Nephrology pharmaceutical care preceptorship: a programmatic and clinical outcomes assessment.

OBJECTIVE: The University of Pittsburgh Nephrology Pharmaceutical Care Preceptorship (NPCP) program was conceived to acquaint health system pharmacists with the pharmacotherapeutic management of dialysis patients, enhance the delivery of pharmaceutical care, and improve clinical outcomes through the development of specialized professional skills. A survey designed to determine the impact of the NPCP program was sent to all 145 participants of the program. METHODS: The survey, designed to collect demographic information and data about the participants' practice sites, professional activities prior to and after the completion of the program, and markers of disease status, was mailed to all participants in September 1997. The 96 respondents (66.2%) were involved in a wide variety of clinical practices; inpatient management of peritoneal dialysis, hemodialysis, or renal transplant patients were most commonly reported. RESULTS: More than 80% of the participants believed that the educational content of the NPCP program was sufficient to allow them to establish a specialized service for the management of dialysis patients. However, two-thirds would have preferred to have more contact time (an additional 1-2 d) with the preceptorship faculty. The percentage of the pharmacists' time devoted to the provision of pharmaceutical care for dialysis patients almost doubled, from 13.1% to 25.2% (p < 0.001). The components of pharmaceutical care performed by these pharmacists also changed as a result of their completion of the NPCP program. Time devoted to clinical services and the provision of educational programs (inservices) increased significantly, while the time allocated to distributive activities decreased from a mean of 32.4% to 26.4% (almost 20% from baseline). The number of pharmacists who provided some component of pharmaceutical care for ambulatory dialysis patients increased significantly, from 10 to 33, after completion of the program. In the survey given after the preceptorship, almost 70% of these 33 pharmacists self-reported that the mean hematocrit of their ambulatory dialysis patients increased; 45% reported that the epoetin dose was lower. Parenteral iron use was also reported to have increased in 78.8% of the dialysis units, and an increase in serum ferritin and transferrin saturation was observed in 54.5% and 60.6% of the units. respectively. Although far fewer pharmacists (n = 15) initiated a renal osteodystrophy management program, 73.3% of those who did so reported an increase in their patients' compliance with phosphate binder therapy, which was reflected in a drop in serum phosphorous in 40% of the units. CONCLUSIONS: The NPCP program resulted in changes in the professional activities of the participants: fewer distributive activities and increased clinical and educational activities. These significant changes were noted in all areas of outpatient care. Participation in the NPCP program enhanced the delivery of pharmaceutical care to dialysis patients and improved the markers of disease status.

Predicting first-year relapses in children with nephrotic syndrome.

OBJECTIVE: More than half of the children diagnosed with nephrotic syndrome will have relapses. These can be infrequent relapses (IRs: <2 in 6 months or <3 in a year) or frequent relapses (FRs: >2 in 6 months or >3 in a year). Patients who relapse while on alternate day steroids or within 1 month of discontinuation of steroid therapy are considered steroid-dependent (SD; J Pediatr. 1982; 101:514-518). Patients with an IR course have a better long-term prognosis, and many of them have minimal-change disease without mesangial hypercellularity or sclerosis. The purpose of our study was to identify factors at initial presentation that could predict the relapse pattern in the first year after diagnosis, without taking into consideration the histopathology found on renal biopsy. DESIGN: We analyzed the medical records of children who were seen by us before March 1997 and followed for at least 1 year. Variables selected in the study were age, sex, race, presence or absence of hematuria, and days to remission (defined as protein-free) at the initial presentation, because they could relate to the pattern of relapses (ie, IR, FR, and SD). RESULTS: Of 70 patients, 14 were excluded because of insufficient data. There were 38 males (67.9%) and 18 females (32.1%), giving a male:female ratio of 1.8:1. Median age at presentation was 3.25 years (range: 1.5-13), and 76.9% were white, 8.9% black, 7.1% Hispanic, and 7.1% other. Of all the patients, 23 were IR (41.1%), 9 were FR (16.1%), and 24 were SD (42. 9%). Median days to remission were 10 (range: 2-60), on Prednisone 60 mg/M(2) daily. Hematuria was present initially in 26 patients (46. 4%), and absent in 30 (53.6%). Age, sex, race, and hematuria, as independent variables, were not predictors of relapses in the first year. However, using a stratified analysis based on the presence or absence of hematuria, we found that if the remission occurred within the first week of therapy, the patients without hematuria were more likely to be IR. The sensitivity and specificity of this finding were 67% and 89%, respectively, with a positive predictive value of 94%. CONCLUSION: We conclude that of all the presenting features, the rapidity of initial response to steroid therapy combined with the presence of hematuria, could predict future relapses and should be well documented.

