Protein A immunoadsorption cannot significantly remove the soluble receptor of urokinase from sera of patients with recurrent focal segmental glomerulosclerosis.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a serious disease, the pathogenesis of which is unknown. Its recurrence after transplantation (Tx) and its partial remission after treatment with immunoadsorption (IA) on a protein A column indicate the existence of a circulating factor responsible for the disease that is able to bind to a protein A column. Recently, the soluble receptor of urokinase (suPAR) was described as the factor responsible for FSGS. We tested the capacity of suPAR to bind to protein A and to be eliminated by IA. METHODS: We measured suPAR in eluates of protein A columns from seven patients with recurrent FSGS after Tx (rFSGS) treated with IA, and in the serum of 13 patients with rFSGS and 11 healthy donors (HDs). Additionally, the plasma of these patients was immunoadsorbed in vitro on a protein A Sepharose column, and we quantified suPAR in the eluates and in pre- and post-column samples. RESULTS: The concentration of suPAR was higher in the plasma of patients with rFSGS than that of HD patients. However, the concentration of suPAR was similar before and after IA on protein A for the rFSGS and HD samples. The suPAR concentration was very low in the eluates from protein A columns incubated with plasma from HD or rFSGS patients. However, 85% of rFSGS patients showed a decrease in immunoglobulin G and proteinuria. CONCLUSIONS: Thus, suPAR does not significantly bind to protein A in vitro or in vivo.

The long-term effect of switching from cyclosporin A to mycophenolate mofetil in chronic renal graft dysfunction compared with conventional management.

BACKGROUND: To overcome toxicity of calcineurin inhibitors, recent trials have proposed substituting cyclosporin (CysA) with mycophenolate mofetil (MMF). No data concerning the long-term side effects and long-term renal outcome of this strategy have been published. METHODS: We retrospectively compared 39 renal transplant patients with chronic graft dysfunction who were subjected to CysA to MMF substitution (group 1) with 39 matched renal transplant patients who were continued on conventional management (group 2). The mean serum creatinine and the slope of deterioration of renal function before the date of the therapeutic intervention (T(0)) were similar in both groups. Follow-up in both groups was 76 +/- 42 months before T(0) and 44 +/- 11 months after T(0). RESULTS: In group 1, conversion was associated with a decrease of mean serum creatinine concentrations from 192 to 172 micro mol/l at 1 year (P = 0.004) and 159 micro mol/l at 3 years (P < 0.003) after T(0), whereas it remained unchanged in group 2. The systolic blood pressure decreased in group 1 from 155 mmHg before T(0) to 145 mmHg at 1 year (P < 0.01) and 133 mmHg at 3 years (P < 0.001) without any increase of the antihypertensive drug, whereas it did not change in group 2. Lipid profile tended to improve in group 1 after T(0) and was unchanged in group 2. None of the patients in group 1 developed acute rejection after T(0), whereas two acute rejections occurred in group 2. Graft survival, however, was similar in both groups. In group 1, several side effects occurred related to MMF treatment, and led to its discontinuation in two cases and the reduction of its dose for 18 patients (64%). CONCLUSION: CysA/MMF substitution improves renal function and blood pressure in chronic allograft dysfunction when compared with conventional management. However, CysA/MMF substitution is associated with a high rate of MMF-related side effects, requiring modulation of its dose.

Incidence of renal and liver rejection and patient survival rate following combined liver and kidney transplantation.

Multiple organ transplantations are used to treat chronic multiple organ failure. However, long-term mortality and graft tolerance remain to be evaluated. We carried out a retrospective and comparative analysis of 45 patients who underwent a combined liver and kidney (LK) transplantation (LKT) from the same donor. They were compared to 86 matched patients who underwent kidney (K) transplantation (KT). All patients had an organic renal failure associated with cirrhosis (n = 35) or with inherited disease (n = 10). Nineteen (42.9%) had been transplanted previously. The patients' survival rate was 85% at 1 year and 82% at 3 years. Seven patients died within the first 3 months, due to severe polymicrobial infection. Two patients in the LK population (4.2%) developed acute rejection of the kidney graft compared to 24 of the 86 matched renal transplanted patients (32.6%). In parallel, acute liver rejection was observed in 14 cases (31.1%) in the LK population. The occurrence of acute rejection was not associated with panel-reactive lymphocytotoxic antibodies (n = 16), nor with positive cross-matches (n = 3). Four of the 45 patients (8.8%) subsequently developed chronic renal allograft rejection, and 16 cases of chronic hepatic dysfunction were noted (42.2%). In conclusion, the overall survival rate following combined liver kidney transplantation is acceptable, and LKT can be proposed to patients with kidney failure associated with liver dysfunction, primary oxaluria or amyloid neuropathy. The main cause of mortality in this population was severe infectious complications. The frequency of acute kidney rejection was lower than in single transplantation.

Long-term results of renal transplantation using kidneys harvested from non-heartbeating donors: a 15-year experience.

PURPOSE: To expand the pool of suitable organ donors we developed an organ procurement program of non-heartbeating donors during the last 15 years. We compare graft survival in patients receiving renal transplants procured from non-heartbeating with recipients of kidneys from heartbeating donors. MATERIALS AND METHODS: From 1986 to 1999, 60 renal transplantations were performed with kidneys harvested from non-heartbeating donors (Mastrich category IV). Kidneys were procured using a double balloon triple lumen catheter inserted into the femoral artery. The 60 kidneys were selected from 70 non-heartbeating donors based on age younger than 50 years, warm ischemia less than 30 minutes, creatinine less than 200 micromol./l., and no hypertension or major histological lesions. Long-term results of graft survival and complications were compared with a series of 1,065 renal transplantations performed during the same period with kidneys procured from heartbeating donors. RESULTS: Mean age of the recipients was statistically different as non-heartbeating donors were older. However, the 10-year graft survival rates were similar in both groups (50% versus 53%). Incidence of ureteral stenosis and fistula, arterial stenosis and thrombosis was not statistically different in both groups. On the other hand, delay graft function was more frequent in non-heartbeating donors (60% versus 40%, p = 0.01). CONCLUSIONS: Despite a high rate of acute tubular necrosis, kidneys harvested from non-heartbeating donors had the same graft survival rates as those procured from heartbeating donors. Surgical complications were not different. Transplantation of selected kidneys procured from non-heartbeating donors should be promoted as a response to organ shortage.

Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann's thrombasthenia and anti-glycoprotein IIb-IIIa antibodies.

Type I Glanzmann's thrombasthenia is a rare congenital platelet function disorder, characterized by undetectable platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa). Severe bleeding is controlled by transfusion of normal platelets, leading in some cases to the occurrence of anti-GPIIb-IIIa isoantibodies, which induces a loss of transfused platelet efficacy. We used immunoadsorption on protein A Sepharose (IA-PA), which has been shown to be efficient in decreasing the titre of antibodies in several immune diseases, in three patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies on five different occasions. IA-PA was well tolerated with no deleterious side-effects reported. It induced a dramatic decrease of total immunoglobulin (Ig)G, including anti-GPIIb-IIIa isoantibody levels, as assessed by the monoclonal antibody-specific immobilization of platelet antigens test and the ex vivo inhibition of normal platelet aggregation induced by the patient's platelet-rich or platelet-poor plasma. Elimination of the antibody was associated with a correction of the bleeding time following platelet transfusion. IA-PA combined with platelet transfusion made it possible to control two life-threatening haemorrhages, and allowed two surgical procedures and one bone marrow transplantation to be performed safely. Our experience suggests that IA-PA, which restores the haemostatic efficacy of platelet transfusion, is a valuable therapeutic strategy in patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies.