Patient knowledge and adherence to maintenance hemodialysis: an International comparison study.

BACKGROUND: Non-adherence to hemodialysis (HD) is associated with increased morbidity and mortality. In this cross-sectional study, we compared correlates and rates of non-adherence between the US and Japan to determine if differences in patient knowledge about HD might account for international variation in adherence. METHODS: We evaluated 100 US and 116 Japanese patients on maintenance HD. Patient knowledge was scored based on the identification of their vascular access, dry weight, cause of kidney disease, and ≥ 3 phosphorus- and potassium-rich foods. Patients were considered non-adherent if they missed > 3% of HD sessions in 3 months. RESULTS: 23% of the US and none of the Japanese patients were non-adherent. Using logistic regression, we found that in the US non-adherence was more common in black patients [Odds ratio (OR) 3.98; 95% confidence interval (CI) 1.42-11.22], while high school graduates (OR 0.20; 95% CI 0.05-0.81) and those on the transplant waiting list (OR 0.25; 95% CI 0.083-0.72) were less likely to miss their treatments. There was no significant association between knowledge and non-adherence in the US. However, Japanese patients had significantly higher levels of HD knowledge than US patients after adjusting for age (p < 0.001). CONCLUSION: Age-adjusted HD knowledge was higher and non-adherence rates were lower in Japan vs. the US. However, because of the unexpected finding of 100% adherence in Japan, we were unable to formally test whether knowledge was significantly associated with adherence across both countries. Further research is needed to understand the reasons behind the higher non-adherence rates in the US.

Saliva Urea Nitrogen Continuously Reflects Blood Urea Nitrogen after Acute Kidney Injury Diagnosis and Management: Longitudinal Observational Data from a Collaborative, International, Prospective, Multicenter Study.

BACKGROUND: Acute kidney injury (AKI) is a growing global concern and often reversible. Saliva urea nitrogen (SUN) measured by a dipstick may allow rapid diagnosis. We studied longitudinal agreement between SUN and blood urea nitrogen (BUN) and the diagnostic performance of both. METHODS: Agreement between SUN and BUN and diagnostic performance to diagnose AKI severity in AKI patients in the United States and Brazil were studied. Bland-Altman analysis and linear mixed effects models were employed to test the agreement between SUN and BUN. Receiver operating characteristics statistics were used to test the diagnostic performance to diagnose AKI severity. RESULTS: We found an underestimation of BUN by SUN, decreasing with increasing BUN levels in 37 studied patients, consistent on all observation days. The diagnostic performance of SUN (AUC 0.81, 95% CI 0.63-0.98) was comparable to BUN (AUC 0.85, 95% CI 0.71-0.98). CONCLUSION: SUN reflects BUN especially in severe AKI. It also allows monitoring treatment responses. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=445041.

Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement.