Physician knowledge and practice patterns relating to diabetic nephropathy.

OBJECTIVE: To assess the knowledge and practice patterns of primary care physicians relating to the detection and treatment of diabetic nephropathy and to compare these findings with current standards of care. DESIGN: National survey. PARTICIPANTS: 1,000 randomly selected physicians. SETTING: Primary care. INTERVENTION: Mailed questionnaire consisting of a six-page "Diabetes Survey." RESULTS: Among the 1,000 primary care physicians, 950 were considered eligible for the survey. Sufficiently completed surveys were returned by 216 physicians, yielding an adjusted response rate of 22%. In general, patients with type 1 diabetes were monitored more intensively than those with type 2 diabetes. Primary care physicians were more likely to monitor patients for overt proteinuria (86%) than microalbuminuria (58%). Of the physicians who claimed to monitor patients for microalbuminuria, 39% chose inappropriate methods for detection, which lowers the percentage of physicians who correctly monitored for microalbuminuria to 37%. More than 95% of the respondents were aware of the benefits of angiotensin-converting enzyme inhibitors (ACEIs) in delaying the progression of diabetic nephropathy. Patients with proteinuria (86%) were more likely to be treated with an ACEI than were patients with microalbuminuria (79%). If a patient presented with proteinuria but without hypertension, the use of ACEIs fell to 75%. Rates of referral to a nephrologist were low at early stages of the disease (3% to 11%) and remained relatively low (28%) at later stages, even when serum creatinine was greater than 3 mg/dL. CONCLUSION: Further efforts directed toward education of primary care physicians about diabetic nephropathy have the potential to improve the care of patients with this disorder. These findings demonstrate a unique opportunity for pharmacists to become educators to physicians in their community.

Measuring total body water in peritoneal dialysis patients using an ethanol dilution technique.

UNLABELLED: Measuring total body water in peritoneal dialysis patients using an ethanol dilution technique. BACKGROUND: The accuracy with which total body water (TBW) is estimated is a direct determinant of the reliability of Kt/V urea measurements in peritoneal dialysis (PD) patients. Ethanol dilution has been previously shown to be a reliable measure of TBW. Advances in breath alcohol technology make this a feasible clinical tool. METHODS: We gave 19 fasting chronic PD patients 0.3 g/kg of ethanol (EtOH) orally on two separate occasions. Breath alcohol concentrations (BrACs), determined by dual-beam infrared analysis, were recorded at baseline and periodically thereafter until BrACs were less than 0.01%. The TBW was then determined by standard pharmacokinetic techniques. RESULTS: TBW measurements were reproducible, with a mean between-run difference of -0.004 liter/kg (95% limits of agreement -0.040 to 0. 032 by Bland-Altman). The Watson equations tended to underestimate TBW, with a mean difference (EtOH - Watson) of +3.0 liters (SD 4.0 liters, P = 0.004) and a mean absolute difference of 4.1 liters (SD 2.7 liters, range -4.4 to 9.5 liters). Kt/V was calculated from dialysate and urine collection, using V as determined from TBW estimates from EtOH and Watson. The mean Kt/V(EtOH) was 2.31 (SD 0. 50) compared with 2.46 (SD 0.52) using Watson. The mean absolute difference between the two Kt/V estimates was 0.26 (SD 0.20, range -0.87 to 0.57), with Kt/V overestimated by Watson in 14 patients. EtOH was well tolerated, and the procedure was completed in about four hours. CONCLUSIONS: Measuring V by the BrAC technique does not require blood sampling, is reliable, and is reproducible. It is a potentially useful method for a periodic determination of volume that may allow for more accurate Kt/V measurement in PD patients.

Pharmacokinetics of vancomycin when administered during high flux hemodialysis.

