Association of renal graft survival with matching at the HLA-DR locus.

The influence of HLA-DR antigen matching in 70 cadaver transplants was studied for up to four years. The overall cumulative renal graft survival at one year was 62 percent, and at two and four years it was 60 percent. The one, two, and four year cumulative graft survival for patients receiving one or two HLA-DR antigen matched grafts was 74 percent, 69 percent, and 69 percent, respectively. In contrast, the one, two, and four year cumulative graft survival for patients receiving zero HLA-DR antigen matched grafts was 51 percent, 47 percent, and 47 percent, respectively. The cumulative graft survival for patients receiving one or two HLA-DR antigen matched grafts was significantly different (p less than 0.05) than for patients receiving zero HLA-DR antigen match grafts. No significant difference in the distribution of other prognostic factors were observed between patients receiving one or two HLA-DR antigen match grafts and patients receiving zero HLA-DR antigen matched grafts. The present authors concluded that matching for HLA-DR antigens exerts an independent beneficial effect on renal graft survival in transplant patients, most of whom have been previously transfused.

Cimetidine, posttransplant peptic ulcer complications, and renal allograft survival: a clinical and investigational perspective.

Upper gastrointestinal (G) tract complications have been a substantial cause of death following renal transplantation. Cimetidine, an H2 receptor antagonist, has been used in the posttransplant period to decrease this hazard. However, H2 receptor antagonists may enhance the immune response and be deleterious for the graft. The magnitude of the hazard of upper GI tract complications after renal transplantation was determined by reviewing 200 renal transplants. The effect of cimetidine treatment on the survival of canine renal allografts was investigated. The upper GI tract complication rate was 1.5% with one related death (0.5%). Treatment of dogs with cimetidine shortened the survival time of renal allografts (18.2 +/- 5.5 [SE] days to 12.5 +/- 2.2 days). Because upper GI tract complications are not a major hazard and H2 receptor antagonist therapy may decrease the survival of dog renal allografts, we believe prophylactic use of cimetidine is not indicated.

Prevention of lymphocele formation following renal allotransplantation.

Lymphocele formation is a recognized complication of renal allotransplantation that can jeopardize the graft and cause major morbidity for the allograft recipient. Previously, emphasis has been placed on treatment as opposed to prevention. We attempted to prevent lymphocele formation by adopting 2 techniques in performing the renal transplantation: 1) we limited the area of dissection in the recipient to that necessary to obtain vessel control of the segment of iliac vessel that was to be used for the vascular anastomosis (to decrease the number of lymphatics that were divided or destroyed) and 2) we practiced lymphostasis as meticulously as we did hemostasis. We did not attempt to ligate any lymphatics in the hilus of the kidney. Using these techniques we have performed 198 consecutive renal allografts without the development of an identifiable lymphocele. The limitation of the area of vessel dissection has not increased either the rate of major vascular complications (2 per cent) or the development of major pulmonary embolism (0.5 per cent) after transplantation. We conclude that extensive dissection of the iliac vessels is not necessary to prevent major vascular complications or pulmonary emboli after renal transplantation, that careful lymphostasis in the allograft recipient will prevent the development of a lymphocele and, therefore, that the lymph fluid in a lymphocele is derived primarily from the allograft recipient and not from the allograft itself.

The effect of dyes used to evaluate the in situ, ex-vivo, and perfused kidney.

Methylene blue, indigo carmine, and fluorescein dyes were evaluated to determine their effect on the dog kidney. Methylene blue and indigo carmine were administered intravenously and intraarterially to the in situ vascularized kidney and serial histologic appearance of the kidney was determined. The three dyes were administered intraarterially to excised kidneys that were then preserved for 1 hour in the cold and autotransplanted; and finally the three dyes were administered to the perfusate of excised kidneys that were perfused for 18 hours by cryoperfusion with an albumin perfusate and then autotransplanted. Renal function and histology were determined 5 days after autotransplantation. Methylene blue dye did not damage the in situ vascularized kidney as judged by renal histology. However, administration of methylene blue to the ex vivo kidney that was subsequently short term cold stored or perfusion stored was associated with marked apparent ischemic damage of the organ. Indigo carmine dye did not adversely affect either the in situ vascularized kidney or the short term cold stored kidney. However, with perfusion storage, indigo carmine produced apparent vasoconstriction that led to perfusion failure. Fluorescein dye was not harmful to the kidney either during short term cold storage or during perfusion preservation. It is concluded that fluorescein is the dye of choice for evaluating the vascular anatomy or macroperfusion status of the kidney.