OBJECTIVE: Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination. The Extracorporeal Treatments in Poisoning workgroup aimed to develop evidence-based consensus recommendations for extracorporeal treatment in methanol poisoning. DESIGN AND METHODS: Utilizing predetermined methods, we conducted a systematic review of the literature. Two hundred seventy-two relevant publications were identified but publication and selection biases were noted. Data on clinical outcomes and dialyzability were collated and a two-round modified Delphi process was used to reach a consensus. RESULTS: Recommended indications for extracorporeal treatment: Severe methanol poisoning including any of the following being attributed to methanol: coma, seizures, new vision deficits, metabolic acidosis with blood pH ≤ 7.15, persistent metabolic acidosis despite adequate supportive measures and antidotes, serum anion gap higher than 24 mmol/L; or, serum methanol concentration 1) greater than 700 mg/L (21.8 mmol/L) in the context of fomepizole therapy, 2) greater than 600 mg/L or 18.7 mmol/L in the context of ethanol treatment, 3) greater than 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker; in the absence of a methanol concentration, the osmolal/osmolar gap may be informative; or, in the context of impaired kidney function. Intermittent hemodialysis is the modality of choice and continuous modalities are acceptable alternatives. Extracorporeal treatment can be terminated when the methanol concentration is <200 mg/L or 6.2 mmol/L and a clinical improvement is observed. Extracorporeal Treatments in Poisoning inhibitors and folic/folinic acid should be continued during extracorporeal treatment. General considerations: Antidotes and extracorporeal treatment should be initiated urgently in the context of severe poisoning. The duration of extracorporeal treatment extracorporeal treatment depends on the type of extracorporeal treatment used and the methanol exposure. Indications for extracorporeal treatment are based on risk factors for poor outcomes. The relative importance of individual indications for the triaging of patients for extracorporeal treatment, in the context of an epidemic when need exceeds resources, is unknown. In the absence of severe poisoning but if the methanol concentration is elevated and there is adequate alcohol dehydrogenase blockade, extracorporeal treatment is not immediately required. Systemic anticoagulation should be avoided during extracorporeal treatment because it may increase the development or severity of intracerebral hemorrhage. CONCLUSION: Extracorporeal treatment has a valuable role in the treatment of patients with methanol poisoning. A range of clinical indications for extracorporeal treatment is provided and duration of therapy can be guided through the careful monitoring of biomarkers of exposure and toxicity. In the absence of severe poisoning, the decision to use extracorporeal treatment is determined by balancing the cost and complications of extracorporeal treatment to that of fomepizole or ethanol. Given regional differences in cost and availability of fomepizole and extracorporeal treatment, these decisions must be made at a local level.

Hemodialysis for the treatment of pulmonary hemorrhage from dabigatran overdose.

Dabigatran is an oral direct thrombin inhibitor indicated for thromboembolism prophylaxis in patients with nonvalvular atrial fibrillation. Since its approval in the United States in 2010, dabigatran-associated hemorrhages have garnered much attention because bleeding rates were higher than initially expected. Additionally, reversing anticoagulation remains challenging. Traditional modes of reversing warfarin-associated coagulopathies are ineffective in reversing anticoagulation from dabigatran. Although hemodialysis is proposed as a method to accelerate dabigatran elimination, evidence supporting its clinical utility remains unproved. We report the case of an 80-year-old man who presented with worsening hemoptysis in the setting of unintentional ingestion of excess dabigatran. Despite transfusion of 2 units of fresh frozen plasma, he continued to bleed, although his international normalized ratio improved from 8.8 to 7.2. He underwent hemodialysis, and serum dabigatran concentration decreased from 1,100 to 18 ng/mL over 4 hours, with an initial extraction ratio of 0.97 and blood clearance of 291 mL/min. Although his serum dabigatran concentration rebounded to 100 ng/mL 20 minutes after the cessation of dialysis, his bleeding stopped and he improved clinically. Hemorrhage in the setting of dabigatran anticoagulation remains a therapeutic predicament. Hemodialysis may play an adjunct role in accelerating the elimination of dabigatran in bleeding patients.

Arteriovenous fistula toxicity.

The arteriovenous fistula (AVF) has been a mainstay of hemodialysis treatments and the preferred access route since its inception in the 1960s, due to its longevity and resistance to infection. However, the AVF is not benign. There is significant primary failure, as well as cardiac, vascular, and other, less well recognized, complications. Together, they represent toxicity, to which considerable morbidity and mortality can be attached. Official policy, based on guidelines where AVF toxicity is given short shrift, drives an increase in use of these devices, and may have undesired consequences.

The impact of residual renal function on hospitalization and mortality in incident hemodialysis patients.

