (vs. > or = 150 ng/ml) correlated with biopsy-proven acute rejection. The correlation for CsA levels < 150 ng/ml (vs. > or = 150 ng/ml) held true for levels at 1 wk (p < 0.05), 1 month (p = 0.0001), 2 months (p = 0.01), and 3 months (p = 0.02) posttransplant. Similar correlation was found for CsA levels < 125 ng/ml (vs. > or = 125 ng/ml) and < 175 ng/ml (vs. > or = 175 ng/ml). Comparative analyses were made (by Chi-square) of acute and chronic rejection rates when recipients were divided into 3 groups by CsA level (< 125 ng/ml, > or = 125 to < 150 ng/ml, and > or 150 ng/ml). At each time point (1 wk, 2 wk, 1 month, 2 months, 3 months), CsA levels < 125 ng/ml (vs. > or = 125 to < 150 ng/ml and > or = 150 ng/ml) were associated with the greatest increased risk of acute rejection--for both cadaver and living related recipients (all p < 0.05). CsA levels < 125 ng/ml at each time point (1 wk, 2 wk, 1 month, 2 months, 3 months) were also associated with a significantly increased risk of chronic rejection (all p < 0.001). The incidence of both acute and chronic rejection was reduced in the group with CsA levels > or = 125 to < 150 ng/ml and further reduced in the > or = 150 ng/ml group. Our data indicate that maintaining CsA levels > or = 150 ng/ml as part of triple therapy reduces the incidence of both acute and chronic rejection. Because chronic rejection is the leading cause of late allograft loss, maintaining adequate CsA levels should improve long-term graft survival. Based on this analysis, we have modified our own immunosuppressive regimens to achieve higher CsA levels earlier posttransplant.

Background: Short- and long-term patient and graft survival rates are better for living donor (vs. cadaver) kidney transplant recipients. However, donor nephrectomy is associated with at least some morbidity and mortality. We have previously estimated the mortality of living donor nephrectomy to be 0.03%. In our present study, to determine associated perioperative morbidity, we reviewed donor nephrectomies performed at our institution from January 1, 1985, to December 31, 1995., Methods: The records of 871 donors were complete and available for review. Of these donors, 380 (44%) were male and 491 (56%) were female. The mean age at the time of donation was 38 years (range: 17-74 years), and mean postoperative stay was 4.9 days (range: 2-14 days)., Results: We noted two (0.2%) major complications: femoral nerve compression with resulting weakness, and a retained sponge that required reexploration. We noted 86 minor complications in 69 (8%) donors: 22 (2.4%) suspected wound infections (only 1 wound was opened), 13 (1.5%) pneumothoraces (6 required intervention, 7 resolved spontaneously), 11 (1.3%) unexplained fevers, 8 (0.9%) instances of operative blood loss > or = 750 ml (not associated with other complications), 8 (0.9%) pneumonias (all of which resolved quickly with antibiotics alone), 5 (0.6%) wound hematomas or seromas (none were opened), 4 (0.5%) phlebitic intravenous sites, 3 (0.3%) urinary tract infections, 3 (0.3%) readmissions (2 for pain control and 1 for mild confusion that resolved with discontinuation of narcotics), 3 (0.3%) cases of atelectasis, 2 (0.2%) corneal abrasions, 1 (0.1%) subacute epididymitis, 1 (0.1%) Clostridium difficile colitis, 1 (0.1%) urethral trauma from catheter placement, and 1 (0.1%) enterotomy. At our institution, no donor died or required ventilation or intensive care. We noted no myocardial infarctions, deep wound infections, or reexplorations for bleeding. Analysis, by logistic regression, identified these significant risk factors for perioperative complications: male gender (vs. female, P<0.001), pleural entry (vs. no pleural entry, P<0.004), and weight > or = 100 kg (vs. < 100 kg, P<0.02). Similar analysis identified these significant risk factors for postoperative stay > 5 days: operative duration > or = 4 hr (vs. < 4 hr, P<0.001) and age > or = 50 years (vs. < 50 years, P<0.001)., Conclusions: Living donor nephrectomy can be done with little major morbidity. The risks of nephrectomy must be balanced against the better outcome for recipients of living donor transplants.

Clinical renal transplantation is limited by the number of cadaver and living related donors. The use of kidneys from older donors and non-first-degree relatives, including grandparents, has increased the supply of organs for transplantation. The purpose of this study was to assess donor and recipient outcomes after living related renal transplants between grandparent donors and grandchild recipients. Fifteen living related renal transplants using grandparent donors were performed at the University of Minnesota from 1971 to 1995. All medical records from donors and recipients were retrospectively reviewed. In addition, all grandparents or, in one case, a surviving family member were contacted to obtain current information on medical health and feedback about the donation process. A current serum creatinine (Cr) level was obtained from 14 donors and 15 recipients. Statistical calculations were performed using the SAS system. Eleven grandmothers and four grandfathers, 34-70 yr old (mean, 55 yr) at the time of transplantation, donated a kidney to 15 grandchildren with end-stage renal disease. There were no major surgical complications in either group. One donor died from unrelated causes; the other 14 donors are alive with stable renal function (1.3 +/- 0.3 mg/dL). Of 15 transplanted kidneys, 10 remain functional (Cr 1.3 +/- 0.7 mg/dL) with 2- and 5-yr graft survival rates of 76% and 63%, respectively. Our results indicate that healthy grandparents provide an excellent population for living related kidney donation.

