Renal allograft rupture: a clinical review.

Rupture of a renal allograft (RAR) is an uncommon but serious complication of renal transplantation. A recent RAR prompted a review of our experience, with the purpose of (1) identifying conditions that may predispose this complication and (2) defining strategies for prevention. A 5-yr, consecutive living-related (LRD) and cadaver donor (CD) cohort of 331 patients was studied retrospectively. Twelve patients (3.6%) had RAR. Donor characteristics, procurement and preservation conditions, and recipient characteristics were major study categories. Data analysis was computer-based and included multivariate analysis. The nine White and two Black cadaver donors were "ideal", mean age 29 yr, with mean high creatinine (CR) of 1.3 and terminal CR of 1.1 mg/dl and mean terminal urine output of 423 ml/min. Nine of 11 CD had low-dose dopamine use (terminal, mean 8, range 5-13 micrograms/kg/min). Eleven of 11 donors had procurement en-bloc, 9 of which were multiple organ procurement. All had 4+/4+ flush and cold storage with UW solution. Mean cold ischemia time (CIT) was 22 h, 28 min (range 15 h, 16 min to 40 h). For patients with RAR mean age was 39 yr; there were 12 Black patients and 7 males, 5 females. HLA match was 1 antigen (AG) for 3, 2 AG for 8, and 4 AG for 1 (mean 1.9). Nine patients had delayed or declining renal function requiring dialysis. The panel reactive antibody was at peak, mean 47% (range 0-100%) and current, mean 18% (range 0-84%). Six of 12 had OKT3 therapy at time of RAR and six had biopsies. Day of RAR was mean 10, median 9 (range 4-21). Pain and drop in hematocrit were observed in most. There was one fatality (8%), and all kidneys were removed. All kidneys showed at least minimal rejection but six had severe acute tubular necrosis (ATN) with edema and minimal rejection. Statistically significant associations with RAR were older recipient age (p = 0.01), donor-recipient race mismatch (White donor to Black recipient) (p = 0.007), and dialysis requirement (p < 0.001). Other variables were not statistically correlated: gender, race, CIT, transplant number, LRD vs. CD, peak or current PRA, and total HLA and BDR mismatch. The data suggest that ATN and rejection act synergistically to cause RAR and that early delayed function requires intensive and perhaps novel immunosuppression, especially in Black recipients.

The quest for living-related kidney donors for children with end-stage renal disease.

In a pediatric renal transplant program that actively seeks living-related kidney donors, we achieved a living donor rate of 55% in 119 children. This approximates the national average but is less than an idealized goal. For black children, the living-donor transplant rate was 41%, a disconcertingly low rate. In an attempt to define factors that negatively affected living-related donor availability, we analyzed our evaluation process by distinct phases (interview, histocompatibility testing and medical evaluation). We classified our families on the basis of locale (urban, suburban and rural), family unit (two or less parents, adult sibs or other relatives presenting at interview) and economic status (designating only economic-disadvantaged and other). While histoincompatibility is predictably a negative factor, the negative impacts of medical illness in the donor pool, economic disadvantage and single parent family are striking and cumulative. Our data validate the relative success of an aggressive recruitment policy in a patient population that includes many economically disadvantaged families. For pediatric renal transplant programs with low living-related donor rates, our data should encourage review and possible modification of the donor recruitment process.

The risks, benefits, and costs of expanding donor criteria. A collaborative prospective three-year study.

The study purpose was to identify risks, benefits and costs associated with an expanded donor protocol. The protocol design evaluated organs rescued using expanded donor criteria and weighed all costs associated with doing so. Costs were measured against conditions experienced with expanded and traditional criteria and recipient outcome. Traditional donors were between 5 and 55, with negative serologies, and no history of hypertension or diabetes. "Expanded donors" were between 55 and 75 or less than 5, with a history of hypertension, diabetes and/or sero-positive for Hepatitis C. During this study 73 donors met criteria from which 200 organs were transplanted. Defined costs and outcomes for recipients were tracked. Using expanded criteria: costs averaged 20% more per organ; OPO personnel spent an average of 6 hours more time on-site; an additional 12-14 hours in placement activity; and average organs per donor decreased. Heart patient and graft survival rates for traditional and expanded donor organs were comparable. Kidney patients transplanted from this pool experienced a decrease in patient (P = .14) and a significant decrease in graft (P = .02) survival rates. Patient (P = .05) and graft (P = .01) survival rates were significantly lower in liver patients transplanted with expanded donor organs. Two hundred transplants occurred using expanded donor criteria. Costs for the OPO increased appreciably. Heart and kidney utilization from these donors seems justified. It is thought that liver recipients' results were due to utilizing them in sicker patients. Recovery of organs from donors using expanded criteria appears to be a reasonable way of increasing organ supply.