BACKGROUND/AIMS: Few data are available on the impact of residual renal function (RRF) on mortality and hospitalization in hemodialysis (HD) patients. The objective of our study was to compare clinical outcomes for HD patients with and without RRF. METHODS: In a cohort of 118 incident HD patients with RRF (n = 51) and without RRF (n = 67) who started dialysis in a single center, we recorded demographics, laboratory data, medication, hospitalizations and mortality. RESULTS: Patients without RRF were older (p = 0.007), had lower baseline serum albumin levels (p = 0.002) and spent 18.6 more days in hospital per year than those with RRF (p = 0.055). Mean survival time was significantly lower in patients without RRF (p = 0.027). In a Cox proportional hazards model, only RRF remained as a significant independent predictor. CONCLUSIONS: RRF is associated with significantly reduced mortality and hospital days, but does not decrease the hospitalization rate and time to first hospitalization.

Sorbent augmented hemodialysis systems: are we there yet?

Recent publications have reintroduced the concept of using sorbent systems to augment the efficiency of the dialysis process, either by making stationary or compact wearable devices to regenerate dialysis fluid or to target larger molecules for removal by direct blood or plasma contact with sorbent particles. Many of the inherent problems associated with older sorbents have been overcome by designing sorbents with improved biocompatibility and potential for removing molecules beyond the limits of conventional dialysis membranes. One system is approved for use in acute renal failure in the United States, but other devices are not approved for use in humans and continue to be tested in animals and humans. A prototype wearable sorbent device under investigation is not yet able to meet acceptable small molecular weight solute removal, and the other sorbent devices that possess the ability to remove unconventional uremic toxins have not been studied sufficiently in dialysis patients to define their role as augmentation devices. That there is a renewal of interest in sorbents in augmentation of dialysis points to the dissatisfaction with current dialysis technology.

Nephrolithiasis: evaluation and management.

Nephrolithiasis is a major cause of morbidity involving the urinary tract. The prevalence of this disease in the United States has increased from 3.8% in the 1970s to 5.2% in the 1990s. There were nearly two million physician-office visits for nephrolithiasis in the year 2000, with estimated annual costs totaling $2 billion. New information has become available on the clinical presentation, epidemiologic risk factors, evaluative approach, and outcome of various therapeutic strategies. In this report, we will review the epidemiology and mechanisms of kidney-stone formation and outline management aimed at preventing recurrences. Improved awareness and education in both the general population and among health-care providers about these modifiable risk factors has the potential to improve general health and decrease morbidity and mortality secondary to renal-stone disease.

A quick and simple estimate of creatinine clearance.

INTRODUCTION: The 2 common estimates of renal function, the Cockcroft-Gault (C-G) and MDRD study equations, calculate glomerular filtration rate (GFR) as a function of serum creatinine. However, these equations require complex calculations and several parameters. We derived an equation to estimate creatinine clearance (eCCr) rapidly. METHODS: We studied 61 randomly selected patients. Our new formulae (eCCr) are eCCr (male) = weight/ creatinine; and eCCr (female) = weight x 0.84/creatinine (both with weight in kg). We compared eCCr to the long and short MDRD and C-G equations. RESULTS: Agreement between the MDRD long and other formulae was determined using intraclass correlation (ICC); agreement with patient staging for estimated GFR <60 was done by kappa coefficient. ICCs were all >0.8, i.e., good overall agreement. ICCs were 0.96 for MDRD short, 0.84 for eCCr and 0.81 for C-G. Agreements for patients with GFR >60 were lower. MDRD short yielded the best agreement (kappa = 0.88; "good" agreement) followed by eCCr (kappa = 0.69; "fair" agreement) and C-G (0.56). ROC curve analysis showed an area under the curve (AUC) of 0.93, 0.98 and 0.90 for C-G, MDRD short and eCCr, respectively, as estimates of MDRD long (pe0.29). ROC curve analysis showed AUC=0.93 for MDRD short and 0.94 for eCCr as estimates of C-G (p=0.22). CONCLUSION: We conclude that eCCr is a simple formula to estimate GFR at bedside, within a reasonable mathematical difference from the MDRD and C-G equations. This estimate can alert the physician to change drug dosing or more formally estimate GFR.

Relationship between proteinuria and venous thromboembolism.

