(HealthDay News) — Low albumin levels at the start of renal replacement therapy are independently associated with mortality during one-year follow-up, according to a study published online in the Journal of Renal Care.
Ana Rebollo Rubio, PhD, from the Carlos Haya Regional University Hospital in Malaga, Spain, and colleagues conducted a one-year prospective follow-up study involving 189 patients. The authors analyzed sociodemographic variables, etiology of renal disease, comorbidities, prior nephrology service monitoring, prior renal transplantation, and biochemical parameters at the time of starting renal replacement therapy, and assessed their correlation with mortality.
The researchers found that 6.87% of participants died during one-year follow-up; 64% of the deaths occurred during the first 6 months. A low albumin level was the only variable independently associated with mortality.
"Although most patients in this center are monitored by a nephrologist prior to starting replacement therapy, many nevertheless fail to achieve the biochemical targets recommended. One such parameter is albumin, which proved at the start of replacement therapy to be an independent predictor of mortality," the authors write. "Findings of this study show the need to intervene on certain biochemical parameters during the pre-dialysis stage and at the start of dialysis, in order to improve survival in this group of patients."
Higher residual kidney function in hemodialysis (HD) patients is associated with better survival unless serum phosphorus or intact parathyroid hormone (iPTH) is markedly elevated, a new study finds.
Greater residual kidney function allows better clearance of solutes, removal of uremic toxins, and volume control, and leads to less anemia, inflammation, intradialytic hypotension, erythropoietin resistance, and ventricular hypertrophy, according to researchers. Previous research has linked parameters of chronic kidney disease and mineral and bone disorder (CKD-MBD)—including serum calcium, phosphorus, iPTH, and alkaline phosphatase—to increased risks of mortality.
Mengjing Wang, MD, and Yoshitsugu Obi, MD, of the University of California Irvine Medical Center, and colleagues examined the relationship of CKD-MBD biomarkers with all-cause mortality according to preserved renal function. They modeled data from 35,114 patients who initiated thrice-weekly HD during 2007 to 2011 and stratified results by residual renal function. The investigators used average residual renal urea clearance during the first 91 days of HD and formed 3 groups: less than 1.5, 1.5 to less than 3.0, and 3.0 mL/min/1.73 m2 or higher.
Over a year of follow up, 23% of patients died, the investigators reported online ahead of print in the Clinical Journal of the American Society of Nephrology. According to Cox proportional hazard models, mortality risk increased along with phosphorus level, particularly among patients with higher residual renal urea clearance. Patients with phosphorus levels at or above 7.0 mg/dL had increased risks of dying regardless of kidney function. Results held after accounting for a range of demographic, clinical, and laboratory variables. Patients'' high phosphorus levels probably indicated poor adherence to diet and medication and high-turnover bone disease, according to the investigators.
In addition, the study found increased mortality among patients with lower iPTH and low residual renal urea clearance or high iPTH and higher residual renal urea clearance, using 1.5 mL/min/1.73 m2 as a cutoff.
Patients with elevated serum corrected total calcium or alkaline phosphatase concentrations had greater risks of dying despite their residual kidney function.
Overall, greater preserved kidney function was associated with better survival. The findings support another recent study by the investigators highlighting the importance of residual kidney function in the HD population.
Clinical applications of the research have yet to be determined. “Future studies with a long-term follow-up period are needed to explain the underlying mechanisms of those associations and examine whether taking account for residual kidney function in the assessment of mortality risk associated with serum phosphorus and intact PTH improves patient management and clinical outcomes among patients on hemodialysis,” the investigators concluded.
Among the study limitations, the team could not investigate some relevant confounders, such as vitamin D deficiency, inflammatory status, elevated fibroblast growth factor-23, treatment adherence, and poor predialysis care.
In addition, renal urea clearance may not be the most accurate measure of residual kidney function. Once a reliable method of estimating renal kidney function is found, it might ultimately improve standard of care for HD patients.
Since 2009, hospital intensive care units have witnessed a stark increase inopioid-related admissions and deaths, according to new study led by researchers at Beth Israel Deaconess Medical Center''s (BIDMC) Center for Healthcare Delivery Science. Published online today ahead of print in the Annals of the American Thoracic Society, the study is believed to be the first to quantify the impact of opioidabuse on critical care resources in the United States. The findings reveal thatopioid-related demand for acute care services has outstripped the available supply.
Analyzing data from the period between January 1, 2009 and September 31, 2015, the researchers documented a 34 percent increase in overdose-related ICU admissions. The average cost of care per ICU overdose admissions rose by 58 percent, from $58,517 in 2009 to $92,408 in 2015 (in 2015 dollars). Meanwhile opioiddeaths in the ICU nearly doubled during that same period.
"This study tells us that the opioidepidemic has made people sicker and killed more people, in spite of all the care we can provide in the ICU, including mechanical ventilation, acute dialysis, life support and round-the-clock care," said the study''s lead author, Jennifer P. Stevens, MD, associate director of the medical intensive care unit at BIDMC and assistant professor of medicine at Harvard Medical School.
Using a national hospital database, Stevens and colleagues analyzed almost 23 million hospital admissions of adult patients in 162 hospitals in 44 states over a seven-year period. Among the more than 4 million patients requiring acute care between 2009 and 2015, the researchers found 21,705 patients who were admitted to ICUs due to opioidoverdoses.
