Alkalemia and Hepatic Encephalopathy in a Chronic Dialysis Patient.

Hepatic encephalopathy (HE) includes cognitive, psychiatric and neuromotor abnormalities observed from brain dysfunction secondary to liver disease and/or porto-systemic shunting. HE can have a wide range of clinical manifestations ranging from trivial lack of awareness, decreased attention span, personality changes to confusion, seizures, coma, and death. The onset of HE in cirrhosis is a poor prognostic factor. While HE has a complex pathogenesis which is not completely understood, hyperammonemia plays an important role in neurotoxicity and brain dysfunction. Alkalemia facilitates the conversion of NH4+ to NH3, which is free to cross the blood-brain barrier exacerbating HE. Prompt recognition and correction of underlying risk factors is central to the management of HE.

Factors associated with the receipt of antimicrobials among chronic hemodialysis patients.

BACKGROUND: Antimicrobial use is common among patients receiving chronic hemodialysis (CHD) and may represent an important antimicrobial stewardship opportunity. The objective of this study is to characterize CHD patients at increased risk of receiving antimicrobials, including not indicated antimicrobials. METHODS: We conducted a prospective cohort study over a 12-month period among patients receiving CHD in 2 outpatient dialysis units. Each parenteral antimicrobial dose administered was characterized as indicated or not indicated based on national guidelines. Patient factors associated with receipt of antimicrobials and receipt of ≥1 inappropriate antimicrobial dose were analyzed. RESULTS: A total of 89 of 278 CHD patients (32%) received ≥1 antimicrobial doses and 52 (58%) received ≥1 inappropriately indicated dose. Patients with tunneled catheter access, a history of colonization or infection with a multidrug-resistant organism, and receiving CHD sessions during daytime shifts were more likely to receive antimicrobials (odds ratio [OR], 5.16; 95% confidence interval [CI], 2.72-9.80; OR, 5.43; 95% CI, 1.84-16.06; OR, 4.59; 95% CI, 1.20-17.52, respectively). Patients with tunneled catheter access, receiving CHD at dialysis unit B, and with a longer duration of CHD prior to enrollment were at higher risk of receiving an inappropriately indicated antimicrobial dose (incidence rate ratio, 2.23; 95% CI, 1.16-4.29; incidence rate ratio, 2.67; 95% CI, 1.34-5.35; incidence rate ratio, 1.11; 95% CI, 1.01-1.23, respectively). CONCLUSIONS: This study of all types of antimicrobials administered in 2 outpatient dialysis units identified several important factors to consider when developing antimicrobial stewardship programs in this health care setting.

Nephrologist-Facilitated Advance Care Planning for Hemodialysis Patients: A Quality Improvement Project.

BACKGROUND: The Renal Physicians Association's clinical practice guideline recommends that physicians address advance care planning with dialysis patients. However, data are lacking about how best to implement this recommendation. STUDY DESIGN: Quality improvement project. SETTINGS & PARTICIPANTS: Nephrologists caring for patients treated with maintenance hemodialysis at 2 dialysis facilities identified patients who might benefit most from advance care planning using the "surprise" question ("Would I be surprised if this patient died in the next year?"). QUALITY IMPROVEMENT PLAN: Patients identified with a "no" response to the surprise question were invited to participate in nephrologist-facilitated advance care planning, including completion of a Medical Orders for Life-Sustaining Treatment (MOLST) form. OUTCOMES: Change in MOLST completion rate and identification of preferences for limits on life-sustaining treatment. MEASUREMENTS: Pre- and postintervention code status, MOLST completion rate, and vital status at 1 year. RESULTS: Nephrologists answered "no" to the surprise question for 50 of 201 (25%) hemodialysis patients. Of these, 41 (82%) patients had a full-code status and 9 (18%) had a do-not-resuscitate (DNR) status. Encounters lasted 15 to 60 minutes. Following the encounter, 21 (42%) patients expressed preference for a DNR status and 29 (58%) maintained full-code status (P=0.001). The MOLST completion rate increased from 10% to 90%. One-year survival for patients whose nephrologists answered "no" to the surprise question was 58% compared to 92% for those with a "yes" answer (P<0.001). LIMITATIONS: Sample size and possible nonrepresentative dialysis population. CONCLUSIONS: Nephrologist-facilitated advance care planning targeting hemodialysis patients with limited life expectancy led to significant changes in documented patient preferences for cardiopulmonary resuscitation and limits on life-sustaining treatment. These changes demonstrate the benefit of advance care planning with dialysis patients and likely reflect better understanding of end-of-life treatment options.