Nephrotic syndrome is known to cause venous thromboembolism (VTE) due to urine loss of antithrombin III and activation of the coagulation system. We hypothesized that the degree of proteinuria may predict the development of VTE. This was a retrospective case-controlled study of in-patients urban academic teaching hospital from April, 2007 to March, 2009 and who had undergone an imaging study for VTE. All radiology reports (N = 1,647) for CT angiography of chest and Doppler sonogram of extremities were reviewed. The following data were collected: race/ethnicity, degree of proteinuria on urinalysis, serum protein and albumin levels, risk factors for VTE and renal function. The study population consisted of 284 patients with VTE and 280 age/sex matched controls. Relative to those who did not have proteinuria, patients who tested positive for protein had a 3.4-fold increased risk of VTE (odds ratio (OR) 3.4, 95% confidence interval [2.4, 5.0]). The association was unchanged when adjusted for other risk factors. Patients with proteinuria may have an increased risk of venous thromboembolism.

Decreased pulse pressure during hemodialysis is associated with improved 6-month outcomes.

Pulse pressure is a well established marker of vascular stiffness and is associated with increased mortality in hemodialysis patients. Here we sought to determine if a decrease in pulse pressure during hemodialysis was associated with improved outcomes using data from 438 hemodialysis patients enrolled in the 6-month Crit-Line Intradialytic Monitoring Benefit Study. The relationship between changes in pulse pressure during dialysis (2-week average) and the primary end point of non-access-related hospitalization and death were adjusted for demographics, comorbidities, medications, and laboratory variables. In the analyses that included both pre- and post-dialysis pulse pressure, higher pre-dialysis and lower post-dialysis pulse pressure were associated with a decreased hazard of the primary end point. Further, every 10 mm Hg decrease in pulse pressure during dialysis was associated with a 20% lower hazard of the primary end point. In separate models that included pulse pressure and the change in pulse pressure during dialysis, neither pre- nor post-dialysis pulse pressure were associated with the primary end point, but each 10 mm Hg decrease in pulse pressure during dialysis was associated with about a 20% lower hazard of the primary end point. Our study found that in prevalent dialysis subjects, a decrease in pulse pressure during dialysis was associated with improved outcomes. Further study is needed to identify how to control pulse pressure to improve outcomes.

Rhabdomyolysis following clarithromycin monotherapy.

Macrolide antibiotics inhibit the metabolism of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) that may result in myopathy and rhabdomyolysis. We report the first case of rhabdomyolysis related to the administration of clarithromycin without concurrent use of other medications. Inhibition of cytochrome P450 could be one of the potential causative mechanisms of myopathy in our case. Clinicians should be aware of this potential adverse effect of a widely used drug.

In-vitro myoglobin clearance by a novel sorbent system.

Rhabdomyolysis may lead to acute kidney injury following deposition of myoglobin in renal tubules. Although high-flux dialysis membranes may remove a substantial amount of myoglobin from plasma, this may still not be sufficient to prevent renal damage. We tested a new polymer sorbent, X-Sorb, in vitro to determine its potential to clear myoglobin from solutions. Normal saline or human serum in which myoglobin was dissolved was perfused by a peristaltic pump through a column packed with the sorbent. After a 4-hour perfusion, the myoglobin level in normal saline fell from 200,000 ng/ml to virtually undetectable (<780 ng/ml). Perfusion through the sorbent was then found to lower concentrations of dissolved myoglobin in 3 different 110-ml samples of human serum consistently by > 90% over 4 hours. X-Sorb appears to be an effective sorbent for myoglobin and warrants a trial in vivo to determine whether it is equally effective and safe.

Extracorporeal removal of toxins.

Holubek et al. reviewed data on extracorporeal removal (ECR) of toxins from the Toxic Exposure Surveillance System (TESS) from 1985 to 2005. Hemodialysis use increased, but hemoperfusion nearly disappeared. Lithium, ethylene glycol, salicylate, and, increasingly, acetaminophen still often necessitate hemodialysis; ECR for theophylline has disappeared. TESS data do not separate continuous renal replacement therapy from hemodialysis, and not all poisonings were reported in this system. Nonetheless, these trends are useful to the nephrology community.

