Ladan Golestaneh

Gender and the Prevalence and Progression of Renal Disease

In most experimental models of CKD, male animals progress more rapidly than females. Modulation of the hormonal milieu can replicate the effects of gender on the course of kidney disease. These observations suggest that sex hormones per se may be important determinants of the greater susceptibility of males to progressive kidney injury. The predominance of data in humans suggests that the course of nondiabetic kidney disease is more aggressive in men than women. Male gender is arguably also a risk factor for progression of diabetic nephropathy. Sex hormones directly or indirectly affect many cellular processes by modulating the synthesis of various cytokines, growth factors, and vasoactive agents. In particular, estrogen acts in a receptor-dependent mechanism to regulate genes involved in extracellular matrix metabolism. Estrogen has profound effects on transforming growth factor-β signal transduction and on the renin-angiotensin system. These effects may contribute to alterations in kidney hemodynamics and affect kidney disease progression. Selective estrogen receptor modulators, agents that mimic many of the beneficial effects of estrogen without reproducing estrogens deleterious effects on reproductive tissue, ameliorate the course of kidney disease in animal models and in postmenopausal women.

Blood oxygenation level-dependent MRI for assessment of renal oxygenation

Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) has recently emerged as an important noninvasive technique to assess intrarenal oxygenation under physiologic and pathophysiologic conditions. Although this tool represents a major addition to our armamentarium of methodologies to investigate the role of hypoxia in the pathogenesis of acute kidney injury and progressive chronic kidney disease, numerous technical limitations confound interpretation of data derived from this approach. BOLD MRI has been utilized to assess intrarenal oxygenation in numerous experimental models of kidney disease and in human subjects with diabetic and nondiabetic chronic kidney disease, acute kidney injury, renal allograft rejection, contrast-associated nephropathy, and obstructive uropathy. However, confidence in conclusions based on data derived from BOLD MRI measurements will require continuing advances and technical refinements in the use of this technique.

Meropenem removal in critically ill patients undergoing sustained low-efficiency dialysis (SLED)

BACKGROUND The purpose of this study was to examine the removal of meropenem during an 8-h sustained low-efficiency dialysis (SLED) session. Using a minimum inhibitory concentration (MIC) = 2 microg/mL as our reference point, we also evaluated the therapeutic adequacy of dosing meropenem as 1 g every 12 h during SLED. METHODS This was a prospective, open-label study involving 10 intensive care unit patients with renal failure needing SLED. Meropenem was dosed as 1 g every 12 h. To ensure a steady state, the patients received at least two doses prior to the study. SLED was initiated at least 2 h after the last meropenem dose, and each session was at least 8 h. Blood samples were collected during SLED at 0, 2, 4 and 8 h. The 8-h sample approximated the trough level. After centrifuging the samples, the supernatants were analysed by high-performance liquid chromatography. RESULTS Most patients were male with a mean age of 63.7 years and a mean weight of 88.9 kg. The SLED prescription was based on each patients needs, and the blood flow, dialysate flow and ultrafiltration rates varied by up to 150 mL/min. The mean reduction of plasma meropenem concentration was 79.1 +/- 7.3%, and the mean half-life was 3.6 +/- 0.8 h during the 8-h SLED. Significantly more meropenem was removed in the first 4 h of SLED compared with the rest of the sessions. The mean plasma trough concentration was 4 +/- 1.6 microg/mL. CONCLUSIONS Meropenem was significantly removed from the blood compartment during SLED. Dosing 1 g of meropenem every 12 h during a typical 8-h SLED session maintains adequate plasma concentrations.

Vascular access in therapeutic apheresis: Update 2013

This review addresses the types of vascular access available for patients who need therapeutic apheresis (TA). As in hemodialysis, vascular access for TA is chosen based on type of procedure prescribed, the patients vascular anatomy, the acuity, frequency and duration of treatment, and the underlying disease state. The types of access available include peripheral vein cannulation, central venous catheters: including nontunneled and tunneled catheters, arterio‐venous grafts and arterio‐venous fistulas. Peripheral veins and central venous catheters are most frequently utilized for the acute administration of TA, and may be used over a period of weeks to months. Arterio‐venous grafts and fistulas are not commonly used in TA procedures, but are an option in patients with an anticipated long course of TA, usually for a period of several months or years. The types and frequency of complications associated with various types of vascular access, including: access dysfunction and infections are reviewed, and strategies for their prevention and management are offered. J. Clin. Apheresis 28:64–72, 2013.