The researchers'' analysis revealed thatopioid-related ICU admissions increased an average of more than half a percent each year over the seven-year study period and that patients admitted to ICUs as a result of overdose required increasingly intensive care, including high-cost renal replacement therapy or dialysis. The mortality rates of these patients climbed at roughly the same rate, on average, with a steeper rise in deaths of patients admitted to the ICU for overdose after 2012.
The opioidcrisis in the United States is resulting in increased admissions to hospital intensive care units and in increased numbers of ICU deaths from opioidoverdoses, according to new research published online, ahead of print in the Annals of the American Thoracic Society.
In "The Critical Care Crisis of OpioidOverdoses in the United States," researchers report that between Jan. 2009 and Sept. 2015, admission to the ICU at 162 U.S. hospitals in 44 states increased by 34 percent. During that same time, deaths from these overdoses averaged 7 percent but rose to 10 percent by 2015. These statistics taken together, the researchers estimate, indicate that deaths in these ICUs from opioidoverdoses nearly doubled over the seven years. The researchers also found that the cost of caring for these patients increased from $58,517 to $92,408 (in 2015 dollars) in the same period. "The opioidepidemic has reached a new level of crisis," said lead study author Jennifer P. Stevens, MD, associate director of the medical intensive care unit at Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School. "This study tells us that the opioidepidemic has made people sicker and killed more people, in spite of all the care we can provide in the ICU, including mechanical ventilation, acute dialysis, life support and round-the-clock care."
The authors believe that their report provides the first description of the impact of the opioidaddiction crisis on the nation''s ICUs. Their data source was the Clinical Data Base/Resource ManagerTM. Over seven years, 4,145,068 patients required ICU care at the hospitals contributing to the data base. Of those, 21,705 were patients who had overdosed onopioids, most commonly heroin.
Among the opioidoverdose patients, 25 percent experienced aspiration pneumonia, 15 percent rhabdomyolosis (release of dead muscle fiber into the bloodstream), 8 percent anoxic brain injury and 6 percent septic shock. Ten percent of patients who overdosed needed mechanical ventilation.
For patients with stage 4 to 5 chronic kidney disease (CKD), the risks of undergoing transcatheter aortic valve replacement (TAVR) may outweigh the benefits. Stage 3 CKD patients, however, appear to fare better from the procedure.
In a study, James W. Hansen, DO, of Lahey Hospital and Medical Center in Burlington, Massachusetts, and colleagues analysed outcomes for nearly 45,000 TAVR patients by CKD stage using a transcatheter valve therapy registry 2011–2015 and Medicare database. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation.
The chances of renal replacement therapy (RRT) or death increased significantly more than would be expected for TAVR patients with pre-procedural eGFR below 30 mL/min/1.73m2, according to results published in JACC: Cardiovascular Interventions (2017;10:2064–2075). Researchers estimated that 1 in 6 stage 4 CKD patients (14.6%) will require dialysis and 1 in 3 will die within 1 year. A third of stage 5 patients will need RRT within 30 days and two-thirds within 1 year. In contrast, just 3.5% of stage 3 CKD patients required RRT within 1 year, marginally more than would be expected.
An increase in eGFR of just 5 mL/min/1.73m2 was associated with a 29% risk reduction for patients with pre-procedure eGFR below 60 mL/min/1.73 m2. Whether this is simply a marker or a potential therapeutic target requires investigation.
Patients hospitalized with acute kidney injury (AKI) often fail to follow up with nephrologists after discharge, researchers reported in the Clinical Journal of the American Society of Nephrology (CJASN).
We discovered that there is a substantial disparity between the opinions of nephrologists and actual processes of care for nephrology evaluation of patients after hospitalization with AKI,” co-leader Matthew James, MD, PhD of the Cumming School of Medicine at the University of Calgary in Alberta, Canada, stated in a press release from the journal''s publisher, the American Society of Nephrology.
In a survey, Dr James and colleagues asked 145 Canadian nephrologists how likely they were to recommend outpatient nephrology for hypothetical AKI patients. Nephrologists responded that they would “definitely or probably” reevaluate AKI patients in 87% of hypothetical cases. Patients with a history of chronic kidney disease (CKD, 89%), heart failure (92%), or acute dialysis (91%), or subpar recovery of renal function (98%) especially warranted nephrology follow-up in their opinion.
Nephrologists'' responses were compared with real-world practice. According to 2005–2014 administrative health data from Alberta, Canada, just 24% of actual patients visited a nephrologist within 12 months of their AKI hospitalization, with a worrisome downtrend in recent years. Guidelines recommend a nephrology visit within 3 months of discharge to assess renal recovery or progression to CKD. Patients with pre-existing CKD (43%) or who consulted with nephrology before (78%) or during hospitalization (41%) were more likely to be seen. Those older than 80 were less likely (20%).
Although many patients did not receive nephrology follow-up, they were attended by at least one other physician after discharge.
“This information is potentially useful to develop strategies to improve transitions in care between the hospital and community after an episode of AKI,” Dr James and his collaborators commented.
Karsanji DJ, Pannu N, Manns BJ, et al. Disparity between nephrologists'' opinions and contemporary practices for community follow-up after acute kidney injury hospitalization. Clin J Am Soc Nephrol. doi: 10.2215/CJN.01450217
Few patients hospitalized with acute kidney injury receive recommended follow-up care [news release]. American Society of Nephrology; October 12, 2017.