Alendronate associated focal segmental glomerulosclerosis: a case report and review of the literature.

Although kidney injury associated with intravenous bisphosphonate therapy is well documented, there are very few reported instances of oral bisphosphonate therapy leading to focal segmental glomerulosclerosis (FSGS) and kidney failure. We report the case of a 79-year-old woman who developed acute kidney injury due to collapsing FSGS while receiving therapy with weekly oral alendronate therapy for osteoporosis. Withdrawal of alendronate and treatment with corticosteroids resulted in partial recovery of kidney function for a period of 16 months until she developed progressive kidney failure needing long-term dialysis. This case report and the literature review highlight the fact that oral bisphosphonates may be associated with a risk of developing FSGS.

Cognitive function and all-cause mortality in maintenance hemodialysis patients.

BACKGROUND: Cognitive impairment is common in hemodialysis patients and is associated with significant morbidity. Limited information exists about whether cognitive impairment is associated with survival and whether the type of cognitive impairment is important. STUDY DESIGN: Longitudinal cohort. SETTING & PARTICIPANTS: Cognitive function was assessed at baseline and yearly using a comprehensive battery of cognitive tests in 292 prevalent hemodialysis patients. PREDICTOR: Using principal component analysis, individual test results were reduced into 2 domain scores, representing memory and executive function. By definition, each score carried a mean of 0 and SD of 1. OUTCOMES: Association of each score with all-cause mortality was assessed using Cox proportional hazards models adjusted for demographics and dialysis and cardiovascular (CV) risk factors. RESULTS: Mean age of participants was 63 years, 53% were men, 23% were African American, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 1.1-3.7) years, 145 deaths occurred. Each 1-SD better executive function score was associated with a 35% lower hazard of mortality (HR, 0.65; 95% CI, 0.55-0.76). In models adjusting for demographics and dialysis-related factors, this relationship was partially attenuated but remained significant (HR, 0.81; 95% CI, 0.67-0.98), whereas adjustment for CV disease and heart failure resulted in further attenuation (HR, 0.87; 95% CI, 0.72-1.06). Use of time-dependent models showed a similar unadjusted association (HR, 0.62; 95% CI, 0.54-0.72), with the relationship remaining significant after adjustment for demographics and dialysis and CV risk factors (HR, 0.79; 95% CI, 0.66-0.94). Better memory was associated with lower mortality in univariate analysis (HR per 1 SD, 0.82; 95% CI, 0.69-0.96), but not when adjusting for demographics (HR, 1.00; 95% CI, 0.83-1.19). LIMITATIONS: Patients with dementia were excluded from the full battery, perhaps underestimating the strength of the association. CONCLUSIONS: Worse executive function and memory are associated with increased risk of mortality. For memory, this association is explained by patient demographics, whereas for executive function, this relationship may be explained in part by CV disease burden.

Acute oxalate nephropathy associated with Clostridium difficile colitis.

We report the case of a 69-year-old man who presented with acute kidney injury in the setting of community-acquired Clostridium difficile-associated diarrhea and biopsy-proven acute oxalate nephropathy. We discuss potential mechanisms, including increased colonic permeability to oxalate. We conclude that C difficile-associated diarrhea is a potential cause of acute oxalate nephropathy.

Antimicrobial use in outpatient hemodialysis units.