A major variable in the cost of kidney transplants is the length of initial hospitalization. Using multivariate analysis, we studied risk factors for hospital stay > 10 d post-transplant. Between 1 January 1985 and 31 August 1995 a total of 1588 patients underwent first or second kidney transplants at the University of Minnesota. Antibody was used for 1 wk in cadaver donor recipients and for 2 wk in pediatric recipients (resulting in a long stay for all pediatric recipients). Adult living related donor recipients were immunosuppressed with triple therapy. Donor risk factors studied were age (< 15, 15-50, > 50 yr) and,- for cadaver recipients, preservation time (< 12, 12-18, 18-24, 24-30, > 30 h) and cause of death (trauma, cerebrovascular accident, or cardiac). Recipient risk factors studied were age (< 18, 18-55, > 55 yr); sex; transplant number; antigen mismatch; peak PRA; PRA at transplant (< 11, 11-50, > 50); diabetic status; pretransplant dialysis (vs. pre-emptive transplant); pretransplant cardiac, peripheral vascular, or respiratory disease; and delayed graft function (DGF) (dialysis in the first week vs. no dialysis). Risk factors were analyzed separately for living donor and cadaver donor recipients. For cadaver donor recipients, DGF was the major risk factor (p < 0.0001); others were age 55 yr (p = 0.03) and diabetes (p = 0.02). For living donor recipients, DGF was also a risk factor (p = 0.003); others were diabetes (p = 0.01), retransplant (p = 0.006), PRA at transplant > 50 (p < 0.0001), age > 55 yr (p = 0.02), pretransplant respiratory disease (p = 0.005), and pretransplant dialysis (p = 0.005). Because DGF was the major risk factor for a prolonged stay, we then studied risk factors for DGF using multivariate analysis. For cadaver donor recipients, risk factors were recipient weight > 90 kg (p = 0.004), preservation time 24 h (p = 0.03), PRA at transplant > 50 (p = 0.03), and donor age < 15 or > 50 yr (p = 0.002). For living donor recipients, risk factors were recipient age < 18 yr (p = 0.01), donor age > 50 yr (p = 0.03), female sex (p = 0.05), pretransplant respiratory disease (p = 0.1), pretransplant peripheral vascular disease (p = 0.05), and recipient weight > 90 kg (p = 0.1). From our data, a profile emerged of recipients likely to have a longer hospital stay. Important variables, either simultaneous with or related to DGF, include donor and recipient age, diabetes, pretransplant recipient weight, PRA at transplant, preservation time, and pretransplant respiratory or peripheral vascular disease.

Chronic rejection (CR) is the most common cause of graft loss beyond the 1st posttransplant year. The aim of this analysis was to identify the risk factors for the development of CR in pediatric renal transplant recipients. Between June 1984 and March 1994, 217 renal transplants were performed in children at our center. Immunosuppression included prednisone, azathioprine, cyclosporine (CsA), and prophylactic antibody. Using multivariate analysis, we studied the impact of the following variables on the development of biopsy-proven CR: age at transplant (< or = 5 years, > 5 years), gender, race, transplant number (primary, retransplant), donor source (cadaver, living donor), donor age (< 20 years, 20-49 years, > 49 years), number of ABDR mismatches (0, 1-2, 3-4, 5-6), number of DR mismatches (0, 1, 2), percentage peak panel reactive antibody (PRA) (< or = 50%, > 50%), percentage PRA at transplantation (< or = 50%, > 50%), dialysis pretransplant, preservation time > 24 h, acute tubular necrosis requiring dialysis, initial CsA dosage (< or = 5 mg/kg per day, > 5 mg/kg per day), CsA dosage at 1 year posttransplant (< or = 5 mg/kg per day, > 5 mg/kg per day), acute rejection (AR), number of AR episodes (ARE) (1, > 1), timing of AR (< or = 6 months, > 6 months), reversibility of AR (complete, partial), and infection [cytomegalovirus (CMV), non-CMV viral, bacterial]. Risk factors for the development of CR in pediatric renal transplant recipients were: AR (P < 0.0001, odds ratio 19.4), multiple ARE (> 1 vs. 1) (P < 0.0001, odds ratio 30.1), and high percentage peak PRA (> 50%) (P < 0.03, odds ratio 3.6).

Colon perforation (CP) is an uncommon but dramatic complication after renal transplantation. Of 1530 consecutive kidney transplants performed at our center, 8 recipients had an CP (incidence of 0.5%), either early (n = 5, 2-14 days) or late (n = 3, 8-48 months) post transplant. Clinical symptoms were generally vague. Biological findings were inconstant. Risk factors for CP included a cadaver graft (versus a living donor), high body weight, history of diverticulitis, and Kayexalate use. Crucial to outcome were: 1) immediate diagnosis and 2) aggressive surgical care consisting of resectional therapy, broad-spectrum antibiotics, and reduced immunosuppression. Applying these principles, mortality in our patients (25%) was lower than in previously reported series (33-64%). All grafts were functioning at the time of diagnosis; graft function was preserved in recipients who recovered from CP. Patients with a documented history of diverticulitis should undergo prophylactic colonic resection. Constipation and colonic dilatation should be treated aggressively in the early post-operative period.

This review describes the immediate and long-term risks to kidney donors. We reviewed their perioperative morbidity and mortality as well as their quality of life after donation. The overall mortality in our series was zero. Nationally, donor mortality has been estimated to be 0.03% (5). Our overall complication rate was 8.2% with only 2 (0.2%) complications considered to be major (16). Complications were associated with male sex, body weight > or = 100 kg, and inadvertent entry into the pleura during the donor operation. Most of our donors were discharged from the hospital in < 5 days. Risk factors for a longer hospital stay were age 50 or older and an operative time of 4 hours or more. The average donor quality of life after donation, as measured by the SF-36, was better than that of the general US population. This finding persisted for years after donation. The vast majority of our donors found the experience to be very rewarding and would readily donate again if it were possible. However, 4% were dissatisfied and regretted their decision to donate a kidney; these were most likely to be donors other than a first-degree relative and donors whose recipient died within the first posttransplant year. Living donation of kidneys appears to be relatively safe, with very few physical and psychologic complications. It may even improve the donor's quality of life. Living donors are an underutilized source of kidneys. We continue to advocate and encourage living kidney donation.