A prospective study of methylprednisolone and prednisone as immunosuppressive agents in clinical renal transplantation.

A prospective double blind crossover study was carried out in 65 patients comparing methylprednisolone (Medrol) and prednisone as immunosuppressive agents in clinical renal transplantation to determine their relative merits vis-a-vis graft survival, hypertension, weight gain, sepsis and patient preference in the posttransplant period. Patients receiving renal allografts were randomly assigned to receive initial treatment with one of the drugs. Once maintenance doses were employed, the drug was switched for a 3-month period. There was no difference in overall graft survival at 1 year, 68% versus 56% (p greater than 0.4), for the two patient groups. Likewise, there was no difference in blood pressure during the maintenance therapy crossover period, mean BP 129/86 during Medrol therapy and 129/86 during prednisone therapy. Overall weight gain was not statistically different with the two drugs, 3.8 kg with prednisone and 2.3 kg with Medrol, p greater than 0.1. However, when Medrol was used in the late posttransplant period, the patient had a significantly smaller weight gain, 0.95 kg versus 3.5 kg with prednisone, p greater than 0.05. The incidence of bacterial sepsis was significantly greater (p less than 0.02) during the early posttransplant period in those patients treated with Medrol. Finally, the majority of patients (65%) had no preference for either drug. Of those with a preference, the majority (69%) preferred Medrol. We conclude that therapy with Medrol does not offer superior graft survival, less hypertension or overriding patient preference but does apparently lead to an increased incidence of bacterial sepsis in the early posttransplant period. Thus it appears that prednisone is the initial drug of choice as an immunosuppressive steroid in clinical renal transplantation.

Renal artery malalignment. Cause for reversible and nonreversible renal allograft artery stenosis.

Two cases of renal allograft artery stenosis secondary to circumferential malalignment of the anastomotic site with the recipient external iliac artery are presented. One stenosis was temporary with apparent resolvement by dilatation of the allograft artery; the other was permanent and required operative correction by patch angioplasty. Circumferential malalignment of the arterial anastomotic site, when the renal artery is placed end to side into the recipient external iliac artery, is proposed as an etiologic mechanism for both temporary and permanent renal allograft artery stenosis. Careful attention to the final position of the graft in the retroperitoneum when the site for arterial anastomosis is chosen will prevent this complication of human renal allotransplantation.

Demonstration of a dog liver immunosuppressive factor active in vitro.

These studies define the presence of an immunosuppressive factor in dog liver that is active in vitro. A crude dog liver extract was prepared by saline extraction and ultracentrifugation. In vitro immunosuppressive activity of the extract was assayed by its influence on standard phytohemagglutinin mitogen stimulation assays (PHA), two-way mixed lymphocyte culture (MLC) reactions, and primed lymphocyte culture (PLC). In six experiments with four extracts, the mean percentage of inhibition (MPI) of dog lymphocytes in PHA mitogen stimulation assays was 102.0 +/- 3.6. In two human MLC experiments, the extract produced an MPI of 102.3 +/- 0.3. In one canine MLC the MPI was 102.5. In three PLC experiments the MPI was 92.7 +/- 8.0, indicating that the extract inhibited sensitization. Cytotoxicity of the extract was shown not to be the mechanism of proliferation inhibition by restimulation of cells washed free of extract, concurrent eosin viability studies, and documentation of normal base proliferation of cells after extract was washed from them. We concluded that there is a naturally occurring immunosuppressive agent in dog liver that is active in vitro as demonstrated by inhibition of PHA MLC, and PLC cellular proliferation assays. The activity is not attributable to cytotoxicity.

Double loop mass closure technique for abdominal incisions.

The technique of double loop mass closure of vertical abdominal incisions converts a vertical incision into a physiologic incision by converting distracting muscular stress into an opposing force. Use of the closure in a small series of high risk patients has demonstrated it to allow closure of vertical incisions with subsequent wound healing without hernia, dehiscence or invasive wound infection.

Successful immunosuppression of renal allograft recipients with alternate day steroid therapy.

