Effect of Bicarbonate-Buffered Dialysate on Ventricular Arrhythmias in Hemodialysis Patients.

BACKGROUND: The etiology of sudden cardiac death in patients with end-stage renal disease (ESRD) on hemodialysis (HD) is largely unknown, though there is evidence to suggest that metabolic alkalosis induced by HD with a high-bicarbonate dialysate/prescription may play a role. METHODS: We investigated the effects of metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate on frequency of ventricular arrhythmia in 47 patients with ESRD on chronic HD using 48-h Holter monitoring in 3 phases: intra-HD, post-HD day 1, and post-HD day 2. Serum levels of bicarbonate, calcium, and potassium along with hemodynamics were measured pre-HD, post-HD, 20-h post-HD, and 44-h post-HD. Correlations were performed to verify the association between bicarbonate prescription and change in serum bicarbonate levels post-HD and to determine if the HD-induced change in serum bicarbonate level (metabolic alkalosis) had any direct association with ambient ventricular arrhythmia (premature ventricular contractions per hour) or indirect associations with ambient ventricular arrhythmia by affecting electrolytes or hemodynamics that are known to increase the risk of ventricular arrhythmia. RESULTS: Mean pre-HD serum bicarbonate level was 21.3 mEq/L. Dialysate bicarbonate prescription (mean of 36.4 mEq/L) correlated with changes in serum bicarbonate levels immediately post-HD 26.7 mEq/L (r = 0.46, p < 0.01), 20-h post-HD 25.2 mEq/L (r = 0.38), and 44-h post-HD 23.2 mEq/L (r = 0.35, p = 0.01). No statistically significant correlations were found between the post-HD change in serum bicarbonate levels (metabolic alkalosis) with ambient ventricular arrhythmia, changes in serum calcium, potassium, or hemodynamics in any phase. CONCLUSIONS: High-bicarbonate dialysate prescription is associated with metabolic alkalosis following the HD procedure. A mild metabolic alkalosis induced by HD with an acetate-containing bicarbonate-buffered dialysate solution had no direct association with ambient ventricular arrhythmia on Holter monitoring and was not associated with changes in hemodynamics or changes in serum total calcium or potassium levels. This study helps to provide guidance for the safe use of high bicarbonate dialysate/prescription in patients with ESRD on HD.

Involvement of the renin-angiotensin system in the development of nephrogenic systemic fibrosis-like lesions in the RenTag mouse model.

BACKGROUND: Renin-angiotensin system (RAS) activation increases angiotensin II production stimulating profibrotic factors, especially in the setting of chronic kidney disease. Nephrogenic systemic fibrosis (NSF) has been associated with gadolinium (Gd) exposure and renal failure. RAS involvement in NSF is unclear compared to transforming growth factor beta and Smad. RenTag mice were chosen to investigate the role of RAS in NSF-like dermal fibrosis because they demonstrated dermal fibrosis at birth, perturbations of RAS in subcutaneous tissue, and renal failure within 4 weeks of age. METHODS: Wild-type and RenTag mice were injected weekly with a supratherapeutic dose of intravenous gadodiamide (3.0 mmol/kg body weight) and killed at 12 weeks of age for skin and kidney histology. RESULTS: RenTag mice had elevated BUN levels, pitted kidneys, and glomerular damage. RenTag mice skin revealed an increased density of fibroblasts, no mucopolysaccharide deposits, and increased collagen fibril density regardless of Gd exposure. Skin and kidney histopathology of wild-type mice were normal regardless of Gd exposure. CD34 positivity was higher in RenTag compared to wild-type. CONCLUSIONS: Since RenTag dermal lesions remained unchanged after gadolinium exposure in the setting of renal failure, this animal model suggests perturbations of subcutaneous RAS may be involved in Gd-naïve dermal fibrosis.

The medical-legal responsibilities of a dialysis unit medical director.

The specialty of Nephrology, by virtue of its relationship with the dialysis procedure, is highly vulnerable to litigation. As is the case with all nephrologists, a dialysis unit medical director is not immune to medical malpractice suits, and can be held liable for any act of perceived or potential harm to any dialysis patient, regardless of the director's level of involvement. The medical director, per the Centers for Medicare and Medicaid Services (CMS) Conditions of Participation, accepts the responsibilities, accountability, and consequent legal liabilities of the quality of the medical care provided to every dialysis patient in the unit. This review is a synopsis of lawsuits filed against medical directors of dialysis units in the past forty years. Six categories of legal actions were noted; medical malpractice, fraudulent claims, self-referral and Stark Law, discrimination, negligence, and violation of patient autonomy and dignity.

Effect of dialysate bicarbonate and sodium on blood pH in maintenance hemodialysis-A prospective study.