We studied the impact of early cyclosporine (CSA) levels on the incidence of rejection in pediatric transplant recipients. Between 1 January 1984 and 31 December 1994, a total of 234 pediatric patients underwent kidney transplants and received CSA immunosuppression. We analyzed the impact of CSA levels (at 1 wk, 2 wk, 1 month, 2 months, and 3 months) on the incidence of rejection in the first 3 and the first 6 months post-transplant. We found that CSA levels at all timepoints correlated, i.e. recipients with low levels in the early post-transplant period tended to have low levels throughout the first 12 months. Multivariate analysis for risk factors by biopsy-proven rejection in the first 3 months revealed that the CSA trough level was the critical factor (p < 0.05). Recipients with CSA trough levels < 100 ng/ml had 2.24 times the risk of rejections vs. those with blood levels > 100 ng/ml. Similarly, the CSA trough level at 1 month was the critical risk factor for biopsy-proven rejection within the first 6 months (p < 0.05). The major risk factor for graft loss within the first 12 months was a biopsy-proven rejection episode. We conclude that in pediatric kidney transplant recipients, early CSA trough levels < 100 ng/ml are associated with a significantly increased incidence of rejection in the first 6 months post-transplant.

Given the organ donor shortage, some question whether a third kidney transplant can be justified. We studied the outcome of 51 third transplants (mean age 28 +/- 2 yr) done between 1 January 1985 and 31 December 1994. We compared hospital stay (mean +/- S.E.), cost, readmissions, readmission days, and outcome of third (vs. first and second) transplants. We found that patient survival for third transplants was equivalent to first and second transplants; graft survival was not as good. However, when third transplant recipients with recurrent disease (specifically, hemolytic uremic syndrome and focal sclerosis) were excluded from our analysis, we found no difference in 5-yr graft survival (vs. first or second transplant recipients). Of the 51 third transplant recipients, 41 had a cadaver donor transplant. Third cadaver transplant recipients tended to have a longer hospital stay (p = NS) than first cadaver transplant recipients but had no more readmissions or readmission days than first and second cadaver transplant recipients. Employment data are available for 28 third transplant recipients; 16 (57%) are currently working or going to school. Of the 21 recipients who responded to quality of life questionnaires, 17 (81%) reported being healthy and all 21 (100%) said transplantation was not a drawback to their health. We conclude that third transplants should be considered for selected patients with renal failure whose first and second transplants have failed. Such patients can often be successfully transplanted.

We previously reported that delayed graft function (DGF) in the absence of biopsy-proven acute rejection (Rej) had no effect on outcome of primary cadaver kidney transplantation (TX). By contrast, DGF in combination with Rej strongly predicted poor long-term graft survival. We asked whether this poor long-term outcome was due to early graft loss associated with DGF, or to an ongoing process leading to late graft loss. To answer this question, we studied a subset of 298 cadaver kidney transplant recipients who had not suffered early graft loss and had a serum creatinine level < or = 2.0 mg/dl at 1 year after TX. The incidence of DGF (defined by dialysis during the first week after TX) in this subset was 19%. DGF was associated with cold ischemia time >24 hr (P = 0.0003) and Rej (P = 0.06). For grafts with versus without DGF, the incidence of late acute Rej (>1 year after TX) was similar. Actuarial graft survival was similar for Rej-free recipients with versus without DGF (P = 0.9) and was worse for those with Rej and no DGF (P < 0.02). Importantly, however, in our recipients who all had a serum creatinine level < or = 2.0 mg/dl at 1 year after TX, the worst long-term outcome was noted in the subgroup with both DGF and Rej (P < 0.0001). By multivariate analysis, DGF was also only a risk factor in combination with Rej (P = 0.002, relative risk = 3.7), while a 0-antigen HLA mismatch had no impact. Patient survival decreased for recipients with both DGF and Rej by univariate (P = 0.009) and multivariate (P = 0.02, relative risk = 2.9) analyses. We conclude that DGF without Rej has no impact on long-term survival. However, our data for recipients with both DGF and Rej suggest that a chronic ongoing process leads to late graft failure. Further research is necessary to identify the exact pathophysiology of this process, which appears to be, at least in part, HLA antigen independent.

Unlabelled: We analyzed 420 kidney retransplants at the University of Minnesota, 87 of which did and 333 which did not share HLA mismatches with the previous transplant. There was no difference in outcome. We conclude that exceptions to routine HLA matching policies do not have to be made for kidney retransplants., Objective: To determine if the kidney graft functional survival rate for retransplants is influenced by presence of HLA mismatches in common with the previous (failed) transplant., Summary Background Data: Kidney retransplants have a lower function rate than primary grafts. An anamnestic response to HLA antigens shared with the previous donor could be one factor responsible, but reports in the literature are conflicting., Methods: Of 420 kidney retransplants with HLA information done at the University of Minnesota, 87 shared > or = 1 HLA antigens specifically mismatched with the previous donor (63 cadaver and 24 living donor retransplants), while 333 did not (247 cadaver, 86 living donor). Patient and graft survival rates were calculated by life-table analysis for recipients with vs. without repeat mismatches, with the significance of differences determined by the Lee-Desu statistic., Results: Patient and kidney graft retransplant survival rate curves were not significantly different (p > or = 0.41) for those exposed or not exposed to the same HLA mismatches as before. At 2 years, 70% vs. 61%, respectively, of cadaver grafts and 71% vs. 78%, respectively, of living donor grafts were functioning., Conclusions: The probability of a successful outcome with a kidney retransplant is no different for patients who do than for those who do not receive an organ sharing HLA mismatches with the previous donor. Exceptions to routine HLA matching policies do not need to be made for kidney retransplants.

