Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double-blind, multicenter, randomized study.

Vitamin D therapy for patients with end-stage renal disease (ESRD) on hemodialysis therapy has relied on patient dry weight to determine the initial dose of medication. Obtaining a patient's dry weight can be difficult, and no correlation has been established between a patient's body weight and severity of secondary hyperparathyroidism. We conducted a double-blind, double-dummy, randomized, 12-week, multicenter trial to compare the incidence of hypercalcemia (single occurrence) between two dosing regimens: one regimen based on baseline intact parathyroid hormone (iPTH; PTH/80) level, and the other regimen based on patient body weight (0.04 microgram/kg). One hundred twenty-five adult patients with ESRD on maintenance hemodialysis therapy were enrolled at multiple sites. Before treatment, all patients were required to have PTH levels of 300 pg/mL or greater, calcium levels of 8.0 mg/dL or greater and 10.5 mg/dL or less, and a calcium x phosphorus (Ca x P) product of 70 or less. Patients were randomized to one of two regimens: the nonrandomized treatment was also administered as a placebo dummy. No incidence of hypercalcemia occurred in either treatment group during the study. Patients treated according to the formula iPTH/80 required fewer dose adjustments and achieved the first of four consecutive reductions from baseline PTH level of 30% or greater more rapidly than patients treated based on body weight (P = 0.0306). Incidences of elevated Ca x P product levels were similar between treatment groups. Treatment with paricalcitol injection based on degree of secondary hyperparathyroidism incurred no greater risk for hypercalcemia and achieved meaningful therapeutic results with fewer dose adjustments than dosing based on patient body weight.

Multicenter evaluation of a polyurethaneurea vascular access graft as compared with the expanded polytetrafluoroethylene vascular access graft in hemodialysis applications.

OBJECTIVES: The purpose of this study was to compare in a randomized, prospective, and controlled study, the performance of a multilayered, self-sealing polyurethane vascular access graft (PVAG) and expanded polytetrafluoroethylene (ePTFE) vascular access grafts in hemodialysis applications. Performance measures included graft survival, complications, time to early cannulation, and hemostasis times after cannulation. STUDY DESIGN: A total of 142 patients were randomized equally to receive one of the two grafts after meeting all eligibility requirements. All patients were followed up prospectively to 12 months or to the end of secondary patency. Specifically, this study documented the performance of the PVAG and ePTFE grafts by determining the patencies and complications for both grafts. RESULTS: Patient characteristics between the two groups were similar with respect to risk factors and demographic characteristics (P >.05). Life-table patencies from the date of first dialysis were primary patency: PVAG 55% versus ePTFE 47% (6 months) and PVAG 44% versus ePTFE 36% (12 months) and secondary patency: PVAG 87% versus ePTFE 90% (6 months) and PVAG 78% versus ePTFE 80% (12 months). None of these differences were significant (P >.05). Both primary and secondary patencies were also not significantly different when the date of implantation was the starting point. Adverse events and complications were similar for the two groups, except the PVAG group had a higher incidence of technical complications manifested by graft kinking when compared with the control cohort (P <.05). Additionally, there was no significant difference in complication rates between these two groups with regard to infection and bleeding. When the time to hemostasis after cannulation was compared at 5minutes or less, there were more PVAG cannulation sites that achieved hemostasis compared with ePTFE sites, and this difference was significant (P <.0001). When time to first dialysis access was compared between the two grafts, 53.9% of all PVAG grafts were cannulated before 9 days versus none with the ePTFE grafts (P <.001). However, long-term graft survival was not significantly different when PVAG patients were stratified into early (< 9 days) and the late access (9 >/= days) groups (P =.29). CONCLUSIONS: The PVAG graft allows for early access without compromising long-term performance. Both PVAG and standard ePTFE grafts have similar long-term outcomes, despite early access with the PVAG vascular access grafts.

Nontransplant therapy for dialysis-related amyloidosis.