Organ and tissue donation in Louisiana: the 1994 experience of the Louisiana Organ Procurement Agency (LOPA).

The Louisiana Organ Procurement Agency (LOPA) operates the organ and tissue procurement system for the entire state. LOPA is experiencing an increase in referrals and actual donors, with 101 donors realized from 34 hospitals in 1994. From these donors, 398 organs were recovered to provide 275 kidney, liver, heart, pancreas, and lung transplants in Louisiana, and 97 organs were shared for transplant elsewhere. However, consent for donation was refused for 40% of medically suitable donors, creating a loss of 180-200 organs for transplant, many of which would have been lifesaving. Nationwide, the shortage of organs continues to worsen as waiting lists grow. This health care problem continues to generate corrective initiatives, such as "required request" and performance standards for the organ procurement organization. Ranked in the top group of procurement organizations, LOPA is well positioned to meet and help define new federal standards.

Chronic endotoxemia reversibly alters respiratory burst activity of circulating neutrophils.

Endotoxin-induced sequestration of neutrophils and ectopic activation of the cytocidal respiratory burst are thought to contribute to the pathophysiology of "endotoxin shock." The effects of endotoxin on the circulating neutrophil population have not been described. A rat model of continuous sublethal endotoxin infusion by minipump was used to study spontaneous and stimulus-specific activation and priming of superoxide anion and chemiluminescence production of circulating neutrophils. At 3 hr of endotoxin infusion there are marked neutropenia, minimal spontaneous activation compared to an active response in the control, and no priming effect. By 30 hr of endotoxin infusion, a neutrophilic leukocytosis, a marked spontaneous activation of superoxide anion and chemiluminescence production are observed, with no priming response and a loss of zymosan-stimulated chemiluminescence. The biologic significance of endotoxin-induced spontaneous activation is unknown. By 78 hr of infusion the host tolerance to endotoxemia is also evident for neutrophils, since neutrophil responses are nearly identical in endotoxin- and saline-infused groups. The loss of zymosan-stimulated chemiluminescence in both groups at 78 hr suggests a foreign-body effect from the minipump and may reflect altered arachidonic acid metabolism.

Ischemic intestinal necrosis as a cause of atypical abdominal pain in a sickle cell patient.

The authors present a case report of a sickle cell patient with end-stage renal disease treated with peritoneal dialysis who presented with abdominal pain. Although the pain was not unlike that typically associated with his crises, the absence of characteristic joint and chest pain made the diagnosis of "crisis" unlikely and favored the admitting diagnosis of peritoneal dialysis-related peritonitis. After the patient failed to improve with a medical regimen, including antibiotics, surgical consultation was obtained. Complete small bowel obstruction and diffuse peritonitis necessitated emergency surgery at which necrosis of terminal ileum was encountered. Histologic study of the resected specimen showed microvascular thrombosis with sickled erythrocytes. The authors review this rare complication and discuss the clinical problems of diagnosing typical and atypical abdominal pain in the sickle cell patient with and without concomitant crisis.