This study was undertaken to evaluate the pharmacokinetics of relatively high-dose vancomycin when administered during high-flux hemodialysis using a polysulfone membrane (F-80, Fresenius). Five noninfected, anuric patients received a single dose of 25 mg/kg of vancomycin infused during hemodialysis at a rate of one gram per hour and timed such that the end of the infusion coincided with the end of dialysis. Blood samples were drawn during the infusion, up to six hours after the end of dialysis and then prior to the next three dialysis treatments. Spent dialysate was collected during the infusion. Samples were analyzed using the EMIT assay. The percent of vancomycin lost during the first dialysis session ranged from 39.1 to 55.1% (mean, 45.7+/-6.4). The concentration of vancomycin at 6 hours after hemodialysis ranged from 18.2 to 45.1 mg/L (mean, 29.6+/-10.0 mg/l). Dialysis clearance ranged from 96.1 to 158.1 ml/min (mean, 130.7 +/-30.0 ml/min). One week after dosing, serum concentrations ranged from 8.14 mg/l to 10.1 mg/l (mean, 9.0+/-1.0 mg/l). This study suggests than an initial dose of 25 mg/kg of vancomycin, given during high-flux dialysis, may provide adequate serum concentrations in anuric hemodialysis patients for up to seven days. This dosing scheme reduces inconvenience to the patient and staff, and potentially can reduce nursing costs associated with post-dialysis administration; its cost is minimal. At this point, subsequent dosing is best determined by therapeutic drug monitoring.

Clinical presentation and analysis of risk factors for infectious complications of implantable cardioverter-defibrillator implantations at a university medical center.

The objective of this report is to describe the characteristics of patients who develop infections associated with implantable cardioverter-defibrillators (ICDs) implanted with sternotomy and thoracotomy approaches. A retrospective chart review identified all patients who underwent ICD implantation at a university medical center from November 1982 through February 1990. Several patient and procedural variables were compared between infected patients and noninfected patients. One hundred fifty-seven patients underwent 202 ICD generator implantations (45 generator changes), and nine of these patients developed infection (4.5% per implantation and 5.7% per patient). Of the patient variables analyzed, a significant correlation (P < .0001) was made only with a diagnosis of diabetes mellitus: 36% of diabetics versus 3.9% of nondiabetics were infected. The only patient- or procedure-specific variable that was found to correlate with the development of infection was the presence of diabetes mellitus.

Effects of probenecid and cimetidine on renal disposition of ofloxacin in rats.

The renal handling of ofloxacin in rats which were given ofloxacin either alone or in combination with probenecid or cimetidine was studied. In the presence of cimetidine or probenecid, ofloxacin's total and renal clearances were reduced and its half-life was prolonged. This suggests that ofloxacin is secreted by both the anionic and cationic transport systems.

Pharmacokinetics of intraperitoneal fluconazole during continuous cycling peritoneal dialysis.

OBJECTIVE: To investigate the pharmacokinetic characteristics of intraperitoneal fluconazole in patients undergoing continuous cycling peritoneal dialysis (CCPD). DESIGN: Prospective, nonrandomized, single-dose, open-label study. PARTICIPANTS: Five noninfected volunteer CCPD patients. INTERVENTIONS: Patients received a single dose of intraperitoneal fluconazole 200 mg during their long daytime dwell. Blood samples were collected before and 1, 3, 6, 12 (end of first dwell), 24 (after overnight cycling), 48, 72, 96, and 120 hours after dosing. Used dialysate was collected throughout the study. Unless the patient was anuric, urine was collected for the first 48 hours. MAIN OUTCOME MEASURE: Fluconazole concentrations were assayed by gas-liquid chromatography. Pharmacokinetic parameters were calculated using standard noncompartmental techniques. RESULTS: The bioavailability of intraperitoneal fluconazole was 96% +/- 2% over a 12-hour dwell, absorption half-life was 2.5 +/- 1.2 hours, serum elimination half-life was 71.65 +/- 12.76 hours, and volume of distribution was 0.66 +/- 0.13 L/kg. Peritoneal clearance was 5.96 +/- 0.93 mL/min and proportional to total dialysate volume. Renal clearance was proportional to renal creatinine clearance. CONCLUSIONS: Current treatment guidelines for fungal peritonitis suggest fluconazole 200 mg intraperitoneally every 24 hours. Our data suggest that this dose, administered every 48 hours, is more than sufficient to maintain serum and peritoneal concentrations above the minimum inhibitory concentration for most Candida spp. Other factors, such as residual renal function and dialysis prescription, may also need to be considered.

Pulse dose oral calcitriol therapy for renal osteodystrophy: literature review and practice recommendations.