Background: Vascular thrombosis is still the leading cause of nonimmunologic, technical pancreatic transplant graft failures. The paucity of published data--coupled with our large institutional experience with pancreatic transplantation in all recipient and transplant categories, using a wide spectrum of surgical techniques--provided the impetus for a retrospective study of graft thrombosis risk factors., Study Design: Four hundred thirty-eight patients with pancreatic transplants (45 percent simultaneous pancreas-kidney [SPK], 23 percent pancreas-after-kidney [PAK], and 32 percent pancreatic transplants alone [PTA] and with Type I insulin-dependent diabetes mellitus were studied retrospectively. Of 438 pancreatic transplants, 90 percent were bladder-drained and 10 percent were enteric-drained. Ninety-three percent were from cadaver donors, 90 percent were whole-organ grafts, and 20 percent were retransplantations. Quadruple immunosuppression was given. For bladder-drained, whole-organ transplantations (n=378), we performed Cox regression analyses to study the impact on pancreatic graft thrombosis of donor, recipient, mode of preservation, and surgical variables., Results: The overall thrombosis rate was 12 percent (5 percent arterial, 7 percent venous). For cadaver, bladder-drained, whole-organ pancreatic transplants, the thrombosis incidence was highest in PAK recipients (20 percent). The PAK category was also found to be an independent risk factor for thrombosis by stepwise Cox regression analysis. In separate stepwise Cox regression analyses for each category, other identified risk factors for thrombosis included the following: donor age (PAK, PTA); cardiocerebrovascular cause of donor death (SPK, PAK); the use of an aortic Carrel patch (SPK); arterial pancreatic graft reconstruction using a splenic artery to superior mesenteric artery anastomosis (SPK, PTA) or an interposition graft between the splenic artery and the superior mesenteric artery (PTA); portal vein extension graft (PAK); left-sided implantation into the recipient (PAK); and graft pancreatitis (defined as hyperamylasemia exceeding five days post-transplant [PAK, PTA])., Conclusions: Older donors or those who died of cardiocerebrovascular disease should not be considered for any recipient category. Preservation time needs to be minimized and strategies need to be developed to decrease graft pancreatitis. Surgically, left-sided implantation and arterial reconstructions other than the Y-graft also increase risk, as do portal vein extensions. Renal transplants alone in prospective PAK recipients with Type I diabetes mellitus should, therefore, always be implanted left-sided to allow for right-sided pancreatic graft placement.

This report describes five infants (3 male, 2 female) with renal artery stenosis diagnosed in their 1st year of life. The age at initial presentation was 5 days to 10 months. All had symptoms of congestive heart failure, cardiomegaly on chest X-ray, and left ventricular hypertrophy by electrocardiogram or echocardiogram. Renograms were abnormal in four of the five infants. An intravenous pyelogram was obtained in three infants and was abnormal in two. Renal ultrasounds were obtained in two infants and were normal in both. Patients were treated for 4.4 +/- 0.9 years with antihypertensive drug therapy until surgical correction of the renal artery stenosis. Blood pressure was persistently elevated above the 95th percentile in four of the infants during the course of antihypertensive therapy prior to surgery. Patients have been followed for 9.4 +/- 2 years since surgery. The blood pressure of four patients is normal, and the blood pressure of the oldest patient (age 23 years) is borderline hypertensive. These data show that infants with renal artery stenosis can be cared for successfully with long-term antihypertensive drug therapy to preserve renal mass with minimal chronic adverse effects.

We studied 822 kidney transplant recipients followed 1-9 years to determine the dynamics of their entering and leaving the work force. Multivariate analysis revealed that not being diabetic and that being employed pretransplant were associated with a higher rate of posttransplant employment. Some recipients in all pretransplant employment categories, including those receiving disability benefits pretransplant, returned to full-time work posttransplant. The most rapid return to work was in those who had been working full-time or attending school pretransplant. After returning to work, a higher percentage of diabetic recipients stopped working; of those who stopped working, 50% received disability benefits. In contrast, nondiabetic recipients who stopped working full-time were more likely to be retired or working part-time; only 22% received disability benefits.

Rejection remains a major obstacle to successful small bowel transplantation in humans, irrespective of the immunosuppressants. Previous large animal studies have not used quadruple immunosuppression (with high-dose intravenous cyclosporine A [CSA]) for induction, followed by triple immunosuppression for maintenance therapy. Nor have immunosuppressive doses been comparable to clinical solid organ transplants. We studied, in 78 nonrelated outbred pigs, the effect of quadruple immunosuppression (including horse anti-pig thymocyte globulin [ATG] and high-dose intravenous CSA) on the incidence and severity of rejection in the early, critical posttransplant period. Group A (n = 19) pigs were nonimmunosuppressed. Group B (n = 20) received quadruple immunosuppression: pig ATG (10 mg/kg/day x 10 days), intravenous CSA (3.0 mg/kg/day), prednisolone (2 mg/kg/day), and azathioprine (2.5 mg/kg/day); prednisolone and azathioprine were each reduced by 50% on posttransplant Days 8 and 15. Trough CSA levels were > or = 400 ng/ml for the first 7 days posttransplant, > 200 ng/ml thereafter. Recipient pigs underwent resection of large and small bowel; orthotopic transplants (proximal duodenojejunostomy, distal ileostomy) were done with systemic vein drainage. We developed a scoring system (no, mild, moderate, severe rejection) to grade the extent of both interstitial and vascular rejection: biopsies were obtained daily from the ileostomy. Rejection-free graft survival at posttransplant Days 7, 10, and 14 was 32, 26, and 16% in the nonimmunosuppressed group versus 95, 90, and 85% in the immunosuppressed group (P < 0.0001). Rejection grades were significantly better over the whole observation period in immunosuppressed pigs: interstitial rejection was not present in up to 67% of all daily biopsy specimens. Rejection was present in all specimens of nonimmunosuppressed pigs. Vascular rejection was uncommon (incidence < 10%) in both groups. Isolated vascular rejection without interstitial rejection was not found. Graft-versus-host reaction was noted in both groups in the skin only; liver and native bowel were not involved. We conclude that quadruple immunosuppression with pig ATG and high-dose intravenous CSA for induction effectively prevents moderate and severe rejection in this model. Since clinical transplant complications (rejection, lymphomas) have persisted under FK 506 treatment, our immunosuppressive regimen should be considered an alternative for bowel transplantation in humans to prevent early rejection.