Removal of vancomycin in sustained low-efficiency dialysis (SLED): a need for better surveillance and dosing

AIMS This study was designed to evaluate the extent of vancomycin removal from the blood compartment during sustained low-efficiency dialysis (SLED) and the efficacy of our current vancomycin dosing practice. MATERIAL 10 ICU patients were selected. They all had oliguric renal failure requiring SLED and were on vancomycin therapy. SLED was provided with the Fresenius 2000K machine and used an AV400 polysulfone dialyzer (sieving coefficient for vitamin B12 = 1, and surface area = 0.7 m2). METHOD SLED prescriptions were individualized for each patient but the duration for all was at least 8 hours. The blood flow rate (Qb) and dialysate flow rate (Qd) did not vary between patients by greater than 100 cc per minute. Blood samples were drawn at 0, 2, 4, and 8 hours to determine the extent of reduction in vancomycin level. RESULTS The total reduction of vancomycin was about 36% with an 8-hour treatment, when following a typical SLED prescription. Serum vancomycin levels dropped below the therapeutic window (< 15 mcg/ml) at the end of an 8-hour SLED session in almost half of the patients. Drug removal was greatest during the first 4 hours (29.5 +/- 6.5%) compared to the last 4 hours (9.1 +/- 7.4%) of SLED. CONCLUSIONS Vancomycin removal during a typical 8-hour SLED treatment approaches 36%. SLED patients are at risk for undertreatment of their infections. A redosing strategy should be considered if the estimated or measured predialysis level is 20 - 30 mcg/ml. Vancomycin should be redosed with at least 500 mg in most patients at the completion of the SLED. Therapeutic drug monitoring (TDM) is an essential part of any dosing scheme, until further studies are done.

Sex and the Risk of AKI Following Cardio-thoracic Surgery: A Meta-Analysis

BACKGROUND AND OBJECTIVES Being a woman is a well established risk factor for the development of cardiothoracic surgery-associated AKI. In striking contrast, women are less likely to develop AKI associated with noncardiac surgical procedures than men. In an attempt to ascertain why being a woman might be protective for ischemic AKI after general surgery but deleterious in patients undergoing cardiothoracic surgery, we examined cardiothoracic surgery-associated AKI in greater detail. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a systematic review and meta-analysis of cardiothoracic surgery-associated AKI studies published between January of 1978 and December of 2015 to further explore the relationship between sex and cardiothoracic surgery-associated AKI. RESULTS Sixty-four studies were identified that provided sex-specific data regarding the incidence of cardiothoracic surgery-associated AKI among 1,057,412 subjects. Using univariate analysis, women were more likely than men to develop AKI postoperatively (odds ratio, 1.21; 95% confidence interval, 1.09 to 1.33; P<0.001). However, when the analysis was restricted to the 120,464 subjects reported in 29 studies that used the Acute Kidney Injury Network criteria, the RIFLE criteria, or the Kidney Disease Improving Global Outcomes criteria to define AKI, there was no significant sex-related difference in risk. Seventeen studies used multivariate analysis to assess risk factors for cardiothoracic surgery-associated AKI and provided sex-specific odd ratios. Among the 1,587,181 individuals included in these studies, the risk of developing cardiothoracic surgery-associated AKI was not significantly associated with sex (odds ratio, 1.04; 95% confidence interval, 0.92 to 1.19; P=0.51). However, when the analysis was restricted to the 5106 subjects reported in four studies that used the Acute Kidney Injury Network criteria to define AKI, the risk of developing AKI was significantly lower in women compared with in men (odds ratio, 0.75; 95% confidence interval, 0.65 to 0.87; P<0.001). CONCLUSIONS Our systematic review and meta-analysis contradict the generally held consensus that being a woman is an independent risk factor for the development of cardiothoracic surgery-associated AKI.

Acute kidney injury as a causal factor in mortality associated with hepatorenal syndrome

PurposeWe examine how acute kidney injury (AKI) contributes to mortality in patients with liver failure.ContentHepatorenal syndrome (HRS) is a form of AKI in cirrhotic patients, which is defined as a purely physiologic derangement in renal function without any effect on renal parenchyma. Recent literature challenges this understanding. Little attention is paid to the presence of renal pathology and inflammatory alterations that occur as a result of HRS and their contribution to morbidity and mortality. In this paper, we propose that any type of AKI in the presence of liver disease is an inflammatory condition. The combination of AKI and liver failure produces a “toxic milieu” of cytokines, chemokines, and nitric oxide pathway metabolites that directly cause endothelial dysfunction affecting multiple organ systems. These global effects contribute to the increased short- and long-term mortality which has been established in the epidemiologic literature.

Hypercoagulability in a patient with chronic chyluria, proteinuria and hypoalbuminaemia

We describe the case of a young man with prolonged and severe chyluria from a previous parasitic infection. He presented with an acute myocardial infarction most likely secondary to increased clotting tendency. He had a spontaneously formed blood clot in his left anterior descending coronary artery. In the setting of hypo-albuminemia (which has occurred because of obligate losses of protein from lymphuria), he has increased production of factor VIII levels and increased clotting tendency. In addition, because of obligate and unregulated fluid losses he has chronic dehydration, miscrovascular ischemia and secondary polycythemia. This polycythemia further increases his risk of hypercoagulability.

