Flow cytometry crossmatching and primary cadaver kidney graft outcome: relevance of T and B cell targets, historic sera and autologous controls.

There is limited information regarding the role of flow cytometry crossmatching (FCXM) in primary cadaver kidney allografting and even less about B cell reactivity and graft survival (GS). Furthermore, there is little or no published data concerning reaction strength (cutoff value), the effect of historic sera reactions, and the usefulness of performing autologous crossmatches (XMs) on GS. These factors were examined retrospectively on 214 primary transplants performed from August 1991 to January 1994 with follow-up to July 1995. Three-color FCXMs were done on a 1024-channel BD-FACScan, and the shift in median channel fluorescence (MCF) over the negative control was calculated. All patients had a negative T cell (AHG) and warm B cell (2 was, extended incubation) cytotoxicity XM, and none was excluded in calculating GS. A quantitative effect was noted as stronger MCF shifts vs. T or B cells correlated with decreased GS (r = 0.98 and 0.92, respectively). Significant differences were seen with cutoff values of T = 50 and B = 110 which were 1.7-1.8 times the SD above the mean MCF of normal sera controls T neg patients (n = 198) and 1- and 3-yr actuarial GS of 86% and 79% compared to T pos patients (n = 16) of 75% and 49%, p = 0.008. B neg patients (n = 177) had 1- and 3-yr GS od 86% and 81% compared to B pos patients (n = 37) of 78% and 47%, p = 0.005. Most informative was the analysis of combined T and B cell FCXM results. Three years GS for T neg - B neg patients (n = 171) was 81% and for T pos - B neg patients (n = 6), it was 83%, p = 0.98. The 27 T neg - B pos group's GS was lower at 62% but did reach significance. Poorest GS was seen for T pos - B pos patients (n = 10) at 23%, p = 0.0001. Reaction patterns showed that T cells detected only HLA Class I antibodies, whereas B cells detected both Class I and II. Historic sera (> or = 1 month old) reactivity influenced GS. Patients with > or = 2 past sera positive but current serum negative reactions vs. T or T plus B cells (n = 7) had a poor 29% GS, while those historically positive only vs. B cells (n = 7) had 100% GS. On the other hand, patients positive only with the current serum (n = 16) had 2-yr GS of 100% (false positive test?), while patients whose current and historic sera reactions were positive (n = 21) had a 25-50% GS (true positive test?). About 1 in 15 patients (19%) displayed positive autologous FCXM reactions. Subtraction of autologous MCF shift values from those vs. the donor converted 17 patients to the T neg - B neg or T pos - B neg group whose 2-yr actual GS was not significantly different (p > 0.8) from those initially testing T neg B neg vs. their donors.

Uses of orthoclone OKT3 for prophylaxis of rejection and induction in initial nonfunction in kidney transplantation.

We have shown that OKT3 can be safely administered to a varied group of transplant recipients, including a high percentage of diabetics and older patients. Used as a prophylactic agent, OKT3 was associated with a decreased incidence and delayed onset of acute rejection. Effectiveness may be reduced by shortening the course of treatment and/or lowering the dose of concomitant azathioprine. Use of OKT3 in patients with ATN (thereby avoiding use of CyA) may be a beneficial strategy. Stimulation of significant titers of antimurine antibody has not been a common event in this study.

Metabolic utilization and renal handling of D-lactate in men.

This study was carried out to investigate the renal handling of d- and l-lactate and the extent of their metabolism in men. Ten healthy male subjects were given an intravenous (IV) infusion of a racemic mixture of d- and l-lactate. At an infusion rate of 1.0 to 1.3 meq/kg body weight of each isomer, d-lactate achieved a concentration in plasma of 1.7 to 3.0 meq/L, and l-lactate 2.8 to 4.2 meq/L. At these levels, fractional excretion of d-lactate ranged from 40% to 65%, while fractional excretion of l-lactate was always less than 5%. At a higher infusion rate, 1.8 to 2.0 meq/kg/h, plasma concentrations of d- and l-lactate reached 4.5 to 6.0 meq/L, and 4.0 to 6.7 meq/L, respectively. Fractional excretion of d-lactate then ranged from 61% to 100%, while that of l-lactate ranged from 9% to 30%. At plasma concentrations of d-lactate less than 3.0 meq/L, reabsorption of l-lactate was nearly complete, but when plasma d-lactate exceeded 3.0 meq/L, reabsorption of l-lactate was considerably impaired. Similarly, for a given concentration of plasma d-lactate, its reabsorption was more efficient when the plasma l-lactate concentration and fractional excretion of l-lactate were low than when they were high. At an infusion rate of d-lactate of 1.0 to 1.3 meq/L, about 90% of the infused lactate was metabolized, and at a higher infusion rate, still more than 75% of the infused lactate was metabolized.(ABSTRACT TRUNCATED AT 250 WORDS)

Minoxidil in a once-a-day step-3 antihypertensive program.

Convenience of medicine-taking and lack of side effects are two major factors that favor compliance. Using a simple and convenient once-a-day regimen of minoxidil, nadolol, and chlorthalidone, we treated successfully 30 patients with moderate to severe hypertension. All patients were previously taking at least three medications, usually three to four times a day. Treatment was started with nadolol (160 mg) and chlorthalidone (50 mg) once daily. If diastolic blood pressure remained above 90 mmHg, minoxidil was added at a starting dose of 2.5 mg/day and increased weekly until blood pressure was controlled or the maximum dose of 100 mg/day was reached. The average blood pressure decreased from 170.9/107.0 mmHg (sitting) and 174.1/110.8 mmHg (standing), before the addition of minoxidil, to 138.8/86.7 mmHg (sitting) and 140.0/89.5 mmHg (standing), at the third month of minoxidil therapy. At the sixth month of minoxidil therapy, the figures were 140.9/86.3 and 141.9/89.8 mmHg. With this single-dose program, smooth blood pressure control throughout 24 hours was documented by 24-hour ambulatory blood-pressure monitoring. Hypertrichosis was common but was bothersome only to women patients. Pericardial effusions occurred in five patients, but they were all small and asymptomatic. Subjective side effects of the regimen were usually so mild that all patients who completed the study decided to remain on the same regimen.

Bartter's syndrome due to a defect in salt reabsorption in the distal convoluted tubule.

Bartter's syndrome is generally attributed to a primary defect in salt reabsorption either in the ascending limb of Henle's loop or in the proximal tubule. 2 siblings presented here have all the clinical and biochemical features of Bartter's syndrome but seem to have defective salt reabsorption in the distal convoluted tubule. A surreptitious use of diuretics was ruled out. Free water clearance was reduced in both patients and also was low after the addition of furosemide when compared with controls. Urine osmolalities following overnight dehydration were 883 and 1,000 mosm/l. The reduced maximal free water clearance argues against a proximal defect, and the normal urine concentration against a Henle's loop defect. Low free water clearance after furosemide suggests a defect in the distal convoluted tubule.