Response to pneumococcal vaccine in renal allograft recipients.

Pneumococcal vaccine, 14-valent, was administered to 75 stable adult renal transplant patients on maintenance immunosuppression. 32 had undergone splenectomy prior to transplantation and 43 had not. Functional opsonizing antibody was measured by chemiluminescence methodology for types 12F and 14, contained in the vaccine, and for type 5, a control strain. Serum was examined prior to and at 1 and 6 months after vaccine injection. 33, 71, and 35% of transplant patients had preexisting antibody to types 5, 12F, and 14, respectively, as compared to 58, 87, and 68% of controls. No differences were observed in nonsplenectomized versus splenectomized patients. Following immunization, 59 and 76% of antibody-negative patients converted to positive for pneumococcus type 12F and 14. These included 70 and 70% for nonsplenectomized patients as compared to 50 and 84% for those splenectomized. Vaccination did not result in the production of opsonizing antibody for the related type 5 pneumococcus. Pneumococcal vaccine generates functional antibody and is safe in renal transplant patients.

Spontaneous resolution of vesicoureteral reflux in a renal transplant recipient.

Vesicoureteral reflux has been considered as a predisposing factor to the development of urinary infection in adults. In renal transplant patients, it has been suggested as a risk factor for graft failure. We report a patient with a normal voiding cystourethrogram after renal transplantation who was demonstrated to have mild reflux during an acute infection. Following treatment of the infection, the reflux disappeared. This patient's course suggests that reversible reflux in renal transplant recipients may be a result of infection and is not necessarily a harbinger of graft failure.

Multicenter clinical evaluation of long-term efficacy and safety of labetalol in treatment of hypertension.

The long-term efficacy and safety of labetalol, an antihypertensive agent with combined beta- and alpha-blocking activity, were evaluated alone (number = 193) and in combination with a diuretic (number = 144) in an open-label multicenter trial of 337 hypertensive patients aged 21 to 75 years, including initially 205 (61 percent) men and 219 (65 percent) Caucasians. There were 219 (65 percent) mild, 85 (25 percent) moderate, and 33 (10 percent) severe hypertensive patients. Labetalol (100 to 1,200 mg twice a day) alone or in combination with a diuretic reduced the mean standing blood pressure by 13/11 and 25/16 mm Hg to 135/88 and 130/91 mm Hg, respectively (p less than 0.01), and supine blood pressure by 6/7 and 18/13 mm Hg to 141/86 and 138/90 mm Hg (p less than 0.01), respectively. Blood pressure reductions observed at one month were maintained after one year; 206 (62 percent) patients had 10 mm Hg or greater reductions and 184 (56 percent) patients were maintained at diastolic blood pressures less than 90 mm Hg. Most frequently reported drug-related side effects included fatigue (14 percent), dizziness (12 percent), nausea (11 percent), nasal stuffiness (8 percent), headache (4 percent), and male sexual dysfunction (14 percent). Side effects were generally of mild to moderate intensity and often transient. In addition, in 27 (8 percent) patients reversible asymptomatic transaminase elevations to greater than twice normal developed at some time during the study. In 13 (4 percent) patients these alterations resolved during continued labetalol therapy, but in five (2 percent) patients these marked elevations led to discontinuation of the drug. A total of 32 (9.5 percent) patients were terminated prematurely due to side effects (most commonly genitourinary or gastrointestinal) possibly attributable to the drug. These findings indicate that labetalol with or without a diuretic is a potentially effective, safe, and relatively well-tolerated long-term antihypertensive therapy.

Vancomycin penetration into CSF during treatment of patients receiving hemodialysis.

Penetration of vancomycin into CSF was determined during therapy with the regimens recently used to treat staphylococcal infections in patients receiving hemodialysis: 1 gm weekly or 750 mg twice weekly. During three episodes in two patients with proved or suspected central nervous system infection, CSF levels of vancomycin ranged from < 0.5 to 1.54 microgram/ml; in only two of six CSF specimens did the antibiotic level exceed its in vitro inhibitory concentration for the infecting organism. Thus, the vancomycin hemodialysis regimens may provide marginal to subtherapeutic CSF drug levels.

Site of action of a uremic serum fraction inhibiting sodium transport in frog skin.

The rate coefficients and fluxes of sodium across the outside and inside barriers of an in vitro, short-circuited frog skin preparation were determined in the presence of a uremic serum fraction to localize the site of action of an inhibitor of sodium transport. In unpaired studies, the mean depression of short-circuit current (SCC) resulting from the addition of the uremic serum fraction (21.9+/-2.2%) was significantly greater than the decrease in SCC resulting from either frog Ringer's wash or normal serum fractions. Paired studies comparing active and inactive uremic serum fractions indicated that the reduction in net sodium transport, whether calculated from changes in SCC(-0.55+/-0.12muEq/h) or changes in unidirectional Na fluxes (-0.56+/-0.15 muEq/h) was significantly greater in hemi-skins treated with the active fraction. The depression in sodium transport was associated with a significant decrease of sodium movement from the skin to the inside compartment, phi22 (-0.62+/-0.2 muEq/h). The results of these studies suggest that the inhibition of sodium transport ascribed to the uremic serum fraction is due to an inhibition of the active transport mechanism located at the serosal barrier.

Tritiated digoxin: studies in renal disease in human subjects.

Digoxin is excreted primarily in the urine as the unchanged glycoside: 60-80% can be recovered from the urine in 7 days after a single intravenous dose in the human subject. Definition of the role of the kidney in digoxin excretion, turnover and metabolism was studied in 57 patients with renal disease, transplant candidates and/or donors and recipients of renal transplants. A single dose of 3H digoxin was given to the subjects, frequent serum samples were obtained and all urine and stools were saved for 7 days. All specimens were extracted with chloroform and digoxin, and its metabolites were separated by column chromatography. Results reveal that the serum T1/2 and the dominant T1/2 of digoxin are prolonged in renal disease in direct proportion to the reduction in creatinine clearance (r = 0.833). The blood urea nitrogen (BUN) is also related to digoxin clearance (r = 0.742). The higher the BUN, the less digoxin excreted in the urine. Anephric patients excrete more digoxin in stool, but this does not compensate for the lack of renal excretion. Transplanted kidneys excrete digoxin in proportion to renal functional capacity, as do patients who have experienced unilateral nephrectomy. Peritoneal or hemodialysis is not effective in removing digoxin from the human subject and may lead to digitalis intoxication if K+ is allowed to fall to critical levels. Digoxin excretion is not volume related, as patients with nephritogenic diabetes insipidus excrete the drug normally with urine volumes of 12 liters a day. Digoxin doses in renal insufficiency should be dictated by knowledge of renal functional ability of the kidneys and after "normal" loading doses, and maintenance doses should be 1/4 to 1/2 those usually administered.