There is no specific treatment for dialysis-related amyloidosis (DRA). Available therapy is directed at removal of large quantities of beta(2)-microglobulin (beta(2)M) and palliation of symptoms. Plasma concentrations of beta(2)M in end-stage renal disease (ESRD) depend on the degree of residual renal function, the type of blood purification therapy, and properties of the dialysis filtration membrane. Retention of beta(2)M appears to be a necessary, although not sufficient, condition for DRA. While preserving residual renal function is important, dialysis modality largely determines beta(2)M removal. Convective dialysis treatments (hemofiltration and hemodiafiltration) remove beta(2)M more efficiently than diffusive treatments (conventional dialysis). In addition, column adsorption of beta(2)M can extensively remove the molecule, as can nocturnal hemodialysis. Hemodialysis membrane properties that are particularly important with regard to beta(2)M removal include permeability, adsorptive capacity, and biocompatibility. As such, beta(2)M removal with highly permeable biocompatible membranes such as polysulfone and polyacrylonitrile is relatively large. Several studies have suggested that use of such membranes can significantly delay DRA development and may be useful in ameliorating DRA-associated symptoms. Non-dialysis-related therapy for DRA is palliative and includes both medical and surgical therapies. Medical therapy includes low-dose corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs). Surgical therapy consists of relief of carpal tunnel syndrome, or palliation of shoulder pain, destroyed weight-bearing joints, or spinal cord compression. DRA is a serious complication of long-term dialysis. It is important for nephrologists to recognize the condition and attempt to slow its progression.

A component analysis of "stereotypy as reinforcement" for alternative behavior.

Results from several studies have suggested that the opportunity to engage in stereotypic behavior may function as reinforcement for alternative, more socially desirable behaviors. However, the procedural components of this intervention include several distinct operations whose effects have not been analyzed separately. While measuring the occurrence of stereotypy and an alternative behavior (manipulation of leisure materials), we exposed 3 participants to three or four components of a "stereotypy as reinforcement" contingency: (a) continuous access to materials, (b) prompts to manipulate materials, (c) restricted access to stereotypy (i.e., response blocking), and (d) access to stereotypy contingent on manipulating the materials. Continuous access to materials and prompting (a and b) produced negligible results. Restriction of stereotypy (c) produced a large increase in the alternative behavior of 2 participants, suggesting that response restriction per se may occasion alternative behavior. However, contingent access to stereotypy (d) was necessary to increase the 3rd participant's object manipulation; this finding provided some support for the use of stereotypy as reinforcement for alternative behavior. Finally, when transfer of the effects of intervention was assessed during periods in which active intervention components were withdrawn, the alternative behavior was maintained for 1 participant.

Skill acquisition in the implementation of functional analysis methodology.

Functional analysis methodology is a powerful assessment tool for identifying contingencies that maintain a wide range of behavior disorders and for developing effective treatment programs. Nevertheless, concerns have been raised about the feasibility of conducting functional analyses in typical service settings. In this study, we examined the issue of skill acquisition in implementing functional analyses by evaluating an instructional program designed to establish a basic set of competencies. Eleven undergraduate students enrolled in a laboratory course in applied behavior analysis served as participants. Their performance was assessed during scripted simulations in which they played the roles of "therapists" who conducted functional analyses and trained graduate students played the roles of "clients" who emitted self-injurious and destructive behaviors. To approximate conditions under which an individual might conduct an assessment with limited prior training, participants read a brief set of materials prior to conducting baseline sessions. A multiple baseline design was used to assess the effects of training, which consisted of reading additional materials, watching a videotaped simulation demonstrating correct procedural implementation, passing a written quiz, and receiving feedback on performance during sessions. Results showed that participants scored a relatively high percentage of correct therapist responses during baseline, and that all achieved an accuracy level of 95% or higher following training that lasted about 2 hr. These results suggest that basic skills for conducting functional analyses can be acquired quickly by individuals who have relatively little clinical experience.

Calcium Oxalate Stone Agglomeration Inhibition [tm] Reflects Renal Stone-Forming Activity.

Louisiana and other Gulf South states comprise a "Stone Belt" where calcium oxalate stone formers (CaOx SFs) are found at a high rate of approximately 5%. In these patients, the agglomeration of small stone crystals, which are visible in nearly all morning urine collections, forms stones that can become trapped in the renal parenchyma and the renal pelvis. Without therapy, about half of CaOx SFs repeatedly form kidney stones, which can cause excruciating pain that can be relieved by passage, fragmentation (lithotripsy), or surgical removal. The absence of stones in "normal" patients suggests that there are stone inhibitors in "normal" urines.At the Ochsner Renal Stone Clinic, 24-hour urine samples are collected by the patient and sent to the Ochsner Renal Stone Research Program where calcium oxalate stone agglomeration inhibition [tm] measurements are performed. Urine from healthy subjects and inactive stone formers has demonstrated strongly inhibited stone growth [tm] in contrast to urine from recurrent CaOx SFs. [tm] data from 1500 visits of 700 kidney stone patients have been used to evaluate the risk of recurrence in Ochsner's CaOx SF patients. These data have also been used to demonstrate the interactive roles of certain identified urinary stone-growth inhibitors, citrate and Tamm-Horsfall protein (THP), which can be manipulated with medication to diminish recurrent stone formation. Our goal is to offer patients both financial and pain relief by reducing their stones with optimized medication, using medical management to avoid costly treatments.