Preoperative immunomodulation of renal allograft recipients by concomitant immunosuppression and donor-specific transfusions.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 113 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor/recipient combinations were at least 1-haplotype disparate and 17 were 2-haplotype disparate. Presensitization, defined as a positive Amos or antiglobulin T cell CM or a positive high-titer (greater than or equal to 1:8) B cell CM was present in 10 patients and not present in 103 patients. Attempts at desensitization of the already sensitized group were uniformly unsuccessful. Treatment of the 103 nonpresensitized patients resulted in transient sensitization in 3 patients, permanent sensitization in 8, and no evidence of sensitization in 92. Ninety-one nonsensitized patients underwent renal transplantation from the specific blood donor, and only 5 have experienced renal allograft rejection loss during a mean follow-up period of 26 months (6 to 70 months). Fifty-four percent have never experienced a rejection episode. The allograft survival rate at 2 years (91%) and 5 years (89%) is significantly better (P less than .01) than our historical experience with 1-haplotype living-related transplants at 2 years (66%) and 5 years (64%). The low rate of sensitization (8%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of rejection (5%) argues for a modification of the immunologic response rather than a selecting out process as the mechanism for improved allograft survival.

Improved renal function after renal artery revascularization.

An experience with 20 patients with renovascular hypertension and renal insufficiency secondary to renal artery stenosis is presented. The mean follow-up was 29 months. Eighteen patients had atherosclerotic renal artery stenosis and two patients had transplant renal artery stenosis. The mean preoperative blood pressure of 162 +/- 5 mmHg decreased significantly to 105 +/- 2 mm Hg (p less than 0.001). The serum creatinine also decreased from a mean preoperative level of 4.7 +/- 0.7 mg/dl to a mean postoperative level of 2.3 +/- 0.3 mg/dl (p less than 0.001). Similarly, the creatinine clearance improved from a mean preoperative level of 28 +/- 2 ml /min to a mean postoperative level of 45 +/- 8 ml/min (p less than 0.03). Four patients (20%) with improved renal function died from 4 days to 15 months postoperatively. Two patients (10%) have progressed to end stage renal disease. These findings demonstrate that renal revascularization is clearly beneficial in the short-term and long-term improvement of renal function.

Thrombolytic therapy for acute arterial occlusion.

To evaluate the role of selective intra-arterial low-dose thrombolytic therapy (SILDT) as an alternative to the surgical management of acute arterial occlusion, the hospital records of 40 patients who underwent 43 SILDT treatments with either streptokinase (36) or urokinase (7) between December 1979 and March 1984 were reviewed. Twenty-eight patients underwent 30 treatments (group 1) for native arterial occlusion and 12 patients underwent 13 treatments (group 2) for prosthetic or autogenous graft occlusions. Therapy was deemed successful if subsequent surgical therapy was obviated. In group 1, SILDT was successful in 13 of 28 (45%) patients with 12 of 25 lower extremity occlusions and one of three upper extremity occlusions. Successful lysis in the native artery occlusion group fell into three categories: five patients were successfully treated for arterial thrombosis complicating percutaneous transluminal angioplasty (PTA); four patients required PTA after complete lysis revealed an underlying arterial stenosis; and only three required no further therapy after SILDT. SILDT failed in all three patients with the aortoiliac occlusions. Eleven patients with femoral artery occlusions and unsuccessful SILDT required six bypass procedures, three amputations, one embolectomy, and one PTA. In group 2 only 3 of 14 treatments (21%) were successful. Bypass revision was not possible in 11 patients and all required amputation. Systemic fibrinolysis was seen in 20 (59%) of 34 patients with available data. Neither fibrinogen levels nor fibrin degradation products predicted the occurrence of complications. Minor complications occurred in 18 of 43 (43%) treatments; small hematomas at the catheter entry site were most common. Minor complications occurred in 20 of 43 treatments (44%) and included severe local hemorrhage (four), distant bleeding (three), pulmonary embolism (four), myocardial infarction (three), unmasking of an aortoduodenal fistula (one), and clot migration requiring emergency thrombectomy (four). SILDT is most effective in acute arterial thrombosis complicating arteriography or percutaneous angioplasty. It may play a role in the patient in whom thrombolysis can reveal an underlying stenosis amenable to percutaneous angioplasty. This experience shows SILDT to be of limited value in the management of prosthetic autogenous graft occlusions. Finally, thrombolytic therapy is associated with significant morbidity and mortality rates and requires cautious monitoring to detect arterial thrombus migration, worsening tissue ischemia, venous thromboembolism, intracerebral hemorrhage, and local or systemic bleeding.