OBJECTIVE: To quantify and characterize overall antimicrobial use, including appropriateness of indication, among patients receiving chronic hemodialysis. DESIGN: Retrospective and prospective observational study. SETTING: Two outpatient hemodialysis units. PATIENTS: All patients receiving chronic hemodialysis. METHODS: The rate of parenteral antimicrobial use (number of doses per 100 patient-months) was calculated retrospectively from September 2008 through July 2011. Indication and appropriateness of antimicrobial doses were characterized prospectively from August 2010 through July 2011. Inappropriate administration was defined as occasions when criteria for infection based on national guidelines were not met, failure to choose a more narrow-spectrum antimicrobial on the basis of culture data, or occasions when indications for surgical prophylaxis were not met. RESULTS: Over the 35-month retrospective study period, the rate of parenteral antimicrobial use was 32.9 doses per 100 patient-months. Vancomycin was the most commonly prescribed antimicrobial, followed by cefazolin and third- or fourth-generation cephalosporins. Over the 12-month prospective study, 1,003 antimicrobial doses were prescribed. Among the 926 (92.3%) doses for which an indication for administration was available, 276 (29.8%) were classified as inappropriate. Of these, a total of 146 (52.9%) did not meet criteria for infection, 74 (26.8%) represented failure to choose a more narrow-spectrum antimicrobial, and 56 (20.3%) did not meet criteria for surgical prophylaxis. The most common inappropriately prescribed antimicrobials were vancomycin and third- or fourth- generation cephalosporins. CONCLUSIONS: Parenteral antimicrobial use was extensive, and as much as one-third was categorized as inappropriate. The findings of this study provide novel information toward minimizing inappropriate antimicrobial use.

Frequency of and risk factors for poor cognitive performance in hemodialysis patients.

OBJECTIVE: There are few detailed data on cognition in patients undergoing dialysis. We evaluated the frequency of and risk factors for poor cognitive performance using detailed neurocognitive testing. METHODS: In this cross-sectional cohort study, 314 hemodialysis patients from 6 Boston-area hemodialysis units underwent detailed cognitive assessment. The neuropsychological battery assessed a broad range of functions, with established age-, sex-, and education-matched normative scores. Principal component analysis was used to derive composite scores for memory and executive function domains. Risk factors for each domain were evaluated using linear regression adjusting for age, sex, race, and education status. Analyses were repeated in those with Mini-Mental State Examination (MMSE) score ≥ 24. RESULTS: Compared with population norms, patients on dialysis had significantly poorer executive function but not memory performance, a finding that persisted in the subgroup with MMSE score ≥ 24. In adjusted analyses, vascular risk factors and vascular disease were associated with lower executive function (p < 0.01). CONCLUSIONS: There is a high frequency of poor cognitive performance in hemodialysis patients, primarily affecting executive function. Risk factors for worse executive function include vascular risk factors as well as vascular disease. Normal performance on the MMSE does not preclude impaired cognitive function, because individuals with MMSE score ≥ 24 also have a high frequency of poor cognitive performance.

Recovery of kidney function following delayed use of Theralite™ dialyzer in a patient with myeloma cast nephropathy.

We report the case of a 60- year- old man who presented with newly diagnosed multiple myeloma complicated by biopsy-proven acute cast nephropathy, requiring hemodialysis, plasmapheresis and chemotherapy. After remaining dialysis dependent for 5 weeks, a high cut-off (HCO) dialyzer, intended to use for the removal of plasma substances with a molecular weight of up to 45 kDa such as free light chains, was introduced to his outpatient 4-hour hemodialysis regimen with an increase in treatment frequency to 4 sessions per week. Following 6 weeks of dialysis with the HCO dialyzer, serum levels of free κ light chains declined by more than 75%. Concurrently, he recovered kidney function and discontinued dialysis. He subsequently received a successful autologous stem-cell transplant. We discuss the potential merit of using the HCO dialyzer late in the course of the care of patients with myeloma cast nephropathy who are dialysis dependent.

Design and evaluation of D-α tocopheryl polyethylene glycol 1000 succinate emulsified poly-ϵ-caprolactone nanoparticles for protein/peptide drug delivery.