Oral pulse dosing of calcitriol has been proposed as an alternative to intravenous administration in the treatment of renal osteodystrophy. A review of the literature suggests it can provide a safe and effective method that is especially convenient for peritoneal dialysis patients with mild to moderate bone disease. However, its use should be accompanied by careful monitoring and control of serum calcium, phosphorus, and parathyroid hormone levels. Some practical suggestions are provided.

Sertraline-associated syndrome of inappropriate antidiuretic hormone: case report and review of the literature.

Selective serotonin reuptake inhibitors have gained widespread use in the treatment of depression. A 78-year-old woman became hyponatremic 3 days after being treated with sertraline and was subsequently diagnosed with the syndrome of inappropriate antidiuretic hormone (SIADH). She became symptomatic, but experienced rapid resolution of the laboratory and clinical abnormalities associated with SIADH on discontinuing sertraline and receiving fluid restriction, hypertonic saline, and demeclocycline. Several mechanisms may relate SIADH and vasopressin release to serotonin.

Prevention and treatment of diabetic nephropathy.

The pathophysiology and natural history of diabetic nephropathy are described, and recent developments in its prevention and treatment are discussed. Diabetic nephropathy can occur in both insulin-dependent and non-insulin-dependent diabetics. It is characterized by arterial hypertension, proteinuria, and progressive loss of renal function. Although the exact mechanism has not been fully elucidated, hyperglycemia with altered intraglomerular hemodynamics is an important contributor to the initiation and progression of the disease. Concurrent hypertension aggravates progression of the disease. Currently accepted strategies to slow the progression of diabetic renal disease have focused on antihypertensive therapy, strict glucose control, and restriction of dietary proteins. Recent publications support the hypothesis that angiotensin-converting-enzyme inhibitors have a unique ability, independent of their antihypertensive effect, to slow the progression of diabetic nephropathy. Investigational agents (e.g., aminoguanidine) may prove helpful in the management of the condition. Information about the prevention of diabetic nephropathy has grown significantly in the past few years.

Disposition of misoprostol and its active metabolite in patients with normal and impaired renal function.

The disposition of misoprostol acid, the active metabolite of misoprostol, was studied in 48 subjects with various degrees of renal function after administration of a single 400 microgram oral dose of misoprostol. Subjects were assigned to one of four treatment groups: group 1, normal renal function with creatinine clearance (CLCR) 80-140 mL/min/1.73 m2; group 2, mild renal impairment with CLCR 50-79 mL/min/1.73 m2; group 3, moderate renal impairment with CLCR 20-49 mL/min/1.73 m2 or group 4, end stage renal disease (ESRD) patients maintained on hemodialysis. The maximum plasma concentration (Cmax) and time to reach Cmax (tmax) for misoprostol acid tended to be larger in group 4 subjects; however, it failed to reach statistical significance. Although not statistically significant, in group 4 subjects the terminal half-life (t1/2) of misoprostol acid was almost twice as large (1.27 +/- 0.77 h) as in groups 1, 2, and 3 (0.70 +/- 0.72, 0.72 +/- 0.67, and 0.73 +/- 0.45 h, respectively). Misoprostol acid's total area under the plasma concentration curve (AUC0 infinity) was larger in group 4 subjects (1173.5 +/- 487.4 pg.h/mL) as compared with groups 1, 2, and 3 (421.4 +/- 263.1, 418.9 +/- 114.5, and 377.0 +/- 145.2 pg.h/mL, respectively; P < .05). The apparent total body clearance (CL) of misoprostol acid was statistically significantly smaller in group 4 subjects (0.094 +/- 0.044 L/kg/min) as compared only with group 3 subjects (0.284 +/- 0.102 L/kg/min). The dose of misoprostol may need to be reduced in ESRD patients on prolonged hemodialysis to prevent unnecessary high plasma levels of misoprostol acid and to avoid possible dose-related adverse effects.

The pharmacokinetics of aminoguanidine in end-stage renal disease patients on hemodialysis.

