Evaluation of pancreas transplant needle biopsy: reproducibility and revision of histologic grading system.

BACKGROUND: Tissue samples for the diagnosis of pancreatic allograft rejection are now obtained routinely through the application of the percutaneous needle biopsy technique. The availability of biopsy material (89% adequate for diagnosis in our setting) presents a challenge for pathologists who are asked to provide a fast and accurate diagnosis of rejection and its severity, while at the same time being able to differentiate rejection from other causes of graft dysfunction. METHODS: To differentiate rejection from other pathologic processes, 26 histologic features were assessed in 92 biopsies performed for confirmation of clinical diagnosis of rejection and the results were compared with 31 protocol biopsies, 12 allograft pancreatectomies with non-rejection pathology, and 30 native pancreas resections with various disease processes. RESULTS: Based on these comparisons, a constellation of findings relating to the vascular, septal, and acinar inflammation was identified for the diagnosis of rejection. Application of these features led us to revise our scheme for grading rejection (ranging from 0-normal to V-severe rejection) to include the categories of "inflammation of undetermined significance" and "minimal rejection." The scheme was used by five pathologist to grade 20 biopsies independently of any clinical data and the interobserver level of agreement was highly significant (kappa=0.83, P<0.0001). This grading scheme was applied blindly to all (183) biopsies from 77 patients with 6-52 months of follow-up. The correlation of the highest degree of rejection on each patient and ultimate graft loss (0% for grades 0-I, 11.5% for grade II, 17.3% for grade III, 37.5% for grade IV, and 100% for grade V) was highly statistically significant (P<0.002). The fraction of grafts lost due to pure immunologic causes increased proportionally to the grade of rejection (0, 50, 66, and 100% for grades II, III, IV, and V, respectively). CONCLUSIONS: This study provides strong support for the proposed pancreas rejection grading scheme and confirms its potential for practical use.

Solitary pancreas allografts. The role of percutaneous biopsy and standardized histologic grading of rejection.

OBJECTIVE: To determine the potential impact of ultrasound-guided percutaneous pancreas allograft biopsy and standardized histologic grading on graft and patient survival in a solitary pancreas transplant program. DESIGN: Retrospective case series survey. SETTING: Tertiary care, university teaching hospital. PATIENTS: Thirty-five recipients of solitary pancreas transplants. INTERVENTIONS: Percutaneous pancreas allograft biopsies were performed in solitary pancreas transplant recipients. MAIN OUTCOME MEASURES: Actuarial graft and patient survival, cause of graft loss. RESULTS: Initiation of ultrasound-guided percutaneous pancreas allograft biopsy with standardized histologic grading is associated with a 70% 1-year graft survival and 93% 1-year patient survival in solitary pancreas transplantation. Acute rejection was responsible for only 11% of cases of graft loss. The presence of endotheliitis, vasculitis, or confluent acinar necrosis is associated with decreased pancreas allograft survival, poor response to corticosteroid therapy, and shortened time interval to ultimate graft loss. Clinical criteria for acute rejection such as elevated serum amylase or lipase levels, 50% decrease in urinary amylase levels, unexplained fever, or hyperglycemia are associated with a positive predictive value of only 72%. CONCLUSION: Pancreas allograft biopsy and standardized histologic grading are associated with significantly improved 1-year graft and patient survival in solitary pancreas transplantation.

Double renal allografts successfully increase utilization of kidneys from older donors within a single organ procurement organization.

BACKGROUND: In 1994, a policy of double renal allografting (DUAL) was used at two centers within our local organ procurement organization to increase utilization of kidneys from older donors that would otherwise be discarded. Both kidneys from an older donor (age > 60 years) were selectively transplanted into a single adult recipient. METHODS: The relative impact of a DUAL policy on the utilization of older donor kidneys is examined for the period of April 1994 to April 1996. Actual utilization is compared with the hypothetical case in which a DUAL policy is not present. RESULTS: In the actual setting, a total of 75 kidneys from older donors (> 60 years) were accepted for transplantation. Thirty-six kidneys were transplanted as singlets, and 16 additional kidneys were transplanted as DUAL renal allografts. Thus, a 44% increase in transplantable kidneys, and a 22% increase in patients transplanted with kidneys from older donors, was realized. In the actual setting, 23 older kidneys were discarded; without the DUAL policy, 39 kidneys would have been deemed untransplantable. When compared with the actual (n = 52) and hypothetical number of kidneys transplanted without a policy of DUAL transplantation (n = 36), the DUAL policy significantly increased the utilization of older donor kidneys (P = 0.01). The actuarial 1-year graft survival rate of the dual kidneys was 100%, with a mean follow-up of 11.1 +/- 2.9 months. Mean 6-month and 1-year serum creatinine level were 1.76 +/- 0.4 and 1.63 +/- 0.6 mg/dl, respectively. CONCLUSIONS: A DUAL policy significantly increased the number of older donor kidneys transplanted in a single organ procurement organization and reduced the rate of discard of older donor kidneys over a 2-year period. Long-term follow-up is necessary to substantiate satisfactory graft function in DUAL from older donors.

Double adult renal allografts: a technique for expansion of the cadaveric kidney donor pool.