INTRODUCTION: The validity of adjusting dialysate bicarbonate based on pre-hemodialysis (HD) serum bicarbonate is unclear. There are no studies of the impact of dialysate sodium on blood pH. AIMS: To understand the impact of dialysate bicarbonate and sodium on blood pH. METHODS: Two hundred arterialized blood samples were obtained on the third session of HD with four configurations of dialysate: sodium (140, 137 mEq/L) and bicarbonate (38, 32 mEq/L). RESULTS: The correlation between pre-HD serum bicarbonate and pH was modest (r = 0.6). A lower dialysate sodium (p = 0.035) and a higher bicarbonate (p = 0.02) associated with a higher post-HD blood pH. The frequency of pre-HD blood pH of <7.4 and a post-HD blood pH of >7.5 did not differ for samples with serum bicarbonate <22, 22-26, or >26 mEq/L. DISCUSSION/CONCLUSIONS: Adjusting dialysate buffer based on pre-HD serum bicarbonate is unnecessary. A higher bicarbonate and lower dialysate sodium associate with post-HD alkalemia.

Use of anti-CD20 antibody in the treatment of post-transplant glomerulonephritis.

Post-transplant glomerulonephritis (PTGN) accounts for 4-10% of late graft loss. Six consecutive patients who developed PTGN 3-72 months post-transplant presented to our center with deteriorating kidney function and proteinuria. Three had focal segmental glomerulosclerosis; one had membranoproliferative glomerulonephritis Type 1; one recurrent membranous nephropathy; and one recurrent immunoglobin A nephropathy. All six were treated with an aggressive immunosuppression regimen including rituximab, pulse steroids and/or maximization of mycophenolic acid and calcineurin inhibitor therapy. Four of the six patients received plasma exchange. The patients were followed for a minimum of nine months after treatment. Proteinuria decreased from 7.2 ± 4.4 to 1.4 ± 1.5g (p = 0.04), while mean estimated glomerular filtration rate was 31.2 ± 13.1 and 42.5 ± 21.7 mL/min (p = 0.07) at nine months. No adverse events were noted. These observations suggest that immune modulating therapy may be of benefit in the treatment of PTGN.

Defining Data Migration Across Multidisciplinary Ambulatory Clinics Using Participatory Design.

OBJECTIVE: This study aimed to develop an institutional approach for defining data migration based on participatory design principles. METHODS: We outline a collaborative approach to define data migration as part of an electronic health record (EHR) transition at an urban hospital with 20 ambulatory clinics, based on participatory design. We developed an institution-specific list of data for migration based on physician end-user feedback. In this paper, we review the project planning phases, multidisciplinary governance, and methods used. RESULTS: Detailed data migration feedback was obtained from 90% of participants. Depending on the specialty, requests for historical laboratory values ranged from 2 to as many as 145 unique laboratory types. Lookback periods requested by physicians varied and were ultimately assigned to provide the most clinical data. This clinical information was then combined to synthesize an overall proposed data migration request on behalf of the institution. CONCLUSION: Institutions undergoing an EHR transition should actively involve physician end-users and key stakeholders. Physician feedback is vital for developing a clinically relevant EHR environment but is often difficult to obtain. Challenges include physician time constraints and overall knowledge about health information technology. This study demonstrates how a participatory design can serve to improve the clinical end-user's understanding of the technical aspects of an EHR implementation, as well as enhance the outcomes of such projects.

Population Pharmacodynamic Modeling of Epoetin Alfa in End-Stage Renal Disease Patients Receiving Maintenance Treatment Using Bayesian Approach.

The ability to control dosage regimens of erythropoiesis-stimulating agents (ESAs) to maintain a desired hemoglobin (HGB) target is still elusive. We utilized a Bayesian approach and informative priors to characterize HGB profiles, using simulated drug concentrations, in patients with end-stage renal disease receiving maintenance doses of epoetin alfa. We also demonstrated an adaptive Bayesian method, applied to individual patients, to improve the accuracy of HGB predictions over time. The results showed that sparse HGB data from daily clinical practice were characterized successfully. The adaptive Bayesian method effectively improved the accuracy of HGB predictions by updating the individual model with new data accounting for within-subject changes over time. The Bayesian approach presented leverages existing knowledge of the model parameters and has a potential utility in clinical practice to individualize dosage regimens of epoetin alfa and ESAs to achieve target HGB. Further studies are warranted to develop an application for practical use.

Application of Reticulocyte-Based Estimation of Red Blood Cell Lifespan in Anemia Management of End-Stage Renal Disease Patients.

