Use of Alteplase for Clearing Peritoneal Dialysis Catheter Occlusion.

Background: Peritoneal dialysis (PD) catheter complications account for 20% of all transfers from PD to hemodialysis. One complication is outflow obstruction caused by fibrin deposits within the lumen of the catheter. Alteplase is frequently used to clear fibrin deposits in PD catheters that are refractory to other therapies. However, the literature basis for this practice is unclear. Method: A review of the literature was conducted to determine the evidence existing for alteplase use in PD catheter occlusion due to fibrin. A literature search of MEDLINE (1967-present) was conducted using the search terms "alteplase", "peritoneal dialysis catheter", "occlusion", "fibrin", and "tissue plasminogen activator". Referenced citations were also searched for pertinent material. All data concerning the use of alteplase for peritoneal dialysis catheter occlusion were included in this review. The search resulted in 1 open-label pilot study, 3 case series, and 2 case reports of alteplase use in declotting occluded PD catheters. Results: Based on the data, alteplase therapy cleared the occlusion of PD catheters in the majority of cases. In those that were unsuccessful, other surgically correctable and mechanical causes were identified in most cases. Conclusion: Alteplase appears to be an intriguing alternative to the surgical removal of the PD catheter in patients with catheter occlusion due to fibrin. Although not inexpensive, it appears safe and may decrease the need for surgical correction of occluded catheters.

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

BACKGROUND: Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. OBJECTIVE: We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. METHODS: This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. RESULTS: A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). CONCLUSION: There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia.

Ranolazine-tacrolimus interaction.

OBJECTIVE: To report the case of a kidney allograft recipient on a stable regimen of tacrolimus who exhibited increased tacrolimus concentrations within 24 hours of initiating ranolazine. CASE SUMMARY: A 64-year-old kidney allograft recipient on a stable dose of tacrolimus (10 mg twice daily) was admitted for recent worsening of her chronic anginal pain. The patient was initiated on ranolazine 500 mg twice daily on hospital day 2. Tacrolimus concentrations rose from 7.0-10.1 ng/mL preadmission to 17.8 ng/mL within 24 hours of ranolazine initiation. Ranolazine therapy was continued due to the patient's beneficial response; therefore, the tacrolimus dose was eventually decreased by 70% to 3 mg twice daily to maintain steady-state trough concentrations between 6.6 and 7.9 ng/mL with ranolazine therapy. Ranolazine dechallenge on a subsequent admission produced subtherapeutic tacrolimus concentrations requiring dosage increases. DISCUSSION: Ranolazine, an antianginal agent, is both a substrate and a weak inhibitor of CYP3A as well as a substrate and moderate inhibitor of the P-glycoprotein (P-GP) efflux transport system. Tacrolimus, an immunosuppressant, is also a substrate of CYP3A and P-GP. Through possible inhibition of both P-GP- and CYP3A-mediated first-pass metabolism and CYP3A systemic metabolism, ranolazine may have significantly increased serum concentrations of tacrolimus necessitating an eventual 70% decrease in the tacrolimus dose. Based on the Horn Drug Interaction Probability Scale, this interaction is possible. CONCLUSIONS: We suggest that the eventual 70% decrease in tacrolimus dose after ranolazine initiation may indicate that ranolazine decreases the metabolism and clearance of tacrolimus, causing an elevation in tacrolimus concentrations and the potential for tacrolimus toxicity. Clinicians should be aware of this possible interaction when initiating ranolazine in patients on tacrolimus.

A probable case of gabapentin-related reversible hearing loss in a patient with acute renal failure.

BACKGROUND: As described in the literature, gabapentin toxicity in patients with impaired renal function can manifest as coma, myoclonus, tremulousness, or altered mental status. Gabapentin is an antiepileptic agent indicated for use as an adjunct therapy in partial seizures and postherpetic neuralgia but is also prescribed for the treatment of diabetic peripheral neuropathy. CASE SUMMARY: A 46-year-old white woman (height, 167 cm; weight, 177 kg; body mass index, 62.8 kg/m2) with a 6-year history of diabetes mellitus and previously normal renal function, presented to the emergency department of Wake Forest University Baptist Medical Center with anuria (a serum creatinine level of 7.4 mg/dL), hearing loss, myoclonus, and confusion with hallucinations lasting for 3 days. Her blood pressure was 110/74 mm Hg. The patient's preadmit medication list included: lisinopril (40 mg QD), hydrochlorothiazide (25 mg QD), and furosemide (80 mg QD) for hypertension; atorvastatin (10 mg QD) for hyperlipidemia; omeprazole (20 mg QD) for gastroesophageal reflux disease; salmeterol/fluticasone inhaler (100/50 microg; 1 puff BID) and albuterol metered-dose inhaler (90 microg as needed) for asthma; metformin (500 mg BID) and insulin lispro per sliding scale for type 2 diabetes mellitus; oxycodone controlled release (60 mg TID) for chronic osteoarthritis and low back pain; alprazolam (0.5 mg every 8 hours as needed) for generalized anxiety disorder; venlafaxine (150 mg BID) for depression; and gabapentin (300 mg TID) for diabetic peripheral neuropathy. The patient's symptoms (hearing loss, myoclonus, and confusion) improved after 1 session of hemodialysis (approximately 10 hours following admission) and had resolved at the time of discharge (4 days later). On admission, the gabapentin concentration was 17.6 microg/mL, and following hemodialysis, the gabapentin concentration was undetectable (by discharge/day 4). The timing of the patient's last dose of gabapentin is unknown. Normal doses for the treatment of diabetic peripheral neuropathy range from 900 to 3600 mg/d divided 3 times daily. CONCLUSIONS: We report a patient with acute renal failure who developed hearing loss, myoclonus, and confusion with hallucinations in the presence of elevated gabapentin concentrations. Due to rapid improvement after hemodialysis and discontinuation of gabapentin, we believe that these symptoms were probably due to gabapentin toxicity.