BACKGROUND: Incorporation of proteins/peptide drugs into nanoparticulate drug delivery system is one of the effective approaches to increase the stability of protein/peptide drugs against enzymatic degradation, to release them in a controlled fashion and to achieve site-specific drug delivery. OBJECTIVE: Our goal was to design and evaluate poly-ϵ-caprolactone (PCL) nanoparticles using bovine serum albumin (BSA) as a model protein. d-α-tocopheryl polyethylene glycol 1000 (vitamin E TPGS) was used as an emulsifier in the fabrication of these nanoparticles. METHODS: Double emulsion solvent evaporation method was employed to formulate BSA-loaded PCL nanoparticles and the nanoparticles thus prepared were further characterized. RESULTS: The size of BSA-loaded PCL nanoparticles were in the range of 400-500 nm with a polydispersity index (PDI) of 0.195 and zeta potential was about -28.6 mV. Scanning electron microscopy (SEM) confirmed the presence of smooth and spherical surface of nanoparticles. Encapsulation efficiency was about 85% and a yield of 70-75% was attained. BSA was released in a biphasic pattern with an initial 20% release within 2 h followed by a slower release patter over 5 days. Flow cytometry and fluorescence microscopy was used to study the uptake of these nanoparticles. Circular dichroism (CD) results showed that there was no significant effect of formulation conditions on the secondary structure of BSA. CONCLUSION: Based on the results obtained, these TPGS-emulsified PCL nanoparticles proved to be potential carriers for the delivery of protein/peptide drugs.

Oral delivery of low molecular weight heparin microspheres prepared using biodegradable polymer matrix system.

Parenteral route is preferred for low molecular weight heparin (LMWH) due to poor oral bioavailability. Biodegradable formulation components were evaluated for possible interactions between the physical mixtures using differential scanning calorimetry. LMWH and an absorption enhancer papain were encapsulated in bovine serum albumin matrix and four formulations were spray-dried (MS.1, MS.2, MS.3, MS.4). Formulations were evaluated for product yield, particle size, particle charge and encapsulation efficiency. In vitro release assessed in pH 7.2 phosphate buffer saline (PBS) revealed a burst release effect (60%) for all the formulations except MS.1. In vivo studies performed in male Sprague Dawley rats showed an enhancement in drug absorption for the MS.2 and MS.3 formulations because of papain action on paracellular tight junctions. A significant increase in LMWH oral bioavailability was demonstrated by MS.3 (21%), among the formulations encapsulated with papain.

Multidrug-resistant gram-negative bacteria among patients who require chronic hemodialysis.

BACKGROUND AND OBJECTIVES: Multidrug-resistant gram-negative bacteria are rapidly spreading throughout the world. The epidemiology of multidrug-resistant gram-negative bacteria in patients who require chronic hemodialysis has not been previously studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective cohort study of an outpatient hemodialysis unit was conducted. Serial surveillance cultures for multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus were collected from patients who were undergoing chronic hemodialysis. RESULTS: Nineteen (28%) of the 67 enrolled patients were colonized with one or more antimicrobial-resistant bacteria at study enrollment. Eleven (16%), nine (13%), and three (5%) patients were colonized with multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Independent risk factors associated with harboring multidrug-resistant gram-negative bacteria at enrollment were residence in a long-term care facility and antibiotic exposure for > or = 7 d in the previous 3 mo. Twenty-two (40%) of 55 patients who had follow-up cultures acquired at least one antimicrobial-resistant bacterium. A total of 20, 15, and 13% of patients acquired multidrug-resistant gram-negative bacteria, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus, respectively. Antibiotic exposure was the only independent risk factor for multidrug-resistant gram-negative bacteria acquisition. Endogenous multidrug-resistant gram-negative bacteria acquisition was detected among 69% of acquired multidrug-resistant gram-negative bacterial strains. CONCLUSIONS: The prevalence and acquisition of multidrug-resistant gram-negative bacteria surpassed that of vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Endogenous acquisition, as opposed to patient-to-patient spread, was the predominant mechanism of acquisition. Residence in a long-term care facility and antibiotic exposure may be important factors promoting the spread of multidrug-resistant gram-negative bacteria among this patient population.

A prospective, randomized, double-blind study evaluating the efficacy of postoperative continuous local anesthetic infusion at the iliac crest bone graft site after spinal arthrodesis.