Pretreatment of renal allograft recipients with immunosuppression and donor-specific blood.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 64 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous azathioprine immunosuppression. All donor/recipient combinations were at least one-haplotype-disparate. Presensitization, defined as a positive Amos or antiglobulin crossmatch or a high-titer (greater than 1:8) B-cell-positive crossmatch, was present in 6 patients and not present in 58 patients. Attempts at desensitization of the already sensitized group were uniformly unsuccessful. Treatment of the 58 nonpresensitized patients resulted in transient sensitization in 2 patients, permanent sensitization in 1 patient, and no evidence of sensitization in 55 patients. Fifty-three patients underwent renal transplantation from the specific blood donor, and only two have experienced renal allograft rejection loss during a mean follow-up period of 22 months (5-45 months); 57% have never experienced a rejection episode. The two-year renal allograft survival rate was 85%. This is significantly (P less than 0.01) better than our historical experience of 64% with one-haplotype living-related transplants. The low rate of sensitization (5%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of rejection (4%) argues for a modification of the immunologic response, rather than a selecting-out process as the mechanism for improved allograft survival.

Renal thromboxane synthesis in excised kidney distal to renovascular lesions.

Excision of a kidney with three distinct zones of perfusion was required in a patient with renovascular hypertension. One third of the kidney was normal, one third was ischemic from a stenotic artery, and one third was severely ischemic from a completely occluded artery. This provided a unique opportunity to study renal prostaglandin production in hypoperfused and control tissue by radioimmunoassays of incubated tissue slices. The thromboxane-prostacyclin synthesis ratio for the outer cortex increased from 2.2 in control tissue to 5.8 in moderately ischemic tissue and 11.3 in severely ischemic tissue; for the inner cortex, 2.1 to 6.3 and 8.8; and for the medulla, 0.4 to 1.2 and 3.0, respectively . Similar ratios were noted for thromboxane-prostaglandin E2. This correlates, for the first time in man, absolute and relative increases in renal thromboxane synthesis with renovascular hypertension.

Prostaglandin synthesis associated with renal allograft rejection in the dog.

Vasospasm and intrarenal thrombosis are characteristics of acute renal allograft rejection. A possible mediator of these phenomena is thromboxane A2. Single kidneys were exchanged between nonimmunosuppressed mongrel dogs. At intervals after transplantation, rejecting and normal kidneys were removed and slices of cortex and medulla were prepared for incubation. The in vitro release of thromboxane B2 (TxB2), prostaglandin E2 (PGE2), and 6-keto-prostaglandin F1a (6-keto-PGF1 alpha) into the incubation media was measured by radioimmunoassay. Within 72 hr of transplantation the cortex of rejecting kidneys synthesized 10 to 30 times as much PGE2 and TxB2 as normal controls. A similar increase was not observed for 6-keto-PGF1 alpha synthesis. In the medulla there was a selective reduction in 6-keto-PGF1 alpha production within five days of transplantation. In both cortex and medulla there was a significant increase in the ratio of TxB2 to 6-keto-PGF1 alpha production. Reversal of the normal TxB2:6-keto-PGF1 alpha ratio could induce the widespread intrarenal thrombosis and vasospasm that characterizes acute renal allograft rejection.

Salvage operations for malfunctioning polytetrafluoroethylene hemodialysis access grafts.

During the study period a cohort of 170 of patients receiving long-term hemodialysis treatment required placement of 214 polytetrafluoroethylene grafts for vascular access; within this period 74 of these patients had significant graft malfunction that required 149 salvage operations. The most common failure/malfunction was thrombosis, and the most commonly appreciated mechanical cause of graft failure was outflow venous stenosis. Complex revisions were required to address this problem. First, second, and third revisions were successful in 65%, 53%, and 44% of cases, respectively. Multiple revisions, including thrombectomy, were required in some, but the functional life of these salvaged grafts was nearly equal to that of grafts that did not require revision. Abandonment of grafts because of secondary infection exacted a toll in both groups.