Patients with end-stage renal and hepatic failure may be treated with combined liver and kidney transplantation (CLKTx). We reviewed the indications and outcomes of 16 CLKTx performed at the University of Minnesota between 1980 and 1994. The majority of the recipients (87.5%) were young patients affected by congenital hepatic anomalies and concomitant end-stage renal failure. Fourteen were treated with cyclosporin-based immunosuppression and had an excellent outcome: with an average of 6 years of follow-up, patient survival was 85.7%, liver graft survival 85.7%, and kidney graft survival 72%. The incidence of rejection episodes was similar to the rate of rejection in our solitary kidney and liver transplants. In conclusion, our experience supports the value of CLKTx in treating patients with simultaneous failure of both organs or with congenital enzymatic hepatic deficits leading to renal failure.

Islet autotransplantation can prevent surgically induced diabetes after total pancreatectomy in adults; however, the efficacy of this procedure has not been established in children. The authors report the case of a 12-year-old boy who underwent total pancreatectomy and islet autotransplantation for intractable pain caused by idiopathic chronic pancreatitis. Islets were prepared from the excised pancreas by collagenase digestion and mechanical dispersion. The resultant preparation, containing 109,500 islets, was injected into the recipient's liver via the portal vein. No complication from the pancreatectomy or transplant occurred. Postoperatively, the patient had complete relief of abdominal pain. He remained insulin-independent, with normal fasting blood glucose and hemoglobin A1c levels, for 21/2 years. Preoperatively, the acute insulin response and the rate of glucose disappearance (Kg) were 213 microU/mL and 2.14% (respectively) after intravenous administration of 20 g of glucose. Although lower than pretransplantation values, both insulin response and Kg remained normal at 4 months (88 microU/mL; Kg, 1.01%); however, these decreased further, to below normal, by 2 years posttransplantation (10 microU/mL; Kg, 0.67%). Two-and-a-half years after transplantation, fasting hyperglycemia (> 200 mg/dL) was evident, and the patient was begun on exogenous insulin. Five years posttransplantation he remains insulin-dependent with a fasting serum C-peptide level of 0.20 ng/mL, which increased to 0.35 ng/mL in response to intravenous arginine, indicating sustained islet function. During the documented decreases in insulin secretion and Kg posttransplantation, the patient's body weight increased by 65% (from 34 to 56 kg) as a result of normal growth; the number of transplanted islets relative to body mass decreased accordingly, from 3,200 to 1,950 islets per kilogram of body weight. In this case, the number of islets transplanted likely could not meet the increased insulin demands of the larger body mass. Thus, exogenous insulin supplementation was needed to prevent hyperglycemia. In conclusion, insulin independence was initially established in a child by islet autotransplantation after total pancreatectomy. The failure of the islets to maintain normoglycemia long-term suggests that a sufficient number must be transplanted (to meet the demands of normal growth and development) for sustained insulin independence.

At the University of Minnesota, outcome of renal transplants for infants and young children is the same as outcome for older children and adults. We reviewed our decision-making process in the pre-, peri-, and postoperative care of these recipients.

Background: Urinary amylase (UA) remains the most common biochemical parameter to detect rejection in bladder-drained pancreas allografts. With the development of the cystoscopic transduodenal pancreas transplant biopsy technique, tissue samples of the pancreas graft are now frequently obtained. A definitive correlative analysis between UA activity and biopsy results has not been done in the three different pancreas transplant categories (simultaneous pancreas-kidney, pancreas transplant alone, and pancreas after kidney)., Methods: We studied 66 pancreaticoduodenal biopsy specimens obtained for hypoamylasuria. Rejection was defined as a greater than 25% decrease from stable posttransplantation baseline on two consecutive measurements at least 12 hours apart. To perform biopsies we used our newly developed 14- and 16-gauge core-cut needles (50 cm long). Biopsy specimens were considered positive if either pancreatic or duodenal rejection was found. To assess the quality of UA activity we studied 13 biopsy specimens from patients with stable UA levels; these 13 specimens were negative for rejection., Results: Acute rejection was diagnosed in 36 biopsy specimens (55%). The mean decrease in UA levels was 67% +/- 8% (range, 28% to 99%) for the positive biopsy results, and 57% +/- 16% (range, 22% to 92%) for the negative biopsy results (p = 0.147). Within 1 month, UA levels returned to baseline in 19% of our patients with positive biopsy results versus 97% with negative results; postbiopsy 1-year graft survival was 64% versus 97% (p < or = 0.05). In assessing the test quality of our biopsy specimens (including 13 obtained for reasons other than hypoamylasuria), we found a sensitivity of 100% (stable UA levels mean no rejection) and a specificity of 30%. The predictive value of a positive test was 53%; of a negative test it was 100%. By performing biopsies we avoided antirejection treatment in 47% of the patients studied. We found no biopsy-related complications., Conclusions: Stable UA levels reliably rule out rejection; a decrease is a marker for acute rejection but is unspecific. Performing biopsy is currently the only way to reliably diagnose rejection in solitary pancreas recipients (pancreas transplant alone and pancreas after kidney) and in simultaneous pancreas-kidney recipients with isolated hypoamylasuria. The procedure is safe and should always be attempted to avoid unnecessary rejection treatment.