Shortened red blood cell (RBC) lifespan is one of the major factors contributing to anemia in end-stage renal disease (ESRD) patients and should be taken into account in anemia management protocols. In this study, we aimed to estimate RBC lifespan and the source of between-subject variability in ESRD patients. The resulting individual parameters (empirical Bayes estimates) were used to predict hemoglobin concentrations 2 weeks in advance. The reticulocyte-based estimation of RBC lifespan (REBEL) and the population modeling of RBC count data were used. A total of 120 blood samples collected biweekly over 10 weeks in 24 patients receiving maintenance doses of recombinant human erythropoietin (rHuEPO) subcutaneously were included in this analysis. Typical RBC lifespan was estimated to be 63.3 days. RBC lifespan was found to increase with erythroferrone, a recently identified hormone participating in iron metabolism. Approximately, a 10% increase in plasma erythroferrone was associated with a 5% increase in RBC lifespan. In addition, RBC lifespan was 18.7% shorter in females compared with males. Out of 24 subjects, 16 had hemoglobin concentrations predicted within 95% prediction intervals. The median absolute prediction error was 15.9% (interquartile range, 9.5 to 24.7%). We demonstrated that REBEL coupled with the population modeling technique can be used effectively to estimate RBC lifespan. Then, individual parameters can be used to predict future hemoglobin concentrations in ESRD patients.

Nephrogenic systemic fibrosis.

Nephrogenic systemic fibrosis is a recently diagnosed disease that occurs in patients with chronic kidney disease and acute renal failure. The patients develop skin thickening and fibrosis which is usually symmetrical, and typically of the upper and lower extremities. In some cases the progression is rapid leading to joint contractures confining the patient to a wheelchair. Systemic involvement may occur, leading to cardiomyopathy, pulmonary fibrosis, pulmonary hypertension, diaphragmatic paralysis and in severe cases death. The pathophysiology of the disease still remains unclear, but recent studies have demonstrated gadolinium deposits in tissues of patients diagnosed with nephrogenic systemic fibrosis. The prevalence of nephrogenic systemic fibrosis after exposure to gadolinium has been reported to be up to 12% in CKD stage 5 patients after a single exposure. No single treatment has been shown to be effective, although there are some patients shown to have improvement of their clinical symptoms with regaining of renal function especially after transplantation. In this article we review the current literature of this disease.

Definition and Validation of a Novel Metric of Erythropoiesis-Stimulating Agent Response in Hemodialysis Patients.

Erythropoiesis-stimulating agents (eg, epoetin alfa) are the primary treatment for anemia in patients with end-stage renal disease. Hemoglobin variability in and out of a narrow target range is common and associated with higher morbidity and mortality risk. More robust erythropoiesis-stimulating agent response metrics are needed to define optimal dosing and their association with clinical outcomes. In this cross-sectional, single-center, retrospective study, 49 patients with end-stage renal disease on hemodialysis were followed over 12 months. To quantify hemoglobin deviations outside the target range (10-12 g/dL), the area under the curve of hemoglobin versus time over a 12-month period (AUC-HGB) was calculated using the trapezoidal rule. Patients were categorized into 4 responder groups based on AUC-HGB quartiles. Comparative analyses of demographic and clinical characteristics between responder groups were performed. Correlations between AUC-HGB, erythropoietin resistance index, and time within therapeutic range were calculated. There were no significant differences in laboratory and dialysis parameters between responder groups except hemoglobin concentration and epoetin alfa dose. There was a negative correlation between AUC-HGB and time within therapeutic range (r = -.92; P < .001) and hemoglobin concentration (r = -.85; P < .01), indicating internal validity of the metric. There was a positive correlation between AUC-HGB and erythropoietin resistance index (r = .70; P < .001) indicating external validity. The poor response group received a higher median epoetin alfa dose (160 U/kg/week) compared to the excellent response group (68.8 U/kg/week; P < .001) with a similar number of dose changes between the groups. AUC-HGB is a valid marker of epoetin alfa response and should be considered in future analyses of larger populations.

Clinical improvement of nephrogenic systemic fibrosis after kidney transplantation.

Nephrogenic systemic fibrosis (NSF) has been observed with increased frequency in recent years. Progressive hardening of the skin advancing to severe woody induration and the development of thickened hyperpigmented plaques on the extremities and the trunk are the main clinical features. Further progression of the disease results in flexion contractures of the upper and lower extremities, resulting in immobilization and severe morbidity. In this study, we reviewed our experience with seven end-stage renal disease patients who were referred to our center between January 2004 and June 2005 for kidney transplant evaluation or for diagnosis and treatment of their deteriorating condition. Diagnosis in all patients was confirmed by skin and muscle biopsy. Three of these patients underwent renal transplantations, and softening of the skin and improved mobility of the joints was noted after kidney transplantation. Three of the four patients who remained on dialysis showed further deterioration of their NSF despite a trial of immunosuppressive therapy. Improvement after transplantation could be secondary to immunosuppression, increased renal clearance and/or more effective fluid management.

