HLA-B*4012: a new allele with unique serological features.

We have defined the new allele HLA-B*4012, which had been isolated from a black individual. It was initially recognized as a serologically unique allele when typing her father for renal transplantation. The HLA class I phenotype was A*0201,*6602; B*4001,*4012; Bw6; Cw*0304,*1505. Sequencing from exon 1 through intron 3 of B*4012 was performed. B*4012 is identical to B*4001 and B*4010 in exon 3, and in the 3' part of exon 2, but it is unique in that exon 1 and the 5' part of exon 2 are identical to B*1503, B*1509, B*1510, B*1518, B*1523, and B*1529. The generation of this allele is best explained by a recombination event in exon 2 (break point between nucleotides 205 and 222 from the beginning of the coding region) of B*4001 or B*4010 with one of these B*15 variants as a donor allele. Its unique serological feature (B48, B60, B70, and B72 reactivity) is consistent with the sequence data of its donor alleles.

In vitro effects of cyclosporine on glomerular function.

Cyclosporine A (CsA) causes vasoconstriction and decrease in glomerular filtration rate. Experiments were conducted in isolated glomeruli to study effects of CsA of glomerular perfusion and independent of systemic or renal factors. CsA caused a dose dependent decrease in glomerular volume consistent with mesangial contraction. The ultrafiltration coefficient Kf was significantly lower after incubation in 4 X 10(-4) M CsA when compared to control (2.81 +/- 0.2 vs 5.19 +/- 0.5 nl/min X mm Hg; p less than 0.001). Hydraulic conductivity Lp was diminished by CsA from 2.69 +/- 0.11 to 1.41 +/- 0.05 microliter/min X mm Hg X cm2 (p less than 0.001). These findings demonstrate a direct effect of CsA on the glomerulus which must be considered in addition to drug-induced changes in perfusion and tubular function.

Dialysis leukopenia, hypoxemia, and anaphylatoxin formation: effect of membrane, bath, and citrate anticoagulation.

The goal of these prospective studies was to determine the effect of different dialyzer membranes and dialysate composition on leukopenia and hypoxemia during hemodialysis with citrate anticoagulation. Significant early leukopenia was found with a cuprophane membrane, while a cellulose acetate membrane was associated with mild early leukopenia. Bath composition had no effect. Bicarbonate dialysate, compared with acetate, eliminated hypoxemia in cellulose acetate membranes and reduced its degree and duration with cuprophane. Membrane composition had no effect on hypoxemia during acetate dialysis. The findings indicate that leukopenia is directly and exclusively related to membrane composition while hypoxemia only relates in part to membrane effects. Serial determinations of complement components C3a and C5a showed significant increases in parallel with leukopenia during heparin anticoagulation, but the anaphylatoxin concentration changes were dissociated during dialysis with citrate anticoagulation. The concentrations of anaphylatoxins C3a and C5a appear not to be directly related to dialysis-induced leukopenia. The dissociation between anaphylatoxin concentrations and leukopenia may be related to changes in generation or unmasked changes in leukocyte response. Citrate anticoagulation may provide a useful probe for further studies on membrane-leukocyte interactions in vivo.

Regional citrate anticoagulation for hemodialysis following cardiovascular surgery.

Coronary artery revascularization and cardiac valve replacement have been performed with increasing frequency over the past decade in patients maintained on chronic hemodialysis. Hemodialysis is frequently required shortly after surgery for treatment of hyperkalemia or volume overload. Use of low-dose or regional heparinization for hemodialysis may cause bleeding in patients who have recently undergone open-heart surgery. We performed 16 hemodialyses using regional citrate anticoagulation in 4 maintenance dialysis patients who had recently undergone cardiothoracic surgery. Systemic anticoagulation did not occur during any of the initial procedures, and in each patient a decrease in sanguineous chest tube drainage was observed during the initial postoperative dialysis.

Long-term comparisons of citrate and heparin as anticoagulants for hemodialysis.

Citrate was compared to heparin as an anticoagulant during chronic hemodialysis. A randomized crossover design was used in six stable male dialysis patients. There were no measurable crossover effects. Use of citrate as the sole anticoagulant for periods of 2 months was easily accomplished, free of complications, and resulted in comparable clearance of solutes. Major laboratory parameters were similar with both anticoagulants. Importantly, there was no significant citrate accumulation. The results also indicate that recurrent use of heparin during dialysis has no measurable effect on lipid metabolism in stable patients.

Percutaneous transluminal angioplasty in transplant renal artery stenosis: experience and review of the literature.

Percutaneous transluminal angioplasty (PTA) was performed in five instances of renal transplant artery stenosis (RTAS) in four patients. Hypertension was present in all cases and improved after angioplasty together with reduction in medicine requirements. Abnormal renal function in four instances also improved after PTA. This reflects the current literature in which 76 of 90 patients were successfully treated by PTA (follow-up to 24 months), with two cases of recurrent stenosis, no mortality, and only a single case of graft loss. Vascular surgical repair succeeded in 130 to 180 patients, but graft loss occurred in 20 cases and recurrent stenosis in 11. Mortality was reported in five cases. Our review of the literature and experience suggests that PTA may be preferred in the treatment of RTAS.

Effective use of streptokinase for peritoneal catheter failure.

The fibrinolytic enzyme streptokinase (streptase) was infused into the peritoneal catheter in 19 episodes of catheter failure in 16 patients. Intraabdominal bleeding prior to infusion was seen in seven of these episodes. Fibrin strands and clots were present in four additional successful cases. Streptokinase successfully relieved the obstruction in 13 episodes in 11 patients. The procedure failed in two cases of omental ingrowth and in another with catheter malposition. Streptokinase infusion also failed in two patients with Pseudomonas aeruginosa and one patient with Staphylococcus epidermidis peritonitis. Intraperitoneal streptokinase infusion is simple and free of side effects. Its use should be considered in peritoneal catheter failure, particularly in cases where bleeding or fibrin accumulation may play a role.

Regional citrate anticoagulation in chronic hemodialysis patients.

The pronounced leukopenia caused by cuprophane dialyzer membranes was significantly blunted by citrate regional anticoagulation. Cellulose acetate produced less leukopenia than the cuprophane, regardless of anticoagulant. The pO2 response to the initiation of hemodialysis was not affected by dialyzer membrane or anticoagulant choice. We therefore conclude that citrate anticoagulation reduces dialyzer-induced leukopenia. Citrate anticoagulation does not, however, change the hypoxemia present with acetate dialysis. The dissociation of leukopenia and hypoxemia with citrate anticoagulation suggests that pulmonary sequestration is not a major cause of hypoxemia during hemodialysis.

Prognosis for recovery of function in acute renal failure. Value of the renal image obtained using iodohippurate sodium I 131.

Twenty-four survivors of acute, nonobstructive, nonnephritic renal failure had a renal scan using iodohippurate sodium I 131 performed early in the acute illness. Scans were judged according to whether the renal images were prominent, faint, or absent during the first 30 minutes after intravenous injection of 100 to 250 microcuries of iodohippurate sodium I 131. All ten patients with prominent renal images attained life-sustaining renal function with an average postrecovery creatinine clearance of 80 ml/min. Of the seven patients with faint renal images, six recovered life-sustaining renal function (average creatinine clearance of 39 ml/min), and one required chronic hemodialysis. Seven patients had no renal image initially; four recovered life-sustaining renal function with an average creatinine clearance of 25 ml/min; three required chronic hemodialysis. We conclude that, for patients with acute renal failure, the appearance of the renal image obtained using this substance is an important indicator of renal viability and of the likelihood for functional recovery.