SAN FRANCISCO—For women aged 50 and older who are on dialysis, routine mammography screening for breast cancer may not be a cost-effective use of medical resources, according to an Australian study.
Given the available data, at best, routine breast cancer screening in this population with a significantly reduced overall survival does not appear good value for money,” the researchers concluded.
A team led by Germaine Wong, MD, who is with the National Health and Medical Research Council Centre for Clinical Research Excellence in Renal Medicine in Sydney, used a technique called Markov decision analytical modeling to weigh the benefits and costs of breast cancer screening in two hypothetical groups of women.
All the women were aged 50 to 69 and on dialysis. One group underwent mammography and one did not. The mathematical simulation used research data from the Australian and New Zealand Data Registry (ANZDATA) on breast cancer rates among women on dialysis, along with expected survival rates and mortality rates.
The cost of once-yearly mammograms, including the costs of diagnosing and treating detected breast cancers, averaged about $4,300 per patient per year (in Australian dollars). The simulation also suggested that yearly mammograms would prevent just one breast cancer death per 1,000 dialysis patients screened. The model estimated that, for each year of life saved, screening would add $154,783 to the total costs of care. By comparison, the average costs of mammography for each year of life saved in the general population range from $20,000 to $40,000.
According to the researchers, several factors affected the costs and benefits of screening, including the rate of breast cancer, the accuracy of mammography, stage at which the cancer was diagnosed, and effectiveness of breast cancer treatment. However, even using the most favorable assumptions, breast cancer screening for dialysis patients was unlikely to be cost-effective, the investigators found.
Currently, regular screening mammograms are recommended for most women aged 50 to 69. How-ever, because patients with end-stage renal disease (ESRD) are at increased risk of death due to kidney disease and other medical problems such as heart disease, it has been unclear whether the costs of routine breast cancer screening are justified for women on dialysis. “Cancer screening is important because the overall cancer risk increases in renal transplant recipients and in patients on dialysis,” Dr. Wong said. “Treatment options for cancers in these populations are limited because of coexisting illnesses.”
“In contrast to most other cancers, the risk of breast cancer in the dialysis population is almost identical to that of the general popu-lation, but data on the effectiveness of screening for breast cancers in women on dialysis is relatively sparse thus far,” Dr. Wong said. “Even though the patients have the same risk, we are unsure whether women on dialysis would achieve the same benefits as patients in the general population.”
Preparedness for the care of dialysis patients during disasters paid off in late August when Hurricane Harvey slammed into the Middle Texas Coast, dropping up to 51.88 inches of rain in places and turning parts of Houston, a city of around 2.4 million people, into lakes. Patients needing dialysis were able to get it, although not necessarily at their usual dialysis center. Still, the monster storm showed that delivery of care could be improved.
Our emergency preparedness program is always a work in progress,” Stephen Z. Fadem, MD, a nephrologist and medical director of DaVita Medical Center in Houston, a facility with 72 dialyzing stations, told Renal & Urology News. “With this flood, We learned that We didn''t have enough staff in the dialysis unit area to dialyze all the patients who were coming in.”
His center, one of approximately 150 DaVita dialysis centers in the path of the storm, was not flooded and did not suffer a power outage. Dr Fadem and his team dialyzed more than 500 patients over 3 days during the hurricane, including 192 patients new to the center because they could not get to the one where they usually dialyze. “We actually had staff sleeping in the dialysis center,” he said. In the future, his center plans to rent a block of rooms at a nearby hotel the next time a major hurricane threatens the Houston area, said Dr Fadem, a clinical professor of medicine at Baylor College of Medicine in Houston.
Doctors were texting one another with regard to which roads were open or closed, he related, and this provided guidance for going to and from the DaVita Medical Center. “I took routes to work that I never traveled before,” he said.
Another problem he encountered was absence of medical records. Even though patients are supposed to bring their records with them in emergency situations such as hurricanes, flooding made it difficult to access them, he said. “One of the biggest delays We had was that We didn''t have any information about a patient,” said Dr Fadem, who added that he spent a lot of time on the telephone trying to reach patients'' doctors and others who could provide clinical information.
He said this experience makes a case for all dialysis centers in the city to cooperate in establishing an emergency online database that contains each patient''s clinical information needed to provide dialysis.
Dr Fadem triaged patients based on their condition. If they had signs of fluid overload or hyperkalemia, they would be dialyzed immediately. Other patients were triaged on a first-come-first-served basis as long as they were healthy.
Hurricane Harvey also exposed problems in getting patients to dialysis centers. “We do need to figure out a better transportation system for patients,” Dr Fadem said.
Controlling blood pressure (BP) to a lower target of less than 130/80 mm Hg does not prevent chronic kidney disease (CKD) progression in patients free of diabetes, according to a new systematic review and meta-analysis. An optimal blood pressure target for this population still needs to be determined.
Targeting BP below the current standard did not provide additional benefit for renal outcomes compared with standard treatment during a follow-up of 3.3 years in patients with CKD without diabetes, Wan-Chuan Tsai, MD, and colleagues concluded in JAMA Internal Medicine. “However, nonblack patients or those with higher levels of proteinuria might benefit from the intensive BP-lowering treatments.