DRO contingencies: an analysis of variable-momentary schedules.

We conducted several comparative analyses to determine the relative effectiveness of variable-momentary differential-reinforcement-of-other-behavior (VM DRO) schedules. Three individuals who had been diagnosed with mental retardation participated. Results of functional analyses indicated that their self-injurious behavior (SIB) was maintained by social-positive reinforcement. Two individuals participated in a two-stage comparative analysis within multielement and multiple baseline designs. Fixed-interval (FI) and variable-interval (VI) DRO were compared in the first stage; VI DRO and VM DRO were compared in the second. All three schedules effectively reduced the participants' SIB. Treatment for the 3rd individual was conducted in a reversal design to examine the effects of VM DRO when it was implemented in isolation, and results indicated that the procedure was effective in reducing SIB. These findings suggest that VM DRO schedules may represent attractive alternatives to traditional FI schedules because momentary schedules do not require continuous monitoring and may result in higher rates of reinforcement.

The risks of exercise.

Patients with end-stage renal disease (ESRD) can benefit from exercise. At a minimum, progressive deconditioning will be prevented and cardiovascular and musculoskeletal status quo maintained, but it is also possible that physical functioning will be improved and mortality reduced. The risks of exercise must be assessed along with potential benefits. The most serious inherent risk of exercise in this population is a cardiac event, but the most common injuries sustained are to the musculoskeletal system. The exercise prescription must include measures to minimize both cardiovascular and musculoskeletal risk. These include provision of a prolonged warm-up and exercise adaptation period and time allowance for adequate cool-down. If these guidelines are followed and the exercise is begun at a low to moderate intensity, the associated risk to the ESRD patients should be minimal. For most ESRD patients, the risk benefit ratio will fall in favor of exercise, with the majority of patients exposed to greater risk by not exercising. Increased physical activity should be fostered in ways so that it becomes a routine part of the medical therapy and the mindset of the patient who then strives for self-improvement.

An innovative approach to temporary hemodialysis vascular access.

The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) has set down explicit and extensive guidelines for temporary and permanent hemodialysis vascular access. It is now incumbent on the nephrologist to ensure compliance to these standards. Two of our interventional nephrologists performed 402 central venous access procedures over a 12-month period (November 1996 to October 1997) to test the hypothesis that increased control over insertion technique would improve outcome. All but eight of the procedures were successfully completed, resulting in a failure rate of 2%. The expected serious procedural complication rate outlined in the NKF-DOQI standards is 2%. Our complication rate was 0.7% if all procedures were accounted for and 0.89% for just internal jugular and subclavian catheters. We conclude that the use of interventionally trained nephrologists and strict control of technique can improve outcome in temporary vascular access procedures.

Osteoporosis in end-state renal disease.

Maintaining the intricate bone mineral homeostasis in patients with chronic renal failure and renal osteodystrophy is a complex and challenging process. In addition to the well described high-turnover bone disease caused by secondary hyperparathyroidism and low-turnover disease in the form of osteomalacia (either from aluminum or a dynamic bone disease) osteopenia also is present in end-stage renal disease patients. In contrast to abnormalities in the ability of bone to remodel, osteopenia is a deficiency in bone mass or volume. The prevalence of fractures in dialysis patients, regardless of histomorphometry appears to exceed that observed in elderly women. This osteopenia that occurs in chronic renal failure patients secondary to multiple factors that include hypogonadism, medications (such as corticosteroids), immobilization, and the typical osteopenia associated with aging. All of these factors amplify the risk of fracture in dialysis patients.

On the relation between object manipulation and stereotypic self-injurious behavior.

Results from a number of studies have shown an inverse relationship between stereotypic behavior and object manipulation. The purposes of this study were to determine whether techniques similar to those used previously (prompting and reinforcement) would be effective in increasing object manipulation under both prompted and unprompted conditions, and to ascertain whether increases in object manipulation would result in decreases in stereotypic self-injurious behavior (SIB). Two individuals with developmental disabilities who engaged in SIB maintained by automatic reinforcement participated. Results showed that object manipulation increased from baseline levels when experimenters prompted participants to manipulate leisure items, but that object manipulation was not maintained under unprompted conditions, and rates of SIB stayed within baseline levels. We then attempted to increase object manipulation further by (a) reinforcing object manipulation, (b) blocking SIB while reinforcing manipulation, and (c) preventing SIB by applying protective equipment while reinforcing object manipulation. Reinforcing object manipulation alone did not affect levels of object manipulation. Blocking effectively reduced attempts to engage in SIB for 1 participant but produced no increase in object manipulation. When the 2nd participant was prevented from engaging in SIB through the use of protective equipment, rates of object manipulation increased dramatically but were not maintained when the equipment was removed. These results suggest that stimulation derived from object manipulation, even when supplemented with arbitrary reinforcement, may not compete with stimulation produced by stereotypic SIB; therefore, direct interventions to reduce SIB are required.