BACKGROUND: A major impediment to kidney transplantation is the current shortage of donor organs. Currently approximately 22,500 candidates are awaiting kidney transplantation, while the number of donors remains stable at approximately 3500 each year in the United States. Alternative approaches to traditional organ donor selection are necessary. In this setting we hypothesized that kidneys with reduced nephron mass from adult donors may provide satisfactory renal function if both donor kidneys are placed into a single recipient. METHODS: Eighteen paired adult renal allografts were transplanted into nine adult recipients (DUAL). Recipient graft outcome variables were examined and compared with outcomes from single kidneys transplanted from randomly selected "ideal" donors younger than 50 years of age (CONT < 50) and "expanded" donors older than 60 years of age (CONT > 60) who underwent transplantation at our center. RESULTS: Six-month serum creatinine levels in the three groups, DUAL (n = 9), CONT < 50 (n = 20), and CONT > 60 (n = 12), were 1.6 +/- 0.3, 2.3 +/- 0.3, and 4.1 +/- 0.9 mg/dl, respectively, (p < 0.0001) between CONT > 60 and the other two groups. Mean estimated creatinine clearance (ml/min/1.73 m2) was 43.2 +/- 3.4, 62.5 +/- 5.4, and 24.5 +/- 5.3 (p < 0.02). Graft and patient survival at last follow-up in DUAL was 100% compared with 95% in CONT < 50 and 75% graft and 83% patient survival in CONT > 60. Delayed graft function occurred in one of nine patients (11%) in DUAL group compared with 4 of 20 (20%) in CONT < 50 group and 6 of 12 (50%) in CONT > 60 group. Mean follow-up of patients in DUAL group was 6.6 months (range, 2 to 14 months). CONCLUSIONS: Double adult kidney transplants (DUAL) are associated with acceptable short-term graft function, graft survival, and patient survival when compared with transplanted kidneys from an ideal donor group (CONT < 50). Double renal allografts are a preferred use for donor kidneys with suboptimal nephron mass. Long-term follow-up is required to validate further the proposed approach.

Equivalent success of simultaneous pancreas kidney and solitary pancreas transplantation. A prospective trial of tacrolimus immunosuppression with percutaneous biopsy.

OBJECTIVE: This study was designed to evaluate the results of solitary pancreas transplantation in a protocol that uses the new immunosuppressant tacrolimus (FK) and liberally applies ultrasound-guided percutaneous pancreas biopsy to diagnose rejection. SUMMARY BACKGROUND DATA: Pancreas graft survival in patients who simultaneously receive a kidney transplant (SPK) historically has been 75% to 90% at 1 year, approaching that of cadaveric kidney transplantations. In sharp contrast, graft survival rates in patients who receive a pancreas atone (PA) have remained static over the past decade, with approximately 50% functional at 1 year. It was hypothesized that the results of PA transplantations would improve with newer maintenance immunosuppressants and biopsy techniques. METHODS: Twenty-seven PA recipients prospectively were treated with FK-based immunosuppression (PA-FK). Percutaneous biopsy was performed for hyperamylasemia, hyperlipasemia, hypoamylasuria, or unexplained fever. One year pancreas graft survival in these patients was compared to 15 cyclosporine treated PA cases (PA-CsA) and 113 SPK recipients. RESULTS: The 1-year pancreas graft survival rate of 90.1% in technically successful PA-FK patients was significantly better than the 53.4% rate in PA-CsA recipients (p = 0.002) and no different than the 87.4% rate in SPK recipients. The only graft lost to acute rejection in the PA-FK group was because of acknowledged patient noncompliance. Percutaneous biopsy substantially improved the diagnostic certainty in cases of suspected rejection and was associated with a low complication rate (3/178 = 1.5%). CONCLUSIONS: Modern immunosuppression and biopsy techniques have improved the success of solitary pancreas transplantations to the point where outcome is now equivalent to that of SPKs.

Late pancreas allograft rejection. Preliminary experience with factors predisposing to rejection.

A case series of 31 cadaveric pancreas transplant recipients who were insulin-independent at least for one year was analyzed for the factors predisposing to late acute rejection (> 12 months posttransplant). Sixty-two pancreas transplants were performed in 61 patients, of whom 53 had functioning allografts 3 months posttransplant; 31 of these had a follow-up > 12 months. Twenty had no evidence of late rejection, whereas 11 had evidence of acute rejection after 12 months. All patients received quadruple induction immunosuppression. No demographic or clinical factors-including donor age, organ cold time, HLA mismatch, age, sex, or race-could distinguish the late acute rejection group. The presence of acute rejection in the first year posttransplant was similar in the late rejectors (21 episodes in 9 of 11 patients) compared with patients without late rejection (31 episodes in 16 of 20 patients). Antilymphocyte induction therapy type had no influence, but the amount of immunosuppression with prednisone and cyclosporine (CsA) at 3 months posttransplant was significantly lower in those patients who experienced late rejection. After the first year posttransplant, CsA 12-hr trough levels were significantly lower in late rejection months (121 +/- 7 ng/ml) compared with each patient's own stable months (183 +/- 5 ng/ml, P < 0.0001). Neither prednisone nor azathioprine dosages differed between teh two groups after the first year posttransplant. Our preliminary results suggest that early under immunosuppression with prednisone and CsA in the first year and 12-hr trough CsA levels less than approximately 180 ng/ml after the first year posttransplant predispose to late pancreatic rejection.

Acute renal failure associated with immunoglobulin therapy.

Four cases of acute renal failure induced by intravenous immunoglobulin are presented, and the literature on the subject is reviewed. The clinical course varies from asymptomatic serum creatinine elevation to anuric renal failure occurring within days of the institution of therapy, followed by the rapid recovery of renal function after termination of therapy. The renal histology demonstrates severe tubular vacuolization with cellular swelling and preservation of the brush border. Glomerular endothelial, mesangial, and epithelial cells also may demonstrate swelling and vacuolization. There is no evidence for inflammatory or immune complex-mediated etiologies. The immunoglobulins or carbohydrate additives in the preparations appear to have a unique and reversible effect on the glomerular and tubular cell function.