The investigators based their meta-analysis on 9 randomized controlled trials of 8127 patients with follow-up times of 1.6 to 7.0 years. Over a median follow-up of 3.3 years, renal outcomes were comparable for patients attaining the lower BP (below 130/80 mm Hg) compared with the standard target (below 140/90 mm Hg). An aggressive strategy did not show a significant difference in the annual decline in glomerular filtration rate (GFR) (mean difference, 0.07 mL/min/1.73 m2 per year), doubling of serum creatinine level, and a 50% reduction in GFR. The odds of end-stage renal disease (ESRD), a composite of renal outcomes, and all-cause mortality also were similar among the groups.
Investigators found a lower risk of progression with intensive BP control among non-black patients and those with proteinuria levels higher than 0.5 or 1 g per day. “Previous studies have reported that the kidney protection with antihypertensive therapy is less favorable in blacks than in whites,” Dr Tsai and the team stated.
Antihypertensive regimens varied. With regard to adverse events, intensive BP treatment did not appear to increase risks, except for dizziness.
Among the study''s limitations, the researchers noted that the follow-up times, typically less than 4 years, may have been too short to detect meaningful differences in renal outcomes. The effect of an intensive blood pressure-lowering strategy on cardiovascular outcomes is another matter and warrants further study.
In 2014, over 600 million adults worldwide were obese. Obesity increases the risk of developing major risk factors for Chronic Kidney Disease (CKD), like diabetes and hypertension, and it has a direct impact on the development of CKD and end-stage renal disease (ESRD). The good news is that obesity is largely preventable. Education and awareness of the risks of obesity and a healthy lifestyle, including proper nutrition and exercise, can dramatically help in preventing obesity and kidney disease. This article reviews the association of obesity with kidney disease on the occasion of the 2017 World Kidney Day.Association of obesity with CKD and other renal complications.
Numerous studies have shown an association between measures of obesity and both the development and the progression of CKD. In general, the associations between obesity and poorer renal outcomes persist even after adjustments for possible mediators of obesity''s cardiovascular and metabolic effects, suggesting that obesity may affect kidney function through mechanisms in part unrelated to these complications. The deleterious effect of obesity on the kidneys extends to other complications such as nephrolithiasis and kidney malignancies.Mechanisms of action underlying the renal effects of obesity.
The exact mechanisms whereby obesity may worsen or cause CKD remain unclear. Some of the deleterious renal consequences of obesity may be mediated by comorbid conditions such as diabetes mellitus or hypertension, but there are also effects of adiposity which impact the kidneys directly via production of (among others) adiponectin, leptin and resistin (Figure 1). These include the development of inflammation, oxidative stress, abnormal lipid metabolism, activation of the renin-angiotensin-aldosterone system, and increased production of insulin and insulin resistance.1
These various effects result in pathologic changes in the kidneys including ectopic lipid accumulation and increased deposition of renal sinus fat, glomerular hypertension and increased glomerular permeability, and ultimately the development of glomerulomegaly, and focal or segmental glomerulosclerosis (Figure 2).2 The incidence of the so-called obesity-related glomerulopathy has increased ten-fold between 1986 and 2000.Figure 1. Putative mechanisms of action whereby obesity causes chronic kidney disease. Courtesy of Dr. Patrick D. Walker, MD; Arkana Laboratories, Little Rock, AR.
Obesity is associated with a number of risk factors contributing to nephrolithiasis, such as lower urine pH and increased urinary oxalate, uric acid, sodium and phosphate excretion. The insulin resistance characteristic of obesity may also predispose to nephrolithiasis through its impact on tubular Na-H exchanger and ammoniagenesis, and the promotion of an acidic milieu.3
The putative mechanisms behind the increased risk of kidney cancersobserved in obese individuals include insulin resistance, chronic hyperinsulinemia and increased production of insulin-like growth factor 1, which may exert stimulating effects on the growth of various types of tumor cells. More recently, the endocrine functions of adipose tissue, its effects on immunity, and the generation of an inflammatory milieu with complex effects on cancers have emerged as additional explanations.4Obesity in patients with advanced kidney disease: The need for a nuanced approach.
In a seemingly counter intuitive manner obesity has been consistently associated with lower mortality rates in patients with CKD and ESRD.5 It is possible that the seemingly protective effect of a high BMI is the result of the imperfection of BMI as a measure of obesity. However, there is also evidence to suggest that higher adiposity, especially subcutaneous (non-visceral) fat, may also be associated with better outcomes in ESRD patients. Such benefits may be present in patients who have very low short term life expectancy.
In the aftermath of Hurricane Maria, which left Puerto Rico in ruins, nearly 100 Fresenius Kidney Care dialysis nurses have volunteered to relieve staff and help care for patients at 27 of the 28 dialysis centers that the company operates on the island of 3.4 million American citizens. Fresenius Kidney Care is scheduled to transport the first 12 nurses to Puerto Rico by passenger plane on October 22.
Much of Puerto Rico is still without electricity and fresh water remains scarce after the hurricane made shambles of the island 3 weeks ago. Nineteen of the 27 operational centers are relying on diesel generators for electricity, and eight centers have municipal electricity available, said Bob Loeper, Head of the Disaster Response Team at Fresenius Medical Care North America (FMCNA). One center was completely destroyed by the hurricane.
The centers are staffed by more than 1000 employees and provide dialysis care to approximately 4000 patients.
A major problem in Puerto Rico is a shortage of gas and diesel fuel. FMCNA rented gas truck and purchased pods and placed them around that island at six strategic locations so staff could get gas to go back and forth to work, Loeper related. “If we don''t take care of our staff, then we can''t take care of our patients,” he said.