Analysis of activity preferences as a function of differential consequences.

Individuals who do not possess the verbal skills to express meaningful choice in the absence of its consequences may have difficulty indicating their preference for protracted activities that are unavailable until some time in the future (e.g., taking a walk, riding a bike). When we examined the preferences of 4 individuals with developmental disabilities by showing them pictorial representations of various activities, their initial choices showed no clear preferences. In a subsequent condition, selecting a photograph resulted in brief access to the depicted activity. When selections produced differential consequences (i.e., access to the activity), clear preferences emerged. In addition, 3 individuals' preferences were later shifted to an initially less preferred but more socially desirable option by superimposing additional reinforcement contingencies for engaging in the less preferred activity. Results are discussed in terms of the conditions under which choice functions as an indicator of preference and how those conditions may be altered to improve the quality of choice making without limiting access to preferred options.

Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19-nor-1,25-dihydroxyvitamin D2.

In this double-blind, placebo-controlled, randomized, multicenter study, 35 patients with end-stage renal disease undergoing maintenance hemodialysis were treated three times weekly for 4 weeks with either 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) intravenously at doses ranging from 0.04 to 0.24 microg/kg or placebo. Eligible patients with secondary hyperparathyroidism (HPT; intact parathyroid hormone [iPTH] level > 300 pg/mL) were initially withdrawn from any existing vitamin D therapy over a 4-week washout period and then randomized to treatment for 4 weeks with either paricalcitol or placebo. Overall, there was a clinically and statistically significant reduction in iPTH level for patients receiving paricalcitol compared with placebo (P = 0.006). The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH level for 75% of the patients receiving paricalcitol per dosing group. The study end point for efficacy was at least a 30% reduction from maximum baseline in iPTH for 75% of patients receiving paricalcitol per dosing group. Sixty-eight percent (15 of 22) of patients receiving paricalcitol attained this efficacy end point regardless of dosage received (0.04, 0.08, 0.16, and 0.24 microg/kg). Eighty-three percent (5 of 6) of the patients in each of the paricalcitol groups receiving 0.16- and 0.24-microg/kg dosages attained the efficacy end point. Only two patients receiving placebo attained the iPTH end point. There were no clinically relevant differences in serum calcium (Ca) or phosphorus (P) levels between the group treated with paricalcitol and that treated with placebo. Although there was a statistically significant difference between the change from baseline to final-visit Ca levels in the paricalcitol group and the placebo group (P < 0.001), the final-visit mean Ca level in the paricalcitol group was within the normal range (9.44 mg/dL). There was no statistically significant difference between groups for the change from baseline in P level (P = 0.625). Only one patient treated with paricalcitol developed hypercalcemia before or coincident with the iPTH end point. Three other patients receiving paricalcitol experienced elevated serum Ca levels subsequent to reaching the iPTH end point, with iPTH reductions of 83% to 98%. There were no significant differences between patients treated with paricalcitol and patients treated with placebo in adverse reactions. These results show that paricalcitol safely and effectively reduces iPTH levels in hemodialysis patients with secondary HPT.

Peritoneoscopic placement of Swan neck peritoneal dialysis catheters.

