Complications associated with arteriovenous fistulas in patients undergoing chronic hemodialysis.

Over a two-year period, 100 venous angiograms were performed on 75 patients because of difficulty with vascular access. Seventy percent of the patients had decreased arterial flow or increased venous resistance. High output failure, sepsis, and aneurysm formation were also found. Venous angiography of the fistula demonstrated significant stenosis in 40% of the cases as well as total occlusion by thrombus in 9%, aneurysm formation in 7%, and abnormal fistula needle placement or anatomic abnormalities in 20% of the cases. Definitive diagnosis with the aid of venous angiography permitted specific surgical intervention in 62% of the cases, and identified new sites for needle placement in 18% of the cases, thus prolonging fistula life and reducing the need for new fistula placement. Our experience with local cellulitis of the fistula site and sepsis is also discussed.

Graft irradiation in the treatment of acute rejection of renal transplants: a randomized study.

A randomized study of graft irradiation in the treatment of acute rejection of renal transplants was conducted from 1978 to 1981. Patients developing clinical signs of an acute graft rejection received customary antirejection treatment in the form of intravenous administration of high-dose (1 gm per day) of methylprednisolone. They were at the same time randomized to either receive therapeutic irradiation (175 rad every other day to a total of 525 rad) or sham irradiation. Neither the patient nor the Transplant Service surgeons knew at any time whether the radiation treatment had been given. Eight-three rejection episodes occurring in 64 grafts were entered into the study. Acute rejection was reversed in 84.5% of grafts in the control and 75% in the treated group. The incidence of recurrent rejection was higher in the treated group (66 vs. 46%) and graft survival was lower (22% vs. 54%). The study failed to demonstrate a beneficial effect of graft irradiation in the treatment of acute renal allograft rejection, when used in conjunction with high dose steroids.

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.

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Renal graft irradiation in acute rejection.

To evaluate the effect of graft irradiation in the treatment of acute rejection of renal transplants, a randomized study was conducted from 1978 to 1981. Patients with acute rejection were given standard medical management in the form of intravenous methylprednisolone, and were chosen randomly to receive either graft irradiation (175 rads every other day, to a total of 525 rads) or simulated (sham) irradiation. Eighty-three rejections occurring in 64 grafts were randomized to the protocol. Rejection reversal was recorded in 84.5% of control grafts and 75% of the irradiated grafts. Recurrent rejections were more frequent and graft survival was significantly lower in the irradiated group (22%) than in the control group (54%). Graft irradiation does not appear to be beneficial in the treatment of acute rejection of renal transplants when used in conjunction with high-dose steroids.

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.

Immune injury from organ preservation. A potential cause of hyperacute rejection in human cadaver kidney transplantation.

Two pairs of plasma-perfused human cadaver kidneys were rejected in a hyperacute manner by recipients who had not previously received a transplant. Crossmatches between recipient sera and donor lymphocytes were negative in all cases. A fifth kidney was plasma-perfused but not transplanted because the perfusate was shown to be cytotoxic to donor lymphocytes. IgM and complement, but not IgG, were demonstrated in these kidneys by immunofluorescent microscopy and confirmed by further immunological studies. The IgM was broadly reactive against multiple HL-A specificities and was present in 11 percent of sera from normal, healthy male donors. It appears from our studies that cytotoxic IgM may be present in homologous plasma and cause immune injury to the kidney during ex vivo pulsatile preservation. This may be responsible for some cases of otherwise unexplained accelerated allograft rejection.

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.

Serum autoleukocytotoxic activity and the positive cross-match in potential allograft recipients.

To evaluate possible causes of the false-positive cross-match test for clinical renal transplantation, the incidence of serum autoleukocytotoxic activity and its relationship to allogeneic sensitization to HLA antigens (the positive cross-match) were determined in 234 sera from 28 sensitized and eight nonsensitized chronic renal failure patients. Seven sera from four patients had autoleukocytotoxic activity. The autoleukocytotoxic activity was detected only in patients who showed transient allogeneic sensitization at some point. This activity could be adsorbed either by autologous or allogeneic platelets, but adsorption with autologous platelets did not remove the synchronous allogeneic leukocytotoxicity. This autoleukocytotoxic activity appears to coexist with alloreactive antibody, and in such a setting the positive alloreactive cross-match should contraindicate the proposed transplant until adsorption studies prove the false-positiveness of the test.

Volvulus of the cecum following transplant donor nephrectomy.

Volvulus of the cecum, a rare postoperative complication, occurred on the first postoperative day following left nephroureterectomy in a volunteer kidney donor. Postoperative cecal volvulus can occur after practically any operation, may present insidiously like adynamic ileus, but may progress rapidly to gangrene of the involved intestine. Etiologic factors, diagnosis, and treatment are reviewed briefly.