According to Federal Emergency Management Agency, power will not be restored to the entire island for about six months.
Infective endocarditis frequently occurs in end-stage renal disease (ESRD) patients and specific subgroups have higher risks, a new study finds.
According to linked data from the Danish National Registry on Regular Dialysis and Transplantation and the Danish National Patient registry, 10,612 patients (mean age 63 years; 36% female) started renal replacement therapy from 1996 to 2012, including 7233 on hemodialysis (HD), 3056 on peritoneal dialysis (PD), and 323 receiving kidney transplants (KT). Endocarditis developed in 2.5%, and 31 of these patients required valve surgery, Mavish Chaudry, MD, of Gentofte Hospital in Denmark, and colleagues reported online ahead of print in the Clinical Journal of the American Society of Nephrology. Given that rate, endocarditis would develop in 627 per 100,000 person-years among patients receiving renal replacement therapy, which is at least 60 times the rate found in general Danish population (purportedly 8 to 10 per 100,000 person-years). Of those developing endocarditis, 22% died in hospital and 51% within 1 year.
HD patients appeared the most prone to infective endocarditis. It was estimated to develop in 1092 HD, 212 PD, and 85 KT patients per 100,000 person-years. HD patients had 5.5 times higher risk compared with PD patients, with patients younger than 66 especially vulnerable; KT patients had less than half the risk.
(HealthDay News) -- Immediate or delayed differences in adverse event rates were seen after generic commercialization of 3 antihypertensivedrugs, according to a study published online in Circulation: Cardiovascular Quality and Outcomes.
Jacinthe Leclerc, RN, from the Institute National de Santé Publique du Québec in Canada, and colleagues examined the impact of 3 generic angiotensin II receptor blockers'' commercialization on adverse events for 136,177 losartan, valsartan, and candesartan users (age ≥66 years). Rates of adverse events were calculated monthly, 24 months before, and 12 months after generic commercialization.
The researchers found that before and after generic commercialization, for all users, there was a monthly mean rate of 100 adverse events for 1000 angiotensin II receptor blockers users. The month of generic commercialization, there was an increase in the rates of adverse events among generic users of losartan, valsartan, and candesartan of 8, 11.7, and 14%, respectively (difference of proportions versus brand name, 7.5 [95% confidence interval, -0.9 to 15.9%], 17.1 [95% confidence interval, 9.9 to 24.3%], and 16.6% [95% confidence interval, 7.9 to 25.3%], respectively). At ≤one year after generic commercialization, the monthly trend of adverse events was affected for generic versus brand-name losartan users only (difference of proportions, 2%). Results were similar in sensitivity analyses.
Risk and survival analysis studies controlling for several potential confounding factors are required to better characterise generic substitution," the authors write.
Several authors disclosed financial ties to the pharmaceutical industry.
Article by: Research Scientist: Soxa Formulations & Research Pvt Ltd
Purpose of review: Iron deficiency is a major contributory cause to the development of anaemia in chronic kidney disease (CKD), and thus, iron replacement therapy plays a critical role in the management of this condition. The two main routes for administering iron are oral and intravenous, and there have been a number of new publications relevant to both routes of administration.
Recent findings: Recent developments on the topic of iron management in CKD include the introduction of new oral iron preparations, as well as two recent meta-analyses on iron therapy in CKD (one on oral versus intravenous iron, and one on high- versus low-dose intravenous iron in haemodialysis patients). There is also increasing interest in other strategies to improve iron availability, such as intradialytic iron, hypoxia-inducible factor stabilization and antihepcidin strategies.
Summary: Even despite the latest publications in this field, we are still left with serious gaps in our evidence base on how best to provide supplemental iron to CKD patients. Most of the evidence suggests that intravenous iron is superior to oral iron in increasing haemoglobin and minimizing the use of erythropoiesis-stimulating agents, but the safety of intravenous iron remains a controversy. The PIVOTAL study will hopefully provide informative data to fill some of the gap in the evidence-base and inform best clinical practice.
Iron deficiency is a major contributory cause to the development of anaemia in chronic kidney disease (CKD). This arises due to both an inadequate supply of iron, as well as increased losses. Inadequate intake is due to poor appetite in uraemia, as well as poor absorption from the gastrointestinal tract caused by increased hepcidin activity, and exacerbated by concomitant medications such as phosphate binders, proton pump inhibitors and certain antibiotics. Increased iron losses occur due to frequent blood sampling, trapping of red cells in the dialyzer and occult gastrointestinal blood loss, the latter of which may be exacerbated by antiplatelet drugs and anticoagulation on dialysis.
Iron supplementation has therefore become a front-line therapy in the management of CKD anaemia, and the majority of patients with this condition are likely to receive additional iron at some stage. How this iron is administered will depend on a number of factors, including the stage of CKD or modality of renal replacement therapy, as well as physician preference.
For more than three centuries, orally administered iron has been available, and is still used widely today. In the mid-1900s, the concept of giving iron parenterally was introduced to the therapeutic armamentarium, and several new intravenous iron preparations have become available for use over the last few years. More recently, several novel strategies for improving iron availability have evolved, including administration of ferric pyrophosphate citrate (FPC) in the dialysate for haemodialysis patients, and newer oral iron preparations (such as ferric citrate), as well as hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors and antihepdidin agents.