Twenty-five renal transplant recipients have been treated long-term with immunosuppressive therapy with conversion from a daily dose to an every other day dose of steroids in conjunction with daily administration of Imuran. The patients were selected by having stable grafts for 6 to 9 months prior to conversion, not by the presence of steroid-induced complications. Alternate day steroid administration has continued to provide successful immunosuppression in that only of 25 patients (4%) has had any evidence of renewed rejection activity during a treatment interval of 7--95 months, median 22 months and mean 28 months. One graft was lost to an acute rejection reaction that occurred in association with a flu-like syndrome 8 months after the conversion was started. It is concluded that in the patient with documented stability of the graft, every other day steroid administration is a successful immunosuppressive regimen.

Clinical renal preservation by cryoperfusion with an albumin perfusate: renal perfusion with albumin.

Eighty-six human kidneys have been preserved by cryoperfusion with an albumin-based perfusate for five to 50 hours prior to transplantation. Sixty-three of the kidneys were transplanted. The overall immediate function rate was 72% and was 100% (34/34) for kidneys with no warm ischemic damage transplanted into recipients without hypotension or prior sensitivity. The overall actuarial one-month kidney survival rate was 87%, the three-month survival was 73%, and the one-year survival rate was 65%. No kidney was discarded because of poor perfusion. Perfusion data, including flow, dastolic pressure, perfusion time, and lactate concentration were not predictive of immediate renal function. Light, electron, and immunofluorescence microscopic study of biopsy specimens showed no evidence of perfusion or immunologic damage to the kidneys. Perfusion of transplantable kidneys with albumin provides reliable preservation for up to 50 hours without producing either structural or immunologic damage to the organ.

Renal donor pretreatment with cytotoxic agents: immunologically ineffective and damaging to the graft.

Simultaneous double renal allografts were performed in 32 dogs to evaluate the effect of pretreatment of the donor kidney with either Medrol, cytoxan, and methotrexate or medrol and procarbazine. There was no prolongation of survival of treated allografts. Immunosuppressive therapy for the transplanted animal unmasked a pretreatment injury of the pretreated kidney. Treatment of an autograft kidney in an intermediate host produced a cytotoxic tubular lesion in the kidney and also appeared to protect the kidney from the double ischemic insult incurred during the transplantation procedure. Pretreatment of dog donors of renal allografts with cytotoxic agents thereby offers no immunologic advantage for graft survival and produces a cytotoxic tubular lesion that is detrimental to kidney survival when ischemic and immunologic injury is minimal.

Foley catheter tip cultures: a valuable diagnostic aid in the immunosuppressed patient.

Cultures of forty-three Foley catheter tips from immunosuppressed renal transplant patients have been analyzed and correlated with the subsequent development of urinary tract infection. Fifteen cultures produced no growth and two showed only coagulase-negative staphylococci; none of these patients subsequently developed a urinary tract infection. Twenty-four of the cultures showed at least one organism known to be a frequent urinary pathogen; sixteen (67 per cent) of these patients developed a urinary tract infection within ten days of the culture, and all sixteen had an infection caused by an organism present on the Foley tip. None of the organisms were identified by simultaneous catheter specimen urine cultures. Foley tip cultures in the immunosuppressed renal transplant patients are predictive of urinary sepsis and diagnostic of the causative organism.

Effect of purification on the accumulation of radioactive gallium labeled leukocytes in abscesses.

In rabbits, autologous peripheral blood leukocytes labeled in vitro with 67Ga citrate have been purified in vitro by the processes of dialysis and cell washing to determine the effect of purification on the accumulation of the labeled cells in abscesses of the abdominal wall. Dialysis was found to be ineffective, but cell washing produced a population of labeled leukocytes that was essentially free of noncell bound radioactivity. The purification process minimally altered the recirculating capacity of the leukocytes but significantly enhanced the relative accumulation of radioactivity in the septic area. Thus, the use of an essentially pure population of labeled leukocytes should offer a significant potential in the definitive scintiscan demonstration of hidden abscesses.

Urinary cytodiagnosis of acute renal allograft rejection using the cytocentrifuge.

The clinical diagnosis of acute renal allograft rejection in immunosuppressed recipients can often be predicted or confirmed on the basis of characteristic urinary cytologic findings. Use of cytocentrifugation permits a simple, rapid, reproducible and semiquantitative means of preparing cytologic urinary specimens of diagnostic quality from small quantities of urine. The cytodiagnosis of acute renal rejection was established before or on the same day a clinical diagnosis of rejection was made in the majority of renal transplant cases studied over a 12-month period. Renal tubular cells were found to be the exfoliated cells of greatest value in predicting an acute rejection episode, and their persistence has prognostic importance.