Dialysis disequilibrium syndrome: a narrative review.

Dialysis Disequilibrium Syndrome (DDS) is characterized by neurological symptoms caused by rapid removal of urea during hemodialysis. It develops primarily from an osmotic gradient that develops between the brain and the plasma as a result of rapid hemodialysis. This results in brain edema that manifests as neurological symptoms such as headache, nausea, vomiting, muscle cramps, tremors, disturbed consciousness, and convulsions. In severe cases, patients can die from advanced cerebral edema. Recent advancements in cell biology implicate the role of urea disequilibrium (with a smaller contribution from organic osmolytes) as the pathophysiological mechanism responsible for this syndrome. In this review, we discuss the pathogenesis, clinical features and prevention of DDS.

Barriers, Facilitators, and Solutions to Optimal Patient Portal and Personal Health Record Use: A Systematic Review of the Literature.

Patient portal and personal health record adoption and usage rates have been suboptimal. A systematic review of the literature was performed to capture all published studies that specifically addressed barriers, facilitators, and solutions to optimal patient portal and personal health record enrollment and use. Consistent themes emerged from the review. Patient attitudes were critical as either barrier or facilitator. Institutional buy-in, information technology support, and aggressive tailored marketing were important facilitators. Interface redesign was a popular solution. Quantitative studies identified many barriers to optimal patient portal and personal health record enrollment and use, and qualitative and mixed methods research revealed thoughtful explanations for why they existed. Our study demonstrated the value of qualitative and mixed research methodologies in understanding the adoption of consumer health technologies. Results from the systematic review should be used to guide the design and implementation of future patient portals and personal health records, and ultimately, close the digital divide.

Changes in Serum Bicarbonate Levels Caused by Acetate-Containing Bicarbonate-Buffered Hemodialysis Solution: An Observational Prospective Cohort Study.

Fresenius Medical Care's NaturaLyte dialysate has been associated with increased risk of sudden cardiac death by causing metabolic alkalosis from its acetate content based on retrospective data using pre-dialysis bicarbonate levels only. The study objective was to measure inter/intra-dialytic changes in serum bicarbonate and degree of alkalosis conferred by varying concentrations of NaturaLyte bicarbonate dialysate. Thirty-nine hemodialysis patients were divided into four groups based on prescribed bicarbonate dialysate concentrations; Group 1 (N = 9): 30-32 mEq/L, Group 2 (N = 5): 33-34 mEq/L, Group 3 (N = 10): 35-36 mEq/L, Group 4 (N = 15): 37-40 mEq/L. Serial (pre-dialysis, immediate post-dialysis, 2 h post-dialysis, and 68 h post-dialysis) bicarbonate levels were measured. Mean pre-dialysis serum bicarbonate levels (representing 44 h post-dialysis levels) in all four groups were not statistically different. Pre-dialysis and 68 h post-dialysis bicarbonate levels in each group were also not significantly different. However, immediate post-dialysis and 2 h post-dialysis bicarbonate levels were significantly increased in all four groups proportional to dialysate dose. There was statistically significant inter-group bicarbonate level difference (P < 0.05) except between the first and second (P = 0.43) and second and third (P = 0.07) groups in the immediate post-dialysis period. Similar results were obtained for the 2 h post-dialysis period. High bicarbonate dialysate causes large and rapid fluctuations in serum bicarbonate levels during the intra/inter-dialytic period, which returns to baseline within 44 to 68 h after dialysis. This refutes the necessity to correct pre-dialysis acidosis with high bicarbonate dialysate since rapid equilibration is likely to occur and unnecessarily exposes patients to large shifts in their acid base balance.

Evaluation of a Renal Transplant Program for Incarcerated ESRD Patients.

Renal transplantation (Tx) improves mortality and morbidity but is limited by availability of suitable organs. Clinical and economic impact of a Tx program for end-stage renal disease (ESRD) prisoners was evaluated. Wait list time and patient and organ survival rates were assessed. Twelve of the 104 ESRD prisoners at a prison dialysis unit were activated; 9 transplanted, 2 released active on the United Network for Organ Sharing list, and 1 died after listing. Kidneys from antibody-positive hepatitis C (HepC) donors were given to consenting HepC antibody-positive recipients. The average waiting period was 6.6 months for HepC-positive kidney recipients and 49.6 months for others. Compared with costs of continuing dialysis, Tx resulted in substantial savings. Patients with HepC experienced good graft and survival rates when given grafts from HepC donors, suggesting that transplantation is a viable, cost-effective option for the incarcerated patient with ESRD including those who have chronic HepC infection.