Background: Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent., Objective: Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis., Patients and Methods: Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables., Results: One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005)., Conclusion: Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

The impact of delayed graft function on outcome after cadaver renal transplantation has been controversial, but most authors fail to control their analyses for the presence or absence of rejection. We studied 457 adult recipients of primary cadaver allografts at a single institution during the cyclosporine era. All patients received sequential immunosuppression. The incidence of delayed graft function (defined as dialysis being required during the first week after transplant) was 23%. There was a significant association between delayed graft function and cold ischemia time > 24 hr (P = 0.0001) and between delayed graft function and the occurrence of at least one biopsy-proven rejection episode (P = 0.004). Actuarial graft survival was not significantly different when comparing delayed graft function versus no delayed graft function for patients without rejection (P = 0.02). However, it was significantly worse for patients with both delayed graft function and rejection versus those with delayed graft function but no rejection (P = 0.005), as well as for grafts preserved > 24 hr versus < or = 24 hr (P = 0.007). By multivariate analysis, delayed graft function per se was not a significant risk factor for decreased graft survival for patients without rejection (P = 0.42). In contrast, rejection significantly decreased graft survival for grafts with immediate function (relative risk = 2.3, P = 0.0002), particularly in combination with delayed graft function (relative risk = 4.2, P < 0.0001). While cold ischemia time > 24 hr was also a significant risk factor (relative risk = 1.9, P = 0.02), other variables (preservation mode, 0 HLA Ag mismatch, age at transplantation, gender, diabetic status, and panel-reactive antibody at transplantation) had no impact on graft survival. Patient survival was significantly affected by the combination of delayed graft function and rejection (relative risk = 3.1, P < 0.0001), age at transplantation > 50 years (relative risk = 2.6, P < 0.0001), and diabetes (relative risk = 1.8, P = 0.006). Further studies are necessary to elucidate the mechanisms linking delayed graft function and rejection, which, in combination, lead to poor allograft outcome.

Objective: The authors determined whether the use of kidney allografts with multiple renal arteries adversely effects post-transplant graft and patient outcome or increases the incidence of vascular and urologic complications., Background: Kidney grafts with multiple renal arteries have been associated with an increased incidence of early vascular and urologic complications. Kidney transplants with single versus multiple renal arteries have not been compared in regard to long-term graft and patient outcome or post-transplant incidence of hypertension, acute tubular necrosis, rejection, and late vascular and urologic complications., Methods: We analyzed 998 adult kidney transplants done from December 1, 1985 through June 30, 1993, in which only the recipient's external or internal iliac artery was used for anastomosis. We divided the study population into 3 groups: Group A-1 renal artery, 1 arterial anastomosis (n = 835), Group B-->1 renal artery, 1 arterial anastomosis (n = 112), Group C-->1 renal artery, > 1 arterial anastomosis (n = 51). We compared the incidence of post-transplant hypertension, acute tubular necrosis, acute rejection, and vascular and urologic complications; mean creatinine levels at 1, 3, and 5 years post-transplant; and patient and graft survival. Univariate and multivariate analyses were done to identify risk factors for vascular complications., Results: We found no significant differences among the three groups for the following variables: post-transplant hypertension, acute tubular necrosis, acute rejection, creatinine levels, early vascular and urologic complications, and graft and patient survival. In kidneys with single arteries, the presence (vs. absence) of an aortic patch and the type of the arterial anastomosis (end-to-end to the hypogastric vs. end-to-side to the external iliac artery) did not have an impact on the incidence of early or late vascular complications. In kidneys with multiple arteries, only the rate of late renal artery stenosis was higher, the rate of early vascular and urologic complications was not different. Our multivariate analysis identified acute tubular necrosis as a risk factor for renal artery and vein thrombosis; graft placement on the left side for arterial thrombosis; and preservation time > or = 24 hours and multiple renal arteries for renal artery stenosis., Conclusions: Results of kidney transplants using allografts with multiple versus single arteries are similar.

Background: Ulcers of the upper gastrointestinal tract after renal transplantation have been reported as a frequent and often lethal complication. Considering the continuous expansion of renal recipient criteria, we reviewed our experience with post-transplant ulcers after 1,034 renal transplants performed during the cyclosporine era., Study Design: Our retrospective study analyzed only endoscopy-proven ulcers of the esophagus, stomach, and duodenum in 439 (42 percent) living related adult recipients and 595 (58 percent) cadaver or living unrelated adult recipients. For ulcer prophylaxis, only oral antacids were routinely given post-transplant., Results: There were 41 ulcers in 33 patients (esophageal: n = 5, 12 percent; gastric: n = 17, 42 percent; duodenal: n = 19, 46 percent). Significant complications (n = 16) included 15 bleeding episodes and one perforation. The pathogenesis was viral in seven cases (gastric: n = 6, 15 percent; duodenal: n = 1, 2 percent). The ulcers occurred significantly earlier post-transplant in cadaver or living unrelated compared with living related recipients (median, 53 compared with 508 days, p = 0.02). Nonoperative treatment was successful for 96 percent of all ulcers. We found no ulcer-related mortality or graft loss. For living related recipients, the actuarial graft survival rate at three years was 69 percent for patients with ulcers compared with 86 percent for those without ulcers (p = 0.02); for cadaver or living unrelated recipients, it was 48 percent for patients with ulcers compared with 77 percent for those without ulcers (p = 0.9). For living related recipients, the actuarial patient survival rate at three years was 92 percent for patients with ulcers compared with 93 percent for those without ulcers (p = 0.8); for cadaver or living unrelated recipients, it was 59 percent for patients with ulcers compared with 88 percent for those without ulcers (p = 0.002)., Conclusions: With more specific immunosuppression and more effective antiviral therapy, the incidence of post-transplant ulcers is low. Considering the excellent results of nonoperative ulcer therapy and a zero percent ulcer-related mortality rate, renal transplantation is safe for patients with specific (e.g., ulcer history) as well as nonspecific (e.g., chronic obstructive pulmonary disease) ulcer risk factors.