This review will focus largely on what is new regarding both oral and intravenous iron supplementation, as the use of prolyl hydroxylase inhibitors and antihepcidin strategies remains largely experimental.Oral Iron Supplementation: What is new?
By far, the most commonly used oral iron preparation in clinical practice remains ferrous sulphate. Other older iron compounds include ferric gluconate, ferric succinate and iron polymaltose. In recent times, however, there have been a number of new oral iron compounds developed and marketed, such as ferric citrate, ferric maltol, heme iron polypeptide (HIP) and oral liposomal (sucrosomial) iron
Background: There is no consensus whether higher intensity dose renal replacement therapy (RRT) compared with standard intensity RRT has survival benefit and achieves better renal recovery in acute kidney injury (AKI).
Methods:In an individual patient data meta-analysis, we merged individual patient data from randomized controlled trials (RCTs) comparing high with standard intensity RRT in intensive care unit patients with severe AKI. The primary outcome was all-cause mortality. The secondary outcome was renal recovery assessed as the proportion of patients who were RRT dependent at key trial endpoints and by time to the end of RRT dependence.
Results: Of the eight prospective RCTs assessing different RRT intensities, seven contributed individual patient data (n = 3682) to the analysis. Mortality was similar between the two groups at 28 days [769/1884 (40.8%) and 744/1798 (41.4%), respectively; P = 0.40] after randomization. However, more participants assigned to higher intensity therapy remained RRT dependent at the most common key study point of 28 days [e.g. 292/983 (29.7%) versus 235/943 (24.9%); relative risk 1.15 (95% confidence interval 1.00–1.33); P = 0.05]. Time to cessation of RRT through 28 days was longer in patients receiving higher intensity RRT (log-rank test P = 0.02) and when continuous renal replacement therapy was used as the initial modality of RRT (log-rank test P = 0.03).
Conclusions: In severe AKI patients, higher intensity RRT does not affect mortality but appears to delay renal recovery.Introduction
Severe acute kidney injury (AKI) often requires renal replacement therapy (RRT) and is associated with high health care costs and a high mortality rate. Moreover, its incidence is >10 times that of end-stage kidney disease (ESKD) and is increasing.[4,5] Finally, AKI survivors carry greater long-term mortality risks, require more institutional care[7,8] and are more likely to develop chronic and end-stage kidney disease.
During almost two decades, after an early influential study suggesting a survival benefit from higher dose intensity, AKI research has focused on the effect of increasing RRT dose intensity. This led to several single-center trials[11–16] with variable findings and spawned two large multicenter trials that failed to confirm such survival benefit. In their aggregate, these randomized studies represent a large, comprehensive, prospectively collected dataset that can be analysed using the technique of individual patient data meta-analysis (IPDMA).
IPDMA uses raw individual-level data from each study for analysis and synthesis.[17,18] By obtaining direct individual data, it allows standardization of analyses across studies while maintaining the benefits of random allocation to study interventions. Thus, in the presence of almost identical patient details and interventions, IPDMA delivers the equivalent of a very large trial. In the AKI setting, it may deliver greater statistical power to elucidate previously undetected effects upon renal outcomes, such as time to independence from RRT.
Accordingly, the Investigation, Management, Prognosis, Recovery, Observation, Value and Evaluation of Acute Kidney Injury (IMPROVE-AKI) collaboration brought together investigators from previous studies of RRT dose intensity in AKI to perform an IPDMA of the effects of RRT dose intensity with a focus on mortality and RRT independence.
A systematic review and meta-analysis of individual patient data were performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Patient Data guideline. First, we identified all relevant studies using a previously reported search strategy involving MEDLINE (1950–July 2017), Embase (1966–July 2017) and the Cochrane Library database for randomized controlled trials (RCTs) of RRT dose in AKI. In studies assessing the effects of dose of continuous renal replacement therapy (CRRT), standard intensity (usually a prescribed dose of 20–25 mL/kg/h) and higher intensity (a prescribed dose of 35–48 mL/kg/h) were defined as published in the original studies. In studies assessing the effects of dialysis dose using intermittent renal replacement therapy (IRRT), higher and standard intensity were similarly defined as published (Supplementary data, Table S1). Trials assessing dialysis dose among ESKD patients were excluded. We then asked the lead investigators from all eligible studies to participate in the IMPROVE-AKI collaboration. We followed an a prioristatistical analysis plan, as agreed by all IPDMA participants.