Guidelines have done more harm than good.

Practice guidelines have proliferated in medicine but their impact on actual practice and outcomes is difficult, if not impossible, to quantify. Though guidelines are based largely on observational data and expert opinion, it is widely believed that adherence to them leads to improved outcomes. Data to support this belief simply does not exist. If guidelines are universally ignored, their impact on treatment and outcomes is minimal. The incorporation of guidelines into treatment protocols and performance measures, as is now common practice in nephrology, increases greatly the likelihood that guidelines will influence practice and hence, outcomes. Practice patterns set up this way may be resistant to change, should new evidence emerge that contradicts certain recommendations. Even if guidelines are entirely appropriate, a 'one-size-fits-all' approach is likely to benefit some, but not all. Certain patients may be harmed by adherence to specific guidelines. Guidelines certainly do not encourage clinicians to consider and treat each patient as an individual. They are unlikely to stimulate original research. They are created by a process that is artificial, laborious and cumbersome. This all but guarantees many guidelines are obsolete by the time they are published. Guidelines are produced with industry support and recommendations often have a major impact on sales of industry products.

Metformin-induced lactic acidosis and acute pancreatitis precipitated by diuretic, celecoxib, and candesartan-associated acute kidney dysfunction.

Polypharmacy may lead to synergistic complications from the different medications. We report the case of a 50-year-old woman who was prescribed 11 drugs, including a diuretic, celecoxib, metformin, and candesartan, and who developed acute kidney dysfunction while on these drugs, manifesting as severe proteinuria, acute azotemia, hyperkalemia. The kidney injury caused the accumulation of metformin, leading to lactic acidosis and acute pancreatitis. Sodium bicarbonate hemodialysis not only improved the metabolic abnormalities but also hastened the removal of metformin.

Relationship between interdialytic weight gain and blood pressure among prevalent hemodialysis patients.

BACKGROUND: Hypertension is common in hemodialysis patients; however, the relationship between interdialytic weight gain (IDWG) and blood pressure (BP) is incompletely characterized. This study seeks to define the relationship between IDWG and BP in prevalent hemodialysis subjects. STUDY DESIGN, SETTING, & PARTICIPANTS: This study used data from 32,295 dialysis sessions in 442 subjects followed up for 6 months in the Crit-Line Intradialytic Monitoring Benefit (CLIMB) Study. OUTCOMES & MEASUREMENTS: Mixed linear regression was used to analyze the relationship between percentage of IDWG (IDWG [%] = [current predialysis weight - previous postdialysis weight]/dry weight * 100) as the independent variable and systolic BP (SBP) and predialysis - postdialysis SBP (deltaSBP) as dependent variables. RESULTS: In unadjusted analyses, every 1% increase in percentage of IDWG was associated with a 1.00 mm Hg (95% confidence interval [CI], +/-0.24) increase in predialysis SBP (P < 0.0001), 0.65 mm Hg (95% CI, +/-0.24) decrease in postdialysis SBP (P < 0.0001), and 1.66 mm Hg (95% CI, +/-0.25) increase in deltaSBP (P < 0.0001). After controlling for other significant predictors of SBP, every 1% increase in percentage of IDWG was associated with a 1.00 mm Hg (95% CI, +/-0.24) increase in predialysis SBP (P < 0.0001) and a 1.08 mm Hg (95% CI, +/-0.22) increase in deltaSBP with hemodialysis (P < 0.0001). However, in subjects with diabetes as the cause of end-stage renal disease, subjects with lower creatinine levels, and older subjects, the magnitude of the association between percentage of IDWG and predialysis SBP was less pronounced. The magnitude of percentage of IDWG on deltaSBP was less pronounced in younger subjects and subjects with lower dry weights. Results were similar with diastolic BP. LIMITATIONS: Hemodialysis BP measurements are imprecise estimates of BP and true hemodynamic burden in dialysis subjects. CONCLUSIONS: In prevalent hemodialysis subjects, increasing percentage of IDWG is associated with increases in predialysis BP and BP changes with hemodialysis; however, the magnitude of the relationship is modest and modified by other clinical factors. Thus, although overall volume status may impact on BP to a greater extent, day-to-day variations in weight gain have a modest role in BP increases in prevalent subjects with end-stage renal disease.