Aminoguanidine is an investigational agent that may slow or prevent many diabetes-related complications. Since the elimination of aminoguanidine is dependent on renal function, its pharmacokinetics was investigated in eight chronic renal failure patients maintained on hemodialysis. Each patient received 300 mg of aminoguanidine hydrochloride during both an interdialytic and an intradialytic period. During the interdialytic period, the maximum aminoguanidine concentration (Cmax) and time to reach Cmax was 4.5 micrograms/mL and 1.5 hours, respectively. The terminal elimination half-life in these patients was prolonged (37.9 hours). The renal clearance was 2.1 mL/min. Only 8.7% of the administered dose was recovered unchanged in the urine, which is markedly reduced from what is recovered in urine in subjects with normal renal function. There was a positive correlation between the renal clearance of aminoguanidine and the patients' residual renal function (P < 0.05). During hemodialysis, the half-life of aminoguanidine was shortened to 3.9 hours. The hemodialysis clearance of aminoguanidine was 203.6 mL/min. After cessation of hemodialysis, a significant rebound in plasma aminoguanidine concentrations (mean, 39%) was observed. Thus, the dose of aminoguanidine hydrochloride will need to be significantly reduced in patients with end-stage renal disease. Given the interdialytic and intradialytic pharmacokinetics of aminoguanidine, three times weekly dosing after each hemodialysis session is suggested.

Calcium-channel blockers for prophylaxis of radiocontrast-associated nephrotoxicity.

Because of both an absence of sufficient data and the concern for increased toxicity in certain patient populations, the use of CCBs to reduce radiocontrast-associated nephrotoxicity is not recommended. Additional prospective, randomized trials are needed.

New therapeutic agents in the management of hypertension: angiotensin II-receptor antagonists and renin inhibitors.

OBJECTIVE: To review the chemistry, pharmacokinetics, and clinical trials of two new classes of antihypertensive drugs, angiotensin II-receptor antagonists and renin inhibitors. DATA SOURCES: Primary literature on angiotensin II-receptor antagonists and renin inhibitors was identified through a comprehensive medical literature search from 1961 through 1993. This search included journal articles, abstracts, and reports of both animal and human research published in the English language. Indexing terms included renin-angiotensin aldosterone system, renin inhibitors, angiotensin II antagonists, DuP 753, losartan, MK954, A-64662, and Ro 42-5892. STUDY SELECTIONS: Emphasis was placed on clinical and pharmacokinetic studies in humans for drugs that are currently in Phase I-III research protocols in the US. DATA EXTRACTION: All available data from human studies were reviewed. DATA SYNTHESIS: Angiotensin II-receptor antagonists and renin inhibitors may be effective antihypertensives with few adverse effects noted in the small studies completed. Their potential advantage over angiotensin-converting enzyme (ACE) inhibitors includes a possible smaller adverse effect profile. In the past, the clinical utility of angiotensin II-receptor antagonists and renin inhibitors has been limited because of poor oral bioavailability, although newer agents are more readily bioavailable. CONCLUSIONS: Angiotensin II-receptor antagonists and renin inhibitors may be the next new classes of antihypertensives marketed. However, definitive conclusions about their roles in the management of hypertension are not possible until larger clinical trials assessing their efficacy and safety and comparing them with ACE inhibitors are completed.

The disposition and protein binding of batanopride and its metabolites in subjects with renal impairment.

We have studied the disposition of batanopride and its three major metabolites (the erythro-alcohol, threo-alcohol, and N-desethyl metabolites) in 27 subjects with various degrees of renal function after intravenous infusion of a single dose of 3.6.mg.kg-1 of batanopride over 15 min. The subjects were assigned to one of three treatment groups: group 1, normal renal function (creatinine clearance > or = 75 ml.min-1 x 1.73 m-2; n = 13); group 2, moderate renal impairment (creatine clearance 30-60 ml.min-1 x 1.73 m-2; n = 8); group 3, severe renal impairment (creatinine clearance < or = 30 ml.min-1 x 1.73 m-2; n = 6). The terminal half-life of batanopride was significantly prolonged from 2.7 h in group 1 to 9.9 h in group 3. The renal clearance of batanopride was significantly lower in group 3 (25 ml.min-1) compared with group 1 (132 ml.min-1). There were no differences in plasma protein binding or steady-state volume of distribution of batanopride among the groups. There were significantly lower renal clearances for all three metabolites in groups 2 and 3 compared with group 1. The half-lives of all three metabolites were significantly prolonged in group 3 compared with group 1. The dose of batanopride may need to be reduced in patients with creatinine clearances less than 30 ml.min-1 x 1.73 m-2 to prevent drug accumulation and avoid possible dose-related adverse effects.