All participating investigators signed an agreement on terms of reference for the collaboration. We obtained Human Research Ethics approval from the New South Wales Population and Health Services Research Ethics Committee (reference LNR2011/004), which obviated the need for individual patient consent beyond that provided for the original studies. We obtained additional approval from the National Institutes Diabetes and Digestive and Kidney Diseases Central Database Repository (reference 3428). We registered the study with the Australian New Zealand Clinical Trials Registry (ANZCTR; registration number ACTRN12615000394549).Data Collection
We obtained the IMPROVE-AKI data entirely from the existing datasets associated with the completed participating studies. The principal investigators (or their delegates) provided de-identified data for individual participants from each study, including demographic characteristics (age, sex, comorbidities, comorbidity scores assessed by the Acute Physiology and Chronic Health Evaluation III (APACHE III) score, Sequential Organ Failure Assessment (SOFA) score, as well as biochemical measures), RRT characteristics (modality, frequency, timing, allocated and received dose intensity), date of death, dates of RRT dependence and cessation and the details of other treatments received.Outcome Measures
The primary study outcome was all-cause mortality. As the duration of patient follow-up varied between studies, all-cause mortality at a fixed time point following randomization was selected (e.g. 28, 60 and 90 days). The secondary outcomes included the proportion of patients who were RRT dependent at 28, 60 and 90 days and time to the end of RRT dependence through 28 days of follow-up. Time to the end of RRT dependence was defined as the time to the last day of RRT. The study protocol planned sensitivity analyses at different time points for the primary outcome, with the intention of maximizing inclusion of study data and minimizing type II error.Statistical Analysis
We pooled individual patient data from each trial and analyzed all outcomes on the intention-to-treat principle. We summarized discrete variables using frequencies and percentages. We reported continuous variables as means with standard deviations (SDs) for normally distributed variables and as medians and interquartile ranges (IQRs) for non-normally distributed variables. Missing data were not imputed, as per the pre-specified protocol.
Background: Elbasvir–grazoprevir is indicated for chronic hepatitis C virus (HCV) genotypes 1 and 4.
Aim: To evaluate the utilization and outcomes of chronic HCV patients treated with elbasvir–grazoprevir in the United States.
Methods: We conducted a retrospective cohort study of adults treated with elbasvir–grazoprevir with or without ribavirin for chronic HCV genotypes 1 or 4 infection. Data were collected from healthcare providers and specialty pharmacies through Innervation Platform, a proprietary, cloud–based disease management program from Trio Health. The primary endpoint was per protocol sustained virological response 12 weeks post–treatment (SVR12).
Results: Among 470 patients treated in 2016, 95% had HCV genotype 1 infection, 80% (373/468) were HCV treatment naïve and 70% (327/468) had non–cirrhotic disease. Almost 3 quarters (73%) of patients received care in community practices. The majority (89%) of patients received elbasvir–grazoprevir for 12 weeks. Per protocol SVR12 rates were 99% (396/402) for HCV genotype 1 and 95% (21/22) for HCV genotype 4. Among patients with Stage 4 or 5 chronic kidney diseases, 99% (113/114) achieved SVR12. In univariate analyses, variables significantly associated with per protocol SVR12 for the entire sample were therapy duration (P = 0.001), treatment experience (P = 0.016), and cirrhosis status (P = 0.001). However, among HCV genotype 1 patients, no variables were significant. Intent–to–treat SVR12 rates were 89% (396/447) for HCV genotype 1 and 91% (21/23) for HCV genotype 4.
Conclusion: Elbasvir–grazoprevir is highly effective, and in this 2016 cohort, its use was predominantly in patients with HCV genotype 1 and as a 12–week therapy without ribavirin.Introduction
In the United States, approximately 2.7 million persons are chronically infected with hepatitis C virus (HCV), which increases the risks of developing cirrhosis and hepatocellular carcinoma. Fortunately, successful treatment can lead to regression of hepatic fibrosis and reduces the likelihood of liver–related complications. Historically, treatment for HCV was limited to combination therapy with the immunomodulator peginterferon and the broad–spectrum anti–viral ribavirin. Interferon and ribavirin combination regimens were long in duration, difficult to administer, poorly tolerated and frequently ineffective. The recent advent of targeted anti–virals to HCV has dramatically changed the treatment landscape, providing options for shorter, simpler and better–tolerated regimens with high likelihood of cure. However, the initial direct–acting anti–viral (DAA) regimens were not approved in certain patient subpopulations, such as those with advanced kidney disease. Patients with renal dysfunction have a higher prevalence of HCV than the general population (9.5% vs 1.6%), and HCV–infected patients on hemodialysis have a higher risk of mortality vs uninfected patients.[6,7]
Background The contribution of the hemoglobin concentration to the incidence of hemorrhagic or ischemic stroke in patients undergoing hemodialysis is unclear.
Methods In total, 3436 patients undergoing prevalent hemodialysis were followed up for 4 years. The primary outcome was the first development of hemorrhagic or ischemic stroke. The baseline hemoglobin concentration was divided into quartiles [hemoglobin (g/dL): Q1, ≤9.7; Q2, 9.8–10.5; Q3, 10.6–11.1; Q4, ≥11.2]. The association between the hemoglobin concentration and each type of stroke was examined using the Kaplan–Meier method and a Cox proportional hazards model.
Results During the follow-up period, 76 (2.2%) patients developed hemorrhagic stroke and 139 (4.0%) developed ischemic stroke. The 4-year incidence rate of hemorrhagic stroke was significantly higher in patients with lower hemoglobin concentrations. Compared with the quartile of patients with the highest hemoglobin concentrations (Q4), the multivariable-adjusted hazard ratios for hemorrhagic stroke were 1.18 (95% confidence interval, 0.56–2.51), 1.59 (0.82–3.21) and 2.31 (1.16–4.73) in patients in Q3, Q2 and Q1, respectively. No association was identified between the 4-year incidence rate of ischemic stroke and the hemoglobin concentration. Compared with the quartile of patients with the lowest hemoglobin concentrations (Q1), the multivariable-adjusted hazard ratios for ischemic stroke were 1.17 (95% confidence interval, 0.73–1.89), 0.88 (0.51–1.51) and 1.10 (0.66–1.83) in patients in Q2, Q3 and Q4, respectively.