Antineutrophil cytoplasmic antibody-positive pauci-immune glomerulonephritis associated with mantle cell lymphoma.

Renal involvement in non-Hodgkin lymphoma, especially mantle cell lymphoma (MCL) is rare. A 77-year-old man presented with acute kidney injury (AKI), which rapidly progressed to dialysis dependence. Kidney biopsy revealed patchy B-cell lymphocytic aggregates in the interstitium, which were positive for cyclin D1, consistent with atypical CD5-negative MCL as confirmed by the detection of translocation t(11;14) by FISH. Crescents were noted in 3 of 26 glomeruli; while PR-3 antineutrophil cytoplasmic antibody (ANCA) positivity and negative immunofluorescence suggested an additional pauci-immune (rapidly progressive) glomerulonephritis pattern of injury. Patient received chemotherapy (cyclophosphamide, vincristine, and prednisone), which improved his renal function and allowed for discontinuation of hemodialysis. However, he died from pulmonary hemorrhage 8 months after initial presentation. This is the first reported case of a patient with coexistence of renal MCL infiltration and ANCA-positive pauci-immune glomerulonephritis.

Disaster Preparedness and Awareness of Patients on Hemodialysis after Hurricane Sandy.

BACKGROUND AND OBJECTIVES: Patients with ESRD on dialysis live in a complex sociomedical situation and are dependent on technology and infrastructure, such as transportation, electricity, and water, to sustain their lives. Interruptions of this infrastructure by natural disasters can result in devastating outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between November of 2013 and April of 2014, a cross-sectional survey was conducted of patients who received maintenance hemodialysis before and after the landfall of Hurricane Sandy on October 29, 2012 in lower Manhattan, New York. The primary outcome was the number of missed dialysis sessions after the storm. Dialysis-specific and general disaster preparedness were assessed using checklists prepared by the National Kidney Foundation and US Homeland Security, respectively. RESULTS: In total, 598 patients were approached, and 357 (59.7%) patients completed the survey. Participants were 60.2% men and 30.0% black, with a median age of 60 years old; 94 (26.3%) participants missed dialysis (median of two sessions [quartile 1 to quartile 3 =1-3]), and 236 (66.1%) participants received dialysis at nonregular dialysis unit(s): 209 (58.5%) at affiliated dialysis unit(s) and 27 (7.6%) at emergency rooms. The percentages of participants who carried their insurance information and detailed medication list were 75.9% and 44.3%, respectively. Enhancement of the dialysis emergency packet after the hurricane was associated with a significantly higher cache of medical records at home at follow-up survey (P<0.001, Fisher's exact test). Multivariate Poisson regression analysis showed that dialysis-specific preparedness (incidence rate ratio, 0.91; 95% confidence interval, 0.87 to 0.98), other racial ethnicity (incidence rate ratio, 0.34; 95% confidence interval, 0.20 to 0.57), dialysis treatment in affiliated units (incidence rate ratio, 0.69; 95% confidence interval, 0.51 to 0.94), and older age (incidence rate ratio, 0.98; 95% confidence interval, 0.97 to 0.99) were associated with a significantly lower incidence rate ratio of missed dialysis. CONCLUSIONS: There is still room to improve the preparedness for natural disasters of patients with ESRD. Provider- or facility-oriented enhancement of awareness of the disease and preparedness should be a priority.