Background: Symptomatic lymphoceles are not uncommon after kidney transplantations. Surgical marsupialization with internal drainage is the treatment of choice. However, laparoscopic drainage is reportedly as effective, with only minimal trauma., Methods: We attempted 14 laparoscopic lymphocele drainages during a 3-year period and studied the indications and limitations, using intraoperative ultrasonography in all cases., Results: Laparoscopic drainage was successful in only 9 (64%) of 14 patients. A conversion to open laparotomy was necessary in five patients; their lymphoceles were lateral and either posterior or inferior to the kidney. Two patients with initially successful laparoscopic drainage required conversion to open laparotomy 21 and 83 days later; their lymphoceles were inferior to the kidney. Laparoscopic drainage shortened the median hospital stay by 4 days versus open surgical drainage and by 7 days versus conversion. Hospital costs for laparoscopic drainage averaged $7400 less versus open drainage and $10,300 less versus conversion., Conclusions: In patients with symptomatic lymphoceles medial and either superior or anterior to the kidney, laparoscopic drainage under intraoperative ultrasonographic guidance is easy, safe, and effective. It decreases hospitalization, convalescence, and costs. In patients with symptomatic lymphoceles lateral and either posterior or inferior to the kidney, laparoscopic drainage may fail because of anatomic inaccessibility and technical impracticability.

Noncompliance is increasingly recognized as a major cause of renal allograft loss, but the results of retransplantation of such patients have never been described. At our center, 52 of 3525 kidney recipients between June 1, 1963 and December 31, 1993 lost their graft due to overt noncompliance. Of these, 14 (27%) underwent retransplantation after thorough interdisciplinary evaluation. All but 1 patient had returned to dialysis before retransplantation. Of the retransplanted grafts, 2 were lost (1 technical failure, 1 chronic rejection in a compliant patient); both recipients were retransplanted once again. Currently, all retransplanted patients are alive and have a functioning graft. We conclude that for selected patients with graft loss due to noncompliance excellent results can be achieved with retransplantation. However, the issue of retransplanting previously noncompliant patients in the face of a significant donor organ shortage requires public debate.

Objective: The authors reviewed renal transplant outcomes in recipients 60 years of age or older., Background: Before cyclosporine, patients older than 45 years of age were considered to be at high risk for transplantation. With cyclosporine, the age limits for transplantation have expanded., Methods: The authors compared patient and graft survival, hospital stay, the incidence of rejection and rehospitalization, and the cause of graft loss for primary kidney recipients 60 years of age or older versus those 18 to 59 years of age. For those patients > or = 60 years transplanted since 1985, the authors analyzed pretransplant extrarenal disease and its impact on post-transplant outcome. In addition, all surviving recipients > or = 60 years completed a medical outcome survey (SF-36)., Results: Patient and graft survival for those > or = 60 years of age versus those 18 to 59 years of age were similar 3 years after transplant. Subsequently, mortality increased for the older recipients. Death-censored graft survival was identical in the two groups. There were no differences in the cause of graft loss. Those 60 years of age or older had a longer initial hospitalization, but had fewer rejection episodes and fewer rehospitalizations. Quality of life for recipients 60 years of age or older was similar to the age-matched U.S. population., Conclusion: Renal transplantation is successful for recipients 60 years of age or older. Most of them had extrarenal disease at the time of transplantation; however, extrarenal disease was not an important predictor of outcome and should not be used as an exclusion criterion. Post-transplant quality of life is excellent.

Use of the vena cava to extend the right renal vein for cadaver transplantation is controversial. Right renal vein extension permits an easier anastomosis and possibly better positioning of the kidney, but may create a low flow or turbulent state. We studied whether use of a vein extension had an impact on outcome. Between January 1986 and April 1993, 305 cadaver transplant recipients received a right kidney. Of these, 76 received a graft with vein extension. None of the 76 experienced technical vascular complications versus 5 of the 229 (2.2%) without vein extension. There was no difference in 1- and 2-year graft survival for those with versus without extension. We conclude that there is no increased risk with use of the vena cava extension and recommend that the donor team routinely provide the right kidney with the vena cava attached. This allows the recipient team to determine whether an extension is appropriate for the particular recipient.