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

Improvement of renal allograft survival by induction of immunologic unresponsiveness was attempted in 24 patients by the pretransplant administration of donor-specific whole blood or buffy coat under continuous azathioprine immunosuppression. All patients and their donors had one or two disparate HLA haplotypes. Crossmatch (CM) testing (22 degrees C) for T cells (Amos and antiglobulin enhanced) and B cells identified sensitization in two patients (8%). One developed a low titer (1:2) positive B-cell CM, which did not preclude successful transplantation. The second, with a preexisting high titer (1:16) positive B-cell CM, developed a low titer (1:1) T-cell antiglobulin CM and had hyperacute graft rejection. Twenty-one recipients received kidneys from their blood donors. Except for one patient who had hyperacute rejection (across positive T-cell CM), none have rejected their kidneys. Three patients died at 2, 13, and 23 months, respectively, with good renal function. Seventeen patients are alive at 3 months to 10 years with a mean serum creatinine concentration of 1.3 +/- 0.4 mg/dl. Donor-specific transfusion with immunosuppressive coverage improves renal allograft survival without significant sensitization.

Renal injury by companion kidney during hypothermic pulsatile perfusion.

To study possible deleterious effects of traumatized kidneys on well harvested ones during hypothermic pulsatile perfusion, paired dog kidneys were monitored on two separate MOX-100 machines connected to pool a common perfusate. First kidneys were optimally harvested and baseline renal vascular resistance (RVR) calculated from pressure divided by flow (mm Hg/ml minute). After 1 hour second kidneys were added and observation was continued for an additional 3 hours. RVR in first kidneys increased immediately and doubled by 3 hours when ischemic traumatized second kidneys were added, 0.70 +/- 0.07 to 1.37 +/- 0.15 (p less than 0.001). No change in RVR was noted when second kidneys were optimally retrieved or if the dogs were heparinized prior to nephrectomy. Histological examination showed no evidence of vascular obstruction in any kidney, but only tubular necrosis in nonheparinized, traumatized second kidneys. Weight gain in optimally removed kidneys was 41%, but only 8% in ischemic kidneys. RVR decreased unexpectedly in ischemic kidneys during 3 hours of perfusion (p less than 0.01). Release of vasoactive substances by damaged kidneys and arteriovenous shunting may explain these findings. Separate perfusion systems seem to be justified when one of two cadaver kidneys is of marginal quality.

Successful revascularization of early posttransplant renal arterial occlusion.

A case involving immediate postoperative prolonged warm ischemia in a transplanted kidney from a living related donor is presented. Repair of the renal artery after 3 hours 15 minutes of complete occlusion resulted in an 18-day course of acute tubular necrosis followed by full return of normal renal function. Significant collateral circulation has been present in all previously salvageable cases of transplant renal artery obstruction. This case demonstrates that a kidney from an optimally prepared donor can withstand more than 3 hours of posttransplant warm ischemia despite the absence of collateral circulation. An aggressive surgical approach to restoring circulation is indicated.

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.

Ischemic bowel disease following bilateral nephrectomy or renal transplant.

In a 2 year period five patients developed pathologically proved ischemic bowel disease (IBD) following either renal transplantation or bilateral nephrectomy in preparations for transplantation. This entity accounted for 42% of all major gastrointestinal complications in this transplant unit. Three patients presented with abdominal pain and ileus, and two patients developed massive lower gastrointestinal hemorrhage. All five patients had nonocclusive ischemic disease because obstruction of a major intestinal vessel could not be documented in any case. Each patient was treated with bowel resection and three of the five patients survived. Although sepsis, shock, and large doses of immunosuppressive drugs have been implicated in predisposing such patients to IBD, these factors were not uniformly present in our cases. Blood volume redistribution with transient episodes of hypotension, especially during postoperative hemodialysis, may be significant. IBD in uremic patients can occur in the presence or absence of renal transplantation and may be the cause of massive intestinal hemorrhage in these individuals.

Blood flow measurements in arteriovenous dialysis fistulas.

Blood flows were measured in 75 arteriovenous dialysis fistulas (AVF) at the time of fistula construction. End cephalic vein to side of radial artery AVF had a mean flow of 242 +/- 89 ml. per minute which was similar to bovine heterograft AVF that also originated from the radial artery (291 +/- 67 ml. per minute). AVF originating from the brachial artery had flow rates twice those originating from the radial artery (599 +/- 163 vs. 251 +/- 89 ml. per minute), respectively). Flow rates were similar for straight arm (641 +/- 111 ml. per minute), curved forearm (561 +/- 187 ml. per minute), and curved thigh (592 +/- 134 ml. per minute) bovine AVF. Initial blood flow through arteriovenous dialysis fistulas is too low to cause heart failure, except in patients with previously compromised cardiac function. In such patients AVF from the radial artery theoretically would be preferred over brachial or femoral artery AVF.