Hidden conflicts of interest in continuing medical education

2128 www.thelancet.com Vol 390 November 11, 2017 Continuing medical education (CME) is an integral part of postgraduate training for medical professionals in the USA and globally. CME enables physicians to maintain and gain knowledge and skills that ensure optimal medical care and outcomes for patients. For these reasons CME is a required component of licensure in the USA. Since most physicians regularly complete CME hours, conflicts of interest that could introduce bias into CME must be avoided to prevent potentially detrimental downstream effects on patient care. However, joint provider activities, which can be undertaken between accredited providers of CME activities and medical education and communication companies (MECCs), raise serious concerns since they are a source of industry (such as pharmaceutical or device companies) influence on CME that circumvents regulatory oversight. Mitigating the risks arising from joint provider activities is needed to preserve the integrity of the CME process. We hope by bringing these new partnerships to light we can refocus attention on hidden conflicts of interest in CME activities. In the USA, physicians must present a certain number of American Medical Association Physician Recognition Award (AMA PRA) CME credits when they apply for renewal of state licences and hospital privileges, and for maintenance of certification with specialty boards. Globally, CME requirements vary. Canada has a maintenance of certification programme similar to the USA, whereas many European countries, Australia, and New Zealand focus on professional development that includes management and social skills training necessary to work in an interdisciplinary health-care system. We focus here on CME activities in the USA and describe differences with other countries where relevant. Physicians in the USA earn AMA PRA credits by participating in educational activities sponsored by CME providers accredited by the Accreditation Council for Continuing Medical Education (ACCME), a non-governmental organisation funded by accredited CME providers and workshop registration fees. ACCME accreditation requires that the CME provider commits to unbiased and scientifically relevant educational content and uses faculty speakers who do not have financial conflicts of interest with the presented material. In some European countries, the funding of CME activities is provided by governmental departments of health but disseminated through medical societies and an emerging CME provider community, both of which are also partly funded by industry. The European Accreditation Council for CME (EACCME) checks the integrity of the content, sets the standards for quality, and accredits content presented. However, critics claim that the ACCME and EACCME are not stringent enough in their oversight, leaving room for influence on content by industry sponsors. Since the early 1990s, US CME providers have partnered directly with the pharmaceutical or device industries to obtain financial support. By 2006 concerns about bias and the promotion of off-label Hidden conflicts of interest in continuing medical education We declare no competing interests. KD is supported by a Wellcome Trust Intermediate Fellowship in Public Health and Tropical Medicine (grant number 201900).

Optimal cut points of plasma and urine neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury among critically ill adults: retrospective determination and clinical validation of a prospective multicentre study

Objectives To determine the optimal threshold of blood and urine neutrophil gelatinase-associated lipocalin (NGAL) to predict moderate to severe acute kidney injury (AKI) and persistent moderate to severe AKI lasting at least 48 consecutive hours, as defined by an adjudication panel. Methods A multicentre prospective observational study enrolled intensive care unit (ICU) patients and recorded daily ethylenediaminetetraacetic acid (EDTA) plasma, heparin plasma and urine NGAL. We used natural log-transformed NGAL in a logistic regression model to predict stage 2/3 AKI (defined by Kidney Disease International Global Organization). We performed the same analysis using the NGAL value at the start of persistent stage 2/3 AKI. Results Of 245 subjects, 33 (13.5%) developed stage 2/3 AKI and 25 (10.2%) developed persistent stage 2/3 AKI. Predicting stage 2/3 AKI revealed the optimal NGAL cutoffs in EDTA plasma (142.0 ng/mL), heparin plasma (148.3 ng/mL) and urine (78.0 ng/mL) and yielded the following decision statistics: sensitivity (SN)=78.8%, specificity (SP)=73.0%, positive predictive value (PPV)=31.3%, negative predictive value (NPV)=95.7%, diagnostic accuracy (DA)=73.8% (EDTA plasma); SN=72.7%, SP=73.8%, PPV=30.4%, NPV=94.5%, DA=73.7% (heparin plasma); SN=69.7%, SP=76.8%, PPV=32.9%, NPV=94%, DA=75.8% (urine). The optimal NGAL cutoffs to predict persistent stage 2/3 AKI were similar: 148.3 ng/mL (EDTA plasma), 169.6 ng/mL (heparin plasma) and 79.0 ng/mL (urine) yielding: SN=84.0%, SP=73.5%, PPV=26.6%, NPV=97.6, DA=74.6% (EDTA plasma), SN=84%, SP=76.1%, PPV=26.8%, NPV=96.5%, DA=76.1% (heparin plasma) and SN=75%, SP=75.8%, PPV=26.1, NPV=96.4%, DA=75.7% (urine). Conclusion Blood and urine NGAL predicted stage 2/3 AKI, as well as persistent 2/3 AKI in the ICU with acceptable decision statistics using a single cut point in each type of specimen.