The purpose of this study was to identify factors associated with the development of cytomegalovirus (CMV) disease and to assess the morbidity of this illness in pediatric renal transplant patients. The authors retrospectively reviewed the records of 135 patients (< 18 years of age) who underwent a total of 151 transplants (146 kidney transplants, five kidney/liver transplants) over 5 years (average follow-up period, 33.0 +/- 21.7 months). They assessed the risk factors that previously have been associated with the development of CMV disease in adults (age, occurrence of acute rejection episodes, and preoperative donor and recipient CMV serological status) and evaluated the incidence of associated graft loss and mortality. Twenty-two episodes of CMV disease were diagnosed based on evidence of CMV infection and on clinical symptoms; the episodes were treated in 17 patients. A multivariate analysis showed that the development of CMV disease was associated with age of > or = 13 years (P = .02), concomitant liver transplantation (P = .01), and treatment of acute rejection (P = .04). In addition, patients who were CMV-seronegative preoperatively and received a graft from a CMV-seropositive donor (P = .04) or who were CMV-seropositive preoperatively and received a graft from a CMV-seronegative donor (P = .02) were more likely to have CMV disease. Although all patients with CMV disease required hospitalization and were treated with intravenous ganciclovir, CMV disease was not associated with increased allograft loss or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Recipient selection criteria for pancreas (Px) transplantation differ among centers, based on perceived recipient risk factors, and their validity has not been determined. At the University of Minnesota we have been very liberal in accepting patients for Tx, some of whom have risk factors cited as exclusion criteria by other centers, giving us the opportunity to determine, retrospectively, the impact of their presence on outcome. Between July 1986 and March 1993, we performed 319 bladder-drained cadaver Px Txs at the University of Minnesota, 166 simultaneous with a kidney (SPK), 68 after a kidney (PAK), and 85 alone (PTA). To determine which putative "risk factors" influence patient and graft survival, we used uni- and multivariate (Cox regression) analyses to assess the impact of recipient category, duration of diabetes, and age at onset and at Tx; presence of pre-Tx cardiac (CD) disease (myocardial infarction, bypass, angioplasty), peripheral vascular disease (PVD) (stroke, bypass, angioplasty, amputation); blindness, hypertension, and excess weight; and of Px re-Txs. The incidences of all risk factors except re-Tx were significantly higher in SPK than PTA recipients. Px re-Txs comprised 40% of PAK, 26% of PTA, and 10% of SPK cases (P < 0.0001). Duration of diabetes correlated (P < or = 0.01) with all risk factors but one (hypertension). Recipient age correlated (P < or = 0.01) with CD, blindness, duration of diabetes, and age at onset of diabetes; CD risk factors correlated (P < 0.015) with hypertension and PVD. Recipient age (> or = 45) influenced the technical failure rate only in SPK recipients, with a relative risk (RR) of 2.13 (P = 0.08). Recipient age influenced Px graft and patient survival rates in both SPK and PAK recipients; for those > or = 45, the RR of graft loss was 1.73 and 1.76, respectively (P < or = 0.25), and the RR for ultimately dying was 3.07 in PAK (P = 0.02) and 5.86 in SPK (P = 0.17) recipients. SPK recipients with CD factors were at higher risk to ultimately die (RR = 3.78, P = 0.009), independent of age. Px re-Txs were not at higher risk to fail in PTA, but were in PAK recipients (RR = 1.86, P = 0.09); the risk for technical failure was higher for re-Txs only in SPK recipients (RR = 2.11, P = 0.24). Blindness, hypertension, PVD, and duration of diabetes did not negatively influence patient and graft outcome in any recipient category.(ABSTRACT TRUNCATED AT 400 WORDS)

We performed 73 kidney transplants in 51 patients with steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerular sclerosis (FSG) ages 18.4 +/- 12.8 (mean +/- SD) years. Recurrence of SRNS, defined by rapid onset of proteinuria, hypoalbuminemia and/or > 95% epithelial cell foot process effacement with or without the presence of FSG, occurred in 26 grafts in 16 patients. Acute renal failure (ARF) occurred in 16 of 26 (61.5%) grafts with recurrence versus 7 of 47 (14.9%) grafts without recurrence (P < 0.0001). ARF occurred in 4 of 9 (44.4%) living-related donor (LRD) recipients with recurrence and 3 of 21 (12.5%) LRD recipients without recurrence (NS). ARF in cadaver donor (CAD) recipients with recurrence was 12 of 17 (70.5%) versus 4 of 23 (17.4%) without recurrence (P < 0.0001). ARF was also higher in LRD or CAD with recurrence than in a control group of non-SRNS patients matched for age, sex and time of transplantation. Graft survival at one year was lower in patients with recurrence and ARF [4 of 16 (25%)] compared to patients with recurrence and no ARF [9 of 11 (82%), P < 0.01]. There was no difference in graft survival in patients without recurrence who did or did not have ARF. One or more acute rejection episodes occurred in all 16 patients with ARF and recurrence, in all 7 patients with ARF without recurrence, and in 7 of 10 patients with recurrence without ARF compared with only 11 of 40 (28%) of patients with neither recurrence nor ARF (P < 0.0001, < 0.001 and < 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical observations suggest that recipients of multiorgan transplants from the same donor can have disparate immunological reactions to each organ. We studied this phenomenon in 36 diabetic (streptozotocin-induced), bilaterally nephrectomized, immunosuppressed (cyclosporine, azathioprine, prednisone) pig recipients of simultaneous (same donor) pancreas (bladder drained) and kidney allografts by grading the histological intensity of rejection in biopsies of each organ at defined intervals posttransplant. Graft function was monitored by plasma glucose (PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr) for the kidney. Interstitial rejection was graded as absent, mild, moderate, and severe in, respectively, 8%, 25%, 42%, and 25% of pancreas vs. 4%, 12%, 27%, and 57% of kidney biopsies at 1 week; and 0%, 43%, 29%, and 29% of pancreases vs. 10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of grades was similar in the two organs (P > 0.1), the grade of rejection for each pair at 1 week (n = 24) was discordant in 75% (42% differed by one and 33% by > or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2 grades). The inability to use the severity of interstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interstitial rejection at one week, the corresponding kidney showed moderate or severe rejection, and for the 1 kidney without rejection the corresponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution for the pancreas (57%, 30%, 9%, 4%) vs. kidney (50%, 38%, 0%, 12%) at 1 week, and at 2 weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11 for the kidney) (P > or = 0.64). However, the grading of vascular rejection in organ pairs was dyssynchronous in 54% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No vascular rejection in the pancreas with rejection in the kidney was seen in 5 pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%).(ABSTRACT TRUNCATED AT 400 WORDS)

15-deoxyspergualin (DSG) is a novel immunosuppressant which has been shown to be effective in preventing and treating rejection in animal allo- and xenotransplant models. Preliminary clinical studies suggest that DSG is an effective antirejection agent. In our study, 4 patients with biopsy-proven rejection episodes that were resistant to steroid and antibody therapy were then treated with DSG. All 4 rejection episodes responded to DSG therapy and all 4 kidneys continue to function (follow-up 7-15 months). However, 2 patients had additional rejection episodes after DSG therapy. Side effects during DSG treatment were minimal; 1 patient, who had also had multiple courses of antibody, developed a lymphoproliferative tumor 2 months after DSG administration. We conclude that DSG is effective in treating refractory renal transplant rejection episodes. Additional studies are necessary to determine the ideal place for DSG in treating renal transplants recipients with rejection.