Conclusions Our results suggest that low hemoglobin concentrations are associated with a high risk of hemorrhagic stroke, but not of ischemic stroke, in patients undergoing hemodialysis.Introduction
Stroke is a major cause of death and disability in patients undergoing maintenance hemodialysis (HD).[1–3] Approximately 7% of deaths in patients undergoing HD in Japan are still caused by stroke despite the fact that these patients have improved longevity and reduced rates of cardiovascular death. Therefore, identifying the risk factors for stroke is urgently needed to facilitate improvements in the prognosis of patients undergoing HD.
A close relationship between high hemoglobin concentrations and the incidence of stroke has been highlighted in the field of chronic kidney disease (CKD), including HD therapy. The Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT) was a large-scale randomized controlled trial involving patients with CKD receiving an erythropoiesis-stimulating agent (ESA). The TREAT study showed that there was a double risk of stroke in the patient group with higher target hemoglobin concentrations. High hemoglobin concentrations increase blood viscosity and promote thrombosis, which may at least in part explain the association between high hemoglobin concentrations and ischemic stroke. However, the TREAT study did not address the risk of ischemic stroke separate from hemorrhagic stroke.
Low hemoglobin concentrations have also emerged as an established risk factor for the development of cardiovascular disease in the general population and in patients with CKD.[7,8] The interactions among a poor cardiovascular prognosis, kidney function and anemia form a vicious circle termed cardiorenal anemia syndrome.
The Q-Cohort Study was a multicenter, prospective observational study of patients undergoing HD at 39 dialysis facilities in Fukuoka and Saga Prefectures in Kyushu, Japan.[13–16] A total of 3598 outpatients aged >18 years who underwent prevalent HD participated in the study. All participants were enrolled from December 2006 to December 2007 and followed up until December 2010. Patients without demographic data (n = 65) and patients whose outcomes were missing (n = 97) were excluded. The remaining 3436 patients were analyzed in this study. All patients provided written informed consent. The Q-Cohort Study was approved by the Kyushu University Institutional Review Board for Clinical Research (Approval Number: 20–31) and was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN000000556). The study was performed according to the Ethics of Clinical Research (Declaration of Helsinki) requirements.Definition of Outcomes
The primary outcomes were the incidence of first development of hemorrhagic or ischemic stroke. The definitions of each type of stroke were previously published. Briefly, stroke was defined as sudden onset of a neurological deficit persisting for more than 24 h. The types of stroke were determined by the attending physician using imaging of the brain, including computed tomography and magnetic resonance imaging. All events were collected from the paper medical records by the local physician in each dialysis facility. Each of these physicians checked the medical records for the occurrence of specified outcomes and reported them to the steering committee annually. Subarachnoid hemorrhage and hemorrhage after ischemic stroke were excluded from the definition of hemorrhage stroke. During the follow-up period, three patients developed both hemorrhagic and ischemic stroke. They were classified as having developed the first type of stroke and were censored for the subsequent stroke.Measurement of Hemoglobin Concentration
For measurement of the baseline hemoglobin concentration, blood samples were collected from a vascular access in the recumbent position before dialysis after a 2-day interdialytic interval. The hemoglobin concentration was measured using standard procedures at multiple facilities depending on the location of each dialysis center.
The purpose of this cross-sectional observational study was to identify ethnic differences in body composition and obesity-related risk factors between Chinese and white males living in China. 115 Chinese and 114 white male pilots aged 28–63 years were recruited. Fasting body weight, height and blood pressure were measured following standard procedures. Whole-body and segmental body composition were measured using an 8-contact electrode bioimpedance analysis (BIA) system. Fasting serum glucose, fasting plasma total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were assessed using automatic biochemistry analyzer. After adjusting for age and body mass index (BMI), Chinese males had significantly higher percentage of body fat (PBF) both with respect to whole body (Chinese: 23.7%±0.2% vs. Whites: 22.4%±0.2%) and the trunk area (Chinese: 25.0%±0.3% vs. Whites: 23.2%±0.3%) compared to their white counterparts. At all BMIs, Chinese males had significantly higher fasting glucose levels (Chinese: 5.7±1.0 mmol/L vs. Whites: 5.2±1.0 mmol/L) but lower high-density lipoprotein levels (Chinese: 0.8±1.0 mmol/L vs. Whites: 1.0±1.0 mmol/L) than white males. In addition, a marginally significantly higher diastolic blood pressure was found among Chinese men than that among white men (Chinese: 80±1.0 mmHg vs. Whites: 77±1.0 mmHg). Chinese males had more body fat and a greater degree of central fat deposition pattern than that seen in white males in the present study. Furthermore, data on blood pressure, fasting glucose and blood lipids suggest that Chinese men may be more prone to obesity-related risk factors than white men.Figures
Citation: Wang D, Li Y, Lee SG, Wang L, Fan J, Zhang G, et al. (2011) Ethnic Differences in Body Composition and Obesity Related Risk Factors: Study in Chinese and White Males Living in China. PLoS ONE 6(5): e19835. https://doi.org/10.1371/journal.pone.0019835
Editor: Murielle Bochud, University Institute of Social and Preventive Medicine, Switzerland
Received: December 24, 2010; Accepted: April 18, 2011; Published: May 19, 2011
Copyright: © 2011 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was funded by the Civil Aviation Administration of China, grant number 200 000 RMB; (http://www.caac.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
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