The effect on peritoneal dialysis pathogens of changing topical antibiotic prophylaxis.

BACKGROUND: Prophylactic gentamicin 0.1% cream has demonstrated efficacy in preventing both exit-site infection (ESI) and peritonitis attributable to gram-positive and gram-negative organisms; however, the effect of this practice on the gentamicin susceptibility patterns of bacterial pathogens isolated from such infections is unknown. We therefore examined the effect of a change in our prophylactic topical antibiotic exit-site protocol (from mupirocin 2% cream to gentamicin 0.1% cream) on infection rates and susceptibility patterns. METHODS: This retrospective observational cohort study examined two periods of time: before and after the change in exit-site protocol. Each period was 30 months in duration, with a 2-month implementation period between, during which patient data were excluded. Demographic, clinical, and microbiology data were collected for each patient and episode of infection. RESULTS: Overall, 377 patients were evaluated. In the mupirocin period (MUP), 145 infections occurred in 79 patients, and in the gentamicin period, 145 infections occurred in 93 patients. No significant effect was found either in overall episodes of infection (0.53 per year) or in episodes of peritonitis (0.429 vs 0.375 per year), but episodes of ESI increased significantly (0.098 vs 0.153 per year; p = 0.024; odds ratio: 1.55; 95% confidence interval: 1.05 to 2.28). Episodes of Staphylococcus aureus peritonitis increased by 38% (0.018 vs 0.025 per year), and episodes of S. aureus ESI increased significantly by 150% (0.022 vs 0.055 per year; p = 0.03; hazard ratio: 3.00; 95% confidence interval: 1.09 to 8.26). Episodes of pseudomonal peritonitis declined by 68% (0.022 vs 0.007 per year), and episodes of pseudomonal ESI increased by 150% (0.007 vs 0.018 per year). The gentamicin susceptibility for gram-positive isolates demonstrated no significant change; however, the gentamicin susceptibility for Enterobacteriaceae decreased by 12% and for Pseudomonas, by 14%. CONCLUSIONS: The significant increase in episodes of ESI and the decrease in susceptibility for both Enterobacteriaceae and Pseudomonas isolates represent a concerning trend. Centers should examine trends in infection rates and in bacterial susceptibilities to determine the most appropriate agent for ESI prophylaxis.

Trisodium citrate: an alternative to unfractionated heparin for hemodialysis catheter dwells.

The use of tunneled hemodialysis catheters, or permcaths, either for temporary dialysis access before arteriovenous fistula or arteriovenous graft maturation or for long-term dialysis access, is associated with increased risk of catheter clotting and infection. Catheter locking solutions are routinely used to maintain patency in these catheters between dialysis sessions. Unfractionated heparin has traditionally been used for this purpose; however, trisodium citrate (also known as sodium citrate or citrate) has recently been shown to be an efficacious alternative to heparin as a locking solution. Citrate exerts both its anticoagulant and antimicrobial properties by chelating calcium to disrupt the normal coagulation pathway and by interfering with the formation of biofilm and the bacterial cell wall. Citrate is at least equivalent to heparin as an anticoagulant and antimicrobial agent for catheter locking, and in some clinical studies citrate was shown to be superior. Two different concentrations of sodium citrate were previously available; however, concerns of safety led to the removal of citrate 46.7% from the United States and Canadian markets in 2000, leaving only citrate 4% available for use as a catheter locking solution. The systemic hypocalcemic effects that were reported with citrate 46.7% have not been observed with citrate 4% in clinical trials, and the risk of systemic anticoagulation and bleeding was shown to be lower than that with unfractionated heparin. In addition, most comparative cost data indicate that citrate is a more cost-effective alternative than heparin; however, costs can vary by institution. Despite inconclusive evidence of clinical superiority, citrate 4% appears to provide a safe and at least equivocal alternative to heparin as a catheter locking agent.