Peritoneoscopic placement of peritoneal dialysis catheters, although accomplished in only about 10% of dialysis centers, is a nonsurgical technique that fulfills requirements for safety and dependability. Over a 40-month period, 136 catheters were placed with the peritoneoscope, 135 of which were double-cuffed, Swan neck curled catheters, with a uniform radiopaque stripe. Patients were followed longitudinally for outcome. Catheters were placed in 44 diabetic patients, 1 human immunodeficiency virus (HIV)-positive patient, and 18 morbidly obese patients. No complications occurred as a direct result of placement. Catheters were used, on average, nine days after placement (many on days 1 to 4) usually with 1.5 to 2 L exchanges. With 1183 patient-months' experience, complications were few: 28 patients experienced catheter-related infections, and there were five leaks that resolved with supine, low-volume dialysis for several days. Leakage did not correlate with time of usage after placement. Of ten outflow/mechanical problems that required catheter removal, nine involved catheter migration, probably due to lack of attention during placement to orientation of the radiopaque stripe. One was due to a preperitoneal placement early in this institution's experience with the peritoneoscope. Five of the migrated catheters were removed and then successfully replaced with the peritoneoscope at the same sitting. Four patients requested surgical removal and replacement. Sixteen catheters were removed because of catheter-related infections: five refractory Staphylococcus aureus, six Pseudomonas aeruginosa, two fungal, two Serratia species, and one Mycobacterium chelonei. Actuarial life-table analysis showed that at the end of the 40-month follow-up, 62% of the catheters were expected to survive. Because more than 50% survived, median catheter survival could not be calculated. The adverse responses were removal because of infection or catheter migration. Peritoneal dialysis catheter implantation with the peritoneoscope represents a safe and dependable method for catheter placement. Literature review and comparison indicate that catheter-related complications are fewer and catheter longevity is better with peritoneoscopic placement than with surgical placement. Our experience with prompt postplacement utilization suggests the need for further evaluation of catheter break-in procedure with the peritoneoscope.

Urinary Tamm-Horsfall protein increased after potassium citrate therapy in calcium stone formers.

OBJECTIVES: To evaluate the effect of oral potassium citrate therapy on urinary excretion rates of citrate. Tamm-Horsfall protein (THP), and on calcium oxalate monohydrate crystal agglomeration inhibition [tm], in patients with recurrent calcium stone formation. METHODS: To evaluate the effect of oral therapy with potassium citrate on urinary citrate, THP, and [tm], 24-hour urine samples were collected before and at least 2 months after initiation of oral potassium citrate therapy in 33 calcium stone-forming patients who had no dietary restrictions. The citrate concentration was measured by an adaptation of a citrate lyase method. Urinary disaggregated THP concentration was determined with a quantitative enzyme-linked immunosorbent assay. The [tm] was determined by observing the effects of patients' urine, before and after oral potassium citrate therapy, on the uptake of 45Ca2+ onto the surfaces of added preformed calcium oxalate crystals in a supersaturated solution of calcium oxalate, using the in vitro kinetic method described by other investigators. RESULTS: We observed an increased urinary excretion rate of citrate from a mean of 1.9 mmol/24 h prealkali to 2.6 mmol/24 h postalkali (P < 0.0004) and of THP from a mean of 94.0 mg/24 h prealkali to 199.3 mg/24 h postalkali (P < 0.0016). A corresponding increase in [tm] from a mean of 177.1 minutes prealkali to 221.0 minutes postalkali (P < 0.024) was also observed. CONCLUSIONS: To our knowledge this is the first report correlating increased urinary citrate with THP excretion rate following oral alkalinization with potassium citrate in calcium stone formers. Of clinical importance is the corresponding increase in [tm], which was previously shown to be inversely related to stone-forming activity. Moreover, urinary citrate and THP are known to have a synergistic effect on [tm]. Our data suggest that the effectiveness of potassium citrate therapy in calcium stone-forming patients may, at least in part, be due to increased levels of THP.

Serratia marcescens peritonitis in a patient receiving chronic ambulatory peritoneal dialysis complicated by osteomyelitis.

Peritonitis, a common complication of chronic ambulatory peritoneal dialysis (CAPD), arises from various bacterial pathogens. We report the case of a patient with CAPD-associated peritonitis caused by Serratia marcescens. This case was further complicated by the development of osteomyelitis believed to have occurred from hematogenous seeding of Serratia marcescens.

Effect of citrate on serum aluminum concentrations in hemodialysis patients: a prospective study.

Twenty hemodialysis patients were prospectively evaluated to determine if concomitant citrate and aluminum administration enhances the absorption of aluminum, thereby increasing the possibility of toxicity. The four-phase study consisted of phase I, a washout phase; phase II, an aluminum treatment phase; phase III, a treatment phase combining aluminum and soluble calcium citrate; and phase IV, a treatment phase with the patient's original prestudy phosphate binder. Results disclosed a progressive rise in serum aluminum levels (microgram/L) from 47 +/- 8 (phase I) to 62 +/- 12 (phase II) to 74 +/- 13 (phase III) and a drop to 58 +/- 12 (phase IV). The difference in levels between phases I and III was significant. Additionally, and despite the fact that serum calcium concentrations did not change, serum phosphate and immunoreactive parathyroid hormone concentrations were significantly lower when aluminum and citrate were used together. This suggests that citrate enhances the absorption of aluminum and therefore increases the possibility of toxicity in the patient with end-stage renal disease.