A pilot program of multiple cadaver organ and tissue retrieval.

A one year pilot project conducted at a 2,000 bed medical center involved a unique approach to the retrieval from cadavers of multiple viable organs and tissues. Aspects of the program included a special unit for sterile evaluation and storage of tissue, a computerized registry of potential donors, a nurse to coordinate and expedite retrieval, and a retrospective chart review to define the incidence and location of potential cadaver donors. There were requests for 121 tissues by 39 investigators. Eleven different tissues were needed within 4 hours of death. Forty-two percent of individuals contacted directly enlisted in the donor registry, three of whom were identified on the computer at the time of death. A five-fold increase in cadaver donor evaluation referrals occurred, and one third of referrals resulted in viable tissue retrieval. A review of 728 deaths indicated that 45% could have been potential eye donors, 27% pancreas donors and 2.5% kidney donors. A coordinated program to retrieve multiple viable organs and tissues for transplantation and research appeared to be effective in this initial pilot study.

Histamine stimulation and inhibition of human cryopreserved parathyroid tissue.

To elucidate the mechanism by which cimetidine, an H2 antagonist, inhibits parathormone secretion, immunoreactive cyclic AMP (cAMP) production was measured at low (0.5 mM) and normal (1.0 mM) calcium concentrations, with histamine stimulation and histamine inhibition by cimetidine, in a cell dispersion preparation from cryopreserved glands of 12 hyperparathyroid patients. At low calcium, histamine-mediated cAMP production increased from a basal level of 382 +/- 44 femtomoles/10(5) cells to 514 +/- 74 femtomoles/10(5) cells (P less than 0.05). Cimetidine inhibition of histamine-stimulated parathyroid cells at low calcium resulted in a decrease in cAMP production from 514 +/- 74 femtomoles/10(5) cells to 410 +/- 62 femtomoles/10(5) cells (P less than 0.01). At normal calcium the cAMP production in the histamine-stimulated experiment increased from a basal level of 293 +/- 66 femtomoles/10(5) cells to 477 +/- 100 femtomoles/10(5) cells (P less than 0.01) and decreased to 321 +/- 69 femtomoles/10(5) cells (P less than 0.01) in the histamine and cimetidine experiment. Stimulation by isoproterenol, a beta-adrenergic agonist, at low calcium in the histamine-primed group showed an increase in cAMP production from 514 +/- 74 femtomoles/10(5) cells to 639 +/- 71 femtomoles/10(5) cells (P less than 0.005). These results suggest that histamine plays an important role in cAMP production in hyperparathyroid cells and that cimetidine inhibition of histamine-stimulated cAMP production may explain the decrease of immunoreactive parathormone by this H2 antagonist reported in patients with hyperparathyroidism.

Venous angiography of subcutaneous hemodialysis fistulas.

Venous angiography was performed on 256 subcutaneous arteriovenous dialysis fistulas. The technique involves temporary arterial inflow occlusion, needle injection of contrast material into the venous segment, and rapid sequence roentgenograms as arterial flow is restored. It requires no fluoroscopy or catheterization, avoids trauma to either the brachial or axillary arteries, and can be performed on an outpatient basis. Indications for fistulography included technical complications during dialysis, high-output cardiac failure, aneurysms, sepsis, and other reasons. Studies demonstrated significant stenosis or occlusion, insignificant stenosis, malpositioned needles, excessive fistula flow, aneurysms, thrombus formation, maturation failure, and other and normal findings. Only one study caused fistula thrombosis. Ninety-one percent of the studies provided information useful in the overall clinical management of the patients.

Delayed renal function and long-term cadaver renal allograft survival.

This study indicates that (1) ATN adversely affects long-term allograft survival but not patient survival, (2) in patients with delayed function the duration of ATN does not influence allograft survival, (3) ATN kidneys with good recovery (SCR less than 3.0) do as well as immediate-function kidneys, (4) poor recovery from ATN (SCR greater than 3.0) is associated with poor long-term allograft survival and may be the result of allograft rejection during ATN, since analysis of multiple characteristics at the time of transplantation failed to discern any difference between the good- and poor-recovery groups, and (5) there are no reliable pretransplant indicators of those kidneys that will never function or be in the poorly recovered group.