STUDY DESIGN: Parallel design, prospective, double-blind, randomized, controlled trial composed of two independent groups treated with a continuous infusion catheter (saline vs. Marcaine) placed into the iliac crest bone graft (ICBG) site. OBJECTIVE: To determine the effects of postoperative continuous local anesthetic agent infusion at the ICBG harvest site in reducing pain, narcotic demand and usage, and improving early postoperative function after spinal fusion. SUMMARY OF BACKGROUND DATA: Harvesting iliac crest bone has been shown to be a source of pain and morbidity. Long-term patient complaints may be more closely associated with the procurement of the iliac crest graft rather than the primary surgical site. METHODS: Thirty-seven patients were enrolled in a prospective, randomized, double-blind parallel-designed study after informed consent and IRB approval was obtained. Twenty-eight patients had ICBG harvested for lumbar arthrodesis and nine for cervical arthrodesis. During spinal arthrodesis surgery, patients were randomly assigned to receive 96 mL (2 mL/hr x 48 hours) of either normal saline (control group, n = 22) or 0.5% Marcaine (treatment group, n = 15) delivered via a continuous infusion catheter placed at the ICBG harvest site. All patients received Dilaudid PCA after surgery. Pain scores, narcotic use/frequency, activity level, and length of stay (LOS) were recorded. Physicians, patients, nursing staff, and statisticians were blinded to the treatment. RESULTS: Mean patient age was 60 years and similar between groups. Narcotic dosage, demand frequency, and mean VAS pain score were significantly less in the treatment (Marcaine) group at 24 and 48 hours (P < 0.05). The average LOS was 4.1 days with no difference between Marcaine or control groups. No complications were attributed to the infusion-catheter system. CONCLUSIONS: Continuous infusion of 0.5% Marcaine at the ICBG harvest site reduced postoperative parenteral narcotic usage by 50% and decreased overall pain scores. No complications were attributed to the infusion-catheter system. The use of continuous local anesthetic infusion at the iliac crest may help in alleviating acute graft-related pain, hastening patient recovery and improving short-term satisfaction.

Iron sucrose in hemodialysis patients: safety of replacement and maintenance regimens.

BACKGROUND: Parenteral iron replacement and maintenance are frequently required in hemodialysis patients. However, serious adverse events have been reported after single doses of some intravenous iron products. This multicenter phase IV clinical trial examined the safety of iron sucrose for the treatment of iron deficiency and for the maintenance of iron sufficiency in hemodialysis patients. METHODS: In this safety study, iron sucrose was given in two dosing regimens. Iron deficient patients were treated with intravenous iron sucrose, 100 mg, during 10 consecutive hemodialysis sessions (replacement regimen). Iron replete patients were given iron sucrose, 100 mg intravenous (iv) over 5 minutes, weekly for 10 weeks (maintenance regimen). At the end of each 10-dose cycle, iron status was reassessed, and dosing during the subsequent cycle was based on the adequacy of iron stores as per Dialysis Outcome Quality Initiative (K/DOQI) Guidelines. With each dosing regimen, adverse events, if any, were recorded and described. RESULTS: Six hundred and sixty-five hemodialysis patients, including 80 who had experienced previous intolerance to other parenteral iron preparations, received a total of 8583 doses of iron sucrose. One hundred eighty-eight patients received more than one iv iron cycle (replacement, maintenance, or both). There were no serious or life-threatening drug-related adverse events. CONCLUSION: Iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores.

Infections associated with use of the LifeSite Hemodialysis Access System.

We observed infection rates associated with the LifeSite Hemodialysis Access System, a novel dialysis device consisting of 2 subcutaneously implanted valves accessed by repeated use of fibrous tissue tracts, of 4.8 total infections and 8.1 first episodes per 1000 patient-days. These rates are higher than those observed elsewhere, which may be related to use of the device in a population of chronically ill patients, to the learning curve associated with use of the device, or to inherent qualities of the device.

Hemodialysis-associated methemoglobinemia in acute renal failure.

Patients on maintenance hemodialysis are vulnerable to chloramine toxicity if chloramines are inadequately removed. We report two critically ill patients with acute renal failure who developed methemoglobinemia during hemodialysis in the intensive care unit. During the same period, methemoglobin levels measured from 30 patients in the outpatient dialysis facility were undetectable. Methemoglobin levels normalized when the carbon filtration system of the portable dialysis machine was replaced with a larger unit to remove chloramines more effectively. Causes, treatment, and prevention of chloramine toxicity in patients receiving dialysis in the intensive care unit are discussed.