Converting hemodialysis patients from intravenous paricalcitol to intravenous doxercalciferol - a dose equivalency and titration study.

AIMS: Doxercalciferol and paricalcitol are used to treat hyperparathyroidism in chronic kidney disease. This study was conducted to define equivalent dose requirements to convert patients from intravenous paricalcitol to intravenous doxercalciferol. METHODS: Following a 4-week baseline period using a fixed dose of paricalcitol, 42 adult hemodialysis subjects were assigned to receive a fixed dose of doxercalciferol for 4 weeks using a conversion factor of either 50 or 65% of the prior paricalcitol dose. During a 12-week titration period the doxercalciferol dose was adjusted to optimize iPTH levels into the range of 150 - 300 pg/ml. Annual costs to achieve equivalent iPTH control were calculated for both vitamin D analogs. RESULTS: During the doxercalciferol fixed-dose period, the average dose of doxercalciferol was 2.1 +/- 1.3 microg and 3.1 +/- 1.8 microg in the 50 and 65% dose conversion groups, respectively. During this period mean iPTH in the 50% dose conversion group increased by 24 pg/ml (p = 0.017). During the dose titration period, doxercalciferol was increased to bring iPTH within the target range. Calcium control was maintained with both conversion factors, while slightly better phosphorus control was seen in the 65% dose conversion group. Annualized treatment cost for doxercalciferol was 28% less expensive per patient than paricalcitol. CONCLUSION: Patients can be managed safely and effectively with conversion and dose titration from paricalcitol to doxercalciferol. Both conversion strategies maintained iPTH at clinically satisfactory levels. Furthermore, doxercalciferol therapy resulted in drug acquisition cost-savings.

Studies on the mechanism of sodium excretion during drug-induced vasodilatation in the dog.

The administration of vasodilating agents such as bradykinin and acetylcholine cause an increase in urinary sodium excretion. Yet the mechanisms involved in this natriuretic effect are not clear. Recent studies with another renal vasodilator, secretin have shown this drug also causes a profound increase in renal blood flow but without major changes in sodium excretion. To attempt to delineate the basis of this difference in sodium excretion with these drugs, the renal functional effects of secretin and bradykinin were compared at an equivalent vasodilating dose. Bradykinin increased renal blood flow from 222 to 342 ml/min, urine volume from 0.2 to 1.2 ml/min, and urine sodium excretion from 28 to 115 mueq/min. Urine osmolality fell from 1,230 to 401 mosmol/kg. Secretin caused a comparable increase in renal blood flow (216 to 325 ml/min) while changes in urine flow, sodium excretion, and urine osmolality were significantly less. In further studies papillary plasma flow was estimated using the albumin accumulation technique. Control papillary plasma flow was 29 ml/min per 100 g. Bradykinin increased urinary sodium excretion 108 mueq/min and decreased urinary osmolality from 1,254 to 516 mosmol/kg in association with a rise in papillary plasma flow to 62 ml/min per 100 g. Urine sodium excretion, urinary osmolality, and urine flow rate, as well as papillary plasma flow rate (32 ml/min per 100 g) were unchanged from control when secretin was administered. Studies with acetylcholine were qualitatively similar to those of bradykinin. Renal blood flow increased from 150 to 248 ml/min, urinary sodium excretion increased from 20 to 243 mueq/min, urinary osmolality decreased from 1,237 to 411 mosmol/kg and papillary plasma flow increased from 39 to 52 ml/min per 100 g. It is suggested that the natriuretic effect of some vasodilators is due, at least in part, to alterations in medullary hemodynamics, as evidenced by the increase in papillary plasma flow seen with bradykinin and acetylcholine, but not secretin.

Quantitative analysis and molecular fingerprinting of methicillin-resistant Staphylococcus aureus nasal colonization in different patient populations: a prospective, multicenter study.

OBJECTIVES: To better understand the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in different patient populations, to perform quantitative analysis of MRSA in nasal cultures, and to characterize strains using molecular fingerprinting. DESIGN: Prospective, multicenter study. SETTING: Eleven different inpatient and outpatient healthcare facilities. PARTICIPANTS: MRSA-positive inpatients identified in an active surveillance program; inpatients and outpatients receiving hemodialysis; inpatients and outpatients with human immunodeficiency virus (HIV) infection; patients requiring cardiac surgery; and elderly patients requiring long-term care. METHODS. Nasal swab samples were obtained from January 23, 2006, through July 27, 2007; MRSA strains were quantified and characterized by molecular fingerprinting. RESULTS: A total of 444 nares swab specimens yielded MRSA (geometric mean quantity, 794 CFU per swab; range, 3-15,000,000 CFU per swab). MRSA prevalence was 20% for elderly residents of long-term care facilities (25 of 125 residents), 16% for HIV-infected outpatients (78 of 494 outpatients), 15% for outpatients receiving hemodialysis (31 of 208 outpatients), 14% for inpatients receiving hemodialysis (86 of 623 inpatients), 3% for HIV-infected inpatients (5 of 161 inpatients), and 3% for inpatients requiring cardiac surgery (6 of 199 inpatients). The highest geometric mean quantity of MRSA was for inpatients requiring cardiac surgery (11,500 CFU per swab). An association was found between HIV infection and colonization with the USA300 or USA500 strain of MRSA (P < or = .001). The Brazilian clone was found for the first time in the United States. Pulsed-field gel electrophoresis patterns for 11 isolates were not compatible with known USA types or clones. CONCLUSION: Nasal swab specimens positive for MRSA had a geometric mean quantity of 794 CFU per swab, with great diversity in the quantity of MRSA at this anatomic site. Outpatient populations at high risk for MRSA carriage were elderly residents of long-term care facilities, HIV-infected outpatients, and outpatients receiving hemodialysis.

Urinary prostaglandin E excretion: effect of chronic alterations in sodium intake and inhibition of prostaglandin synthesis in the rabbit.

On the basis of acute experiments in animals, a role for prostaglandin E (PGE) in the regulation of urinary sodium excretion has been suggested. Limited information is available, however, concerning the possible role of PGE in chronic adjustments to sodium intake. These studies were designed to determine whether chronic changes in sodium balance would modify renal PGE excretion and whether partial inhibition of prostaglandin synthesis would alter the ability of the kidney to adjust to an alteration in sodium intake. Thus, we measured sodium and PGE excretion in rabbits on chronic high and low salt diets before and after inhibition of prostaglandin synthesis with indomethacin or meclofenamate. Although the alterations in salt intake resulted in large changes in sodium excretion there was no significant change in urinary PGE excretion. After administration of either indomethacin or meclofenamate for several days there was a significant fall in PGE excretion, but no significant change in sodium excretion. These results suggest that in the rabbit 1) chronic changes in sodium excretion can occur without modifying PGE excretion (and presumably renal PGE synthesis) and 2) inhibition of PGE synthesis does not impair the kidney's ability to adjust to a chronic high or low sodium intake.

Gastrointestinal blood loss in patients with chronic renal failure.

In the management of patients with chronic failure one of the persistent medical problems is that of anemia. Since iron deficiency can be an important component of this anemia, this study was designed to evaluate the possible contribution of gastrointestinal blood loss to their anemia. Blood loss was quantitated by 51 chromium labeling red cells in normals and in patients with chronic renal failure both before and during chronic hemodialysis. Four normal volunteers had a gastrointestinal blood loss of 0.83 ml/day, six azotemic patients not yet on hemodialysis had significantly greater gastrointestinal blood loss of 3.15 ml/day (p less than 0.05). Ten patients on chronic regular hemodialysis had a daily gastrointestinal blood loss of 6.27 ml/day which was significantly greater than both the normals (p less than 0.01) and the predialysis azotemic patients (p less than 0.05). Complete gastrointestinal tract evaluation in the chronic dialysis patients revealed several upper gastrointestinal tract mucosal abnormalities although discrete bleeding sites were not identified. In conclusion, azotemic patients both before and after chronic hemodialysis have increased gastrointestinal blood loss. This increased blood loss contributes to the increased iron loss in this patient population.

Study of factors which modify the development of norepinephrine-induced acute renal failure in the dog.

Previous studies have demonstrated that the fall in inulin clearance which occurs 3 hours after the intrarenal administration of norepinephrine can be markedly attenuated by the prior administration of intrarenal prostaglandin E2 (PGE). Since in the previous studies PGE led to a marked increase in both renal blood flow and solute excretion, we designed the present series of experiments to investigate whether an increase in renal blood flow, solute excretion, or other factors were responsible for the protective effect in the norepinephrine model. Two renal vasodilators, bradykinin and secretin, were evaluated initially. Bradykinin administration prior to norepinephrine administration had a protective effect similar to that previously found with PGE, whereas secretin did not. Both of these vasocilators increased renal blood flow to the same degree, but only bradykinin increased urine flow and solute excretion. The fall in inulin clearance 3 hours after the administration of norepinephrine was also attenuated by two diuretics (mannitol and furosemide) which tended to increase renal blood flow. In contrast, two natriuretic agents, which are also renal vasoconstrictors (chlorothiazide and benzolamide), had no protective effect. Further, chlorothiazide and benzolamide obviated the protective effect of bradykinin. These studies demonstrate that there are several types of pharmacologic agents which can modify the magnitude of renal functional impairment resulting from extreme renal ischemia. Although the mechanism of the protective effects remain unclear, the findings are compatible with the view that the protective effect noted with PGE, bradykinin, mannitol, and furosemide may be related to an increase in osmolar excretion which occurred with administration of each of these agents. This potentially salutory effect (increased osmolar excretion), however, could be overcome by an agent (e.g., chlorothiazide or benzolamide) which also increased renal resistance prior to the administration of norepinephrine.

Severe pulmonary vascular disease in systemic lupus erythematosus.

A young woman with systemic lupus erythematosus (SLE) had clinical evidence of acute cor pulmonale. Autopsy disclosed vascular lesions in the lungs resembling those seen in advanced pulmonary hypertension. This case illustrates that severe pulmonary vascular disease may complicate SLE and mimic pulmonary thromboembolic disease.